• Allergy
    • 1

      Allergic Response

      By Joud Hajjar, MD; Lawrence B Schwartz, MD, PhD
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      Allergic Response

      • JOUD HAJJAR, MDAllergy and Immunology Fellow, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
      • LAWRENCE B SCHWARTZ, MD, PHDCharles & Evelyn Thomas Professor of Medicine, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA

      The term hypersensitivity refers to diseases caused by an immune response, regardless of whether the response is against a pathogen, nonpathogen, or self and regardless of whether the response is directed by antibodies, lymphocytes, or innate pathways. The term anaphylaxis was coined in 1902 by Charles Richet, who received the Nobel Prize in 1913; this systemic allergic response is now known to be an immediate hypersensitivity reaction, initiated by allergen delivered to a host having allergen-specific IgE, thereby causing an IgE-mediated immunologic response and activating mast cells and basophils to secrete bioactive mediators. In 2005, the National Institutes of Health organized a consensus conference to develop a working definition of anaphylaxis, designed to be used by physicians at the bedside, as a serious allergic reaction that is rapid in onset, typically eliciting various combinations of cutaneous, cardiovascular, respiratory, and gastrointestinal manifestations, and may cause death.1,2This facilitated the early treatment of such patients with epinephrine. Confusion arises over the misapplication of the term allergy or hypersensitivity to describe any untoward reaction to food, medications, or environmental exposures. Furthermore, non–IgE-mediated forms of local and systemic mast cell or basophil activation events can occur, causing signs and symptoms similar to those mediated by IgE. 

      This review contains 3 figures, 11 tables, and 64 references.

      Keywords: allergy, hypersensitivity, anaphylaxis, interleukin, chemokines, immunoglobulin E, mast cell, eosinophil

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    • 2

      Urticaria and Angioedema

      By Justin R Chen, MD; David A. Khan, MD
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      Urticaria and Angioedema

      • JUSTIN R CHEN, MDFellow Physician, Division of Allergy & Immunology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
      • DAVID A. KHAN, MDProfessor of Internal Medicine and Pediatrics, Division of Allergy & Immunology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX

      Urticaria and angioedema are common diseases with diverse origins that constitute a substantial component of medical practice. Urticaria, or hives, refers to one or more areas of intensely pruritic papules or plaques with swelling of the superficial dermis (wheal) surrounded by local erythema (flare). Angioedema refers to deep dermal subcutaneous swelling that may manifest as swelling of the mucosa of the face, tongue, pharynx, larynx, or intestines that can be alarming and, in some cases, life threatening. These conditions are heterogeneous in their presentation and chronicity. Although allergies are responsible for some cases, autoimmunity and dysregulation of the bradykinin system often play a significant role, leading to challenging diagnostic and therapeutic dilemmas. This review discusses the epidemiology, natural history, pathophysiology, diagnosis, and treatment of acute and chronic urticaria and angioedema. Emphasis is placed on physical triggers, the role of proper laboratory testing, and alternative agents for refractory cases. Emerging therapies for hereditary and acquired angioedema syndromes are also covered. Tables list the causes of acute and chronic urticaria, an escalating treatment approach for difficult cases, and a comparison of available parenteral therapies specific to bradykinin-mediated angioedema. Figures illustrate the mechanisms of urticaria, photographs of typical presentations, and an evidence-based diagnostic algorithm for clinicians. 

      This review contains 9 figures, 8 tables, and 104 references.

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    • 3

      Anaphylaxis

      By Cem Akin, MD, PhD
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      Anaphylaxis

      • CEM AKIN, MD, PHDAssociate Physician, Harvard Medical School, Brigham and Women’s Hospital, Department of Rheumatology, Immunology, and Allergy, Boston, MA

      Anaphylaxis, a serious allergic reaction, is rapid in onset and marked by flushing, urticaria, angioedema, pruritus, bronchospasm, and abdominal cramping with nausea, vomiting, and diarrhea. It is not uncommon; approximate lifetime prevalence of anaphylaxis was estimated to be 0.5 to 2% or possibly higher due to the common academic belief that the incidence of anaphylactic reactions is underreported. Rarely, anaphylaxis may cause death, most commonly from drugs, foods, and insect stings. This review covers the epidemiology, etiology, pathogenesis, diagnosis, clinical manifestations, treatment, and prognosis. Figures show inflammatory pathways in allergic inflammation and mast cell degranulation and pathways of activation. 

      This review contains 2 figures, 5 tables, and 72 references. 

      Keywords: Anaphylaxis, allergy, shock, auto-injector epinephrine, inflammation, mast cell, venom

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    • 4

      Drug Allergies

      By James L Baldwin, MD; Aimee L. Speck, MD
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      Drug Allergies

      • JAMES L BALDWIN, MDDivision Chief, Division of Allergy and Clinical Immunology, Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI
      • AIMEE L. SPECK, MDFellow, Division of Allergy and Clinical Immunology, University of Michigan School of Medicine, Ann Arbor, MI

      Adverse drug reactions (ADRs) are an important public health problem. An ADR is defined by the World Health Organization as an unintended, noxious response to a drug that occurs at a dose usually tolerated by normal subjects. The classification of ADRs by Rawlins and Thompson divides ADRs into two major subtypes: (1) type A reactions, which are dose dependent and predictable, and (2) type B reactions, which are uncommon and unpredictable. The majority of ADRs are type A reactions, which include four subtypes: overdosage or toxicity, side effects, secondary effects, and interactions. Type B reactions constitute approximately 10 to 15% of all ADRs and include four subtypes: drug intolerance, idiosyncratic reactions, pseudoallergic reactions, and drug hypersensitivity reactions. This chapter reviews the epidemiology of ADRs, risk factors for drug hypersensitivity reactions, the classification of drug reactions, diagnostic tests, reactions to specific drugs, and management of the patient with drug allergy. Figures illustrate drugs as haptens and prohaptens, the Gell and Coombs system, the four basic immunologic mechanisms for drug reactions, the chemical structure of different β-lactam antibiotics, penicillin skin testing, sulfonamide metabolism and haptenation, nonsteroidal antiinflammatory drug effects, and patient management. Tables outline the classification of ADRs, drugs frequently implicated in allergic drug reactions, and reagents and concentrations recommended for prick and intradermal skin testing.

      This review contains 8 figures, 9 tables, and 60 references

      Key Words: Adverse drug reactions, drug hypersensitivity reactions, overdosage, toxicity, Type A reactions, Type B reactions, human leukocyte antigen, pruritus, angioedema, urticarial, bronchospasm, laryngeal edema, rhinoconjunctivitis

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    • 5

      Food Allergies

      By Matthew Greenhawt, MD, MBA, MSc
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      Food Allergies

      • MATTHEW GREENHAWT, MD, MBA, MSCAssistant Professor, Division of Allergy and Clinical Immunology, University of Michigan Medical School, University of Michigan Health System, Ann Arbor, MI

      Food allergy represents a rapidly growing public health problem in the United States and other westernized nations. Adverse reactions to foods are categorized as either immunologic or nonimmunologic reactions. This distinction is highly important but often confusing to patients and physicians unfamiliar with allergy, who may simply describe any adverse reaction to a food as an “allergy.” A food allergy is an immune-mediated, adverse reaction to one or more protein allergens in a particular food item involving recognition of that protein by specifically targeted IgE or allergen-specific T cells. This chapter discusses the definition, pathophysiology, epidemiology, testing, management, prognosis, and natural history of food allergy. Clinical manifestations are systematically covered, including cutaneous, respiratory, cardiovascular, and gastrointestinal reactions, as well as eosinophilic esophagitis, food protein–induced enterocolitis syndrome, and oral allergy syndrome. Emerging treatments such as food oral immunotherapy are also reviewed. Tables outline signs and symptoms of immediate hypersensitivity reactions to food, the prevalence of major food allergens in the United States, common patterns of cross-reactivity among foods, clinical criteria for the diagnosis of anaphylaxis, and clinical studies involving treatment for food allergies. Figures illustrate the classification of adverse reactions to food, esophageal histology, visual and radiographic features of eosinophilic esophagitis, and a food allergy action plan.

      This review contains 4 figures, 10 tables, and 66 references.

      KeyWords: Food allergy, Hypersensitivity, IgE-mediated allergy, Eosinophilic esophagitis, Anaphylaxis



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    • 6

      Allergic Rhinitis, Conjunctivitis, and Sinusitis

      By Robert Naclerio, MD
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      Allergic Rhinitis, Conjunctivitis, and Sinusitis

      • ROBERT NACLERIO, MDProfessor and Chief, Department of Surgery, Section of Otolaryngology, Head and Neck Surgery, University of Chicago, Chicago, IL

      Allergic rhinitis is an IgE-mediated inflammatory response in the nose to foreign substances known as allergens. It can be classified as seasonal or perennial, depending on the allergens triggering the reaction. This characterization is good for identifying allergen triggers but is limited because it is based on the duration of outdoor exposure (e.g., grass pollinates for 2 months in Chicago and nearly 11 months in Texas). Also, some perennial allergens, such as dust mites, have seasons. The Allergic Rhinitis in Asthma (ARIA) classification was developed to focus on therapy. It assumes that exposure to perennial and to seasonal allergen leads to the same immunologic response. ARIA places patients into the categories of mild intermittent, mild persistent, moderate/severe intermittent, and moderate/severe persistent to recommend treatment and emphasizes the link between allergic rhinitis and asthma.1

      This review contains 5 figures, 12 tables, and 59 references.

      Key Words: Sinusitis, infection, allergy, antibiotic, decongestant, antihistamine

       

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    • 7

      Anaphylaxis

      By Cem Akin, MD, PhD
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      Anaphylaxis

      • CEM AKIN, MD, PHDAssociate Physician, Harvard Medical School, Brigham and Women’s Hospital, Department of Rheumatology, Immunology, and Allergy, Boston, MA
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    • 8

      Food Allergies

      By Matthew Greenhawt, MD, MBA, MSc
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      Food Allergies

      • MATTHEW GREENHAWT, MD, MBA, MSCAssistant Professor, Division of Allergy and Clinical Immunology, University of Michigan Medical School, University of Michigan Health System, Ann Arbor, MI
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    • 9

      Allergic Rhinitis, Conjunctivitis, and Sinusitis

      By Robert Naclerio, MD
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      Allergic Rhinitis, Conjunctivitis, and Sinusitis

      • ROBERT NACLERIO, MDProfessor and Chief, Department of Surgery, Section of Otolaryngology, Head and Neck Surgery, University of Chicago, Chicago, IL
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    • 10

      Allergic Response

      By Joud Hajjar, MD; Lawrence B Schwartz, MD, PhD
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      Allergic Response

      • JOUD HAJJAR, MDAllergy and Immunology Fellow, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
      • LAWRENCE B SCHWARTZ, MD, PHDCharles & Evelyn Thomas Professor of Medicine, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
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    • 11

      Urticaria and Angioedema

      By Justin R Chen, MD; David A. Khan, MD
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      Urticaria and Angioedema

      • JUSTIN R CHEN, MDFellow Physician, Division of Allergy & Immunology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
      • DAVID A. KHAN, MDProfessor of Internal Medicine and Pediatrics, Division of Allergy & Immunology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
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    • 12

      Drug Allergies

      By James L Baldwin, MD; Aimee L. Speck, MD
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      Drug Allergies

      • JAMES L BALDWIN, MDDivision Chief, Division of Allergy and Clinical Immunology, Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI
      • AIMEE L. SPECK, MDFellow, Division of Allergy and Clinical Immunology, University of Michigan School of Medicine, Ann Arbor, MI
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  • Cardiovascular
    • 1

      Ventricular Arrhythmias

      By Roy M. John, MD, PhD; William G Stevenson, MD
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      Ventricular Arrhythmias

      • ROY M. JOHN, MD, PHDAssociate Director EP Laboratory, Director, Experimental Research, Cardiac Arrhythmia Service, Brigham and Women’s Hospital, Assistant Professor of Medicine, Harvard Medical School, Boston, MA
      • WILLIAM G STEVENSON, MDDirector, Clinical Cardiac Electrophysiology, Brigham and Women’s Hospital, Boston, MA

      Ventricular arrhythmias are common in all forms of heart disease and are an important cause of cardiac arrest and sudden death. Many ventricular arrhythmias are benign but may serve as a marker for underlying disease or its severity. Others are life threatening. The significance of an arrhythmia is determined by the specific characteristics of the arrhythmia and the associated heart disease, and these features guide evaluation and therapy. This review discusses various mechanisms and types of ventricular arrhythmias and management based on clinical presentation (including patients with symptomatic arrhythmia and increased risk of sudden death without arrhythmia symptoms). Genetic arrhythmia syndromes, such as abnormalities of repolarization and the QT interval, catecholaminergic polymorphic ventricular tachycardia (VT), and inherited cardiomyopathies, are discussed in depth. Under the rubric of management of ventricular arrhythmias, drug therapy for ventricular arrhythmias, implantable cardioverter-defibrillators (ICDs), and catheter ablation for VT are also covered. Tables chart out guideline recommendations for ICD therapy, drugs for the management of ventricular arrhythmias, and indications and contraindications for catheter ablation of ventricular arrhythmias. Electrocardiograms are provided, as well as management algorithms for ventricular arrhythmias based on patient presentation, and an algorithm for identifying patients with systolic heart failure and left ventricular ejection less than or equal to 35% who are candidates for consideration of an ICD for primary prevention of sudden cardiac death.

      This review contains 5 figures, 8 tables, and 61 references.

      Keywords: Ventricular arrhythmias, implanted cardioverter-defibrillator (ICD), Ventricular tachycardia (VT), Premature Ventricular Contractions (PVC), Myocardial Infarction (MI), Brugada syndrome, Arrhythmogenic right ventricular cardiomyopathy (ARVC), electrocardiographic (ECG)

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    • 2

      The Cardiac System

      By David C Mauchley, MD
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      The Cardiac System

      • DAVID C MAUCHLEY, MD

      The circulatory system, which consists of the heart, arterial system, venous system, and lymphatics, constitutes a complicated network of vessels and ducts that are responsible for the delivery of oxygenated blood to the body and return of deoxygenated blood to the heart and lungs. The heart is at the center of the circulatory system, and its pumping mechanism provides energy and nutrition to all organs in the body. This review focuses on the anatomy and physiology of the heart and describes anatomic details that are important to the planning of many common cardiac operations.   

      This review contains 28 figures, and 25 references.

      Key words: aortic root, aortic valve, atrial septum, atrioventricular node, coronary artery, fibrous skeleton of heart, mitral valve, myocardium, pericardium, pulmonic valve, sinoatrial node, tricuspid valve, ventricular septum 

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    • 3

      Diseases of the Aorta

      By Anna M Booher, MD; Kim A Eagle, MD
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      Diseases of the Aorta

      • ANNA M BOOHER, MDClinical Assistant Professor, Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI
      • KIM A EAGLE, MDAlbion Walter Hewlett Professor of Internal Medicine, Chief of Clinical Cardiology, Clinical Director, Cardiovascular Center, Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI

      This review covers the major presentations affecting the aorta: aortic aneurysms (abdominal aortic aneurysms and thoracic aortic aneurysms), acute aortic syndromes (including aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcer), other nonacute aortic processes, and traumatic disease of the aorta. The section on abdominal aortic aneurysms covers screening, clinical presentation, diagnostic evaluation, management to reduce the risk of aneurysm rupture, open surgical treatment and endovascular aortic repair, and the role of medical therapy. The section on thoracic aortic aneurysms also covers pathophysiology, etiology, and inherited and inflammatory conditions. Aortic dissections affect either the ascending aorta (type A) or the descending aorta (type B) and may be classified as acute or chronic. The discussion of aortic dissection describes the clinical presentation, diagnostic steps and decisions, and treatment for both type A and type B dissections. The figures include two algorithms: a potential management strategy for patients with thoracic aortic aneurysm and a logical procedure for the evaluation and treatment of a suspected aortic dissection. Figures also include illustrations, computed tomographic images, and echocardiograms of various aortic presentations. Tables list normal aortic dimensions by computed tomographic angiography and echocardiography, etiology and associated factors in diseases of the aorta, revised Ghent criteria for the diagnosis of Marfan syndrome, size criteria for elective surgical intervention in thoracic aortic aneurysm, and independent predictors of in-hospital death. Also included is a follow-up imaging timeline for acute aortic syndromes.

      This review contains 9 figures, 6 tables, and 132 references.

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    • 4

      Congenital Heart Disease in Adults

      By Susan E. Haynes, MD; Heather L. Bartlett, MD; David J Skorton, MD; Luke J Lamers, MD
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      Congenital Heart Disease in Adults

      • SUSAN E. HAYNES, MDAssociate Professor, Department of Pediatrics, University of Iowa Children’s Hospital, Iowa City, IA
      • HEATHER L. BARTLETT, MDAssistant Professor, Department of Pediatrics, Director, Adult Congenital Heart Disease Program, University of Iowa Children’s Hospital, Iowa City, IA
      • DAVID J SKORTON, MDProfessor, Departments of Medicine and Pediatrics, Weill Cornell Medical College, New York, NY and Department of Biomedical Engineering, Cornell University, Ithaca, NY
      • LUKE J LAMERS, MDAssistant Professor, Department of Pediatrics, Director, Pediatric Cardiac Catheterization Laboratory, University of Wisconsin, Madison, WI

      With advances in medical and surgical care, an increasing number of children with congenital diseases of the heart and vasculature now survive to adulthood. The proportion of adults who are affected by congenital heart disease is expected to continue to increase. Thus, it is important for clinicians to be knowledgeable about the care of these patients. This review examines acyanotic disorders (shunts and valvular lesions), vascular anomalies, cyanotic disorders, and women’s health issues. Figures show the anatomy of atrial septal defects, transcatheter closure of atrial septal defects, an anatomic cross section showing the atrioventricular septum, the anatomic positions of ventricular septal defects, a computed tomography scan of aortic coarctation, angiogram of a persistent left superior vena cava draining into the right atrium, systemic artery-to-pulmonary artery shunts, magnetic resonance image of a patient with repaired tetralogy of Fallot and long-standing pulmonary valve insufficiency, treatment of pulmonary valve regurgitation with a transcatheter pulmonary valve, computed tomographic images of a patient with atrial switch palliation of transposition of the great arteries and multiple baffle obstructions, stages in the repair of functional single ventricles, and echocardiograms of a patient with Ebstein anomaly. Tables list recommendations for pulmonary valve replacement in repaired tetralogy of Fallot, conditions in which pregnancy is high risk, and cardiac indications for fetal echocardiography.

      This review contains 12 figures, 4 tables, and 62 references.

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    • 5

      Hypertension

      By Marc P Bonaca, MD, MPH
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      Hypertension

      • MARC P BONACA, MD, MPHVascular Section, Cardiovascular Division, Brigham and Women’s Hospital, Assistant Professor, Harvard Medical School, Boston, MA

      Hypertension is a common chronic disorder with an increasing prevalence in the context of an aging population. Patients with hypertension are at risk for adverse cardiovascular, renal, and neurologic outcomes. Treatment of hypertension reduces this associated risk; therefore, early diagnosis and systematic management are critical in reducing morbidity and mortality. Although hypertension is multifactorial, a large component is related to lifestyle, including excess sodium intake, lack of physical activity, and obesity. Lifestyle intervention and education, therefore, are critical to both prevention and treatment of hypertension. Patients diagnosed with hypertension should be evaluated for their overall risk, with specific therapies and treatment targets guided by their characteristics and comorbidities. Several professional and guideline societies have published recommendations with regard to the diagnosis and treatment of hypertension, which have many similarities but also several areas of discussion and ongoing debate. Recent evolutions in the field include the expanded indications for home-based and ambulatory blood pressure monitoring and outcomes trials, which add important data regarding optimal treatment targets. These evolutions are likely to be addressed in ongoing guideline updates.

      This review contains 10 figures, 15 tables, and 67 references.

      Key words: ambulatory blood pressure monitoring, antihypertensive therapy, blood pressure, blood pressure targets, cardiovascular risk, high blood pressure, home blood pressure monitoring, hypertension, screening, secondary hypertension

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    • 6

      Atrial Fibrillation

      By Gregory F. Michaud, MD; Roy M. John, MD, PhD
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      Atrial Fibrillation

      • GREGORY F. MICHAUD, MDDirector, Center for the Advanced Management of Atrial Fibrillation, Brigham and Women’s, Hospital, Assistant Professor of Medicine, Harvard Medical School, Boston, MD
      • ROY M. JOHN, MD, PHDAssociate Director EP Laboratory, Director, Experimental Research, Cardiac Arrhythmia Service, Brigham and Women’s Hospital, Assistant Professor of Medicine, Harvard Medical School, Boston, MA

      Atrial fibrillation (AF) is an abnormal rhythm characterized by chaotic atrial electrical activity resulting in loss of atrial contraction, an irregular and unpredictable heart rate, and a tendency for thrombus formation. The prevalence of AF is estimated at 1 to 2%, but it’s likely higher than that because one-third of patients may have no symptoms and might never seek medical attention. Data suggest that 1 in 4 people over the age of 40 will develop AF in their lifetime. About 10% of patients over age 80 have experienced the arrhythmia, and some estimates predict the prevalence will double in the next 50 years. This chapter discusses the pathophysiology, genetics, diagnosis, classification, and treatment of AF. Figures show atrial fibrillation and coarse atrial fibrillation plus common right atrial flutter. One algorithm is for oral anticoagulation therapy, and a second shows a recommended hierarchical choice of antiarrhythmic therapies versus catheter ablation for recurrent symptomatic atrial fibrillation. Tables list classification, diagnostic evaluation of, clinical consequences of, and conditions often associated with atrial fibrillation. Three scoring systems are included: 1) for congestive heart failure, hypertension, diabetes, stroke, and transient ischemic attack; 2) to assess the risk of bleeding with oral anticoagulation, and 3) data and proportion of patients from the Euro Heart Survey. Other tables include long-term anticoagulation guidelines for atrial fibrillation, intravenous drugs used for acute rate control, oral drugs used for chronic rate control, and antiarrhythmic drugs for conversion of atrial fibrillation and/or maintenance of sinus rhythm. In addition, there’s a summary of randomized trials weighing rate control and rhythm control strategies, plus schemes for categorizing thromboembolism risk.

      This review contains 4 figures, 15 tables, and 131 references.

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    • 7

      Chronic Stable Angina

      By Benjamin J Scirica, MD, MPH; J. Antonio T. Gutierrez, MD
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      Chronic Stable Angina

      • BENJAMIN J SCIRICA, MD, MPHSenior Investigator, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Associate Professor of Medicine, Harvard Medical School, Boston, MA
      • J. ANTONIO T. GUTIERREZ, MDCardiovascular Medicine Fellow, Brigham and Women's Hospital, Boston, MA

      By definition, chronic stable angina is angina that has been stable with regard to frequency and severity for at least 2 months. Chronic stable angina is the initial manifestation of coronary heart disease in approximately 50% of patients. Typically, this type of angina occurs in the setting of atherosclerotic coronary arterial narrowing, although other causes are possible. This review covers the epidemiology, pathophysiology, initial evaluation, differential diagnosis, management, and treatment of patients with chronic stable angina. Figures show noninvasive testing and the probability of coronary artery disease; diagnosis of patients with suspected ischemic heart disease; probability of severe coronary artery disease; coronary outcomes for high- versus low-intensity statin therapy; optimal medical therapy (OMT) versus OMT and percutaneous coronary intervention for chronic angina; OMT versus percutaneous coronary intervention for stable coronary heart disease; and coronary artery bypass grafting versus percutaneous coronary intervention for diabetes and coronary artery disease. Tables list the grading of angina pectoris by the Canadian Cardiovascular Society classification system, the differential diagnosis of chest pain, conditions promoting myocardial oxygen supply and demand mismatch, the features of typical angina, the classification of chest pain, a comparison of the pretest likelihood of coronary heart disease (CHD) in low-risk and high-risk symptomatic patients, the posttest probability of significant CHD based on pretest probabilities of CHD and normal or abnormal results of noninvasive studies, survival according to risk groups based on Duke treadmill scores, high- and moderate-intensity statin therapy, revascularization to improve survival compared with medical therapy, revascularization to improve symptoms with significant anatomic (≥ 50% left main or ≥ 70% nonleft main coronary artery disease) or physiologic (fractional flow reserve ≤ 0.80) coronary artery stenoses, and questions recommended by an expert panel for patients with chronic stable angina at follow-up visits.

      This review contains 7 highly rendered figures, 13 tables, and 109 references.

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    • 8

      Heart Failure

      By Sachin P Shah, MD; Mandeep R. Mehra, MD
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      Heart Failure

      • SACHIN P SHAH, MDCenter for Advanced Heart Disease, Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA, Director, Cardiovascular Intensive Care Unit, Lahey Hospital and Medical Center, Burlington, MA
      • MANDEEP R. MEHRA, MDMedical Director, Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA

      Heart failure is a syndrome related to abnormal cardiac performance with a consequence of impaired cardiac output at rest or with exertion and/or congestion, which usually leads to symptoms of fatigue, dyspnea, and edema. The syndrome is characterized by various phenotypes related to a vast array of etiologies with diverse management targets. The current broad categorization of heart failure separates patients based on ejection fraction. Further description of the phenotype beyond ejection fraction is imperative to correctly identify the etiology of heart failure and, ultimately, to choose medical, device, and surgical therapies appropriately. This review covers the epidemiology of heart failure, defining the phenotype and etiology of heart failure, recognition and management of acute decompensated heart failure, management of chronic heart failure with a reduced ejection fraction, implantable cardioverter-defibrillators in heart failure with a reduced ejection fraction, management of heart failure with a preserved ejection fraction, and advanced heart failure. Figures show the evolution of therapy in chronic heart failure from the symptom-directed model, the complex pathophysiology and principal aberrations underlying heart failure with preserved ejection fraction, and concepts underlying surgical therapy in advanced heart failure using Laplace’s law. Tables list various etiologies of heart failure; sensitivity and specificity of clinical, biomarker, and radiographic data in the diagnosis of acute decompensated heart failure; drugs and devices with a demonstrated survival benefit in heart failure with a reduced ejection fraction; neurohormonal antagonist dosing in heart failure with a reduced ejection fraction; randomized, placebo-controlled trials in heart failure with a preserved ejection fraction; categorization of heart failure according to American Heart Association/American College of Cardiology heart failure stage, New York Heart Association functional class, and Interagency Registry for Mechanically Assisted Circulatory Support level; and poor prognostic indicators in heart failure.

      This review contains 4 figures, 8 tables, and 114 references.

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    • 9

      Venous Thromboembolism

      By Samuel Z. Goldhaber, MD
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      Venous Thromboembolism

      • SAMUEL Z. GOLDHABER, MDProfessor of Medicine, Harvard Medical School Director, Venous Thromboembolism Research Group

      Venous thromboembolism, which involves venous thrombosis and pulmonary embolism, is a leading cause of morbidity and mortality in hospitalized patients and is being seen with increasing frequency in outpatients. This chapter discusses the risk factors, etiology, classification, pathophysiology, natural history, prognosis, diagnosis (including venous thrombosis, recurrent venous thrombosis, and pulmonary embolism), prophylaxis, and treatment of venous thromboembolism (including the pharmacology of antithrombotic agents), as well as venous thromboembolism in pregnancy and miscellaneous thromboembolic disorders (including thrombosis of unusual sites). 

      This review contains 8 figures, 16 tables, and 79 references.

      Keywords: Venous thromboembolism, pulmonary embolism, deep vein thrombosis, embolectomy, thrombolysis, hypercoagulability, duplex ultrasonography, D-dimer, anticoagulation

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    • 10

      Risk Factors and Epidemiology of Pulmonary Embolism

      By Aaron B Waxman, MD, PhD; Aaron W Aday, MD
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      Risk Factors and Epidemiology of Pulmonary Embolism

      • AARON B WAXMAN, MD, PHDPulmonary and Critical Care Medicine, Director, Pulmonary Vascular Disease Program, Executive Director, Center for Pulmonary-Heart Diseases, Brigham and Women’s Hospital Heart and Vascular Center, Associate Professor of Medicine/Harvard Medical School, Boston, MA
      • AARON W ADAY, MDDivision of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States

      More than 200,000 individuals are hospitalized with an acute pulmonary embolism in the United States annually. Despite advances in diagnosis and treatment, pulmonary embolism accounts for nearly 1% of all cardiovascular-related deaths each year in the United States alone. Those who survive an acute episode remain at a risk of recurrent events as well as ongoing dyspnea, reduced quality of life, and chronic thromboembolic pulmonary hypertension. Recognized risk factors for pulmonary embolism include advanced age, obesity, smoking, malignancy, immobilization from any cause, pregnancy and the postpartum period, oral contraceptives, and hormone replacement therapy. Numerous heritable and acquired thrombophilias increase the risk of pulmonary embolism. Additionally, inflammation and autoimmune disorders are increasingly recognized as potent risk factors for pulmonary embolism.

      This review contains 3 figures, 6 tables, 54 references.

      Key Words: anticoagulation, deep vein thrombosis, epidemiology, genetics, inflammation, malignancy, pulmonary embolism, thrombosis, venous thromboembolism

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    • 11

      Aortic Valve Stenosis

      By Stephen H Little, MD, FRCPC, FACC, FASE; Jeffrey R Parker, MD
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      Aortic Valve Stenosis

      • STEPHEN H LITTLE, MD, FRCPC, FACC, FASEMedical Director, Valve Clinic, Houston Methodist Hospital, Houston, TX, United States
      • JEFFREY R PARKER, MDHouston Methodist Hospital, Houston, TX, United States

      Valvular heart disease is a common clinical syndrome that physicians face on a routine basis. Aortic stenosis (AS) accounts for a substantial amount of these cases with differing etiologies from rheumatic, congenital bicuspid to calcific AS. Clinical history and physical examination can assist in assessing the presence and severity of AS, but echocardiography has been the gold standard for the diagnosis of AS and to assess severity. Multimodality imaging including cardiac computed tomography, magnetic resonance imaging, and 3D printing have evolved over the years, lending aid in the diagnosis and prognostication of AS. This review provides a succinct overview of the prevalence, pathophysiology, clinical assessment, and diagnosis of AS.

      This review contains 10 figures, 3 tables and 49 references.

      Key Words: aortic stenosis, cardiac computed tomography, cardiac magnetic resonance imaging, 3D printing, low-flow low-gradient aortic stenosis

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    • 12

      Diseases of the Pericardium, Cardiac Tumors, and Cardiac Trauma

      By Terrence D. Welch, MD; Salima Shafi, MD; Jae K. Oh, MD
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      Diseases of the Pericardium, Cardiac Tumors, and Cardiac Trauma

      • TERRENCE D. WELCH, MDAssistant Professor of Medicine, Section of Cardiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
      • SALIMA SHAFI, MDCardiovascular Consultant, United Heart and Vascular Clinic, St. Paul, MN
      • JAE K. OH, MDSamsung Professor of Cardiovascular Diseases, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN

      The pericardium consists of an outer fibrous layer and an inner serous layer. The serous layer covers the surface of the heart and the proximal portion of the large vessels (visceral pericardium), folds back on itself, and lines the fibrous layer (parietal pericardium). Normal pericardial thickness is less than or equal to 2 mm. The space between the visceral and the parietal layer forms the pericardial cavity, which normally contains 10 to 50 mL of fluid. The pericardium lubricates and reduces friction, serves as a barrier against infection, maintains the heart in a relatively stable position within the thoracic cavity, and prevents acute distention of the cardiac chambers. None of these functions, however, is essential for life, and the pericardium may, in fact, be absent at birth.

      This review contains 16 figures, 1 table, and 50 references.

      Key Words: Pericardium, parietal pericardium, visceral pericardium

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    • 13

      Unstable Angina and Other Acute Coronary Syndromes

      By R Scott Wright, MD, FACC, FESC, FAHA; Joseph G Murphy, MD, FACC, FESC
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      Unstable Angina and Other Acute Coronary Syndromes

      • R SCOTT WRIGHT, MD, FACC, FESC, FAHAProfessor of Medicine, Consultant in Cardiology and the Coronary Care Unit, Mayo Clinic, Rochester, MN
      • JOSEPH G MURPHY, MD, FACC, FESCProfessor of Medicine, Consultant in Cardiology and the Coronary Care Unit, Chair, Section of Scientific Publications, Mayo Clinic, Rochester, MN

      Patients with coronary artery disease (CAD) present clinically when their disease enters an unstable phase known as an acute coronary syndrome (ACS), in which the cap of a previously stable atheromatous coronary plaque ruptures or erodes, which in turn activates a thrombotic cascade that may lead to coronary artery occlusion, myocardial infarction (MI), cardiogenic shock, and patient death. There are nearly 2 million episodes of ACS in the United States annually; it is the most common reason for hospitalization with CAD and is the leading cause of death in the developed world.

      This review contains 2 figures, 13 tables, and 78 references.

      Key Words: coronary artery disease, myocardial infarction, cardiogenic shock

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    • 14

      Medical Management of Pulmonary Arterial Hypertension

      By Inderjit Singh, MD, MRCPI ; Aaron B Waxman, MD, PhD
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      Medical Management of Pulmonary Arterial Hypertension

      • INDERJIT SINGH, MD, MRCPI Department of Pulmonary and Critical Care Medicine Brigham and Women’s Hospital Harvard Medical School Boston, USA
      • AARON B WAXMAN, MD, PHDPulmonary and Critical Care Medicine, Director, Pulmonary Vascular Disease Program, Executive Director, Center for Pulmonary-Heart Diseases, Brigham and Women’s Hospital Heart and Vascular Center, Associate Professor of Medicine/Harvard Medical School, Boston, MA

      The medical management of pulmonary arterial hypertension (PAH) has advanced considerably over the years. Once the diagnosis of PAH is made, the medical management includes both conventional and PAH-pathway specific therapies. Five different classes of drugs are now available targeting the endothelin, prostacyclin, and nitric oxide pathways (i.e. endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, prostacyclin analogues, and prostacyclin receptor agonists). These targeted therapies are approved for treatment of patients with PAH and chronic thromboembolic pulmonary hypertension (CTEPH) only. Long-term and event-driven studies of novel drugs have led to further improvement in the medical management of PAH and CTEPH. In this review, we will focus on the medical management of patients with PAH and CTEPH.

       

      This review contains 4 figures, 7 Tables and 50 references

      Keywords: Pulmonary arterial hypertension, Chronic thromboembolic pulmonary hypertension, Medical management, Pulmonary vasodilators, Phosphodiesterase inhibitor, Soluble guanylate cyclase stimulator, Endothelin receptor antagonist, Prostacyclin receptor agonist

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    • 15

      Valvular Heart Disease - Part II

      By Miriam S. Jacob, MD; Brian P Griffin, MD
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      Valvular Heart Disease - Part II

      • MIRIAM S. JACOB, MDAdvanced Fellow in Heart Failure, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland OH
      • BRIAN P GRIFFIN, MDJohn and Rosemary Brown Chair in Cardiovascular Medicine, Cleveland Clinic, Cleveland OH

      Valvular heart disease is an important cause of cardiac morbidity in developed countries despite a decline in the prevalence of rheumatic disease in those countries. This chapter discusses the many etiologies of valvular heart disease and presents methods for assessment and management. Specific valvular lesions discussed include mitral stenosis, mitral regurgitation, mitral valve prolapse, aortic stenosis, aortic regurgitation, and tricuspid and pulmonary disease. The section on tricuspid disease includes a discussion of mechanical prostheses (ball-in-cage and tilting-disk) and biologic prostheses (xenografts, allografts, and autografts) and their complications. 

      This review contains 5 figures, 9 tables, and 53 references.

      Keywords: Valvular heart disease, stenosis, regurgitation, mitral regurgitation, mitral valve prolapse (MVP), aortic stenosis, congenital bicuspid valve, senile valvular calcification, aortic regurgitation, chordae or papillary muscles

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    • 16

      Valvular Heart Disease - Part I

      By Miriam S. Jacob, MD; Brian P Griffin, MD
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      Valvular Heart Disease - Part I

      • MIRIAM S. JACOB, MDAdvanced Fellow in Heart Failure, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland OH
      • BRIAN P GRIFFIN, MDJohn and Rosemary Brown Chair in Cardiovascular Medicine, Cleveland Clinic, Cleveland OH

      Valvular heart disease is an important cause of cardiac morbidity in developed countries despite a decline in the prevalence of rheumatic disease in those countries. This chapter discusses the many etiologies of valvular heart disease and presents methods for assessment and management. Specific valvular lesions discussed include mitral stenosis, mitral regurgitation, mitral valve prolapse, aortic stenosis, aortic regurgitation, and tricuspid and pulmonary disease. The section on tricuspid disease includes a discussion of mechanical prostheses (ball-in-cage and tilting-disk) and biologic prostheses (xenografts, allografts, and autografts) and their complications. 

      This review contains 6 figures, 13 tables, 69 references.

      Keywords: Valvular heart disease, stenosis, regurgitation, mitral regurgitation, mitral valve prolapse (MVP), aortic stenosis, congenital bicuspid valve, senile valvular calcification, aortic regurgitation, chordae or papillary muscles

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    • 17

      Syncope

      By Annalee M Baker, MD
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      Syncope

      • ANNALEE M BAKER, MDAttending Physician and Clinical Instructor, Ronald O. Perelman Department of Medicine, NYU Langone Medical Center, Bellevue Hospital, New York, NY

      Syncope is a common presenting complaint in the emergency department, accounting for approximately 1 to 3% of presentations and up to 6% of admissions. Syncope is properly defined as a brief loss of consciousness and postural tone followed by spontaneous and complete recovery. Often syncope must be distinguished from other etiologies of transient loss of consciousness, such as seizures and hypoglycemia. Comprehension of the pathogenesis, clinical presentation, and prognosis of the varied causes of syncope is essential if emergency physicians are to succeed in identifying patients at risk for adverse events while also reducing unnecessary syncope admissions. This review covers the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes of syncope. Figures show heart block, prolonged QTc and torsades de pointes, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, and Brugada syndrome. 

      This review contains 6 figures, 15 tables, and 58 references.

      Keywords: Syncope, near-syncope, pre-syncope, arrhythmia, dysrhythmia, sudden cardiac death, vasovagal, passing out, neurocardiogenic

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    • 18

      Medical Management of Lower Extremity Manifestations of Peripheral Artery Disease

      By Mary M. McDermott, MD
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      Medical Management of Lower Extremity Manifestations of Peripheral Artery Disease

      • MARY M. MCDERMOTT, MDDepartment of Medicine, and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL

      Lower extremity peripheral artery disease (PAD) affects eight million people in the United States and over 200 million men and women worldwide. Furthermore, recent evidence from the Global Disease Burden suggests that the prevalence of PAD increased worldwide by 20% between 2000 and 2010. Patients with PAD are at increased risk for cardiovascular events, functional impairment, and mobility loss. With advancements in medical science and improved treatments for cardiovascular disease, rates of cardiovascular events have declined in the United States and in other high socioeconomic countries. Consequently, people are living longer with chronic debilitating diseases, such as PAD. Optimal medical management of patients with PAD is essential to help these patients survive longer with optimal quality of life and without disability. This review covers medical therapies to improve lower extremity functioning in people with PAD, additional medications to improve walking performance in PAD, and both walking and nonwalking exercise interventions for lower extremity PAD,  Tables outline outcome measures typically used to assess improvement in response to medical therapies for PAD; FDA-approved medications and medications that may be beneficial but are not FDA-approved for intermittent claudication symptoms; exercise therapies that benefit patients with PAD; and additional considerations regarding exercise therapy in PAD. Graphs showcase ramipril versus placebo and changes in walking time according to home-based versus supervised walking exercise.

      This review contains 2 figures, 5 tables, and 68 references.

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    • 19

      Peripheral Artery Diseases

      By Mark A Creager, MD
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      Peripheral Artery Diseases

      • MARK A CREAGER, MD Professor of Medicine, Harvard Medical School, Director, Vascular Center, Head, Vascular Medicine Section, Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA

      Peripheral arterial diseases (PADs) compromise blood flow to the limbs. Common causes of arterial obstruction include atherosclerosis, thrombus, embolism, vasculitis, arterial entrapment, adventitial cysts, fibromuscular dysplasia, arterial dissection, trauma, and vasospasm. The most frequently encountered cause of PAD is peripheral atherosclerosis. This chapter considers its epidemiology and risk factors, as well as its diagnosis, including clinical presentation and noninvasive diagnostic tests. This chapter also discusses acute arterial occlusion, atheroembolism, popliteal artery entrapment, thromboangiitis obliterans, and acrocyanosis, as well as the etiology, diagnosis, and treatment of Raynaud phenomenon. The chapter contains 4 tables and 7 figures. Tables describe the Fontaine classification and clinical categories of chronic limb ischemia, provide examples of leg segmental pressure measurements in a patient with calf claudication and foot pain, and summarize secondary causes of Raynaud phenomenon. Figures include a photograph of an ischemic foot demonstrating dependent rubor, measurement of the ankle:brachial index, ultrasonography of a stenosis of the right common femoral artery, magnetic resonance angiograms of patients with calf claudication, arteriograms of critical ischemia of the foot and of disabling claudication of the leg, and ischemia of the toes caused by atheroemboli. This chapter contains 80 references.

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    • 20

      The Clinical Use of Nonimaging Exercise Stress Testing

      By Aswini Kumar, MD; Brinda Muthuswamy, MD; W Lane Duvall, MD; Paul D Thompson, MD
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      The Clinical Use of Nonimaging Exercise Stress Testing

      • ASWINI KUMAR, MDDivision of Cardiology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT
      • BRINDA MUTHUSWAMY, MDDivision of Cardiology, Hartford Hospital, Hartford, CT
      • W LANE DUVALL, MDHeart and Vascular Institute, Hartford Healthcare, Hartford, CT
      • PAUL D THOMPSON, MDHeart and Vascular Institute, Hartford Healthcare, Hartford, CT

      Exercise stress testing is an exceptionally useful cardiovascular test providing a wealth of information that can be used in patient management. It can be used in the diagnosis and/or management of chest pain, hypertension, arrhythmia, and heart failure.  Non-imaging exercise stress testing not only helps evaluate the etiology of clinical symptoms but also provides an opportunity to evaluate ECG changes with exercise, total exercise capacity, heart rate response or chronotropic index, blood pressure response, heart rate recovery, and to make estimates of the risk of coronary artery disease using tools such as the Duke Treadmill Score.  These parameters, individually and collectively, provide valuable information on the likelihood of disease and an individual’s prognosis. In addition, exercise testing is inexpensive, quick and widely available compared to imaging studies. 

      This review contains 6 figures, 5 tables, and 68 references. 

      Keywords: blood pressure response, chronotropic incompetence, coronary artery disease,
      Duke Treadmill Score, exercise physiology metabolic equivalents (METs), exercise stress test, exercise treadmill test, exercise-induced hypertension, heart rate recovery, maximal exercise capacity, ST-segment deviation

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    • 21

      Acute Pulmonary Embolism

      By Brett J Carroll, MD; Eric A Secemsky, MD, MSc
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      Acute Pulmonary Embolism

      • BRETT J CARROLL, MDDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
      • ERIC A SECEMSKY, MD, MSCDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

      Pulmonary embolism (PE) is a frequently encountered clinical condition with both short- and long-term adverse consequences. An integrated approach to diagnosis is important to maximize early diagnosis but also to minimize the unnecessary utilization of diagnostic imaging. Comprehensive risk stratification with clinical features and assessment of right ventricular strain by diagnostic imaging and cardiac biomarker results are essential to guide initial management decisions. There is a growing treatment arsenal for acute PE, including increased anticoagulation and advanced therapeutic options such as catheter-based therapy.  Despite such advances, mortality remains high, particularly among those who present critically ill with PE, and long-term physical and psychological effects can persist in many patients for years after the initial diagnosis.

      This review contains 7 figures, 6 tables, and 69 references.

      Key Words: anticoagulation, catheter-directed therapy, chronic thromboembolic pulmonary hypertension pulmonary embolism, computed tomography, echocardiography, fibrinolysis, risk stratification, venous thromboembolism

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    • 22

      Pulmonary Arterial Hypertension: Advancing Insights Into a Historically Neglected Disease

      By Michael V. Genuardi, MD, MS; Stephen Y. Chan, MD, PhD
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      Pulmonary Arterial Hypertension: Advancing Insights Into a Historically Neglected Disease

      • MICHAEL V. GENUARDI, MD, MSCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
      • STEPHEN Y. CHAN, MD, PHDCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA

      Pulmonary arterial hypertension (PAH) is a rare spectrum of closely related diseases with myriad genetic, infectious, toxic, and immunologic triggers characterized by pathologic pulmonary vascular remodeling. While the natural history of PAH is marked by progressive dyspnea, hypoxia, right ventricular failure, and death, modern insights into disease pathogenesis, combined with breakthroughs in therapeutics, has greatly improved morbidity and time to disease worsening over the past two decades. Traditionally thought of as a disease of imbalance between vasodilators, such as nitric oxide and prostacyclin, and vasoconstrictors such as endothelin-1, more recent investigations have revealed important roles for perturbations in cellular metabolism, fibroblast activity, extracellular matrix maintenance, and apoptosis which contribute to pulmonary artery smooth muscle cell proliferation. Careful history and physical exam, along with echocardiography and right heart catheterization, remain essential for accurate workup and diagnosis. Cardiopulmonary exercise testing, cardiac magnetic resonance, and genetic testing have important ancillary roles. The number of approved pulmonary vasodilator therapies for PAH continues to expand, with evidence demonstrating the survival benefits of up-front combination therapy. Future prospects of next generation therapies that address the molecular origins of disease combined with comprehensive molecular profiling may usher in a new era of precision medicine for PAH.

      This review contains 7 figures, 5 tables, and 57 references.

      Keywords: pulmonary hypertension, vascular biology, therapeutics, hemodynamics, epidemiology, exercise physiology, genetic basis of disease, connective tissue disease, cardiac magnetic resonance imagining

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    • 23

      Heritable and Acquired Thrombophilias in Clinical Practice

      By Hanny Al-Samkari, MD; Nathan T. Connell, MD, MPH
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      Heritable and Acquired Thrombophilias in Clinical Practice

      • HANNY AL-SAMKARI, MDDivision of Hematology, Massachusetts General Hospital, Boston, MA
      • NATHAN T. CONNELL, MD, MPHHematology Division, Brigham & Women’s Hospital, Boston, MA; Harvard Medical School, Boston, MA

      Thrombosis is common in clinical practice. Venous thromboembolism in particular raises questions of a possible underlying hereditary or acquired thrombophilic state. Despite considerable data describing the impact of various thrombophilic states on risks of initial and recurrent thromboembolic events, thrombophilia testing is not standardized. An understanding of the utility and pitfalls of clinical thrombophilia testing is necessary to employ this testing properly. When utilized appropriately, thrombophilia testing can be vital in informing an individual patient’s thrombosis risk and pursuing optimal anticoagulant management. Hereditary thrombophilia testing involves investigation for factor V Leiden, the prothrombin G202010A gene mutation, and deficiencies of the natural anticoagulants protein C, protein S, and antithrombin. Assessment for acquired thrombophilias is perhaps even more important, recognizing the possibility for myeloproliferative neoplasms, antiphospholipid antibody syndrome, occult malignancy and other important acquired thrombotic predispositions. Timing of thrombophilia testing in relation to anticoagulation, acute thrombosis, and use of hormonal agents or pregnancy is critical to ensure accurate diagnosis. This review describes each of the most important hereditary and acquired thrombophilias, explains their relationship to venous and arterial thrombosis, delineates evidence-based indications for thrombophilia testing, identifies potential testing pitfalls, and synthesizes the key points in outlining algorithms for thrombophilia testing in clinical practice.

      This review contains 4 figures, 4 tables, and 48 references.

      Key words: thrombophilia, venous thromboembolism, pulmonary embolus, deep vein thrombosis, factor V Leiden, prothrombin gene mutation, protein C deficiency, protein S deficiency, antiphospholipid antibody syndrome, hypercoagulability of malignancy

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    • 24

      Hypertension

      By Marc P Bonaca, MD, MPH
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      Hypertension

      • MARC P BONACA, MD, MPHVascular Section, Cardiovascular Division, Brigham and Women’s Hospital, Assistant Professor, Harvard Medical School, Boston, MA
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    • 25

      Chronic Stable Angina

      By Benjamin J Scirica, MD, MPH; J. Antonio T. Gutierrez, MD
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      Chronic Stable Angina

      • BENJAMIN J SCIRICA, MD, MPHSenior Investigator, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Associate Professor of Medicine, Harvard Medical School, Boston, MA
      • J. ANTONIO T. GUTIERREZ, MDCardiovascular Medicine Fellow, Brigham and Women's Hospital, Boston, MA
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    • 26

      Valvular Heart Disease - Part I

      By Miriam S. Jacob, MD; Brian P Griffin, MD
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      Valvular Heart Disease - Part I

      • MIRIAM S. JACOB, MDAdvanced Fellow in Heart Failure, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland OH
      • BRIAN P GRIFFIN, MDJohn and Rosemary Brown Chair in Cardiovascular Medicine, Cleveland Clinic, Cleveland OH
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    • 27

      Valvular Heart Disease - Part II

      By Miriam S. Jacob, MD; Brian P Griffin, MD
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      Valvular Heart Disease - Part II

      • MIRIAM S. JACOB, MDAdvanced Fellow in Heart Failure, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland OH
      • BRIAN P GRIFFIN, MDJohn and Rosemary Brown Chair in Cardiovascular Medicine, Cleveland Clinic, Cleveland OH
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    • 28

      Venous Thromboembolism

      By Samuel Z. Goldhaber, MD
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      Venous Thromboembolism

      • SAMUEL Z. GOLDHABER, MDProfessor of Medicine, Harvard Medical School Director, Venous Thromboembolism Research Group
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    • 29

      Congenital Heart Disease in Adults

      By Susan E. Haynes, MD; Heather L. Bartlett, MD; David J Skorton, MD; Luke J Lamers, MD
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      Congenital Heart Disease in Adults

      • SUSAN E. HAYNES, MDAssociate Professor, Department of Pediatrics, University of Iowa Children’s Hospital, Iowa City, IA
      • HEATHER L. BARTLETT, MDAssistant Professor, Department of Pediatrics, Director, Adult Congenital Heart Disease Program, University of Iowa Children’s Hospital, Iowa City, IA
      • DAVID J SKORTON, MDProfessor, Departments of Medicine and Pediatrics, Weill Cornell Medical College, New York, NY and Department of Biomedical Engineering, Cornell University, Ithaca, NY
      • LUKE J LAMERS, MDAssistant Professor, Department of Pediatrics, Director, Pediatric Cardiac Catheterization Laboratory, University of Wisconsin, Madison, WI
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    • 30

      Risk Factors and Epidemiology of Pulmonary Embolism

      By Aaron B Waxman, MD, PhD; Aaron W Aday, MD
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      Risk Factors and Epidemiology of Pulmonary Embolism

      • AARON B WAXMAN, MD, PHDPulmonary and Critical Care Medicine, Director, Pulmonary Vascular Disease Program, Executive Director, Center for Pulmonary-Heart Diseases, Brigham and Women’s Hospital Heart and Vascular Center, Associate Professor of Medicine/Harvard Medical School, Boston, MA
      • AARON W ADAY, MDDivision of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
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    • 31

      Heart Failure

      By Sachin P Shah, MD; Mandeep R. Mehra, MD
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      Heart Failure

      • SACHIN P SHAH, MDCenter for Advanced Heart Disease, Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA, Director, Cardiovascular Intensive Care Unit, Lahey Hospital and Medical Center, Burlington, MA
      • MANDEEP R. MEHRA, MDMedical Director, Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA
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    • 32

      Atrial Fibrillation

      By Gregory F. Michaud, MD; Roy M. John, MD, PhD
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      Atrial Fibrillation

      • GREGORY F. MICHAUD, MDDirector, Center for the Advanced Management of Atrial Fibrillation, Brigham and Women’s, Hospital, Assistant Professor of Medicine, Harvard Medical School, Boston, MD
      • ROY M. JOHN, MD, PHDAssociate Director EP Laboratory, Director, Experimental Research, Cardiac Arrhythmia Service, Brigham and Women’s Hospital, Assistant Professor of Medicine, Harvard Medical School, Boston, MA
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    • 33

      Ventricular Arrhythmias

      By Roy M. John, MD, PhD; William G Stevenson, MD
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      Ventricular Arrhythmias

      • ROY M. JOHN, MD, PHDAssociate Director EP Laboratory, Director, Experimental Research, Cardiac Arrhythmia Service, Brigham and Women’s Hospital, Assistant Professor of Medicine, Harvard Medical School, Boston, MA
      • WILLIAM G STEVENSON, MDDirector, Clinical Cardiac Electrophysiology, Brigham and Women’s Hospital, Boston, MA
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    • 34

      Aortic Valve Stenosis

      By Stephen H Little, MD, FRCPC, FACC, FASE; Jeffrey R Parker, MD
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      Aortic Valve Stenosis

      • STEPHEN H LITTLE, MD, FRCPC, FACC, FASEMedical Director, Valve Clinic, Houston Methodist Hospital, Houston, TX, United States
      • JEFFREY R PARKER, MDHouston Methodist Hospital, Houston, TX, United States
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    • 35

      Supraventricular Tachycardia

      By Laurence M. Epstein, MD; Saurabh Kumar, BSc(Med)/MBBS, PhD
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      Supraventricular Tachycardia

      • LAURENCE M. EPSTEIN, MDChief, Cardiac Arrhythmia Service, Associate Professor of Medicine, Harvard Medical School, Cardiac Arrhythmia Service, Brigham and Women’s Hospital, Boston, MA
      • SAURABH KUMAR, BSC(MED)/MBBS, PHDAdvanced Clinical Electrophysiology Fellow, Cardiac Arrhythmia Service, Brigham and Woman’s Hospital, Boston, MA

      Supraventricular tachycardias (SVTs) comprise a group of usually benign arrhythmias that originate from cardiac tissue at or above the His bundle. SVTs include inappropriate sinus tachycardia, atrial tachycardias (ATs), atrial flutter (AFL), junctional tachycardia, atrioventricular nodal reentrant tachycardia (AVNRT), and forms of accessory pathway–mediated reentrant tachycardias (atrioventricular reentrant tachycardia [AVRT]). Although mostly benign, symptoms can be debilitating, in the form of palpitations, shortness of breath, chest discomfort, dizziness, and/or syncope; rarely, SVTs can result in cardiomyopathy due to incessant arrhythmia. This review covers the epidemiology, diagnosis, management, and classification of SVTs. 

      This review contains 14 figures, 17 tables, and 61 references.

      Keywords: Supraventricular tachycardia, cardioversion, arrhythmia, atrial flutter, atrial fibrillation, Wolff-Parkinson-White syndrome, MAZE procedure, catheter ablation

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    • 36

      Supraventricular Tachycardia

      By Laurence M. Epstein, MD; Saurabh Kumar, BSc(Med)/MBBS, PhD
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      Supraventricular Tachycardia

      • LAURENCE M. EPSTEIN, MDChief, Cardiac Arrhythmia Service, Associate Professor of Medicine, Harvard Medical School, Cardiac Arrhythmia Service, Brigham and Women’s Hospital, Boston, MA
      • SAURABH KUMAR, BSC(MED)/MBBS, PHDAdvanced Clinical Electrophysiology Fellow, Cardiac Arrhythmia Service, Brigham and Woman’s Hospital, Boston, MA
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    • 37

      Medical Management of Pulmonary Arterial Hypertension

      By Inderjit Singh, MD, MRCPI ; Aaron B Waxman, MD, PhD
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      Medical Management of Pulmonary Arterial Hypertension

      • INDERJIT SINGH, MD, MRCPI Department of Pulmonary and Critical Care Medicine Brigham and Women’s Hospital Harvard Medical School Boston, USA
      • AARON B WAXMAN, MD, PHDPulmonary and Critical Care Medicine, Director, Pulmonary Vascular Disease Program, Executive Director, Center for Pulmonary-Heart Diseases, Brigham and Women’s Hospital Heart and Vascular Center, Associate Professor of Medicine/Harvard Medical School, Boston, MA
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  • Competency-based Patient Care
    • 1

      On Being a Physician

      By Elizabeth G Nabel, MD, FACP
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      On Being a Physician

      • ELIZABETH G NABEL, MD, FACPPresident, Brigham and Women’s Hospital, Professor of Medicine, Harvard Medical School, Boston, MA

      The role of a physician as healer has grown more complex, and emphasis will increasingly be on patient and family-centric care. Physicians must provide compassionate, appropriate, and effective patient care by demonstrating competence in the attributes that are essential to successful medical practice. Beyond simply gaining medical knowledge, modern physicians embrace lifelong learning and need effective interpersonal and communication skills. Medical professionalism encompasses multiple attributes, and physicians are increasingly becoming part of a larger health care team. To ensure that physicians are trained in an environment that fosters innovation and alleviates administrative burdens, the Accreditation Council for Graduate Medical Education has recently revamped the standards of accreditation for today’s more than 130 specialties and subspecialties.

      This review contains six references.

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    • 2

      Ethical and Social Issues in Medicine

      By Roberta Springer Loewy, PhD (PHIL, ETHICS); Erich H. Loewy, MD, FACP (deceased); Faith T. Fitzgerald, MD, MACP
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      Ethical and Social Issues in Medicine

      • ROBERTA SPRINGER LOEWY, PHD (PHIL, ETHICS)Professor and Bioethics Education Consultant, VCF, University of California, Davis, Sacramento, CA
      • ERICH H. LOEWY, MD, FACP (DECEASED)Professor and Founding Chair of the Bioethics Program (Emeritus), University of California, Davis, Sacramento, CA
      • FAITH T. FITZGERALD, MD, MACPProfessor of Internal Medicine, University of California, Davis, Sacramento, CA

      So rapidly has the field of health care ethics continued to grow that, when recently “googled,” the term produced 28.2 million hits. The challenge is to address the ethical and social issues in medicine in this very limited article space. It remains an impossible task to present more than a superficial discussion of these complex issues and the complicated cases in which they are to be found. Like good medicine, good ethics cannot be practiced by algorithm. The authors have opted to provide an operational guide to help clinicians sort through the ethical and social quandaries they must face on a daily basis. To that end, the authors have chosen to divide this chapter into the following sections:
      1. A brief description of the biopsychosocial nature of ethics and how it differs from personal morality
      2. A method for identifying and dealing with ethical issues
      3. A discussion of the role of bioethicists and ethics committees
      4. The professional fiduciary role of clinicians
      5. Listings of some of the common key bioethical and legal terms (online access only)
      6. A very brief discussion of the terms cited in the above listings (online access only)

      This reviews contains 4 tables, 8 references, 1 appendix, and 20 additional readings.

      Keywords: Ethical, social, right, wrong, good, bad, obligation, moral authority, critically reflective, and multiperspectival activity, Curiosity, Honesty, Patience, Open-mindedness

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    • 3

      Quality of Care: Performance Measurement and Quality Improvement in Clinical Practice

      By Sonali P. Desai, MD, MPH; Allen Kachalia, MD, JD
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      Quality of Care: Performance Measurement and Quality Improvement in Clinical Practice

      • SONALI P. DESAI, MD, MPHAmbulatory Director, Patient Safety, Center for Clinical Excellence, Associate Director of Quality, Department of Medicine, Division of Rheumatology, Brigham and Women's Hospital, Boston, MA
      • ALLEN KACHALIA, MD, JDAssociate Chief Quality Officer, Co-Director, Center for Clinical Excellence, Brigham and Women's Hospital, Boston, MA

      Attention to the quality of care within the United States health care system has grown tremendously over the past decade. We have witnessed a significant change in how quality improvement and clinical performance measurement are approached. The current focus on quality and safety stems in part from the increasingly clear realization that more services and technological advancement are not automatically equivalent to high-quality care. Much of the discussion about cost and quality in health care is shifting towards the concept of value. Value is defined as health outcomes achieved per dollar spent (in other words, an assessment of the quality of care per cost). This chapter reviews the current state of quality improvement in health care and, because improvement cannot be determined without measurement, reviews several aspects of effective clinical performance measurement. Since many measures are already in place, the chapter describes some of the organizations involved in quality measurement and improvement, as well the approaches they utilize. It looks at the multiple strategies in place to improve quality, from process management to collaboration, from financial incentives to transparency, and reviews newer models of care delivery that may materialize in the near future. Tables list types of quality measures, characteristics to consider when developing a quality measure, and organizations involved in quality improvement and performance measurement. A figure shows strategies used by the federal government to spur performance measurement and quality improvement.

      This review contains 1 figure, 3 tables, and 56 references

      Keywords: Quality of care, performance measure, quality improvement, clinical practice, sigma six, transparency

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    • 4

      Practicing Evidence-based Medicine

      By Michael Barnett, MD; Niteesh Choudhry, MD, PhD
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      Practicing Evidence-based Medicine

      • MICHAEL BARNETT, MDFellow in General Internal Medicine, Division of General Internal Medicine and Primary Care, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
      • NITEESH CHOUDHRY, MD, PHDAssociate Professor, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

      Today, a plethora of resources for evidence-based medicine (EBM) are available via alert services, compendia, and more. In theory, a clinician researching a topic or looking for information regarding a clinical decision should easily find the literature or synopses needed. However, the real challenge lies in recognizing which resources (out of hundreds or possibly thousands) present the best and most reliable evidence. As well, evidence from research is only part of the decision calculus, and the clinician, not the evidence, makes the final decisions. Medical decision analysis attempts to formalize the process and reduce it to algebra, but it is difficult or impossible to represent all the components of a decision mathematically and validly let alone do so in “real time” for individual patients. This review discusses these challenges and more, including how to ask answerable questions, understand the hierarchy for evidence-based information resources, critically appraise evidence, and apply research results to patient care. Figures show the total number of new articles in Medline from 1965 to 2012, a “4S” hierarchy of preappraised medicine, percentage of physician and medical student respondents with a correct or incorrect answer to a question about calculating the positive predictive value of a hypothetical screening test, a nomogram for Bayes’s rule, an example of nomogram use for pulmonary embolism, and a model for evidence-informed clinical decisions. Tables list selected barriers to the implementation of EBM; Patient, Intervention, Comparison, and Outcome (PICO) framework for formulating clinical questions; guides for assessing medical texts for evidence-based features; clinically useful measures of disease frequency and statistical significance and precision; definitions of clinically useful measures of diagnostic test performance and interpretation; definitions of clinically useful measures of treatment effects from clinical trials; summary of results and derived calculations from the North American Symptomatic Carotid Endarterectomy Trial (NASCET); and selected number needed to treat values for common therapies.

      This review contains 6 highly rendered figures, 9 tables, and 28 references.

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    • 5

      Team Based Care

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      Team Based Care

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    • 6

      Social Determinants of Health

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      Social Determinants of Health

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    • 7

      Leadership in Health Care

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      Leadership in Health Care

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    • 8

      Population Health (biostatistics, Epidemiology, Health Policy and Disparities)

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      Population Health (biostatistics, Epidemiology, Health Policy and Disparities)

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    • 9

      Quality of Care: Performance Measurement and Quality Improvement in Clinical Practice

      By Sonali P. Desai, MD, MPH; Allen Kachalia, MD, JD
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      Quality of Care: Performance Measurement and Quality Improvement in Clinical Practice

      • SONALI P. DESAI, MD, MPHAmbulatory Director, Patient Safety, Center for Clinical Excellence, Associate Director of Quality, Department of Medicine, Division of Rheumatology, Brigham and Women's Hospital, Boston, MA
      • ALLEN KACHALIA, MD, JDAssociate Chief Quality Officer, Co-Director, Center for Clinical Excellence, Brigham and Women's Hospital, Boston, MA
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  • Dermatology
    • 1

      Approach to the Diagnosis of Skin Disease

      By Robert T Brodell, MD; Stephen E Helms, MD; Lindsey B Dolohanty, MD
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      Approach to the Diagnosis of Skin Disease

      • ROBERT T BRODELL, MDProfessor and Chair, Department of Dermatology and Professor of Pathology, University of Mississippi Medical School, Jackson, MI, Instructor in Dermatology, University of Rochester School of Medicine and Dentistry, Rochester, NY
      • STEPHEN E HELMS, MDAssociate Professor of Internal Medicine, Dermatology Section, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio, Assistant Clinical Professor of Dermatology, Case Western Reserve University School of Medicine, Cleveland, Ohio, Professor of Dermatology, University of Mississippi Medical School, Jackson, MI
      • LINDSEY B DOLOHANTY, MDAssistant Professor, Department of Dermatology, University of Rochester School of Medicine, Rochester, NY

      The diagnosis of skin disease is not something that changes radically year to year. In fact, for hundreds of years physicians have been assessing the skin to diagnose and treat skin diseases and  to “view” internal diseases. The latest edition of this review provides several updates that enhance our approach to the diagnosis of skin disease with active links to updated digital references and atlases. These will be valuable to students, residents, and physicians interested in improving their dermatologic diagnostic skills. A new algorithm highlights our suggested approach to cutaneous diagnoses. It is our hope that readers will begin to “think like dermatologists” as they digest the contents of this review. 

      Key words: Macule, papule, vesicle, bulla, plaque, excoriation, scale, ulceration, diagnosis, errors

      This review contains 13 figures, 5 tables, 17 references, and 7 additional readings.

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    • 2

      Papulosquamous Disorders

      By Elizabeth A Abel, MD
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      Papulosquamous Disorders

      • ELIZABETH A ABEL, MDAdjunct Clinical Professor of Dermatology, Stanford University School of Medicine, Stanford, CA, Private Practice, California Skin Institute, Mountain View, CA

      Papulosquamous disorders comprise a group of dermatoses that have distinct morphologic features. The characteristic primary lesion of these disorders is a papule, usually erythematous, that has a variable amount of scaling on the surface. Plaques or patches form through coalescence of the primary lesions. Some common papulosquamous dermatoses are pityriasis rosea, lichen planus, seborrheic dermatitis, tinea corporis, pityriasis rubra pilaris, psoriasis, and parapsoriasis. The etiology, diagnosis, and treatment of pityriasis rosea, lichen planus, and seborrheic dermatitis (including seborrheic dermatitis associated with AIDS) are discussed in this chapter. Also discussed are the diagnosis and treatment of pityriasis rubra, parapsoriasis (pityriasis lichenoides and small- and large-plaque parapsoriasis), and erythroderma. This chapter includes color photographs of the aforementioned dermatoses plus the Koebner phenomenon, lichen planus of the mucous membranes, and erythroderma in Sézary syndrome.

      This review contains 11 highly rendered figures and 79 references.

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    • 3

      Cutaneous Adverse Drug Reactions

      By Neil H. Shear, MD, FRCPC; Sandra Knowles, BScPhm; Lori Shapiro, MD, FRCPC
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      Cutaneous Adverse Drug Reactions

      • NEIL H. SHEAR, MD, FRCPCProfessor and Chief of Dermatology, Department of Medicine, Divisions of Dermatology and Clinical Pharmacology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, CA
      • SANDRA KNOWLES, BSCPHMAssistant Professor (Status Only), Department of Pharmacy, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, CA
      • LORI SHAPIRO, MD, FRCPCAssistant Professor of Medicine, Department of Medicine, Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, CA

      An adverse drug reaction is defined as any noxious, unintended, and undesired effect of a drug that occurs at doses used in humans for prophylaxis, diagnosis, or therapy. A cutaneous eruption is one of the most common manifestations of an adverse drug reaction. This chapter reviews the epidemiology, etiology, diagnosis, clinical manifestations, and differential diagnosis of adverse drug reactions, as well as laboratory tests for them. Also discussed are the types of cutaneous eruption: exanthematous eruption, urticarial eruption, blistering eruption, pustular eruption, and others. The simple and complex forms of each type of eruption are reviewed. The chapter includes 4 tables and 12 figures. Tables present the warning signs of a serious drug eruption, clinical features of hypersensitivity syndrome reaction and serum sickness-like reaction, characteristics of Stevens-Johnson Syndrome and toxic epidermal necrolysis, and clinical pearls to identify anticoagulant-induced skin necrosis. Figures illustrate hypersensitivity syndrome reaction, a fixed drug eruption from tetracycline, pseudoporphyria from naproxen, linear immunoglobulin A disease induced by vancomycin, pemphigus foliaceus from taking enalapril, pemphigus vulgaris from taking penicillamine, toxic epidermal necrolysis after starting phenytoin therapy, acneiform drug eruption due to gefitinib, acute generalized exanthematous pustulosis from cloxacillin, coumarin-induced skin necrosis, a lichenoid drug eruption associated with ramipril, and leukocytoclastic vasculitis from hydrochlorothiazide.

      This chapter contains 12 figures, 8 tables and 108 references

      Keywords: Adverse drug reaction, rash, urticaria, blisters, pustular eruption, exanthema, Stevens-Johnson syndrome, toxic epidermal necrolysis, skin necrosis

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    • 4

      Psoriasis

      By Elizabeth A Abel, MD; Mark Lebwohl, MD
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      Psoriasis

      • ELIZABETH A ABEL, MDAdjunct Clinical Professor of Dermatology, Stanford University School of Medicine, Stanford, CA, Private Practice, California Skin Institute, Mountain View, CA
      • MARK LEBWOHL, MDSol and Clara Kest Professor and Chairman, Department of Dermatology, Mount Sinai School of Medicine, New York City, NY

      Psoriasis is an immune-mediated inflammatory cutaneous disorder characterized by chronic, scaling, erythematous patches and plaques of skin. It can begin at any age and can vary in severity. Psoriasis can manifest itself in several different forms, including pustular and erythrodermic forms. In addition to involving the skin, psoriasis frequently involves the nails, and some patients may experience inflammation of the joints (psoriatic arthritis). Because of its highly visible nature, psoriasis can compromise both the personal and the working lives of its victims. Breakthroughs in the treatment of psoriasis have led to a better understanding of its pathogenesis.

      This review contains 12 figures, 8 tables, and 79 references.

      Keywords: Psoriases, Pustulosis of Palms and Soles, Pustulosis Palmaris et Plantaris, Palmoplantaris Pustulosis, Pustular Psoriasis of Palms and Soles

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    • 5

      Infestations

      By Dirk Elston, MD
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      Infestations

      • DIRK ELSTON, MDDirector, Ackerman Academy of Dermatopathology, New York, NY

      This review looks at parasitic diseases of the skin. Scabies, caused by the human itch mite (Sarcoptes scabiei), and pediculosis, caused by the bloodsucking louse, are the most prevalent parasitic diseases in temperate regions. For treatment of scabies, ivermectin is suitable for mass drug administration during severe outbreaks, although patients with heavy scabies infestation may exhibit Mazzotti reactions during treatment with oral ivermectin. Another promising scabicide is Tinospora cordifolia lotion. The increase in global travel has also meant a worldwide increase in parasitic disorders endemic to tropical regions; these disorders include cutaneous larva migrans, pyodermas, arthropod-reactive dermatitis, myiasis, tungiasis, urticaria, and cutaneous and mucocutaneous leishmaniasis. Finally, patients with delusional parasitosis will express the belief that parasitical organisms are infesting their skin. Pimozide, an antipsychotic, has been successfully used to treat delusional parasitosis.

      This module contains 16 highly rendered figures, 2 tables, 15 references, and 5 MCQs.

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    • 6

      Malignant Cutaneous Tumors

      By Allan C Halpern, MD; Patricia L. Myskowski, MD
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      Malignant Cutaneous Tumors

      • ALLAN C HALPERN, MDChief, Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York, NY
      • PATRICIA L. MYSKOWSKI, MDAttending Physician, Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York, NY

      This chapter reviews the most common malignant cutaneous tumors. The section on malignant tumors of the epidermis discusses nonmelanoma skin cancer (i.e., basal cell carcinoma and squamous cell carcinoma) and malignant melanoma. The section on malignant tumors of the dermis covers metastatic tumors, primary tumors (Merkel cell carcinoma, Paget disease, extramammary Paget disease, angiosarcoma, and dermatofibrosarcoma protuberans), and Kaposi sarcoma (i.e., classic Kaposi sarcoma, African Kaposi sarcoma, organ-transplant Kaposi sarcoma, and HIV-associated Kaposi sarcoma). The final section covers cutaneous lymphomas. The coverage of each disease includes a discussion of epidemiology, etiology, diagnosis, differential diagnosis, treatment, and prognosis. Tables provide the adjusted estimated relative risks of melanoma by nevus type and number, the American Joint Committee on Cancer (AJCC) TNM classification and staging system, the estimated probability of 10-year survival in patients with primary cutaneous melanoma, and an overview of overview of therapy for cutaneous T cell lymphoma. Figures illustrate the presentation of many malignant cutaneous tumors.

      This review contains 10 figures, 11 tables, and 111 references.

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    • 7

      Benign Cutaneous Tumors

      By Elizabeth A Abel, MD
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      Benign Cutaneous Tumors

      • ELIZABETH A ABEL, MDAdjunct Clinical Professor of Dermatology, Stanford University School of Medicine, Stanford, CA, Private Practice, California Skin Institute, Mountain View, CA

      Tumors of the cutaneous surface may arise from the epidermis, dermis, or subcutaneous tissue or from any of the specialized cell types in the skin or its appendages. Broad categories include tumors derived from epithelial, melanocytic, or connective tissue structures. Within each location or cell type, lesions are classified as benign, malignant, or, in certain cases, premalignant. Benign epithelial tumors include tumors of the surface epidermis that form keratin, tumors of the epidermal appendages, and cysts of the skin. Melanocytic (pigment-forming) lesions are very common. One of the most frequently encountered forms is the nevus cell nevus. Tumors that are derived from connective tissue include fibromas, histiocytomas, lipomas, leiomyomas, and hemangiomas. This chapter provides an overview of each type of tumor, including sections on epithelial tumors, tumors of the epidermal appendages, familial tumor syndromes, melanocytic tumors, neural tumors, connective tissue tumors, vascular birthmarks, acquired vascular disorders, Kimura disease, lipoma, leiomyoma, and lymphangioma circumscriptum. The sections discuss various forms and their diagnosis, differential diagnosis, and treatment. Figures accompany the descriptions.

      This review contains 22 tables, 26 figures, and 88 references

      Keywords: Epithelial tumor, melanosis, cyst, angioma, hemangioma, neurofibromatosis, lipoma, leiomyoma, seborrheic dermatitis, nevus

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    • 8

      Acne Vulgaris and Rosacea

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      Acne Vulgaris and Rosacea

      Acne vulgaris is the most common disorder seen in general dermatology practice, accounting for approximately 10% of visits each year. Both sexes and all ethnicities are affected, usually in the late preteenage or early teenage years. Both inflammatory and comedonal lesions of acne vulgaris characteristically involve the face, but truncal involvement is also relatively common. Multiple clinical presentations may be observed, with severity often progressing over time during adolescence. Severe forms of acne vulgaris can be especially disfiguring and debilitating, and are more likely to lead to permanent scarring. Therapeutic options are chosen primarily on the basis of clinical severity, with adjustments in treatment made on the basis of response or disease progression. Rosacea begins in adulthood, usually in the third decade of life or later. The disorder predominantly affects the central face in fair-skinned people, mostly those of northern European ancestry, although individuals of any race may be affected. Rosacea may present as one or more of a variety of clinical phenotypes (subtypes); it is a chronic disorder characterized by periods of exacerbation and remission. Fortunately, rosacea is not associated with scarring, although a subset of patients may develop localized proliferations of sebaceous and fibrous tissue called a phyma. Like acne vulgaris, rosacea may also adversely impact quality of life. Figures in this chapter illustrate acne vulgaris and inflammatory papules. Tables detail laboratory evaluation for women with acne vulgaris and hyperandrogenism, surgical/physical modality options for specific acne lesions and acne scars, major topical therapies for acne vulgaris, and commonly prescribed systemic therapies for acne. This chapter contains 50 references.

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    • 9

      Disorders of Hair

      By James Q Del Rosso, DO
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      Disorders of Hair

      • JAMES Q DEL ROSSO, DOAdjunct Clinical Professor (Dermatology), Touro University College of Osteopathic Medicine, Henderson, NV

      A basic knowledge of the hair growth cycle is needed to evaluate disorders of hair growth. This chapter presents a broad overview of the physiology and evaluation of hair growth, as well as discussions of specific types of alopecia. The epidemiology, pathogenesis, diagnosis, and treatment of androgenetic alopecia, the most common type of nonscarring hair loss, are covered. Diffuse hair shedding is generalized hair loss over the entire scalp. Diagnosis and treatment of telogen effluvium, anagen arrest (anagen effluvium), and other causes of diffuse hair shedding are covered in detail. Alopecia areata, typically characterized by patchy hair loss; cicatricial alopecia, which results from permanent scarring of the hair follicles; and miscellaneous causes of hair loss are also discussed. Tables list the causes of diffuse and cicatricial alopecia, telogen effluvium, and miscellaneous chemicals and categories of drugs that can cause alopecia, as well as miscellaneous causes of hair loss. Included is an algorithm outlining the approach to diagnosing nonscarring alopecia, as well as a variety of clinical photographs.

      This review contains 9 highly rendered figures, 6 tables, and 42 references.

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    • 10

      Diseases of the Nail Unit

      By Jennifer Nguyen, MD; George Cotserelis, MD
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      Diseases of the Nail Unit

      • JENNIFER NGUYEN, MDAssistant Professor of Dermatology, Department of Dermatology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA
      • GEORGE COTSERELIS, MDMilton Bixler Hartzell Professor of Dermatology, Department of Dermatology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA

      The human nail is a complex unit that includes five major modified cutaneous structures: the nail matrix, nail bed, nail plate, nail folds, and cuticle (eponychium). This chapter discusses the function and structure of the five nail components and the pathophysiology affecting each. Also reviewed are nail findings associated with underlying systemic and dermatologic conditions: splinter hemorrhages, koilonychia, transverse nail-plate depressions (Beau’s lines), onycholysis, leukonychia, clubbing, nail-plate pitting, and longitudinal pigmented bands. Infections of the nail are discussed, which include bacterial paronychia, chronic paronychia, and onychomycosis. Figures illustrate the longitudinal section of the fingernail, multiple pigmented longitudinal bands, psoriasis involving the fingernail, late-stage lichen planus of the fingernail, transverse linear grooves, Pseudomonas aeruginosa causing a green nail, psoriasis of the nail, melanonychia striata, and a nail specimen for potassium hydroxide preparation. Tables describe antifungal treatment for toenail onychomycosis as well as selected dermatologic disorders that affect the nail unit. This chapter contains 50 references.

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    • 11

      Disorders of Pigmentation

      By Pearl E. Grimes, MD
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      Disorders of Pigmentation

      • PEARL E. GRIMES, MDClinical Professor of Dermatology, Division of Dermatology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA; Director of the Vitiligo and Pigmentation Institute of Southern California, Los Angeles, CA

      The disorders of skin pigmentation discussed in this chapter fall into two categories: disorders of hyperpigmentation (melasma, postinflammatory hyperpigmentation, drug-induced hyperpigmentation, erythema dyschromicum perstans, lentigines, confluent and reticulated papillomatosis of Gougerot and Carteaud, and Dowling-Degos disease) and disorders of hypopigmentation (vitiligo, albinism, piebaldism, and idiopathic guttate hypomelanosis). The definition, epidemiology, etiology and pathogenesis, diagnosis, differential diagnosis, and treatment are discussed for each condition. Figures show examples of melasma, hyperpigmentation secondary to acne, vitiligo and its response to treatment with tacrolimus and with narrow-band ultraviolet B (UVB) light, Vogt-Koyanagi-Harada syndrome, and piebaldism. A table lists therapeutic approaches to vitiligo. This chapter contains 182 references.

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    • 12

      Pruritus

      By Hong-Liang Tey, MRCP(UK); Gil Yosipovitch, MD; Jeffrey D Bernhard, MD, FRCP(Edin)
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      Pruritus

      • HONG-LIANG TEY, MRCP(UK)Consultant, National Skin Centre, Singapore
      • GIL YOSIPOVITCH, MDProfessor and Chair, Department of Dermatology and Itch Center, Temple University School of Medicine, Philadelphia, PA
      • JEFFREY D BERNHARD, MD, FRCP(EDIN)Editor Emeritus, Journal of the American Academy of Dermatology, Professor Emeritus, University of Massachusetts Medical School, MA

      Pruritus, or itch, can be defined as a sensation that elicits the desire to scratch. Normal physiologic "acute" itch occurs daily and can usually be abolished by scratching the affected area. On the other hand, chronic itch (defined as itch that persists for 6 weeks or more) is often made worse by scratching and is associated with significant morbidity. The focus of this chapter is on chronic pruritus. Discussion includes causes, clinical evaluation, investigation of, and treatment for chronic pruritus. Tables cover the etiologic classification of chronic pruritus, a morphologic approach to typically pruritic dermatoses and their classic distribution (with illustrative images), systemic diseases and associated clinical signs, localized pruritus and underlying neuropathy, screening tests for pruritus, further investigations following results of clinical findings and screening tests, general measures for patients managing pruritus, topical treatment, topical calcineurin inhibitors, systemic therapies, recommended stepwise treatment options, and phototherapy. Also included are a patient history checklist, an algorithm outlining the approach to chronic pruritus, and images depicting various forms of pruritus.

      This review contains 16 highly rendered figures (including table images), 13 tables, and 41 references.

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    • 13

      Cutaneous Manifestations of Systemic Diseases

      By Mark Lebwohl, MD
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      Cutaneous Manifestations of Systemic Diseases

      • MARK LEBWOHL, MDSol and Clara Kest Professor and Chairman, Department of Dermatology, Mount Sinai School of Medicine, New York City, NY

      This chapter reviews key cutaneous manifestations of systemic diseases that should be recognized by most physicians and highlights recent developments in the diagnosis and management of those disorders. In many of the disorders presented, workup and therapy of the underlying systemic condition are essential to a favorable outcome. Cardiopulmonary, vascular, endocrinologic, gastrointestinal, hematologic, immunodeficiency, infectious, neurologic, renal, and rheumatologic diseases are discussed. Many of the syndromes characterized by physical symptoms are accompanied by photographs demonstrating the manifestations for the reader's reference.

      This review contains 28 figures and 104 references.

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    • 14

      Skin Infections

      By Jan V. Hirschmann, MD
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      Skin Infections

      • JAN V. HIRSCHMANN, MDProfessor of Medicine, University of Washington School of Medicine, Staff Physician, Puget Sound VA Medical Center, Seattle, WA

      The skin can become infected by viruses, fungi, and bacteria, including some that ordinarily are harmless colonizing organisms. The most common fungal infections are caused by dermatophytes, which can involve the hair, nails, and skin. Potassium hydroxide (KOH) preparations of specimens from affected areas typically demonstrate hyphae, and either topical or systemic antifungal therapy usually cures or controls the process. The most common bacterial pathogens are Staphylococcus aureus and group A streptococci, which, alone or together, can cause a wide variety of disorders, including impetigo, ecthyma, and cellulitis. Topical antibiotics may suffice for impetigo, but ecthyma and cellulitis require systemic treatment. S. aureus, including methicillin-resistant strains, can also cause furuncles, carbuncles, and cutaneous abscesses. For these infections, incision and drainage without antibiotics are usually curative. Warts are the most common cutaneous viral infection, and eradication can be difficult, especially where the skin is thick, such as the palms and soles, or the patient is immunocompromised. Most therapies consist of trying to destroy the viruses by mechanical, chemical, or immune mechanisms. This review covers dermatophyte infections, yeast infections, bacterial infections, and viral infections of the skin. Figures show the classic annular lesion of tinea corporis, a typical kerion presenting as a zoophilic Microsporum canis infection of the scalp (tinea capitis), tinea corporis, tinea barbae, tinea pedis between and under the toes and on the plantar surface, inflammatory tinea pedis, tinea unguium, tinea manuum, angular cheilitis, prominent satellite lesions of discrete vesicles associated with candidiasis, facial candidiasis, Candida paronychia, tinea versicolor, nonbullous impetigo, bullous impetigo, ecthyma, leg cellulitis, erythema and edema on the cheeks, eyelids, and nose, furuncle, carbuncle, nasal folliculitis, pitted keratolysis, trichomycosis axillaris, necrotizing fasciitis, Fournier gangrene, folliculitis, plantar wart, condyloma acuminatum, and benign lesions of bowenoid papulosis. Tables list dermatophyte species, terminology of dermatophyte infections, topical agents for dermatophyte infections, treatment options for impetigo (adult doses), and treatment options for erythrasma.

      This review contains 28 highly rendered figures, 5 tables, and 33 references

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    • 15

      Eczematous Disorders, Atopic Dermatitis, and Ichthyoses

      By Seth R Stevens, MD
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      Eczematous Disorders, Atopic Dermatitis, and Ichthyoses

      • SETH R STEVENS, MDPartner Physician, Southern California Permanente Medical Group, Woodland Hills, CA, and Assistant Clinical Professor, Case Medical School, Cleveland, OH

      This review describes eczematous dermatitis, or eczema, a skin disease that is characterized by erythematous vesicular, weeping, and crusting patches; atopic dermatitis, a common chronic inflammatory dermatosis that generally begins in infancy; and the ichthyoses, a group of diseases of cornification that are characterized by excessive scaling. The purpose of this review is to examine the major variants, epidemiology, etiology, diagnosis, differential diagnosis, and treatment of these dermatologic diseases. Figures depict chronic eczematous dermatitis, allergic contact dermatitis to poison ivy, seborrheic dermatitis, nummular eczema, acute eczematous patches, lichenified patches that appear after chronic rubbing of eczematous patches, erythroderma (total body erythema), and marked scaling (acquired ichthyosis). Tables list the diagnostic criteria for atopic dermatitis and the differential diagnosis of atopic dermatitis.

      This review contains 9 highly rendered figures, 2 tables, and 88 references.

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    • 16

      Pemphigus and Bullous Pemphigoid

      By Aakaash Varma, BA; Annette Czernik, MD, FAAD; Jacob Levitt, MD, FAAD
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      Pemphigus and Bullous Pemphigoid

      • AAKAASH VARMA, BACollege of Medicine, SUNY Downstate Health Sciences University
      • ANNETTE CZERNIK, MD, FAADDepartment of Dermatology at the Mount Sinai Hospital
      • JACOB LEVITT, MD, FAADDepartment of Dermatology at the Mount Sinai Hospital

      Pemphigus disorders are characterized by acantholysis, whereas pemphigoid disorders are characterized by a dermal-epidermal split. Diagnosis of pemphigus or pemphigoid relies on a combination of positive anti-desmoglein or anti-collagen XVII serology, confirmatory direct immunofluorescence, and clinical features. Treatment for immunobullous disease revolves around various immunosuppressants, most often some combination of rituximab, prednisone, and IVIg. Paraneoplastic pemphigus is characterized by hemorrhagic crusting of the lips with positive indirect immunofluorescence on rat bladder epithelium, which should prompt a search for malignancy. Hailey-Hailey disease is a genetically mediated pemphigus that typically occurs in skin folds and responds to a number of agents including botulinum toxin, topical steroids, and other anecdotal therapies.

      This review contains 17 figures, 2 tables, and 109 references.

      Keywords: blister, pemphigus, bullous, rituximab, bullae, prednisone

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    • 17

      Other Vesiculobullous Diseases

      By Annette Czernik, MD, FAAD; Aakaash Varma, BA; Jacob Levitt, MD, FAAD
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      Other Vesiculobullous Diseases

      • ANNETTE CZERNIK, MD, FAADAssistant Professor, The Mount Sinai School of Medicine, New York, NY
      • AAKAASH VARMA, BACollege of Medicine, SUNY Downstate Health Sciences University
      • JACOB LEVITT, MD, FAADDepartment of Dermatology at the Mount Sinai Hospital

      Less common immunobullous diseases include cicatricial pemphigoid, epidermolysis bullosa acquisita, and linear IgA bullous dermatosis. Diagnosis of these entities are made through direct immunofluorescence, sometimes requires salt-split skin, as well as, in the case of cicatricial pemphigoid, mucosal scarring. As in pemphigus vulgaris and bullous pemphigoid, common therapies include rituximab, prednisone, and IVIg. Dapsone can be particularly effective in linear IgA bullous dermatosis and bullous lupus. Dermatitis herpetiformis is a rare cutaneous manifestation of gluten sensitivity, characterized by pruritic vesicles on extensor surfaces, that responds to dapsone and gluten avoidance. This diagnosis is confirmed with biopsy and positive serology for anti-tissue transglutaminase IgA. Blistering hypersensitivity reactions include TEN, SJS, erythema multiforme, and fixed drug eruption. All are characterized by varying degrees of keratinocyte necrosis. Common to the management of all include cessation of the offending agent. TEN can be managed by cyclosporine, TNF-inhibition, or—more controversially—IVIg. SJS can be effectively managed with systemic steroids. EM responds variably to a number of agents, including antiviral nucleoside analogues, prednisone, thalidomide, apremilast, and tofacitinib. Infectious causes of blisters include Staphylococcus aureus, HSV, and varicella zoster virus. Epidermolysis bullosa comprises a variety of genetically defective structural proteins of the skin. Recessive variants and those affecting deeper proteins carry more severe phenotypes. Management is best achieved at specialty centers and involves careful wound care as well as prevention of friction. Gene therapy is on the horizon for these disorders. Other blistering entities, mechanical or inflammatory in nature, are also discussed at the end of this chapter.

      This review contains 13 figures, 1 table, and 86 references.

      Keywords: Blisters, bullae, bullous, pemphigoid, necrolysis

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    • 18

      Malignant Cutaneous Tumors

      By Allan C Halpern, MD; Patricia L. Myskowski, MD
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      Malignant Cutaneous Tumors

      • ALLAN C HALPERN, MDChief, Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York, NY
      • PATRICIA L. MYSKOWSKI, MDAttending Physician, Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York, NY
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    • 19

      Benign Cutaneous Tumors

      By Elizabeth A Abel, MD
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      Benign Cutaneous Tumors

      • ELIZABETH A ABEL, MDAdjunct Clinical Professor of Dermatology, Stanford University School of Medicine, Stanford, CA, Private Practice, California Skin Institute, Mountain View, CA
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    • 20

      Cutaneous Adverse Drug Reactions

      By Neil H. Shear, MD, FRCPC; Sandra Knowles, BScPhm; Lori Shapiro, MD, FRCPC
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      Cutaneous Adverse Drug Reactions

      • NEIL H. SHEAR, MD, FRCPCProfessor and Chief of Dermatology, Department of Medicine, Divisions of Dermatology and Clinical Pharmacology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, CA
      • SANDRA KNOWLES, BSCPHMAssistant Professor (Status Only), Department of Pharmacy, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, CA
      • LORI SHAPIRO, MD, FRCPCAssistant Professor of Medicine, Department of Medicine, Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, CA
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  • Endocrinology
    • 1

      The Endocrine System: Adrenal Glands

      By Abbas Al-Kurd, MD; Haggi Mazeh, MD, FACS
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      The Endocrine System: Adrenal Glands

      • ABBAS AL-KURD, MDClinical Instructor, Department of Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel
      • HAGGI MAZEH, MD, FACSAssociate Professor, Department of Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel

      The adrenal glands represent an essential component of the endocrine system, and their failure can have catastrophic consequences to several aspects of bodily homeostasis. Each adrenal gland can be divided into two different endocrine components, the cortex and the medulla, each with distinct functions. This in-depth review of normal adrenal embryology, anatomy, and physiology also emphasizes the clinical relevance of various irregularities in adrenal functioning. Every surgeon attempting to manage adrenal diseases is expected to be familiar with the detailed pathophysiology of these conditions because such an understanding is essential for sound preoperative evaluation and perioperative management of this potentially complicated patient group. 

      This review contains 4 figures, 1 table, and 70 references.

      Key words: adrenal, adrenal glands, adrenal pathophysiology, adrenal physiology, anatomy of adrenal glands, cortex, embryology, endocrine system, medulla

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    • 2

      Cushing Syndrome

      By Lynnette Nieman, MD
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      Cushing Syndrome

      • LYNNETTE NIEMAN, MDProgram on Adult and Reproductive Endocrinology, National Institutes of Health, Bethesda, MD

      Cushing syndrome is a condition with protean manifestations that are caused by chronic exposure to excess glucocorticoids. Treatment with supraphysiologic doses of glucocorticoids is the most common cause. Pathologic hypercortisolism may result from autonomous adrenal production or as a result of the action of excessive adrenocorticotropic hormone (ACTH) production by a tumor, which stimulates adrenal cortisol production. Primary adrenal forms include unilateral adenoma or carcinoma or, rarely, bilateral hyperplasia and/or nodules. This chapter covers the epidemiology, etiology, pathophysiology, and diagnosis of Cushing syndrome. Clinical manifestations, physical examination findings, and laboratory tests, including tests of the blood and other body fluids, imaging studies, and biopsy, are discussed. The differential diagnosis, treatment options, complications, and prognosis are described. Tables outline clinical features and causes of Cushing syndrome, abnormalities associated with primary adrenal causes of Cushing syndrome, diagnostic accuracy of screening tests, endogenous hypercortisolism without Cushing syndrome, and medical therapy for Cushing syndrome. Figures illustrate the causes of Cushing syndrome and a comparison of the hypothalamic-pituitary-adrenal axis in patients with ACTH-dependent Cushing syndrome and those with pseudo–Cushing syndrome. Algorithms show the evaluation of possible Cushing syndrome and evaluation of the causes of Cushing syndrome. Second-line treatments for Cushing syndrome when surgery fails or is not possible are also detailed.

      This chapter contains 5 figures, 7 tables, 50 references.

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    • 3

      The Endocrine System: Pituitary Gland

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      The Endocrine System: Pituitary Gland

      The pituitary gland is the main point where the neural and endocrine systems function in continuity, maintaining homeostasis of many functional elements of the human body. Located inside the sella turcica, it is separated from the rest of the central nervous system (CNS); however, it plays a crucial part in the regulation of the fundamental endocrine profile, inhibiting or promoting CNS signaling to the rest of the human body. Made up of two distinct tissue subtypes, this gland is fed by a complex vascular network, which enables communication beyond the blood-brain barrier. Lying in close proximity to both important neural and vascular structure, changes in gland size and function result in significant clinical impact. The pituitary gland controls many processes, among which are thermoregulation; metabolism and metabolic rate; glucose, solute, and water balance; growth and development; blood pressure; and sexual drive, pregnancy, childbearing, birth, and breast-feeding. The devastating effects of pituitary dysfunction underscore the importance of the pituitary gland in maintenance of the various functions that underlie normal everyday human activity. This review covers the basic aspects of pituitary gland development, anatomy, and physiologic function.

      This review contains 3 figures, and 38 references,

      Key words: adenohypophysis, neurohypophysis, pituitary-hypothalamic axis, pituitary portal system, sella turcica

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    • 4

      Testes and Testicular Disorders

      By Elizabeth G Nabel, MD, FACP
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      Testes and Testicular Disorders

      • ELIZABETH G NABEL, MD, FACPPresident, Brigham and Women’s Hospital, Professor of Medicine, Harvard Medical School, Boston, MA

      The testes begin to function in utero and continue to function into senescence, with the major roles of testosterone secretion and sperm production. This review discusses how testicular function can be affected by diseases of the hypothalamus and pituitary, as well as by diseases of the testes themselves. These diseases may be either congenital or acquired. The clinical manifestation, history and physical examination, laboratory studies, diagnoses, and treatment of these diseases, as well as other conditions, including gynecomastia and erectile dysfunction, are discussed. Specific therapies, such as the off-label use of tamoxifen (gynecomastia) and the various oral phosphodiesterase inhibitors (for erectile dysfunction), are also covered.

      This review contains 2 figures, 21 tables, and 51 references.

      Keywords: Testes, hypogonadism, erectile dysfunction, gynecomastia, dihydrotestosterone, gonadotropine, luteinizing hormone, follicular-stimulating hormone

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    • 5

      Hypoglycemia

      By F John Service, MD, PhD; Adrian Vella, MD
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      Hypoglycemia

      • F JOHN SERVICE, MD, PHDEmeritus Professor of Medicine, Mayo Clinic College of Medicine, Rochester, MN
      • ADRIAN VELLA, MDProfessor of Medicine, Mayo Clinic College of Medicine, Rochester, MN

      Hypoglycemia is a clinical syndrome that has diverse causes and is characterized by episodes of low blood glucose and typically marked by autonomic and neuroglycopenic manifestations. This review discusses the classification, etiology, and diagnosis for hypoglycemia, including the Whipple triad, and the classic diagnostic test, the prolonged (72-hour) fast. Specific attention is given to the conditions that cause hypoglycemia, including insulinomas, factitious hypoglycemia, insulin autoimmune hypoglycemia, and post–gastric bypass hypoglycemia, as well as the diagnosis and management of these conditions. 

      This review contains 2 figures, 6 figures, and 43 figures. 

      Keywords: Blood glucose, hypoglycemia, neuroglycopenic manifestations, Whipple triad, 72-hour fast, insulinoma, post-gastric bypass, factitious hypoglycemia

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    • 6

      Obesity

      Obesity and its associated disorders are leading causes of morbidity and premature mortality around the world. Obese persons are also vulnerable to low self-esteem and depression because of the psychological and social stigmata that often accompany being overweight. Despite conventional wisdom that obesity results from deficient self-control, research has provided insight into the physiology behind unwanted weight gain. Obesity is recognized as a chronic condition resulting from an interaction between environmental influences and an individual’s genetic predisposition.

      This review contains 3 figures, 13 tables, and 126 references.

      Keywords: Obesity, Body mass index, Hypertension, impaired glucose tolerance or diabetes, hyperlipidemia, heart disease, pulmonary disease, gastroesophageal reflux, sleep apnea

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    • 7

      Type I Diabetes Mellitus

      By Joseph I. Wolfsdorf, MB, BCh; Katharine Garvey, MD, MPH
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      Type I Diabetes Mellitus

      • JOSEPH I. WOLFSDORF, MB, BCHProfessor of Pediatrics, Harvard Medical School, Boston, MA
      • KATHARINE GARVEY, MD, MPHInstructor of Pediatrics, Harvard Medical School, Boston, MA

      Type 1 diabetes mellitus is characterized by severe insulin deficiency, making patients dependent on exogenous insulin replacement for survival. These patients can experience life-threatening events when their glucose levels are significantly abnormal. Type 1 diabetes accounts for 5 to 10% of all diabetes cases, with type 2 accounting for most of the remainder. This review details the pathophysiology, stabilization and assessment, diagnosis and treatment, disposition and outcomes of patients with Type 1 diabetes mellitus. Figures show the opposing actions of insulin and glucagon on substrate flow and plasma levels; plasma glucose, insulin and C-peptide levels throughout the day; the structure of human proinsulin; current view of the pathogenesis of Type 1 autoimmune diabetes mellitus; pathways that lead from insulin deficiency to the major clinical manifestations of Type 1 diabetes mellitus; relationship between hemoglobin A1c values at the end of a 3-month period and calculated average glucose levels during the 3-month period; different combinations of various insulin preparations used to establish glycemic control; and basal-bolus and insulin pump regimens. Tables list the etiologic classification of Type 1 diabetes mellitus, typical laboratory findings and monitoring in diabetic ketoacidosis, criteria for the diagnosis of Type 1 diabetes, clinical goals of Type 1 diabetes treatment, and insulin preparations.

      This review contains 10 figures, 9 tables, and 40 references.

      Keywords: Type 1 diabetes mellitus, optimal glycemic control, hypoglycemia, hyperglycemia, polyuria, polydipsia, polyphagia, HbA1c, medical nutrition therapy, Diabetic Ketoacidosis

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    • 8

      Type II Diabetes Mellitus

      By Matthew C. Riddle, MD; Saul Genuth, MD, FACP
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      Type II Diabetes Mellitus

      • MATTHEW C. RIDDLE, MDProfessor, Department of Medicine, and Head, Section of Diabetes, Oregon Health & Sciences University, Portland, OR
      • SAUL GENUTH, MD, FACPProfessor, Division of Clinical and Molecular Endocrinology, Case Western Reserve University School of Medicine, Cleveland, OH

      Hyperosmotic hyperglycemic nonketotic (HHNK) state (also known as hyperosmolar hyperglycemic state) is a significant acute complication of type 2 diabetes mellitus, especially for those over 65 years of age. It is characterized by extreme hyperglycemia and hyperosmolarity with little ketosis. The main clinical effect of extreme hyperosmolarity is somnolence or confusion. The absence of severe ketonemia is attributed to residual insulin secretion that is sufficient to restrain lipolysis. HHNK state is marked by extreme dehydration, with both a marked deficit of free water and serious compromise of intravascular volume and tissue perfusion. Most patients with HHNK state have hypotension, extremely dry mucous membranes, and gross elevation of urea nitrogen and creatinine. Urinary tract infection, pneumonia, stroke, myocardial infarction, and sepsis may precipitate HHNK state. Elderly patients are particularly vulnerable because their thirst mechanisms are less sensitive to a rising serum osmolality. Fluid replacement is the most important component of therapy for HHNK state. Restoration of circulating volume is an urgent first priority and is accomplished by relatively rapid intravenous infusion of 2 L of 0.9% normal saline followed by 0.45% normal saline. Later, when plasma glucose levels have declined to 250 to 300 mg/dL, 5% dextrose in water is given. Insulin treatment is started soon after administration of isotonic saline. Potassium must be added to intravenous fluids to prevent hypokalemia caused by insulin action but should not be started until hypokalemia is proven, because potassium levels can be high initially. The mortality from the HHNK state is high, ranging from 10 to 20%, and is most often from the precipitating illness.

      This review contains 6 figures, 7 tables, and 73 references

      Keywords: dehydration, fluid deficit, hyperglycemia, hyperglycemic nonketotic state, hyperosmolar, hyperosmotic insulin, potassium, type 2 diabetes mellitus

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    • 9

      Hypothyroidism and Thyrotoxicosis

      By Paul W. Ladenson, MD
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      Hypothyroidism and Thyrotoxicosis

      • PAUL W. LADENSON, MDJohn Eager Howard Professor of Endocrinology & Metabolism, Professor of Medicine, Pathology, Oncology, Radiology & Radiological Sciences, and International Health, University Distinguished Service Professor, Director, Division of Endocrinology & Metabolism, Johns Hopkins Medical Institutions, Baltimore, Maryland

      Thyroid disorders are the most common endocrine conditions encountered in clinical practice and can range from clinically obvious to clinically silent. This review provides the definition and epidemiology of the conditions of hypothyroidism and hyperthyroidism. Hypothyroidism can be congenital or acquired, and its pathogenesis, diagnosis, and management are presented. The three most common disorders of thyrotoxicosis (diffuse toxic goiter [Graves disease], toxic nodular goiter, and iatrogenic thyrotoxicosis in thyroid hormone–treated patients are addressed, as well as the many diseases in each of these categories. This review also discusses thyroiditis, goiter, thyroid nodules, and thyroid cancer. Tables list the causes of elevated serum thyroid-stimulating hormone (TSH) levels, the etiologic classification of thyrotoxicosis, characteristic features of thyroiditis, and causes of elevated serum total thyroxine levels. Figures show the prevalence of abnormalities in thyroid function tests in different populations, certain forms of hyperthyroidism that result from pathophysiologic activation of the TSH receptor, and inflammation of thyroid tissue in acute thyroiditis.

       

      This review contains 3 figures, 12 tables, and 61 references.

      Key Words: Hypothyroidism, Thyrotoxicosis, Thyrotropin, celiac disease, vitiligo, pernicious anemia, Sjögren syndrome, Graves disease, Munchausen syndrome

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    • 10

      Thyroiditis, Goiter, Thyroid Nodules, and Thyroid Cancer

      By Paul W. Ladenson, MD
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      Thyroiditis, Goiter, Thyroid Nodules, and Thyroid Cancer

      • PAUL W. LADENSON, MDJohn Eager Howard Professor of Endocrinology & Metabolism, Professor of Medicine, Pathology, Oncology, Radiology & Radiological Sciences, and International Health, University Distinguished Service Professor, Director, Division of Endocrinology & Metabolism, Johns Hopkins Medical Institutions, Baltimore, Maryland

      Thyroid disorders are the most common endocrine conditions encountered in clinical practice. Persons of either sex and any age can be affected, although almost all forms of thyroid disease are more frequent in women than in men, and many thyroid ailments increase in incidence with age. The presentation of thyroid conditions can range from clinically obvious to clinically silent. Their consequences can be widespread and serious, even life-threatening. With proper testing, the diagnosis and differential diagnosis can be established with certainty, and effective treatments can be instituted for almost all patients.

      This review contains 1 figure, 7 tables, and 31 references

      Keywords: Hypothyroidism, Thyrotoxicosis, Thyrotropin, celiac disease, vitiligo, pernicious anemia, Sjögren syndrome, Graves disease, Munchausen syndrome

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    • 11

      Management of Dyslipidemia

      By John D. Brunzell, MD, FACP; R Alan Failor, MD
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      Management of Dyslipidemia

      • JOHN D. BRUNZELL, MD, FACPProfessor Emeritus, Active, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA
      • R ALAN FAILOR, MDClinical Professor, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA

      Disorders of lipoprotein metabolism, in conjunction with the prevalence of high-fat diets, obesity, and physical inactivity, have resulted in an epidemic of atherosclerotic disease in the United States and other developed countries. The interaction of common genetic and acquired disorders of lipo­proteins with these adverse environmental factors leads to the premature development of atherosclerosis. In the United States, mortality from coronary artery disease (CAD), particularly in persons younger than 60 years, has been declining since 1970; however, atherosclerotic cardiovascular disease remains the most common cause of death among both men and women.

      This review contains 7 tables and 51 references.

      Keywords: Lipoprotein, Hepatic Lipase, Dyslipoproteinemias, hyper­lipoproteinemia, hypoalphalipoproteinemia

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    • 12

      Diagnosis of Dyslipidemia

      By John D. Brunzell, MD, FACP; R Alan Failor, MD
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      Diagnosis of Dyslipidemia

      • JOHN D. BRUNZELL, MD, FACPProfessor Emeritus, Active, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA
      • R ALAN FAILOR, MDClinical Professor, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA

      Disorders of lipoprotein metabolism, in conjunction with the prevalence of high-fat diets, obesity, and physical inactivity, have resulted in an epidemic of atherosclerotic disease in the United States and other developed countries. The interaction of common genetic and acquired disorders of lipo­proteins with these adverse environmental factors leads to the premature development of atherosclerosis. In the United States, mortality from coronary artery disease (CAD), particularly in persons younger than 60 years, has been declining since 1970; however, atherosclerotic cardiovascular disease remains the most common cause of death among both men and women.

      This review contains 6 figures, 12 tables, and 47 references.

      Keywords: dyslipoproteinemias, hepatic lipase,  hyper­lipoproteinemia, hypoalphalipoproteinemia, lipoprotein

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    • 13

      Diseases of Calcium Metabolism and Metabolic Bone Disease

      By Carolyn Becker, MD
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      Diseases of Calcium Metabolism and Metabolic Bone Disease

      • CAROLYN BECKER, MDAssociate Professor, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA

      The precise regulation of body calcium stores and of the calcium concentration in both extracellular and intracellular compartments is critically important. Calcium is the chief mineral component of the skeleton; calcium serves major roles in neurologic transmission, muscle contraction, and blood coagulation; and calcium is a ubiquitous intracellular signal.

      This review contains 5 figures, 9 tables, and 114 references.

      Key Words: hyperglycemia, hypoglycemia, macrovascular, microvascular, neuropathic

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    • 14

      Complications of Diabetes Mellitus

      By Samuel Dagogo-Jack, MD, MBBS, FRCP, FACP
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      Complications of Diabetes Mellitus

      • SAMUEL DAGOGO-JACK, MD, MBBS, FRCP, FACPA. C. Mullins Professor & Chief, Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, Memphis, TN

      The long-term complications of diabetes mellitus include those attributable to hyperglycemia-mediated small vessel (microvascular)and neuropathic complications and syndromes resulting from multifactorial large vessel disease (macrovascular complications). Diabetic patients with evidence of chronic complications are best managed in consultation with appropriate specialists. The microvascular and neuropathic complications, which are specifically related to hyperglycemia, include retinopathy, nephropathy, and diabetic neuropathy.

      This review contains 8 figures, 9 tables, and 83 references.

      Key Words: Hyperglycemia, hypoglycemia, macrovascular, microvascular, neuropathic

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    • 15

      Secondary Forms of Diabetes Mellitus

      By Ildiko Lingvay, MD, MPH, MSCS; Philip Raskin, MD, FACP
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      Secondary Forms of Diabetes Mellitus

      • ILDIKO LINGVAY, MD, MPH, MSCSAssistant Professor, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
      • PHILIP RASKIN, MD, FACPProfessor of Medicine, Clifton and Betsy Robinson Chair in Biomedical Research, University of Texas Southwestern Medical Center at Dallas, Director, University Diabetic Treatment Center, Parkland Memorial Hospital, Dallas, TX

      Secondary forms of diabetes mellitus are those cases of diabetes mellitus that have a specific identifiable cause and do not meet the diagnostic criteria for type 1, type 2, or gestational diabetes. This review discusses the etiology, pathogenesis, diagnosis, management, complications, and prognosis of these forms, which include diabetes mellitus occurring as a result of pancreatic disorders; endocrinopathies; drugs, chemical agents, or toxins; and genetic mutations or syndromes. Tables list the endocrinopathies; the drug, chemicals, and toxins; and the genetic disorders causing secondary forms of diabetes mellitus.

      This review contains 3 tables and 15 references.

      KeyWords: chronic pancreatitis, pancreatic carcinoma, cystic fibrosis, hemochromatosis, malnutrition, diabetic ketoacidosis or symptomatic hyperglycemia or hypoglycemia



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    • 16

      Metabolic Disorders: Inborn Errors of Carbohydrate Metabolism

      By Sameer S Chopra, MD, PhD; Gerald T Berry, MD
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      Metabolic Disorders: Inborn Errors of Carbohydrate Metabolism

      • SAMEER S CHOPRA, MD, PHDClinical Fellow in Medicine, Dana-Farber Cancer Institute, Boston, MA
      • GERALD T BERRY, MDDirector, Metabolism Program, Division of Genetics and Genomics, Boston's Children's Hospital, Boston, MA

      The small molecule diseases include the inborn errors of carbohydrate, ammonia, amino acid, organic acid, and fatty acid metabolism. They are central to the cohort of biochemical genetic diseases that are often associated with catastrophic presentations and life-threatening illness during infancy and childhood. Many of these entities are now routinely detected through newborn screening in the majority, if not all, of the states in the United States. Several of these diseases have effective therapies that largely eliminate the signs and symptoms of disease. In many, however, the disease process is without an effective treatment or may be brought under control but not corrected.

      This review contains 1 figure, 6 tables, and 11 references.

      Keywords: glycogen storage diseases, galactosemia, hyperbilirubinemia, hyperchloremic metabolic acidosis, hypofibrinogenemia, and thrombocytopenia, hypophosphatemia, fructose-1,6-bisphosphatase deficiency

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    • 17

      Testes and Testicular Disorders

      By Elizabeth G Nabel, MD, FACP
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      Testes and Testicular Disorders

      • ELIZABETH G NABEL, MD, FACPPresident, Brigham and Women’s Hospital, Professor of Medicine, Harvard Medical School, Boston, MA
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    • 18

      Hypothyroidism and Thyrotoxicosis

      By Paul W. Ladenson, MD
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      Hypothyroidism and Thyrotoxicosis

      • PAUL W. LADENSON, MDJohn Eager Howard Professor of Endocrinology & Metabolism, Professor of Medicine, Pathology, Oncology, Radiology & Radiological Sciences, and International Health, University Distinguished Service Professor, Director, Division of Endocrinology & Metabolism, Johns Hopkins Medical Institutions, Baltimore, Maryland
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    • 19

      Thyroiditis, Goiter, Thyroid Nodules, and Thyroid Cancer

      By Paul W. Ladenson, MD
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      Thyroiditis, Goiter, Thyroid Nodules, and Thyroid Cancer

      • PAUL W. LADENSON, MDJohn Eager Howard Professor of Endocrinology & Metabolism, Professor of Medicine, Pathology, Oncology, Radiology & Radiological Sciences, and International Health, University Distinguished Service Professor, Director, Division of Endocrinology & Metabolism, Johns Hopkins Medical Institutions, Baltimore, Maryland
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    • 20

      Type II Diabetes Mellitus

      By Matthew C. Riddle, MD; Saul Genuth, MD, FACP
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      Type II Diabetes Mellitus

      • MATTHEW C. RIDDLE, MDProfessor, Department of Medicine, and Head, Section of Diabetes, Oregon Health & Sciences University, Portland, OR
      • SAUL GENUTH, MD, FACPProfessor, Division of Clinical and Molecular Endocrinology, Case Western Reserve University School of Medicine, Cleveland, OH
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    • 21

      Diagnosis of Dyslipidemia

      By John D. Brunzell, MD, FACP; R Alan Failor, MD
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      Diagnosis of Dyslipidemia

      • JOHN D. BRUNZELL, MD, FACPProfessor Emeritus, Active, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA
      • R ALAN FAILOR, MDClinical Professor, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA
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    • 22

      Adrenal Insufficiency

      By D. Lynn Loriaux, MD, PhD, MACP
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      Adrenal Insufficiency

      • D. LYNN LORIAUX, MD, PHD, MACPProfessor of Medicine and Chief, Division of Endocrinology and Metabolism, Oregon Health and Science University, Portland, OR

      Adrenal insufficiency (Addison disease) can be categorized as primary or secondary; the former results from adrenal cortex destruction, whereas the latter is caused by disruption of pituitary secretion of adrenocorticotropic hormone. The clinical pictures are the same, and their signs can be differentiated only by the presence of hyperpigmentation and vitiligo in autoimmune disease. Diagnosing both chronic and acute syndromes requires laboratory confirmation; however, the only available diagnostic test for adrenal insufficiency is cosyntropin stimulation. Relative adrenal insufficiency is a hypothetical situation stemming from misinterpretation of this test, and there is no pathophysiologic evidence of its existence. The most common form of congenital adrenal hyperplasia is the 21-hydroxylase deficiency syndrome.

      This review contains 1 figure, 5 tables and 7 references

      Keywords: Adrenal insufficiency, Addison disease, adrenocorticotropic hormone, cosyntropin, congenital adrenal hyperplasia

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    • 23

      Adrenal Insufficiency

      By D. Lynn Loriaux, MD, PhD, MACP
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      Adrenal Insufficiency

      • D. LYNN LORIAUX, MD, PHD, MACPProfessor of Medicine and Chief, Division of Endocrinology and Metabolism, Oregon Health and Science University, Portland, OR
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  • Ethics and Professionalism
    • 1

      Management of Psychosocial Issues in Terminal Illness

      By Jane DeLima Thomas, MD; Eva Reitschuler-Cross, MD; Susan D Block, MD
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      Management of Psychosocial Issues in Terminal Illness

      • JANE DELIMA THOMAS, MDAttending Physician, Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Instructor in Medicine, Harvard Medical School, Boston, MA
      • EVA REITSCHULER-CROSS, MDClinical Assistant Professor of Medicine, University of Pittsburgh, Section of Palliative Care and Medical Ethics, University of Pittsburgh Medical Center, Pittsburgh, PA
      • SUSAN D BLOCK, MDChair, Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute and Brigham and Women’s Hospital Co-Director, HMS Center for Palliative Care, Professor of Psychiatry and Medicine, Harvard Medical School, Boston, MA

      Patients facing serious or life-threatening illness experience challenges to their psychological, social, and spiritual lives as well as to their physical function and comfort. Physicians may be accustomed to focusing on the biomedical aspects of illness, but they have a critical role in assessing the patient's psychosocial issues to identify sources of distress and help implement a plan for mitigating them. An appropriate psychosocial assessment requires a methodical and rigorous approach and includes assessment of any psychosocial issue affected by or affecting a patient's experience of illness. This chapter outlines a structured approach to addressing psychosocial issues by discussing (1) the doctor-patient relationship; (2) coping with illness; (3) family dynamics and caregiving; (4) ethnic and cultural issues; (5) religious, spiritual, and existential issues; (6) mental health issues, including adjustment disorder, depression, anxiety, personality disorders, aberrant drug behaviors, and major mental health issues; and (7) grief and bereavement. Tables outline psychosocial assessment questions, factors predisposing patients with serious illness to depression, risk factors for suicide in patients with terminal illness, and classes of antidepressants, anxiolytics, and sedatives. The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire is provided, as well as a list of Web sites with further resources about psychosocial issues in serious illness.

      This review contains 1 highly rendered figure, 6 tables, and 216 references.

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    • 2

      Advance Care Planning

      By Lauren Jodi Van Scoy, M.D.; Michael Green, M.D., M.S.; Benjamin Levi, M.D., Ph.D.
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      Advance Care Planning

      • LAUREN JODI VAN SCOY, M.D.Assistant Professor, Departments of Medicine and Humanities, Penn State College of Medicine, Hershey, PA
      • MICHAEL GREEN, M.D., M.S.Professor, Departments of Humanities and Medicine, Penn State College of Medicine, Hershey, PA
      • BENJAMIN LEVI, M.D., PH.D.Professor, Departments of Humanities and Pediatrics, Penn State College of Medicine, Hershey, PA

      Advance care planning (ACP) is defined by the Institute of Medicine as an iterative process that involves discussing end-of-life issues, clarifying relevant values and goals of care, and embodying preferences through written documents and medical orders. ACP is predicated on the principle of respect for autonomy, which recognizes an individual’s right to accept or decline medical therapies. With the development of medical technologies that can sustain life (including mere physiologic existence), effective ACP has become a critical yet underused process for patients, their families, and clinicians. This review discusses the emergence of ACP, promises and pitfalls of advance directives, and promising approaches, including ACP interventions and research, as well as a focus on public engagement and future directions. Figures show a timeline of important advances in ACP since 1990, key features of the comprehensive ACP process, the three core aspects or pillars for implementation of ACP, stages of change for ACP behaviors, and two commercially available end-of-life games. Tables list theoretical pros and cons of advance directives, ACP resources, examples of recent research studies on ACP interventions, types and examples of ACP resources, and public engagement campaigns.

       

      This review contains 5 figures, 12 tables, and 101 references

      Keywords: Advance care planning, advance directive, end-of-life

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    • 3

      Withdrawing Life Support and Medical Futility

      By David Oxman, MD
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      Withdrawing Life Support and Medical Futility

      • DAVID OXMAN, MD

      Life support technologies have the potential to save many lives. However, in some cases – particularly when disease is advanced or incurable – the use of these interventions may simply prolong the dying process while causing significant pain and suffering. The ethical basis for withdraw of life support has been clearly elucidated in medical ethics and the law, but given the emotions surrounding these issues, it is not surprising that controversy still exists.  This review discusses withdrawal of life support and withdrawal of artificial nutrition. Additionally, this review explores medical futility, including the historical background, futility and the law, focus on process: hospital futility policies and ethics committees, and current practice and the future of medical futility. Illustrative case reports are presented. The table lists some examples of responding to requests for non-beneficial care from patients or surrogates.

      This review contains 1 figure, 4 tables, and 28 references

      Key Words: Withdrawal of life support; Withdrawal of care; Medical futility  

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    • 4

      Psychosocial Issues in Whole Family Care

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      Psychosocial Issues in Whole Family Care

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    • 5

      Withdrawing Life Support and Medical Futility

      By David Oxman, MD
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      Withdrawing Life Support and Medical Futility

      • DAVID OXMAN, MD
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    • 6

      Advance Care Planning

      By Lauren Jodi Van Scoy, M.D.; Michael Green, M.D., M.S.; Benjamin Levi, M.D., Ph.D.
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      Advance Care Planning

      • LAUREN JODI VAN SCOY, M.D.Assistant Professor, Departments of Medicine and Humanities, Penn State College of Medicine, Hershey, PA
      • MICHAEL GREEN, M.D., M.S.Professor, Departments of Humanities and Medicine, Penn State College of Medicine, Hershey, PA
      • BENJAMIN LEVI, M.D., PH.D.Professor, Departments of Humanities and Pediatrics, Penn State College of Medicine, Hershey, PA
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  • Gastroenterology
    • 1

      Esophageal Disorders

      By Michael F. Vaezi, MD, PhD, MSc (EPI)
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      Esophageal Disorders

      • MICHAEL F. VAEZI, MD, PHD, MSC (EPI)Professor of Medicine, Clinical Director of Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN

      Typically, symptoms that may indicate the presence of an esophageal disorder include heartburn, dysphagia, odynophagia, and regurgitation. Endoscopy is the technique of choice to evaluate the mucosa of the esophagus and to detect structural abnormalities, whereas esophageal manometry is the standard test to diagnose motor disorders of the esophageal body and the lower esophageal sphincter. This review examines normal esophageal anatomy and physiology, the diagnosis of esophageal disorders, disease states causing dysphagia, and gastroesophageal reflux disease. Figures show the cross-sectional anatomy of the esophagus; an algorithm for the evaluation of dysphagia; the anatomy of the gastroesophageal junction; esophagograms of patients with achalasia, late-stage achalasia, and diffuse esophageal spasm; endoscopic views of esophageal strictures; a proximal esophageal web on barium swallow in a patient with Plummer-Vinson syndrome; an endoscopic view of the esophagus of a 25-year-old man with a 3-year history of severe dysphagia; photographs of midesophageal traction diverticulum, multiple epiphrenic diverticula, long-segment Barrett esophagus, and severe Candida esophagitis; and a treatment algorithm for extraesophageal manifestations of gastroesophageal reflux disease. Tables list the high-resolution manometry classification of esophageal motility disorders, causes of esophageal strictures, classic endoscopic findings in patients with eosinophilic esophagitis, the Los Angeles classification of erosive esophagitis, categories of dysplasia, surveillance of Barrett metaplasia, medications implicated in pill-induced esophagitis, and classification of caustic esophageal injury.

      This review contains 13 figures, 40 tables, and 82 references

      Keywords: achalasia, dysphagia, esophagus, reflux, strictures, diverticula, endoscopy, larynx

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    • 2

      Diverticulosis, Diverticulitis, and Appendicitis

      By William V. Harford, MD, FACP
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      Diverticulosis, Diverticulitis, and Appendicitis

      • WILLIAM V. HARFORD, MD, FACPProfessor, Internal Medicine, University of Texas Southwestern Medical Center, Director, GI Endoscopy, VA Medical Center, Dallas, TX

      Colonic diverticula are herniations of colonic mucosa and submucosa through the muscularis propria. They occur where perforating arteries traverse the circular muscle layer, in parallel rows between the mesenteric and antimesenteric taenia. Colonic diverticular disease may present as diverticulosis, diverticulitis, or diverticular bleeding. Of patients with known diverticulosis, only 10% to 20% will develop diverticulitis. Diverticulitis varies in presentation and severity. This chapter discusses the diagnosis, differential diagnosis, and management of diverticulitis and its complications. Appendicitis is generally caused by obstruction of the lumen of the appendix, followed by infection. In the United States, the lifetime risk of appendicitis is about 9% for males and 7% for females. This chapter also discusses the diagnosis of appendicitis (including typical and atypical presentations and appendicitis as it presents in special groups of patients) and its management.

      This review contains 3 figures, 21 tables, and 76 references.

      Keywords: Diverticulosis, diverticulitis, gastrointestinal bleeding, appendicitis, abdominal infection, appendiceal perforation, antibiotics, appendectomy, colectomy, laparoscopy

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    • 3

      Diseases of the Pancreas

      By Sunil Sheth, MD; Gyanprakash Ketwaroo, MD, MSc; Steven Freedman, MD, PhD
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      Diseases of the Pancreas

      • SUNIL SHETH, MDCo-Director, The Pancreas Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA
      • GYANPRAKASH KETWAROO, MD, MSCClinical Fellow, The Pancreas Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA
      • STEVEN FREEDMAN, MD, PHDDirector, The Pancreas Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA

      Acute pancreatitis is characterized by an acute inflamatory process of the pancreas associated with abdominal pain and elevations in serum levels of pancreatic enzymes. The acute inflammation usually completely resolves with restoration of normal pancreatic architecture and function. By contrast, chronic pancreatitis is characterized by the presence of ongoing inflammation and irreversible damage to the gland. Recurrent attacks of acute pancreatitis may lead to chronic pancreatitis over time. This chapter discusses the epidemiology, etiology, pathogenesis, diagnosis, and treatment of acute and chronic pancreatitis. Figures illustrate findings on imaging studies in patients with pancreatic disorders. 

      This review contains 6 figures, 25 tables, and 86 references.

      Keywords: Acute pancreatitis, chronic pancreatitis, pseudocyst, exocrine insufficiency, endocrine insufficiency, magnetic retrograde cholangiopancreatography, endoscopic ultrasonography

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    • 4

      Gallstones and Biliary Tract Disease

      By Vinay Chandrasekhara, MD; Gregory G. Ginsberg, MD
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      Gallstones and Biliary Tract Disease

      • VINAY CHANDRASEKHARA, MDInstructor of Medicine, Gastroenterology Division, Penn Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
      • GREGORY G. GINSBERG, MDProfessor of Medicine, Gastroenterology Division, Director of Endoscopic Services, Penn Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA

      Gallstones (cholelithiasis) are hardened deposits of digestive fluid that can form in the gallbladder and bile ducts. Gallstones range in size from as small as a grain of sand to as large as a billiard ball. Some people develop a single gallstone, whereas others develop many. Gallstone disease or disorders may encompass biliary pain, acute and chronic cholecystitis, choledocholithiasis, and gallstone pancreatitis. Gallstones (cholelithiasis) and biliary tract diseases constitute a common and costly health problem in the United States. This chapter reviews the formation of the two principal types of stone, the cholesterol stone and the pigment stone, that form in the gallbladder and biliary tract. The prevention of gallstones is discussed. The diagnosis, differential diagnosis, treatment, and complications of acute cholecystitis are presented. Diagnosis and treatment of chronic cholecystitis, asymptomatic cholelithiasis, choledocholithiasis, Mirizzi syndrome, and gallbladder polyps are also discussed. Common bile duct stricture, primary sclerosing cholangitis, recurrent pyogenic cholangitis, choledochal cyst, and sphincter of Oddi dysfunction are summarized. 

      This review contains 6 figures, 19 tables, and 111 references. 

      Keywords: Gallbladder, gallstones, cholecystectomy, biliary sludge, cholangitis, choledocholithiasis, cholecystitis, endoscopic retrograde cholangiopancreatography

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    • 5

      Tumors of the Stomach and Small Bowel

      By Jeffrey D. Wayne, MD, FACS; L. Mark Knab, MD; David J. Bentrem, MD, FACS
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      Tumors of the Stomach and Small Bowel

      • JEFFREY D. WAYNE, MD, FACSAssociate Professor, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL
      • L. MARK KNAB, MDGeneral Surgery Resident, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL
      • DAVID J. BENTREM, MD, FACSHarold L. and Margaret N. Method Research Professor in Surgery, Associate Professor in Surgery, Division of Surgical Oncology, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL

      The overall incidence of gastric carcinoma has decreased in the past few decades, but it remains the second leading cause of cancer death worldwide. Malignant tumors of the small intestine are rare, and account for fewer than 5% of all gastrointestinal tract malignancies. This review details the classification, risk factors, clinical evaluation, investigative studies, staging, management, and follow-up and management of recurrent disease in gastric adenocarcinoma; in addition, it examines nonadenocarcinomatous gastric malignancies and small bowel malignancies. 

      This review contains 7 figures, 21 tables, and 97 references.

      Keywords:Gastric adenocarcinoma, gastrointestinal stromal tumor, gastric lymphoma, Helicobacter pylori, small bowel adenocarcinoma, surgical resection, staging, chemotherapy, radiation therapy

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    • 6

      Hernias in the Emergency Department

      By Mary C. Westergaard, MD, FACEP; Daniel Berhanu, MD; Ciara J. Barclay-Buchanan, MD, FACEP
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      Hernias in the Emergency Department

      • MARY C. WESTERGAARD, MD, FACEPResidency Program Director, Assistant Professor (Clinical Health Sciences), Department of Emergency Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
      • DANIEL BERHANU, MDResident Physician, Department of Emergency Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
      • CIARA J. BARCLAY-BUCHANAN, MD, FACEPAssociate Residency Program Director, Assistant Professor (Clinical Health Sciences), Department of Emergency Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI

      Hernia is defined as an abnormal protrusion of an organ or tissue through a pathologic defect in its surrounding wall. Overall, hernia is common and is generally believed to be a benign condition associated with some morbidity, although it is not thought to be associated with significant mortality. Between 2001 and 2010, 2.3 million inpatient abdominal hernia repairs were performed in the United States, of which 567,000 were performed emergently. In some cases, a hernia can be a deadly condition. In 2002, hernia was listed as the cause of death for 1,595 US citizens. This review covers the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes of hernia. Figures show anatomic locations of the various abdominal wall, groin, lumbar, and pelvic floor hernias; a direct inguinal hernia; an indirect inguinal hernia; point-of-care sonograms showing a ventral wall hernia and an abdominal wall hernia; and the differential diagnosis of an abdominal mass based on anatomic location. Tables list risk factors for the development of inguinal hernia, sex-based differences in inguinal hernia development, risk factors for the development of incisional hernia, factors to consider when assessing the patient for a hernia, and factors associated with the highest rates of incarceration in patients with groin hernia.

      Key words: emergent hernia, hernia incarceration, incisional hernia, inguinal hernia, strangulated hernia

      This review contains 6 highly rendered figures, 5 tables, and 66 references.

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    • 7

      Pathophysiology and Diagnosis of Ulcerative Colitis and Crohn Disease

      By Julia B. Greer, MD, MPH; Miguel D. Regueiro, MD
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      Pathophysiology and Diagnosis of Ulcerative Colitis and Crohn Disease

      • JULIA B. GREER, MD, MPHAssistant Professor of Medicine, Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA
      • MIGUEL D. REGUEIRO, MDProfessor of Medicine, Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Co-Director, Inflammatory Bowel Disease Center, University of Pittsburgh Medical Center, Pittsburgh, PA

      Inflammatory bowel disease (IBD) encompasses both ulcerative colitis and Crohn disease, and is characterized by recurrent bouts of inflammation of the gastrointestinal tract. IBD affects approximately 4 million people worldwide, and rates are gradually increasing. This review covers the etiology, epidemiology, definition and pathophysiology, extraintestinal manifestations, and other disease-related complications of IBD. Figures show the distribution of ulcerative colitis and Crohn disease by location, several colonoscopic photographs of patients with ulcerative colitis as well as those with Crohn disease, computed tomography images of patients with Crohn disease, small bowel follow-through and fluoroscopic spot images of a patient with chronic structuring Crohn disease, and a computed tomographic scan showing extraenteric manifestations of Crohn disease. Tables list the differential diagnosis of ulcerative colitis, types of infectious colitis, complications of IBD, diagnostic criteria of toxic colitis, physical signs of Crohn disease, differences between Crohn disease and ulcerative colitis, and common extraintestinal manifestations of IBD.

      This review contains 11 highly rendered figures, 7 tables, and 63 references.

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    • 8

      Management of Ulcerative Colitis and Crohn Disease

      By Julia B. Greer, MD, MPH; Miguel D. Regueiro, MD
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      Management of Ulcerative Colitis and Crohn Disease

      • JULIA B. GREER, MD, MPHAssistant Professor of Medicine, Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA
      • MIGUEL D. REGUEIRO, MDProfessor of Medicine, Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Co-Director, Inflammatory Bowel Disease Center, University of Pittsburgh Medical Center, Pittsburgh, PA

      There have been considerable advances in the treatment of inflammatory bowel disease (IBD) since the 20th century, and there are multiple options available to the clinician. The management of IBD depends on the location of disease, as well as its clinical, endoscopic and histologic severity. The field is currently undergoing a paradigm shift from a step-up approach (starting treatment with a “milder” medication and, if this treatment fails, moving on to a more powerful medication) to a top-down approach (in which stronger medications are given earlier in the disease course). This review details the medications used to treat IBD, nutrition in IBD patients, and surgical treatment of IBD. Figures show step-up therapy, top-down therapy, strictureplasty technique, gross pathology image of a patient with Crohn disease and previous ileocecal resection, and ileal pouch anal anastomosis surgery. Tables list 5-aminosalicylic acid medications, antibiotics, corticosteroids, immunomodulators, and biologic medications used to treat IBD, as well as causes of nutritional deficiencies in IBD patients.

      This review contains 5 highly rendered figures, 6 tables, and 96 references.

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    • 9

      Peptic Ulcer Diseases

      By Edward A Lew, MD, MPH
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      Peptic Ulcer Diseases

      • EDWARD A LEW, MD, MPHStaff Gastroenterologist, VA Boston Healthcare System, Brigham and Women’s Hospital, Assistant Professor of Medicine, Harvard Medical School, Boston, MA

      Peptic ulcers are defects or breaks in the inner lining of the gastrointestinal (GI) tract. Although the pathogenesis is multifactorial they tend to arise when there is an imbalance between protective and aggressive factors, such as when GI mucosal defense mechanisms are impaired in the presence of gastric acid and pepsin. Peptic ulcers extend through the mucosa and the muscularis mucosae, a thin layer of smooth muscle separating the mucosa from the deeper submucosa, muscularis propria, and serosa. Peptic ulcer disease affects up to 10% of men and 4% of women in Western countries at some time in their lives. This chapter discusses the pathogenesis of peptic ulcer disease and the etiologic contribution of Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs, and gastrinoma or other hypersecretory states. Also addressed are rare and unusual causes for ulcers and GI bleeding. A section on the diagnosis of peptic ulcers discusses clinical manifestations, physical examination findings, laboratory and imaging studies, and surgical diagnosis. Differential diagnosis is also reviewed. Tests to establish the etiology of peptic ulcer disease include endoscopy, quantitative serologic tests, the urea breath test, and the fecal antigen test. Discussed separately are treatments for uncomplicated duodenal ulcers, uncomplicated gastric ulcers, intractable duodenal or gastric ulcers, complicated peptic ulcers (bleeding ulcers, acute stress ulcers, perforated ulcers, obstructing ulcers, fistulizing ulcers, and Cameron ulcers), H. pylori ulcers, and gastric cancer. Figures illustrate the etiopathogenesis of peptic ulcers, prevalence of H. pylori infection in duodenal and gastric ulcer patients compared with normal controls, the approach to a patient with new and undiagnosed ulcerlike symptoms refractory to antisecretory therapy, an upper GI series showing an uncomplicated duodenal ulcer, a chest x-ray showing pneumoperitoneum from a perforated duodenal ulcer, gastric biopsy samples showing H. pylori organisms, and the approach to treatment and follow-up in patients with either complicated or uncomplicated duodenal or gastric ulcer. Tables list differential diagnoses of peptic ulcer disease, commonly used regimens to eradicate H. pylori, additional antimicrobial agents with activity against H. pylori, and FDA-approved antisecretory drugs for active peptic ulcer disease.

      This chapter contains 5 figures, 6 tables and 78 references.

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    • 10

      Gastrointestinal Motility and Functional Disorders

      By Adil E Bharucha, MBBS, MD
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      Gastrointestinal Motility and Functional Disorders

      • ADIL E BHARUCHA, MBBS, MDProfessor of Medicine, Director, Motility Interest Group, Mayo Clinic, Rochester, MN

      Gastrointestinal (GI) motility disorders represent diseases characterized by abnormal, predominantly impaired, sometimes exaggerated, movement of contents through the GI tract due to neuromuscular dysfunctions in the absence of mucosal disease and mechanical causes of impaired passage. By contrast, functional GI disorders represent illnesses, defined only by GI symptoms, which occur in the absence of mucosal or structural abnormality or of known biochemical or metabolic disorders. The first section of this chapter discusses the enteric and extrinsic neural regulation of GI sensorimotor functions and normal GI motility in humans. Disorders such as gastroparesis (including diabetic gastroparesis, idiopathic gastroparesis, and postsurgical gastroparesis), dumping syndrome, intestinal pseudo-obstruction, small intestinal bacterial overgrowth, megacolon (including Hirschsprung disease, toxic megacolon, and colonic pseudo-obstruction), chronic constipation (including defecatory disorders, normal transit constipation, and slow transit constipation), functional dyspepsia, functional diarrhea and irritable bowel syndrome, and fecal incontinence are then discussed in depth. Tables present a comparison of GI motility and functional disorders, the causes of gastroparesis, the etiology of intestinal pseudo-obstruction and fecal incontinence, common medical conditions and medications associated with constipation, and the symptom severity scale in fecal incontinence. Illustrations, graphs, magnetic resonance images, and algorithms are provided.
      This chapter contains 10 highly rendered figures, 6 tables, 92 references, and 5 MCQs.

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    • 11

      Irritable Bowel Syndrome With Diarrhea

      By Judy Nee, MD; Jacqueline L. Wolf, MD
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      Irritable Bowel Syndrome With Diarrhea

      • JUDY NEE, MDInstructor in Medicine, Harvard Medical School, BIDMC, Beth Israel Deaconess Medical Center, Boston, MA
      • JACQUELINE L. WOLF, MDAssociate Professor of Medicine, Harvard Medical School, BIDMC, Beth Israel Deaconess Medical Center, Boston, MA

      Irritable bowel syndrome (IBS) is a complex, functional gastrointestinal condition characterized by abdominal pain and alteration in bowel habits without an organic cause. One of the subcategories of this disorder is IBS with diarrhea (IBS-D). Clinically, patients who present with more than 3 months of abdominal pain or discomfort associated with an increase in stool frequency and/or loose stool form are defined as having IBS-D. This review addresses IBS-D, detailing the epidemiology, etiology and genetics, pathophysiology and pathogenesis, diagnosis, clinical manifestations and physical examination findings, differential diagnosis, treatment, emerging therapies, complications, and prognosis. Figures show potential mechanisms and pathophysiology of IBS, IBS-D suspected by clinical assessment and Rome III criteria, pharmacologic and nonpharmacologic treatment options, potential mechanisms of action of probiotics, and potential treatment modalities. Tables list the Rome criteria for IBS, alarm signs and symptoms suggestive of alternative diagnoses, IBS criteria, differential diagnosis of IBS-D, dietary advice options for IBS-D, and alternative and emerging therapies in IBS-D.

      This review contains 5 highly rendered figures, 6 tables, and 99 references. 

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    • 12

      Constipation

      By Charles H Knowles, MBBChir, PhD, FRCS
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      Constipation

      • CHARLES H KNOWLES, MBBCHIR, PHD, FRCS

      This review presents an overview of the management of constipation. The review addresses the diagnosis of primary and secondary forms and then discusses in greater detail the investigative workup and modern management of chronic constipation (primary). The review addresses what simple and more advanced investigations are relevant for determining pathophysiology and gives an overview of treatment options, including pharmacologic, behavioral, and surgical approaches for thus defined subgroups of patients (evacuation disorder, slow transit constipation).

      This review contains 3 figures, 6 tables, and 89 references.

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    • 13

      Gastrointestinal Bleeding

      By Romeo Fairley, MD; Truman J. Milling Jr, MD
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      Gastrointestinal Bleeding

      • ROMEO FAIRLEY, MDResident, University of Texas, Austin Emergency Medicine Residency Program, Austin, TX
      • TRUMAN J. MILLING JR, MDDeputy Director of Clinical Research, Department of Emergency Medicine, University of Texas, Dell Medical School, Austin, TX

      Gastrointestinal bleeding occurs when a pathologic process such as ulceration, inflammation, or neoplasia leads to erosion of a blood vessel. Bleeding can occur in the upper gastrointestinal tract (50%) or the lower gastrointestinal tract (40%) or may be obscure (10%), meaning that no definitive source is identified. Gastrointestinal bleeding is common, with major bleeding leading to 1 million hospitalizations every year in the United States. This review details the pathophysiology of gastrointestinal bleeding and the stabilization and assessment, diagnosis, treatment, and disposition and outcomes of patients with gastrointestinal bleeding. Situations requiring special consideration are also discussed. Figures show how gastrointestinal bleeding occurs when a pathologic process causes erosion of the mucosa and exposes a submucosal blood vessel; an ulcer with a raised, red, variceal spot; a Mallory-Weiss tear; the formation of varices; vascular ectasia; treatment of esophageal varices with balloon tamponade; and a wireless capsule. Tables list the major causes of gastrointestinal bleeding, terms relating to gastrointestinal bleeding and their definitions, Blatchford score, substances that interfere with occult blood testing, clinical factors differentiating gastrointestinal bleeding placed in descending order of likelihood ratio, and a summary of American College of Radiology recommendations for angiography in nonvariceal gastrointestinal bleeding.

      This review contains 8 figures, 15 tables, and 107 references.

      Key Words: gastrointestinal bleeding, inflammation, occult blood testing, UGIB, LGIB, Blatchford score, angiography, wireless capsule endoscopy (WCE)

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    • 14

      Gastrointestinal Tract Infections

      By Marcia B Goldberg, MD; Molly Paras, MD
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      Gastrointestinal Tract Infections

      • MARCIA B GOLDBERG, MDAssociate Professor of Medicine, Division of Infectious Diseases, Harvard Medical School, and Physician, Massachusetts General Hospital, Boston, MA
      • MOLLY PARAS, MDDivision of Infectious Diseases, Department of Medicine

      Gastrointestinal infections, which present with acute diarrhea, sometimes accompanied by vomiting, are an extremely common medical complaint, with an annual incidence of 0.6 illnesses per person. Transmission can occur from animals to person, from person to person, or by the ingestion of contaminated foodstuffs. In the United States, more than 90% of cases are caused by viruses, with norovirus being by far the most common. Common among bacterial causes of acute gastrointestinal infection are SalmonellaCampylobacterShigella, Shiga toxin–producing Escherichia coliVibrio,Yersinia, and Clostridium difficile. These infections are typically self-limited, but depending on the etiologic agent and characteristics of the host, antibiotic therapy may be indicated. Certain gastrointestinal infections are associated with significant complications, including reactive arthritis, Guillain-Barré syndrome, or septicemia.

      This review contains 4 figures, 7 tables, and 60 references.

      Key words: CampylobacterEscherichia coli, Guillain-Barré syndrome,reactive arthritis, Shiga toxin, ShigellaVibrioYersinia

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    • 15

      Evaluation and Treatment of Monogenic Forms of Inflammatory Bowel Diseases

      By Dror S Shouval, MD, MMSc
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      Evaluation and Treatment of Monogenic Forms of Inflammatory Bowel Diseases

      • DROR S SHOUVAL, MD, MMSCPediatric Gastroenterology Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

      Inflammatory bowel diseases (IBDs) are complex disorders that develop in genetically susceptible hosts due to dysregulated immune responses to microbial dysbiosis and environmental changes. Although in the vast majority of cases, the genetic contribution to development of these diseases is small, in rare cases, IBD develops directly as a result of deleterious mutations in the genes involved in immune and epithelial cell function. In these cases, intestinal inflammation is usually severe, which develops in most cases in the first years of life and occasionally is accompanied by recurrent or atypical infections. In this review, the approach to different monogenic disorders that cause IBD is discussed, including mutations in the IL-10 pathway, neutrophil defects, regulatory T-cell disorders, autoinflammatory conditions, epithelial cell diseases, and disorders affecting B- and T-lymphocyte dysfunction. Moreover, a multidisciplinary diagnostic approach is suggested, which highlights in which cases a monogenic disorder should be suspected.

      This review contains 3 figures, 3 tables, and 42 references.

      Key Words: inflammatory bowel disease, IL-10, chronic granulomatous disease, common variable immune deficiency, epithelial cells, genetics, immune cells, mucosal homeostasis, pathogenesis, very early–onset disease.

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    • 16

      Nutrition Management in Mechanical Circulatory Support

      By Dane A Coyne, MD; Mitali P Shah, MD; Kris M Mogensen, MS, RD-AP, LDN, CNSC; John C Klick, MD, FCCP, FASE, FCCM
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      Nutrition Management in Mechanical Circulatory Support

      • DANE A COYNE, MD
      • MITALI P SHAH, MD
      • KRIS M MOGENSEN, MS, RD-AP, LDN, CNSC
      • JOHN C KLICK, MD, FCCP, FASE, FCCM

      Heart failure is a devastating progressive disease process that is rising in incidence throughout the world. For patients with end-stage heart failure, orthotopic heart transplantation had been the only therapeutic option. Unfortunately, the number of patients requiring such therapy far exceeds the number of available organs. Recent advancements in technology have made implantable cardiac assist devices a reality. Outcomes with these devices are superior to maximal medical therapy and may serve either as a bridge to the availability of a donor organ or as “destination” therapy for the patient with end-stage heart failure. In addition, new technology can also provide temporary mechanical support for patients with acute decompensated cardiogenic shock, allowing preservation of end-organ function until more definitive long-term mechanical support can be coordinated. Patients with end-stage heart failure experience unique nutritional challenges. Mechanical circulatory support adds yet another unique dimension to the nutritional support challenges of this patient population.

      This review contains 2 figures, 5 tables, and 29 references.

      Key words: cardiogenic shock, enteral nutrition, extracorporeal membrane oxygenation, heart failure, mechanical circulatory support, nutritional support, parenteral nutrition, ventricular assist device

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    • 17

      Diseases Producing Malabsorption and Maldigestion

      By Rupa Mukherjee, MD; Ciarán P Kelly, MD
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      Diseases Producing Malabsorption and Maldigestion

      • RUPA MUKHERJEE, MDClinical Instructor in Medicine, Department of Gastroenterology, The Celiac Center, Harvard Medical School, Boston, MA
      • CIARÁN P KELLY, MDProfessor of Medicine, Medical Director of The Celiac Center, Director of Gastroenterology Fellowship Training Program, Harvard Medical School, Boston, MA

      Malabsorption refers to the impaired intestinal absorption of nutrients. It can result from congenital defects in absorption and the transport of ions and nutrients, defects in hydrolysis within the intestinal lumen, acquired defects in the intestinal absorptive cells that line the surface of the intestine, impaired bile production, or interruption of enterohepatic circulation or secondary to pancreatic insufficiency. Maldigestion, another factor in nutrient absorption, refers to the impaired digestion of nutrients within the intestinal lumen or at the terminal digestive site of the brush border membrane of mucosal epithelial cells. Although malabsorption and maldigestion are pathophysiologically distinct, they are interdependent, and in clinical practice, malabsorption has come to signify derangements in either or both processes. This chapter discusses the clinical manifestations of malabsorption and tests for suspected malabsorption. The diseases that can cause malabsorption, their diagnosis, and treatment recommendations are included. Figures illustrate the diagnosis and management of celiac disease; an approach to gluten challenge for the diagnosis or exclusion of celiac disease in patients maintained on a gluten-free diet without previous definitive diagnostic testing; and the histologic features of celiac disease, Crohn disease, collagenous sprue, autoimmune enteropathy, eosinophilic gastritis, and intestinal lymphangiectasia. 

      This review contains 9 figures, 25 tables, and 116 references.

      Keywords: Malabsorption, maldigestion, Crohn disease, celiac disease, tropical sprue, diarrhea, endoscopy, short bowel syndrome, bacterial overgrowth

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    • 18

      Irritable Bowel Syndrome With Constipation

      By Loni Tang, MD; Brooks D. Cash, MD
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      Irritable Bowel Syndrome With Constipation

      • LONI TANG, MDResident, Department of Internal Medicine, University of South Alabama, Mobile, AL
      • BROOKS D. CASH, MDProfessor of Medicine, Division of Gastroenterology, Department of Internal Medicine, University of South Alabama, Mobile, AL

      Irritable bowel syndrome (IBS) is characterized by recurrent abdominal pain or discomfort that has occurred at least 3 days per month in the 3 months prior to diagnosis. One of the subtypes of this disorder is IBS with constipation (IBS-C), where individuals experience hard or lumpy stools at least 25% of the time and loose or watery stools less than 25% of the time with defecation. This review addresses IBS-C, detailing the epidemiology, etiology, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, and prognosis. A figure shows the Bristol stool form scale. Tables list IBS subtypes, components of digital rectal examination, differential diagnoses for IBS and IBS-C, alarm features, and the American College of Gastroenterology Recommendations.

      This review contains 1 highly rendered figure, 6 tables, and 71 references. 

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    • 19

      Overview of Enteral Nutrition

      By Rebecca Lynch, MS, RD, LDN, CNSC; Erin Sisk, MS, RD, LDN, CNSC
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      Overview of Enteral Nutrition

      • REBECCA LYNCH, MS, RD, LDN, CNSC
      • ERIN SISK, MS, RD, LDN, CNSC

      Enteral nutrition (EN) is recognized as a medical nutrition therapy for patients with a functional gastrointestinal tract who are unable to maintain their weight and health by oral intake alone either due to a highly catabolic medical condition or a functional limitation. EN support provides calories and protein to help improve or maintain adequate weight, lean body mass, and overall nutritional status. EN also provides nonnutritive benefits such as maintaining intestinal integrity, supporting the immune system, and preventing infection. EN support can be tailored to a patient’s nutrient needs, and there are various formulas that vary in composition of macronutrients, concentration, and electrolytes for specific disease processes or conditions that may help with tolerance and absorption. EN support complications include issues with access, diarrhea, constipation, electrolyte abnormalities, hyperglycemia, and dehydration/overhydration. Generally, EN is well tolerated. While a patient is on this type of nutrition support, it is important to closely monitor tolerance, weight, laboratory values if indicated, and overall clinical progress, with adjustment to the regimen as needed.

      This review contains 1 figure, 4 tables, and 48 references.

      Key words: enteral access, enteral formula, enteral nutrition support, gastric residuals, gastrointestinal tract, immunonutrition, malnutrition, medical nutrition therapy, tube feed formula, tube feed tolerance, tube feeding, volume-based feeding

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    • 20

      Intestinal Obstruction

      By Lilah F Morris-Wiseman, MD
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      Intestinal Obstruction

      • LILAH F MORRIS-WISEMAN, MDAssistant Professor, Department of Surgery, University of Arizona, Tucson, AZ

      Bowel obstruction (mechanical and functional) is a common cause of hospitalization for abdominal pain; patients with complaints of abdominal pain, nausea, vomiting, distention, and lack of flatus or bowel movement should be evaluated for obstruction. The surgeon must approach this diagnosis in a stepwise fashion to determine whether the patient has ischemia necessitating emergent operative intervention or whether initial nonoperative management is warranted. Mechanical obstruction in the small bowel is most commonly caused by adhesions from previous surgery, hernia, or mass, whereas mechanical obstruction in the colon is most often caused by volvulus, cancer, and diverticular stricture. Initial evaluation includes a detailed history, physical examination, and biochemical evaluation with initiation of resuscitative efforts as needed. CT with intravenous contrast is often most readily available and most helpful in diagnosing bowel obstruction type; specific CT findings can suggest the need for urgent operative intervention. Water-soluble contrast medium challenge has emerged as an important adjunct in evaluating the likelihood that a patient with nonischemic bowel obstruction will require operative intervention.  

      This review contains 14 figures, 15 tables and 65 references

      Keywords:Adhesive bowel obstruction, ileus, ischemic bowel obstruction, laparoscopic adhesiolysis, large bowel obstruction, postoperative bowel obstruction, small bowel obstruction, volvulus, water-soluble contrast medium

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    • 21

      Diseases of the Stomach

      By Tara C. Sheets, MD, FACEP; Moath Amro, MD
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      Diseases of the Stomach

      • TARA C. SHEETS, MD, FACEPBaylor College of Medicine, Assistant Professor, Section of Emergency Medicine Department of Medicine
      • MOATH AMRO, MDBaylor College of Medicine, Emergency Medicine Resident, Section of Emergency Medicine Department of Medicine

      There are multiple diseases of the stomach and esophagus that will lead a patient to seek emergent care, including peptic ulcer disease (PUD), esophagitis, dysphagia, esophageal foreign bodies, and gastroesophageal reflux disease (GERD). Hemorrhage and perforation are major emergencies in peptic ulcer disease and esophageal disease requiring early recognition with immediate resuscitative efforts to stabilize. This review covers the risk factors, pathophysiology, assessment and stabilization, diagnosis and treatment, and disposition and outcomes for patients with diseases of the stomach and esophagus. Figures show illustrations of esophageal anatomy, an algorithm for the evaluation of dysphagia, the pathogenesis of peptic ulcers, and radiographs demonstrating an esophageal button battery and pneumoperitoneum caused by a perforated ulcer. Tables list some common causes of esophageal stricture and pill-induced esophagitis, differential diagnosis of peptic ulcer disease and commonly used regimens to eradicate Helicobacter pylori infection.

      Key Words: Peptic ulcer disease, esophagitis, dysphagia, esophageal foreign body, GERD, H. Pylori, button battery

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    • 22

      Appendicitis

      By James Creswell Simpson, MD; Sarah Sebbag, MD, CM, CCFP(EM)
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      Appendicitis

      • JAMES CRESWELL SIMPSON, MDResident Physician, Department of Anesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA
      • SARAH SEBBAG, MD, CM, CCFP(EM)Director, Emergency Ultrasound, Ochsner Health System, Department of Emergency Medicine, New Orleans, LA

      Appendicitis is defined as inflammation of the vermiform appendix. It is the most common abdominal surgical emergency and occurs at an annual rate of approximately one in 10,000 in the United States. The lifetime risk of appendicitis is about 9% for males and 7% for females; approximately 80% of cases occur before 45 years of age. Appendicitis rarely occurs in infants; it increases in frequency between 2 and 4 years of age and reaches a peak between the ages of 10 and 19 years. However, clinicians must maintain a high index of suspicion in patients of all age groups. This review covers the pathophysiology, stabilization and assessment, and diagnosis and treatment of complicated and uncomplicated appendicitis. The disposition and outcomes are also reviewed. Figures show an image of appendicitis on a bedside sonogram, and a computed tomographic image of appendicitis. Tables list likelihood ratios of signs and symptoms of appendicitis, the sonographic appearance of appendicitis, the Alvarado scoring system, and the differential diagnosis of appendicitis.

       This review contains 2 figures, 7 tables, and 36 references.

      Key words: appendicitis, obstructed appendiceal lumen, rebound abdomen, right lower quadrant pain, ruptured appendix

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    • 23

      Gallstones and Biliary Tract Disease

      By Vinay Chandrasekhara, MD; Gregory G. Ginsberg, MD
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      Gallstones and Biliary Tract Disease

      • VINAY CHANDRASEKHARA, MDInstructor of Medicine, Gastroenterology Division, Penn Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
      • GREGORY G. GINSBERG, MDProfessor of Medicine, Gastroenterology Division, Director of Endoscopic Services, Penn Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
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    • 24

      Diseases of the Pancreas

      By Sunil Sheth, MD; Gyanprakash Ketwaroo, MD, MSc; Steven Freedman, MD, PhD
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      Diseases of the Pancreas

      • SUNIL SHETH, MDCo-Director, The Pancreas Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA
      • GYANPRAKASH KETWAROO, MD, MSCClinical Fellow, The Pancreas Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA
      • STEVEN FREEDMAN, MD, PHDDirector, The Pancreas Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA
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    • 25

      Tumors of the Stomach and Small Bowel

      By Jeffrey D. Wayne, MD, FACS; L. Mark Knab, MD; David J. Bentrem, MD, FACS
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      Tumors of the Stomach and Small Bowel

      • JEFFREY D. WAYNE, MD, FACSAssociate Professor, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL
      • L. MARK KNAB, MDGeneral Surgery Resident, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL
      • DAVID J. BENTREM, MD, FACSHarold L. and Margaret N. Method Research Professor in Surgery, Associate Professor in Surgery, Division of Surgical Oncology, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL
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    • 26

      Diverticulosis, Diverticulitis, and Appendicitis

      By William V. Harford, MD, FACP
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      Diverticulosis, Diverticulitis, and Appendicitis

      • WILLIAM V. HARFORD, MD, FACPProfessor, Internal Medicine, University of Texas Southwestern Medical Center, Director, GI Endoscopy, VA Medical Center, Dallas, TX
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    • 27

      Esophageal Disorders

      By Michael F. Vaezi, MD, PhD, MSc (EPI)
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      Esophageal Disorders

      • MICHAEL F. VAEZI, MD, PHD, MSC (EPI)Professor of Medicine, Clinical Director of Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN
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    • 28

      Intestinal Obstruction

      By Lilah F Morris-Wiseman, MD
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      Intestinal Obstruction

      • LILAH F MORRIS-WISEMAN, MDAssistant Professor, Department of Surgery, University of Arizona, Tucson, AZ
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    • 29

      Peptic Ulcer Diseases

      By Edward A Lew, MD, MPH
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      Peptic Ulcer Diseases

      • EDWARD A LEW, MD, MPHStaff Gastroenterologist, VA Boston Healthcare System, Brigham and Women’s Hospital, Assistant Professor of Medicine, Harvard Medical School, Boston, MA
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    • 30

      Approach to the Patient With Abdominal Pain

      By Dana Sajed, MD
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      Approach to the Patient With Abdominal Pain

      • DANA SAJED, MDDirector of Ultrasound Education, Continuing Medical Education Director, Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA

      Abdominal pain is the most common presenting complaint in the emergency department (ED), accounting for nearly 8% of ED visits. Although many chronic conditions may cause pain in the abdomen, acute abdominal pain, defined as undiagnosed pain present for less than 1 week, is of greatest concern to the emergency practitioner. For many reasons, acute abdominal pain is often diagnostically challenging. Abdominal pain may be due to numerous causes, including gastrointestinal, genitourinary, cardiovascular, pulmonary, and other sources. Symptoms may fluctuate or change in nature, and the quality of pain can be difficult for the patient to describe. Physical examination findings, although important, are variable and can even be misleading. Despite being such a common presenting complaint, misdiagnosis is not uncommon and results in a high percentage of medicolegal actions in both and adult and pediatric populations.

      This review contains 5 figures, 8 tables, and 92 references

      Key words: abdominal computed tomography, abdominal pain, abdominal ultrasonography, pain management, point-of-care ultrasonography

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    • 31

      Gastroesophageal Reflux Disease

      By R. Thomas Finn III, MD, MBA; Walter W Chan, MD, MPH
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      Gastroesophageal Reflux Disease

      • R. THOMAS FINN III, MD, MBAClinical Fellow in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
      • WALTER W CHAN, MD, MPHDirector, Center for Gastrointestinal Motility, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Assistant Professor of Medicine, Harvard Medical School, Boston, MA

      Gastroesophageal reflux disease (GERD) is the most common gastrointestinal diagnosis made in outpatient clinics, responsible for over 5 million annual outpatient visits and likely hundreds of thousands of inpatient stays for noncardiac chest pain. GERD’s current definition, based on international consensus, is a “condition which develops when the reflux of stomach contents causes troublesome symptoms (i.e., at least two heartburn episodes per week) and/or complications.” Also defining GERD is the presence of erosive esophagitis on upper endoscopy (esophagogastroduodenoscopy [EGD]) with or without the presence of troublesome symptoms or the presence of troublesome symptoms without endoscopic evidence of erosive esophagitis (also known as nonerosive reflux disease). This review looks at GERD in detail, including its epidemiology and risk factors, genetics, pathogenesis and etiologic factors, clinical presentation and symptoms, differentials, diagnosis, and complications. Figures presented are an EGD image showing signs of erosive esophagitis, Barrett esophagus, and hiatal hernia and sample recordings from a 24-hour combined multichannel intraluminal impedance and pH testing. Tables list differential diagnoses for GERD, indications for performing EGD in patients with GERD symptoms, and a summary of GERD therapies.

      This review contains ­2 figures, 4 tables, and 74 references. 

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    • 32

      Gastroesophageal Reflux Disease

      By R. Thomas Finn III, MD, MBA; Walter W Chan, MD, MPH
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      Gastroesophageal Reflux Disease

      • R. THOMAS FINN III, MD, MBAClinical Fellow in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
      • WALTER W CHAN, MD, MPHDirector, Center for Gastrointestinal Motility, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Assistant Professor of Medicine, Harvard Medical School, Boston, MA
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    • 33

      Mesenteric Ischemia

      By Ugo A. Ezenkwele, MD, MPH
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      Mesenteric Ischemia

      • UGO A. EZENKWELE, MD, MPHChief, Emergency Department, Mount Sinai Queens, Associate Professor, Department of Emergency Medicine, Icahn Mount Sinai School of Medicine, New York, NY

      Acute mesenteric ischemia is interruption of intestinal blood flow by embolism, thrombosis, or a low-flow state. Bowel infarction is the end result of a process initiated by mediator release and inflammation. On clinical assessment, the early hallmark is severe abdominal pain but minimal physical findings. The abdomen remains soft, with little or no tenderness. Mild tachycardia may be present. Early diagnosis is difficult, but selective mesenteric angiography and computed tomographic angiography have the most sensitivity; other imaging studies and serum markers can show abnormalities but lack sensitivity and specificity early in the course of the disease, when diagnosis is most critical. Treatment is by embolectomy, anticoagulation, revascularization of viable segments, or resection; sometimes vasodilator therapy is successful. If diagnosis and treatment take place before infarction occurs, mortality is low; after intestinal infarction, mortality approaches 30 to 70%. For this reason, in the emergency department, clinical diagnosis should supersede diagnostic tests, which may delay treatment.

      This review contains 6 figures, 4 tables and 40 references

      Key words: acute mesenteric ischemia; bowel necrosis; chronic mesenteric ischemia; mesenteric occlusive disease; mesenteric venous thrombosis; nonocclusive mesenteric ischemia; postprandial abdominal pain; superior mesenteric artery thromboembolism

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    • 34

      Lower Gastrointestinal Bleeding

      By Jennifer Nayor, MD; John R. Saltzman, MD
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      Lower Gastrointestinal Bleeding

      • JENNIFER NAYOR, MDClinical Research Fellow, Division of Gastroenterology, Brigham and Women’s Hospital, Boston, MA
      • JOHN R. SALTZMAN, MDDirector of Endoscopy, Division of Gastroenterology, Brigham and Women’s Hospital, Boston, MA, Associate Professor of Medicine, Harvard Medical School, Boston, MA

      Of patients who present with major gastrointestinal (GI) bleeding, 20 to 30% will ultimately be diagnosed with bleeding originating from a lower GI source. Lower GI bleeding has traditionally been defined as bleeding originating from a source distal to the ligament of Treitz; however, with the advent of capsule endoscopy and deep enteroscopy allowing for visualization of the entire small bowel, the definition has been updated to GI bleeding originating from a source distal to the ileocecal valve. Lower GI bleeding can range from occult blood loss to massive bleeding with hemodynamic instability and predominantly affects older individuals, with a mean age at presentation of 63 to 77 years. Comorbid illness, which is a risk factor for mortality from GI bleeding, is also more common with increasing age. Most deaths related to GI bleeding are not due to uncontrolled hemorrhage but exacerbation of underlying comorbidities or nosocomial complications. This review covers the following areas: evaluation of lower GI bleeding (including physical examination and diagnostic tests), initial management, and differential diagnosis. Disorders addressed in the differential diagnosis include diverticulosis, arteriovenous malformations (AVMs), ischemic colitis, anorectal disorders, radiation proctitis, postpolypectomy bleeding, and colorectal neoplasms. Figures show an algorithm for management of patients with suspected lower GI bleeding, tagged red blood cell scans, diverticular bleeding, colonic AVM, ischemic colitis, bleeding hemorrhoid, chronic radiation proctitis, and ileocolonic valve polyp. Tables list descriptive terms for rectal bleeding and suggested location of bleeding, imaging modalities and differential diagnosis for lower GI bleeding, endoscopic techniques for hemostasis, and an internal hemorrhoids grading system.

      This review contains 9 figures, 8 tables, and 103 references.

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    • 35

      Lower Gastrointestinal Bleeding

      By Jennifer Nayor, MD; John R. Saltzman, MD
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      Lower Gastrointestinal Bleeding

      • JENNIFER NAYOR, MDClinical Research Fellow, Division of Gastroenterology, Brigham and Women’s Hospital, Boston, MA
      • JOHN R. SALTZMAN, MDDirector of Endoscopy, Division of Gastroenterology, Brigham and Women’s Hospital, Boston, MA, Associate Professor of Medicine, Harvard Medical School, Boston, MA
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    • 36

      Nonvariceal Upper Gastrointestinal Bleeding

      By John R. Saltzman, MD; Wasif Abidi, MD, PhD
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      Nonvariceal Upper Gastrointestinal Bleeding

      • JOHN R. SALTZMAN, MDDirector of Endoscopy, Division of Gastroenterology, Brigham and Women’s Hospital, Boston, MA, Associate Professor of Medicine, Harvard Medical School, Boston, MA
      • WASIF ABIDI, MD, PHDResearch Fellow in Medicine, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA

      Gastrointestinal (GI) bleeding that is proximal to the ligament of Treitz is considered upper GI bleeding (UGIB). UGIB can be further divided into variceal and nonvariceal, differentiated by etiology, presentation, management, and mortality. This review of nonvariceal UGIB addresses the epidemiology, diagnosis, treatment (including endoscopic therapy), prognosis, and differential diagnosis. Recommendations presented are evidence based and consistent with consensus statements and society guidelines. Figures show stigmata of recent hemorrhage, endoscopic therapy, peptic ulcer disease, Mallory-Weiss syndrome, angiodysplasia, Dieulafoy lesion, and arterioenteric fistula. Tables list the manifestation of GI bleeding and the presumed source of the bleeding, clues in the symptom and presentation of the patient that may suggest the diagnosis, medical history and physical examination findings that can suggest a specific diagnosis, a comparison of different prognostic scoring systems, differential diagnosis of UGIB, various etiologies of peptic ulcer disease, and treatment regimens for Helicobacter pylori.

      This review contains 7 figures, 10 tables, and 85 references

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    • 37

      Nonvariceal Upper Gastrointestinal Bleeding

      By John R. Saltzman, MD; Wasif Abidi, MD, PhD
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      Nonvariceal Upper Gastrointestinal Bleeding

      • JOHN R. SALTZMAN, MDDirector of Endoscopy, Division of Gastroenterology, Brigham and Women’s Hospital, Boston, MA, Associate Professor of Medicine, Harvard Medical School, Boston, MA
      • WASIF ABIDI, MD, PHDResearch Fellow in Medicine, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA
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  • Geriatric Medicine
    • 1

      Rehabilitation of Geriatric Patients

      By Stephanie Studenski, MD, MPH; Cynthia R. Brown, MD, MSPH; Susan E. Hardy, MD, PhD
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      Rehabilitation of Geriatric Patients

      • STEPHANIE STUDENSKI, MD, MPHProfessor, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA
      • CYNTHIA R. BROWN, MD, MSPHAssistant Professor, Division of Geriatrics, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
      • SUSAN E. HARDY, MD, PHD

      Primary care physicians play an important role in the rehabilitation of geriatric patients: they must be able to assess rehabilitation potential, determine specific patient needs, and then determine the appropriate setting to optimize patient care. Rehabilitation service planning is usually based on a different model of diagnosis and treatment than traditional medical care. This chapter describes the key aspects of rehabilitation planning for stroke, amputation and peripheral vascular disease, hip fracture, rheumatoid arthritis, and arthroplasty. The revised World Health Organization International Classification of Functioning, Disability and Health (ICIDH-2), included in a figure, can be used to assess the causes of disability, plan treatment approaches, and determine the outcomes of care. Tables describe selected results of the neurologic examination of a patient with stroke, assessment and management of complications of stroke and other disabling conditions, and pharmacologic therapy for poststroke depression. An algorithm shows the selection of the appropriate setting for rehabilitation after hospitalization for acute stroke. The Orpington Prognostic Scale for estimating stroke recovery is provided, as is a list of current Internet resources pertaining to geriatric care. This chapter contains 96 references.

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    • 2

      Mistreatment of Elders

      By Emily I Gorman, MD; Judith Linden, MD
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      Mistreatment of Elders

      • EMILY I GORMAN, MDDepartment of Emergency Medicine, Boston Medical Center and Boston University School of Medicine, Boston, MA
      • JUDITH LINDEN, MDAssociate Professor and Vice Chair for Education, Department of Emergency Medicine, Boston University School of Medicine, Boston Medical Center, Boston, MA

      Elder mistreatment affects a considerable proportion of individuals older than 60 to 65 years of age and may include intentional abuse (physical, sexual, emotional, or financial) and neglect. As the proportion of the population that is older than 65 years of age increases, elder mistreatment will become an increasingly common issue. Only a minority of cases of elder abuse are reported; thus, an interview with the patient should be conducted in private if elder mistreatment is suspected. Patient risk factors for elder mistreatment include cognitive or behavioral impairment, poor physical health, and poor social supports. This review examines the approach to the patient, as well as definitive treatment, disposition, and outcomes for victims of elder abuse. The figure shows an algorithm for elder abuse assessment and intervention. Tables list types of elder abuse, factors predisposing to elder mistreatment, indicators of abuse, and the Elder Abuse Suspicion Index.

      This review contains 1 highly rendered figure, 4 tables, and 42 references.

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    • 3

      Approach to the Geriatric Patient

      By Tia Kostas, MD; Mark Simone, MD; James L Rudolph, MD, SM
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      Approach to the Geriatric Patient

      • TIA KOSTAS, MDAssistant Professor of Medicine, Section of Geriatrics & Palliative Medicine, Department of Medicine, University of Chicago, Chicago, IL
      • MARK SIMONE, MDInstructor of Medicine, Harvard Medical School, Associate Program Director-Primary Care, Mount auburn Hospital Internal Medicine Residency, Director, Quality Improvement, Division of Geriatric Medicine, Department of Medicine, Mount Auburn Hospital, Cambridge, MA
      • JAMES L RUDOLPH, MD, SMAssociate Professor of Medicine, Harvard Medical School, Chief (Interim) Geriatrics and Palliative Care, Director, Boston, GRECC, VA Boston Healthcare System, Jamaica Plain, MA, Acting Clinical Chief, Associate Epidemiologist, Division of Aging, Department of Medicine, Brigham and Women’s Hospital, Boston, MA

      As of 2012, over one in eight Americans is over the age of 65, and this number is rising, particularly in the 85+ age group. This segment of the population has a rate of hospitalization three times higher than that for persons of all ages. General internists and family medicine physicians provide a large portion of care for this age group and should therefore be comfortable using a comprehensive approach to geriatric assessment. This review describes general considerations regarding geriatric care, including the process of taking a functional history and clinical implications of geriatric care. The geriatric assessment process is discussed in terms of physical, cognitive, social, and medical domains. The benefits of geriatric assessment in primary care, specialty care, and hospitalized patients are described. Tables outline activities of daily living, sensory changes with aging, major causes of visual impairment in the geriatric population, major neurocognitive disorder diagnostic criteria, medications to avoid or use with caution based on Beers criteria and Screening Tool of Older individuals’ Potentially inappropriate Prescriptions criteria, U.S. Preventive Services Task Force–recommended services relevant to older adults, and vaccinations in older adults. Figures illustrate the key vulnerabilities of older adults; outcomes linked to functional dependence; common disorders associated with cognitive concerns; domains of cognition and examples of impairment in theDiagnostic and Statistical Manual of Mental Disorders, fifth edition; the social and medical domains of geriatric assessment; barriers to medication adherence in older patients; and resources for medication appropriateness in older adults.

      This review contains 8 highly rendered figures, 8 tables, 110 references, and 5 MCQs.

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    • 4

      Assessment of the Geriatric Patient

      By Michelle Martinchek, MD
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      Assessment of the Geriatric Patient

      • MICHELLE MARTINCHEK, MD

      Geriatric syndromes are complex conditions that are common in older adults and often have multiple contributing factors. These syndromes do not fit into discrete disease or organ system categories like other conditions. As the population of older adults continues to grow, it is important that providers are equipped to assess older adults for these geriatric syndromes. These syndromes are associated with functional disability and other poor outcomes. Examples of these syndromes include cognitive impairment, delirium, falls, frailty, weight loss, and pressure ulcers. Understanding the epidemiology, pathogenesis, and predisposing factors may help providers identify patients at risk for these syndromes. Furthermore, a thorough assessment is key in the evaluation of these syndromes.

      This review contains 4 figures, 17  tables and 52 references

      Key Words: cognition, dementia, delirium, fall, frailty, gait, geriatric, malnutrition, pressure ulcer, weight loss

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    • 5

      Management of the Geriatric Patient

      By Michelle Martinchek, MD
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      Management of the Geriatric Patient

      • MICHELLE MARTINCHEK, MD

      Geriatric syndromes are complex conditions in older adults that often have many contributing factors. Examples of common geriatric syndromes include cognitive impairment, delirium, falls, frailty, weight loss, and pressure ulcers. Identifying the patients at risk for these syndromes and enacting preventive measures are also important to try to reduce the impact that many of these syndromes may have on outcomes. These syndromes can happen across many different care settings including in the community, outpatient setting, hospital, and nursing facilities. Once these syndromes are identified, management techniques often include multifactorial approaches and use both nonpharmacologic and pharmacologic means. Management strategies may include assistance from interdisciplinary team members, families, and caregivers of the patient.

      This review contains 4 figures, 5 tables and 30 references

      Keywords:cognition, delirium, dementia, fall, frailty, gait, geriatric, malnutrition, pressure ulcer, weight loss

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    • 6

      Assessment of the Geriatric Patient

      By Michelle Martinchek, MD
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      Assessment of the Geriatric Patient

      • MICHELLE MARTINCHEK, MD
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    • 7

      Assessment of the Geriatric Patient

      By Michelle Martinchek, MD
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      Assessment of the Geriatric Patient

      • MICHELLE MARTINCHEK, MD
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    • 8

      Management of the Geriatric Patient

      By Michelle Martinchek, MD
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      Management of the Geriatric Patient

      • MICHELLE MARTINCHEK, MD
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  • Hematology
    • 1

      Transfusion Therapy

      By Ronald Chang, MD; John B. Holcomb, MD
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      Transfusion Therapy

      • RONALD CHANG, MD
      • JOHN B. HOLCOMB, MD

      Exsanguination occurs rapidly after trauma (median 2 to 3 hours after admission) and is the leading cause of preventable trauma deaths. The modern treatment for traumatic hemorrhagic shock is simultaneous mechanical hemorrhage control and damage control resuscitation (DCR), which emphasizes using plasma as the primary means for volume expansion. Other core DCR principles include minimization of crystalloid, permissive hypotension, and balanced blood product resuscitation. The treatment of traumatic hemorrhage is complicated by trauma-induced coagulopathy (TIC); DCR is thought to address TIC directly despite incomplete understanding of the underlying mechanisms. Recent data point to a 1:1:1 ratio of plasma and platelets to red blood cells as the optimal blood product ratio for acute traumatic hemorrhage. However, this paradigm may soon be supplanted by a transition back to whole blood. Although it is intuitive to apply these same protocols and algorithms to patients with nontraumatic hemorrhage, the scientific evidence is lacking.

      This review contains 5 figures, 8 tables and 76 references

      Keywords: massive transfusion, hemorrhage, endotheliopathy, trauma-induced coagulopathy

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    • 2

      Plasma Cell Disorders

      By Morie A. Gertz, MD, MACP
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      Plasma Cell Disorders

      • MORIE A. GERTZ, MD, MACPChair, Department of Medicine, Roland Seidler Junior Professor of the Art of Medicine, Mayo Clinic, Rochester, MN

      Multiple myeloma represents 1.4% of all new patients with cancer and will result in an estimated 11,090 deaths in 2014. It is twice as common in black men as in white men and 2.5 times more common in black women than in white women. Myeloma is the 14th most common cause of cancer in the United States, with a median age at diagnosis of 69 years. Multiple myeloma is defined by the presence of a clonal growth of plasma cells, usually in the bone marrow, but patients may also present with extramedullary disease. Anemia and bone disease are common in patients with multiple myeloma. Multiple myeloma cells display multiple genetic abnormalities, with no one specific genetic lesion common to a majority of patients. This module describes the immunologic profile of multiple myeloma and its diagnosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, plasmacytoma, plasma cell leukemia, the clinical presentation of multiple myeloma bone disease, anemia, renal impairment, hypercalcemia, and neurologic symptoms associated with multiple myeloma. Therapy for transplantation-eligible and non–transplantation-eligible patients, maintenance treatment for multiple myeloma, Waldenström macroglobulinemia, and amyloidosis are also discussed. Tables outline the risk of monoclonal gammopathy of undetermined significance evolution, the myeloma staging system, recommended diagnostic testing and uniform response criteria for myeloma, and commonly used regimens in the treatment of myeloma. Figures include a magnetic resonance image showing multiple plasmacytomas, tibial lytic lesion from myeloma, calvarial lytic lesions, a positron emission tomographic scan in a myeloma patient, and hyperviscosity causing retinal hemorrhages.

      This review contains 5 highly rendered figures, 5 tables, and 149 references.

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    • 3

      Lymphomas

      By Kieron Dunleavy, MD; Wyndham H Wilson, MD, PhD
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      Lymphomas

      • KIERON DUNLEAVY, MDAttending Physician/Investigator, Lymphoma Therapeutics Section, Metabolism Branch, National Cancer Institute, Bethesoa, Maryland
      • WYNDHAM H WILSON, MD, PHDSenior Investigator, Chief, Lymphoma Therapeutics Section, Metabolism Branch, National Cancer Institute, Bethesoa, Maryland

      Lymphoma is the fifth most common type of cancer in the United States, with 74,490 new cases estimated in 2009. Approximately 15% of patients with lymphoma have Hodgkin lymphoma; the remainder have one of the non-Hodgkin lymphomas. The incidence of non-Hodgkin lymphoma has increased steadily over recent decades. This chapter reviews the epidemiology, classification, clinical features, pathology, diagnostic evaluation, staging and prognosis, and treatment of Hodgkin and non-Hodgkin lymphoma. Other topics discussed include the acute and chronic effects of therapy for Hodgkin disease, as well as the subtypes of non-Hodgkin lymphomas, including indolent B cell lymphoma, follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, marginal-zone lymphoma, diffuse large B cell lymphoma (DLBCL), primary central nervous system lymphoma (PCNSL), Burkitt lymphoma, and HIV-related non-Hodgkin lymphoma. Figures illustrate the cellular appearance of Hodgkin lymphoma subtypes and DLBCL, diagnosis of DLBCL subtypes by gene expression, computed tomography and plain chest film in primary mediastinal cell lymphoma, MRI of the brain in PCNSL, and gene expression and gene expression predictors of survival among patients with DLBCL treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine [Oncovin], and prednisone (R-CHOP). Tables describe the Ann Arbor classification and the Cotswold modification for staging of lymphoma; the International Prognostic Score for advanced Hodgkin lymphoma; the World Health Organization classification of hematopoietic neoplasms; chromosomal translocations in non-Hodgkin lymphoma; the Eastern Cooperative Oncology Group performance scale; the International Prognostic Index for aggressive non-Hodgkin lymphoma; and the Follicular Lymphoma International Prognostic Index. This chapter has 185 references.

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    • 4

      Deep Venous Thrombosis

      By Boaz Zadok Weiss, MD; Evan Avraham Alpert, MD
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      Deep Venous Thrombosis

      • BOAZ ZADOK WEISS, MDDepartment of Emergency Medicine, Shaare Zedek Medical Center, Jerusalem, Israel
      • EVAN AVRAHAM ALPERT, MDDepartment of Emergency Medicine, Shaare Zedek Medical Center, Jerusalem, Israel

      In a patient with DVT, a clot forms in the large veins of the extremities, typically the leg, which can lead to a pulmonary embolus, a potentially life-threatening medical problem. Risk factors include provoking factors such as recent surgery, acquired factors such as obesity or cardiovascular disease, and genetic factors such as protein C or S deficiency. The Wells DVT score is a clinical scoring system that allows the assessment of the pretest probability of DVT. However, clinical gestalt has been found to be equally accurate. This can then guide the clinical work-up of the patient, with low and moderate pretest probabilities, allowing one to start with D-dimer testing, versus high probability, requiring one to begin with lower extremity US. The current trend in treatment of DVT is the novel oral anticoagulants as they can be given at fixed doses, do not require laboratory monitoring, and have a better safety profile than warfarin. Pregnant patients, those with cancer, as well as many with recurrent DVT are treated with low-molecular-weight heparin. Most patients with DVT may be treated as an outpatient. A small percentage of patients with severe DVT may benefit from catheter-directed thrombolysis. 

      This review contains 1 figures, 2 tables, and 48 references.

      Key Words: anticoagulants, D-dimer, diagnostic ultrasonography, DVT, low molecular weight heparin, postthrombotic syndrome, unfractionated heparin, warfarin

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    • 5

      Transfusion Medicine

      By Harvey G Klein, MD
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      Transfusion Medicine

      • HARVEY G KLEIN, MDThe Department of Transfusion Medicine is at the National Institutes of Health (NIH). I am Chief, Department of Transfusion Medicine. I also hold Professorships in both the Departments of Medicine and Pathology at the Johns Hopkins School of Medicine

      Transfusion medicine has advanced to a laboratory-based clinical discipline because of key discoveries and technical advances. These include the discovery of blood group antigens and the understanding of the host immune response to these antigens, development of methods of anticoagulation and storage of blood, and creation of plastic bags that allow sterile fractionation of whole blood into components. The potential of blood to act as an agent of disease transmission has heavily shaped both the donation process and transfusion practice. This chapter offers information to help the physician decide whether to transfuse. It includes sections on blood donation (autologous and directed), on postdonation screening procedures for the presence of viral agents (e.g., hepatitis, retrovirus, and emerging infectious pathogens), on pretransfusion testing (i.e., antigen phenotyping and testing for the presence of antibodies), and on blood components. Sections give specific information on transfusion of red cells, platelets, fresh frozen plasma, and recombinant clotting factors. Indications and complications of apheresis are described. Complications of transfusions are discussed, as are future prospects for transfusion therapy. Tables detail the advantages and disadvantages of autologous donation, estimated risks of blood transfusion, characteristics of blood products and indications for their use, plasma and recombinant clotting factors, indications for recombinant factor VIIa therapy, indications for the use of irradiated blood products, indications for the use of cytomegalovirus-negative blood products, and recommendations for therapeutic apheresis. This chapter contains 154 references.

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    • 6

      Anemia: Production Defects Generally Associated With a Normal or Largely Normal Bone Marrow

      By Nancy Berliner, MD; John M Gansner, MD, PhD
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      Anemia: Production Defects Generally Associated With a Normal or Largely Normal Bone Marrow

      • NANCY BERLINER, MDProfessor of Medicine (Hematology), Harvard Medical School, Boston, MA
      • JOHN M GANSNER, MD, PHDInstructor in Medicine (Hematology), Harvard Medical School, Boston, MA

      This review focuses on anemia resulting from production defects generally associated with a normal or largely normal bone marrow. The definition, epidemiology, etiology, pathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis of the following production defects are discussed: Anemia of inflammation (AI; formerly known as anemia of chronic disease), and anemia in kidney disease, as well as anemia secondary to other conditions such as alchohol abuse and starvation. Iron deficiency anemia (IDA) is discussed elsewhere in this publication.  A figure depicts peripheral smear changes in the size and shape of red blood cells seen in starvation. A table lists the differential diagnoses of hypochromic anemias.

      This review contains 1 figure; 1 table; 79 references

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    • 7

      Anemia: Production Defects Generally Associated With Marrow Aplasia or Replacement

      By Nancy Berliner, MD; John M Gansner, MD, PhD
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      Anemia: Production Defects Generally Associated With Marrow Aplasia or Replacement

      • NANCY BERLINER, MDProfessor of Medicine (Hematology), Harvard Medical School, Boston, MA
      • JOHN M GANSNER, MD, PHDInstructor in Medicine (Hematology), Harvard Medical School, Boston, MA

      This review focuses on anemia resulting from production defects generally associated with marrow aplasia or replacement. The definition, epidemiology, etiology, pathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis of the following production defects are discussed: Acquired aplastic anemia and acquired pure red cell aplasia. Figures depict a leukoerythroblastic blood smear, a biopsy comparing normal bone marrow and bone marrow showing almost complete aplasia, and a marrow smear. A table lists the causes of aplastic anemia.

      This review contains 3 figures; 1 table; 108 references.

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    • 8

      Anemia: Production Defects Generally Associated With Marrow Erythroid Hyperplasia and Ineffective Erythropoiesis

      By Nancy Berliner, MD; John M Gansner, MD, PhD
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      Anemia: Production Defects Generally Associated With Marrow Erythroid Hyperplasia and Ineffective Erythropoiesis

      • NANCY BERLINER, MDProfessor of Medicine (Hematology), Harvard Medical School, Boston, MA
      • JOHN M GANSNER, MD, PHDInstructor in Medicine (Hematology), Harvard Medical School, Boston, MA

      This review focuses on anemia resulting from production defects generally associated with marrow erythroid hyperplasia and ineffective erythropoiesis. The definition, epidemiology, etiology, pathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis of the following production defects are discussed: Megaloblastic anemias, megaloblastic anemia caused by cobalamin deficiency, megaloblastic anemia caused by folic acid deficiency, copper deficiency, and sideroblastic anemias. Figures depict intracellular interdependent cofactor activity of cobalamin and folic acid, synthesis of succinyl–coenzyme A from methylmalonyl–coenzyme A, folic acid functions as a coenzyme in single-carbon transfer reactions, cobalamin assimilation, peripheral blood smear in folic acid or cobalamin deficiency, and a Prussian blue stain showing ring sideroblasts. Tables list causes of cobalamin deficiency and folic acid deficiency.

      This review contains 5 figures; 2 tables; 95 references.

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    • 9

      Red Blood Cell Function and Disorders of Iron Metabolism

      By Robert T. Means Jr, MD, FACP
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      Red Blood Cell Function and Disorders of Iron Metabolism

      • ROBERT T. MEANS JR, MD, FACPDean of Medicine, Professor of Internal Medicine, Office of the Dean, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN

      The red blood cell, or erythrocyte, is an anucleate biconcave disk, approximately 7 µm in diameter. The principal function of the red blood cell is to exchange carbon dioxide for oxygen while in the pulmonary circulation, exchange that oxygen for carbon dioxide in the peripheral tissue, and carry that carbon dioxide back to the lungs. The physicochemical composition of the red cell is aligned to optimize that function. The state of tissue oxygenation, in turn, regulates the production of red cells. This review covers red blood cell function, iron metabolism, iron deficiency, iron overload, and primary iron overload. Figures show a model of the hemoglobin molecule showing the relative alignment of the α chains and β chains; the normal oxygen-hemoglobin dissociation curve shifted by changes in temperature, pH, and the intracellular concentration of 2,3-diphosphoglycerate; body iron supply and storage; regulation of hepcidin expression and its role in disease; blood smear from a patient with iron deficiency; and mechanisms contributing to iron overload in iron-loading anemias. Tables list laboratory results associated with decreased iron balance, causes of iron deficiency, oral iron replacement therapy, parenteral iron replacement therapy, primary iron overload syndromes, secondary iron overload syndromes, laboratory results associated with increased iron stores, and other rare disorders of iron overload.

      This review contains 6 figures, 20 tables, and 111 references

      Keywords: Red blood cell, iron deficiency anemia, iron overload, hemochromatosis, hemoglobin, iron balance

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    • 10

      Acute Leukemia

      By Richard A. Larson, MD; Roland B Walter, MD, PhD, MS
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      Acute Leukemia

      • RICHARD A. LARSON, MDProfessor of Medicine, Pritzker School of Medicine, University of Chicago. Chicago, IL
      • ROLAND B WALTER, MD, PHD, MSAssistant Member, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, Associate Professor of Medicine, Division of Hematology/Department of Medicine, University of Washington, Seattle, WA

      The acute leukemias are malignant clonal disorders characterized by aberrant differentiation and proliferation of transformed hematopoietic progenitor cells. These cells accumulate within the bone marrow and lead to suppression of the production of normal blood cells, with resulting symptoms from varying degrees of anemia, neutropenia, and thrombocytopenia or from infiltration into tissues. They are currently classified by their presumed cell of origin, although the field is moving rapidly to genetic subclassification. This review covers epidemiology; etiology; classification of leukemia by morphology, immunophenotyping, and cytogenetic/molecular abnormalities; cytogenetics of acute leukemia; general principles of therapy; acute myeloid leukemia; acute lymphoblastic leukemia; and future possibilities. The figure shows the incidence of acute leukemias in the United States. Tables list World Health Organization (WHO) classification of acute myeloid leukemia and related neoplasms, expression of cell surface and cytoplasmic markers for the diagnosis of acute myeloid leukemia and mixed-phenotype acute leukemia, WHO classification of acute lymphoblastic leukemia, WHO classification of acute leukemias of ambiguous lineage, WHO classification of myelodysplastic syndromes, European LeukemiaNet cytogenetic and molecular genetic subsets in acute myeloid leukemia with prognostic importance, cytogenetic and molecular subtypes of acute lymphoblastic leukemia, terminology used in leukemia treatment, and treatment outcome for adults with acute leukemia.

      This review contains 2 figures, 15 tables, and 119 references.

      Keywords: Acute leukemia, acute myeloid leukemia, acute lymphoblastic leukemia, cancer, cytogenetics, chromosomal abnormality

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    • 11

      Thrombotic Disorders

      By Lawrence L K Leung, MD
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      Thrombotic Disorders

      • LAWRENCE L K LEUNG, MDChief of Staff, Maureen Lyles D’Ambrogio Professor of Medicine, Stanford University School of Medicine, Chief of Staff, Veterans Affairs Palo Alto Health Care System, Stanford, CA

      The three main elements in the pathophysiology of thrombosis are endothelial injury, a decrease in blood flow, and an imbalance between procoagulant and anticoagulant factors. The latter element can be either hereditary (e.g., antithrombin deficiency) or acquired (e.g., antiphospholipid syndrome). This review details the assessment of patients with thrombotic disorders, hereditary and acquired hypercoagulable states, and the management of venous thromboembolism. Figures show how the degradation of thrombin-activated factor V Leiden by activated protein C (APC) is significantly slower than that of normal activated factor V (factor Va), leading to enhanced thrombin generation; how normal factor V serves as a cofactor of APC in the inhibition of factor VIIIa, whereas factor V Leiden has a poor cofactor function; and how IgG antibodies recognize platelet factor 4–heparin complexes in heparin-induced thrombocytopenia. Tables list inherited and acquired hypercoagulable states, questions for assessing thrombosis, screening tests for patients with suspected hypercoagulable states, clinical features that suggest thrombophilia, frequency and relative risk of venous thrombosis in selected hypercoagulable states, proposed clinical and laboratory criteria for antiphospholipid syndrome, the classification of antiphospholipid antibodies, the 4Ts scoring system for heparin-induced thrombocytopenia, and general guidelines for the management of patients with venous thromboembolism.

      This review contains 2 figures, 27 tables, and 174 references

      Keywords: Venous thromboembolism, deep vein thrombosis, pulmonary embolism, protein S, protein C, factor V Leiden, heparin-induced thrombosis, antiphospholipid syndrome

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    • 12

      Acute Leukemia

      By Richard A. Larson, MD; Roland B Walter, MD, PhD, MS
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      Acute Leukemia

      • RICHARD A. LARSON, MDProfessor of Medicine, Pritzker School of Medicine, University of Chicago. Chicago, IL
      • ROLAND B WALTER, MD, PHD, MSAssistant Member, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, Associate Professor of Medicine, Division of Hematology/Department of Medicine, University of Washington, Seattle, WA
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    • 13

      Thrombotic Disorders

      By Lawrence L K Leung, MD
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      Thrombotic Disorders

      • LAWRENCE L K LEUNG, MDChief of Staff, Maureen Lyles D’Ambrogio Professor of Medicine, Stanford University School of Medicine, Chief of Staff, Veterans Affairs Palo Alto Health Care System, Stanford, CA
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    • 14

      Transfusion Therapy

      By Ronald Chang, MD; John B. Holcomb, MD
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      Transfusion Therapy

      • RONALD CHANG, MD
      • JOHN B. HOLCOMB, MD
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  • Hepatology
    • 1

      Viral Hepatitis A

      By Kenrad E Nelson, MD; Brittany L Kmush, PhD
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      Viral Hepatitis A

      • KENRAD E NELSON, MDProfessor, Department of Epidemiology and Department of International Health, Johns Hopkins University, Baltimore, MD
      • BRITTANY L KMUSH, PHDAssistant Professor, Department of Public Health, Food, Studies and Nutrition, Falk College of Sport and Human Dynamics, Syracuse University, Syracuse, NY

      Epidemics of infectious jaundice have been reported throughout recorded history. However, the proof that many of these outbreaks and individual cases of acute hepatitis were caused by a viral infection, the hepatitis A virus (HAV), did not appear until the 1960s. After the transmission of infection to marmosets and humans, the epidemiologic and virologic characteristics that differed between hepatitis A and hepatitis B virus infections were defined more clearly. After the development and licensure of hepatitis A vaccines in the 1990s, it became possible to implement an effective prevention program involving routine immunization of young children in the United States and several other Western countries. However, despite the dramatic efficacy of the childhood immunization program in reducing the incidence of acute hepatitis from HAV in the population, older children and adults remained susceptible. Significant morbidity continues to occur in the United States among international travelers, injection drug users, persons with underlying liver disease, and other high-risk populations. Since HAV is a global pathogen, the prevention of increasing morbidity from hepatitis A attributable to the incidence of clinically more severe disease increases in countries transitioning from high to intermediate or low endemic status is a major public health challenge. In this review, we discuss the epidemiology, virology, clinical characteristics, and prevention of hepatitis A infections.

      This review contains 8 figures, 3 tables and 89 references

      Key words: epidemiology, global impact, hepatitis A vaccine, hepatitis A virus, prevention, reservoirs, risk factors, treatment

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    • 2

      Chronic Liver Diseases

      By Sandra Ciesek, MD; Michael P Manns, MD
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      Chronic Liver Diseases

      • SANDRA CIESEK, MDDepartment of Gastroenterology, Hepatology, and Enterology, The Hannover Medical School, Hannover, Germany
      • MICHAEL P MANNS, MDProfessor and Chairman, Department of Gastroenterology, Hepatology, and Enterology, The Hannover Medical School, Hannover, Germany

      The term chronic hepatitis encompasses many distinct clinical and pathologic diseases affecting the liver, the most important of which are autoimmune hepatitis (AIH), chronic hepatitis B with or without hepatitis D, and chronic hepatitis C caused by hepatitis C virus (HCV). The standard treatment of AIH is immunosuppressive therapy either with prednisolone alone or in combination with azathioprine. Although mycophenolate mofetil or cyclosporine can be used for retherapy in the case of treatment failure, controlled clinical trials are missing for these immunosuppressive drugs; thus, they are not part of the American Association for the Study of Liver Diseases (AASLD) practice guidelines for AIH.

      Chronic hepatitis B is a major global health care problem as 5% of the world’s population, or approximately 350 million persons, is chronically infected. Anti–hepatitis B virus (HBV) drugs can be divided into three classes: alfa interferons, nucleoside analogue (lamivudine, entecavir, telbivudine), and nucleotide analogue (adefovir dipivoxil, tenofovir dipivoxil). Interferon alfa has a number of potential side effects, and careful consideration must be given to its use. Tenofovir, which falls under the nucleotide analogue class, was approved by the Food and Drug Administration in 2008 and has been shown in clinical trials to have more potent activity in serum-suppressing HBV DNA levels than the comparable adefovir.

      More prevalent than chronic hepatitis B is chronic hepatitis C due to the high chronicity rate of HCV infection (approximately 160 million people are chronically infected with HCV worldwide). Until 2011, the only treatment for chronic HCV was a combination therapy of pegylated interferon alfa and ribavirin (RBV); however, new treatments for chronic hepatitis C include the directly acting antivirals (DAAs) sofosbuvir and simeprevir, although host-targeting agents are also being developed. The side effects of pegylated interferon/RBV therapy and DAAs should be considered, of which only sofosbuvir has shown no specific side effects so far in clinical studies.

      This module contains 5 highly rendered figures, 6 tables, 61 references, and 5 MCQs.

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    • 3

      An Approach to the Patient With Abnormal Liver Tests and Jaundice

      By Adrian Reuben, BSc, MBBS, FRCP, FACG, FAASLD
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      An Approach to the Patient With Abnormal Liver Tests and Jaundice

      • ADRIAN REUBEN, BSC, MBBS, FRCP, FACG, FAASLDProfessor of Medicine Emeritus, Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC

      Patients who present with abnormal liver test results and jaundice are generally suffering from an affliction of the liver and/or biliary tree; however, extrahepatic disorders can affect hepatobiliary function and even microscopic structure when there is no intrinsic primary liver or biliary abnormality. Extrahepatic disease may impinge directly on the liver and/or biliary system, and remote extrahepatic conditions, such as sepsis, systemic and localized inflammatory processes, and malignancy, can interfere with liver function without direct contact. This review covers history of the patient with abnormal liver tests and jaundice, physical findings in the patient with abnormal liver tests and jaundice, abnormal liver tests and elevated bilirubin, and recommended approaches to the patient with abnormal liver tests and jaundice. Figures show a case of renal cell cancer (hypernephroma) in a 69-year-old man, potential sites of interference with hepatobiliary metabolism and transport of bilirubin from hepatocyte to duodenum (with examples), a decision tree to evaluate suspected idiosyncratic drug-induced liver injury, physical signs in liver disease, a decision tree for investigation of the patient with aminotransferase-predominant abnormal liver tests and jaundice, and a decision tree for investigation of the patient with alkaline phosphatase elevation with or without abnormal liver tests with or without jaundice. Tables list symptom and risk factor evaluation in patients with abnormal liver tests and jaundice, comparison of features scored in two causality assessment methods, physical signs in liver disease, and disease-specific laboratory investigations, imaging, and tissue analysis.

      This review contains 6 highly rendered figures, 4 tables, and 18 references

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    • 4

      Cirrhosis and Complications of Portal Hypertension

      By Andres Cardenas, MD; Isabel Graupera, MD; Elsa Sola, MD; Pere Ginès, MD, PhD
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      Cirrhosis and Complications of Portal Hypertension

      • ANDRES CARDENAS, MDGI Unit, Hospital Clínic and University of Barcelona, Institut d’Investigacions Biomèdiques August Pi-Sunyer, Ciber de Enfermedades Hepaticas y Digestivas, Instituto Reina Sofía de Investigación Nefrológica, Barcelona, Spain
      • ISABEL GRAUPERA, MDLiver Unit, Hospital Clínic and University of Barcelona, Institut d’Investigacions Biomèdiques August Pi-Sunyer, Ciber de Enfermedades Hepaticas y Digestivas, Instituto Reina Sofía de Investigación Nefrológica, Barcelona, Spain
      • ELSA SOLA, MDLiver Unit, Hospital Clínic and University of Barcelona, Institut d’Investigacions Biomèdiques August Pi-Sunyer, Ciber de Enfermedades Hepaticas y Digestivas, Instituto Reina Sofía de Investigación Nefrológica, Barcelona, Spain
      • PERE GINÈS, MD, PHDChairman, Liver Unit, Hospital Clínic, Professor of Medicine, University of Barcelona, Institut d’Investigacions Biomèdiques August Pi-Sunyer, Ciber de Enfermedades Hepaticas y Digestivas, Instituto Reina Sofía de Investigación Nefrológica, Barcelona, Spain

      Cirrhosis is the most advanced stage of all the different types of chronic liver diseases. It is defined as a diffuse disorganization of normal hepatic structure by extensive fibrosis associated with regenerative nodules. Hepatic fibrosis is potentially reversible if the causative agent is removed. However, advanced cirrhosis leads to major alterations in the hepatic vascular bed and is usually irreversible. Cirrhosis is a progressive and severe clinical condition associated with considerable morbidity and high mortality. It leads to a wide spectrum of characteristic clinical manifestations, mainly attributable to hepatic insufficiency and portal hypertension. Major complications of portal hypertension include ascites, gastrointestinal (GI) variceal bleeding, hepatic encephalopathy (HE), renal failure, and bacterial infections. In recent years, major advances in the understanding of the natural history and pathophysiology of cirrhosis and the treatment of its complications have led to improved management, quality of life, and life expectancy of patients with this disease. Cirrhosis is also a risk factor for developing hepatocellular carcinoma (HCC). Decompensated cirrhosis carries a poor short-term prognosis; thus, orthotopic liver transplantation (OLT) should always be considered in suitable candidates. This chapter describes the epidemiology, etiology and genetic factors, pathogenesis, diagnosis, general management, and treatment of cirrhosis. Complications of cirrhosis are discussed, including ascites, spontaneous bacterial peritonitis, dilutional hyponatremia, hepatorenal syndrome, variceal bleeding, hepatopulmonary syndrome and postpulmonary hypertension, HE, and HCC. Indications and contraindications for liver transplantation are described. Figures show liver biopsy results and ultrasound images in cirrhosis from hepatitis C, a patient with tense ascites, transjugular intrahepatic portosystemic shunting (TIPS), large esophageal varices with red spots, and HCC. Tables outline the main causes of cirrhosis and the diagnostic methods for identifying them, the Child-Pugh score, diagnostic criteria for hepatorenal syndrome, grades of HE, and indications for liver transplantation.
      This chapter contains 6 highly rendered figures, 8 tables, 73 references.

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    • 5

      Autoimmune Hepatitis/overlap Syndromes

      By Albert J Czaja, MD
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      Autoimmune Hepatitis/overlap Syndromes

      • ALBERT J CZAJA, MDDivision of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota USA.

      When autoimmune hepatitis has features of primary biliary cholangitis or primary sclerosing cholangitis, these mixed clinical phenotypes constitute overlap syndromes. Diagnostic criteria have been promulgated, but clinical judgement and liver tissue examination remain cornerstones of diagnosis. Cholestatic laboratory and histological findings, concurrent inflammatory bowel disease, or non-response to conventional corticosteroid therapy compel practitioners to consider overlap in patients with autoimmune hepatitis. Laboratory indices of marked liver inflammation and histological findings of moderate to severe interface hepatitis, especially with lymphoplasmacytic infiltration, also warrant consideration of overlap in patients with primary biliary cholangitis or primary sclerosing cholangitits. Treatment recommendations to date have been based on weak clinical evidence, and disease management should be individualized and guided by the predominant disease component. Prednisone or prednisolone in combination with azathioprine has been used in patients with predominantly autoimmune hepatitis, whereas low dose ursodeoxycholic acid in conjunction with corticosteroid-based regimens has been recommended in syndromes with predominately cholestatic disease. All treatments have been variably effective, especially in patients with overlapping features of primary sclerosing cholangitis. Mycophenolate mofetil and calcineurin inhibitors have been used as salvage therapies in limited experiences, and liver transplantation has been associated with graft and overall survivals similar to those of the classical unmixed diseases.

       This review contains 6 figures, 7 tables and 50 references

      Keywords: autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, overlap, cholestatic laboratory and histological features

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    • 6

      Hepatitis B Virus

      By Ming V. Lin, MD; April Wall, MD
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      Hepatitis B Virus

      • MING V. LIN, MDInstructor of Medicine, Harvard Medical School, Associated Physician, Division of, Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA
      • APRIL WALL, MDResident, Department of Internal Medicine, Brigham and Women’s Hospital, Boston, MA

      Chronic hepatitis B virus (HBV) infection is a major health burden worldwide, with approximately 257 million people with chronic infection. HBV is a small partially double-stranded DNA virus that replicates within the nucleus of the hepatocyte and commonly leads to chronic infection. Chronic HBV infection can cause cirrhosis, hepatocellular carcinoma, and extrahepatic manifestations such as glomerulonephritis or vasculitis. The latter is due to deposition of circulating immune complex in the different tissues. The natural history of HBV infection can be conceptualized as a spectrum encompassing different phases, including immune tolerance, immune clearance, inactive carrier, and reactivation and resolution. The diagnosis of the different phases of chronic HBV infection relies on various HBV serologies, liver enzyme levels, and histology findings. There are currently eight therapies approved for the treatment of HBV. Tenofovir alafenamide was the most recently approved therapy with a better side effect profile compared with tenofovir disoproxil fumarate. With the recent advances in the basic research in hepatitis B, new treatment options may become available in the near-future.

      This review contains 9 figures, 11 tables and 80 references

      Key words: cirrhosis, entecavir, Hepadnaviridae, hepatitis B virus, hepatocellular carcinoma, precore mutation, tenofovir

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    • 7

      Viral Hepatitis C: Epidemiology, ­pathogenesis, Transmission, and ­natural History

      By Raymond T. Chung, MD; Anna Lidofsky, BS; Jacinta A Holmes, MBBS, PhD
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      Viral Hepatitis C: Epidemiology, ­pathogenesis, Transmission, and ­natural History

      • RAYMOND T. CHUNG, MDLiver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
      • ANNA LIDOFSKY, BSPredoctoral Research Fellow, Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA
      • JACINTA A HOLMES, MBBS, PHDPostdoctoral Research Fellow, Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Postdoctoral Research Fellow, Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Australia

      Chronic infection with the hepatitis C virus (HCV) remains a significant global health issue, with more than 71 million infected worldwide and accounting for over 720,000 deaths annually in the United States alone. It can be associated with significant liver-related morbidity and mortality owing to complications from cirrhosis and end-stage liver disease. The aging HCV population, together with changing patterns of drug use, has seen an increase in these complications of HCV and an increase in the number of acute HCV infections. Screening and managing complications of chronic hepatitis C are an important consideration. The changing epidemiology, risk factors, transmission, diagnosis, natural history (including complications) and patient evaluation and education are discussed.

      This review contains 4 figures, 2 tables, and 70 references

      Key words: epidemiology, hepatitis C virus, transmission, risk factors, natural history, patient education, evaluation

       

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    • 8

      Viral Hepatitis C: Treatment

      By Jay Luther, MD; Raymond T. Chung, MD; Anna Lidofsky, BS; Jacinta A Holmes, MBBS, PhD; Stephanie M Rutledge, MBBCh BAO MRCPI
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      Viral Hepatitis C: Treatment

      • JAY LUTHER, MDLiver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
      • RAYMOND T. CHUNG, MDLiver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
      • ANNA LIDOFSKY, BSPredoctoral Research Fellow, Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA
      • JACINTA A HOLMES, MBBS, PHDPostdoctoral Research Fellow, Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Postdoctoral Research Fellow, Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Australia
      • STEPHANIE M RUTLEDGE, MBBCH BAO MRCPIResident, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA

      Infection with the hepatitis C virus (HCV) leads to chronic infection in the majority, and is associated with the development of complications including cirrhosis, end-stage liver failure, hepatocellular carcinoma and death. HCV is curable, and successful viral eradication is associated with a reduction in cirrhosis and liver-related mortality. However, previous HCV therapy, consisting of pegylated interferon plus ribavirin, was associated with poor cure rates and significant adverse events. The development of direct-acting antiviral agents (DAAs) that specifically target HCV replication has revolutionized the treatment of HCV. Current regimens are now highly potent, all-oral, interferon-free combinations of these DAAs. The Food and Drug Administration has now approved many of these regimens. The changing management of HCV infection, including recent advances in HCV therapy, are discussed.

      This review contains 1 figure, 5 tables and 59 references

      Key words: direct-acting antiviral agents, hepatitis C virus, interferon-free therapy, management, treatment

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    • 9

      Viral Hepatitis Other Than A, B, or C

      By Nadeem Anwar, MD ; Kenneth E. Sherman, MD, PhD
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      Viral Hepatitis Other Than A, B, or C

      • NADEEM ANWAR, MD University of Cincinnati College of Medicine, Cincinnati, OH
      • KENNETH E. SHERMAN, MD, PHD University of Cincinnati College of Medicine, Cincinnati, OH

      Viral hepatitis is a global, although variably distributed, health problem associated with significant morbidity and mortality. Infection with a hepatitis virus leads to acute inflammation and liver cell damage (hepatocyte injury). Such infection may be symptomatic or subclinical and may result in disease resolution, death from fulminant hepatic failure, or development of  a chronic disease state. Whereas the chronic infection with hepatitis B and C accounts for a global burden of more than 500,000,000 cases, the global death rate from all types of hepatitis is approximately 1 million people annually. This review focuses on the virology, epidemiology, clinical features, diagnosis, treatment, and prevention of hepatitis D and hepatitis E, as well as other viruses associated with hepatitis. Figures show the global distribution of hepatitis D infection, elevation of anti–hepatitis D virus antibodies in hepatitis B/hepatitis D virus coinfection, geographic distribution of hepatitis E virus by genotype, factors significant in the pathogenesis of hepatitis E, and pattern of antibody elevation in hepatitis E. The table lists proposed diagnostic criteria for hepatitis E virus.

      This review contains 5 highly rendered figures, 1 table, and 42 references.

      Key words: hepatitis D, hepatitis D virus, hepatitis E, hepatitis E virus, non-A hepatitis, non-B hepatitis, non-C hepatitis, viral hepatitis 

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    • 10

      Viral Hepatitis E

      By Kenrad E Nelson, MD; Brittany L Kmush, PhD
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      Viral Hepatitis E

      • KENRAD E NELSON, MDProfessor, Department of Epidemiology and Department of International Health, Johns Hopkins University, Baltimore, MD
      • BRITTANY L KMUSH, PHDAssistant Professor, Department of Public Health, Food, Studies and Nutrition, Falk College of Sport and Human Dynamics, Syracuse University, Syracuse, NY

      Hepatitis E Virus (HEV) infections are among the most frequent causes of viral hepatitis globally. They are especially common in southern Asia where large epidemics of waterborne hepatitis, primarily affect adults with increased mortality in pregnant women, occur frequently during and after monsoon rains when there is contamination of the drinking water supply. These epidemics have been recognized throughout modern history. Similar epidemics have been reported from Sub-Saharan Africa during humanitarian crises, when the water supply is compromised. The causal virus, HEV, was discovered in 1983. About a decade later, similar HEV viruses were found to be transmitted as a foodborne infection from infected pigs, deer, wild boar, and other zoonotic reservoirs. There are 4 genotypes of HEV that infect humans: genotypes 1 and 2 are strictly human pathogens, and genotypes 3 and 4 have zoonotic reservoirs and are transmitted as a foodborne infection or from contact with the zoonotic reservoir. Although most HEV infections cause asymptomatic infections or acute selflimited hepatitis in humans, in recent years, chronic infections among immunocompromised patients after solid organ transplants or other immunocompromising conditions have been reported among persons with genotype 3 infections.

      This review contains 4 figues, 4 tables and 162 references

      Key Words: epidemiology, global impact, Hepatitis E Vaccine, HEV, prevention, reservoirs, risk factors, treatment

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    • 11

      Nonalcoholic Fatty Liver Disease

      By Michael Fuchs, MD, PhD; Puneet Puri, MD
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      Nonalcoholic Fatty Liver Disease

      • MICHAEL FUCHS, MD, PHDAssociate Professor of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University Medical Center, Staff Physician, Hepatology Service, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA
      • PUNEET PURI, MDAssociate Professor of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University Medical Center and Gastrointestinal & Hepatology Service, Hunter Holmes McGuire Department of Veterans Affairs Med¬ical Center, Richmond, VA

      Nonalcoholic fatty liver disease (NAFLD) is defined by the pathologic accumulation of fat in more than 5% of hepatocytes in the absence of significant alcohol consumption (daily intake < 20 g in women and < 30 g in men) and by excluding secondary causes of hepatic steatosis. NAFLD can be categorized into two principal phenotypes: nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is defined by the presence of macrovesicular steatosis without inflammation, whereas NASH sees inflammation and hepatocyte ballooning injury, is associated with varying degrees of fibrosis, and can progress to cirrhosis and end-stage liver disease. This review addresses the epidemiology, etiology, pathophysiology, diagnosis, treatment, and prognosis of NAFLD. Figures show the spectrum of fatty liver disease, hepatic consequences of insulin resistance, role of liver biopsy in evaluation of NAFLD, histologic features of NASH, and principles of NAFLD. Tables list risk factors and clinical manifestations for NAFLD, physical examination findings in NAFLD, comparison of imaging modalities, and noninvasive fibrosis markers.

      This review contains 6 figures, 9 tables and 167 references

      Keywords: Nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, non-invasive assessment, vibration controlled transient elastography, magnetic resonance elastography, diet and lifestyle treatment

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    • 12

      Viral Hepatitis A

      By Kenrad E Nelson, MD; Brittany L Kmush, PhD
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      Viral Hepatitis A

      • KENRAD E NELSON, MDProfessor, Department of Epidemiology and Department of International Health, Johns Hopkins University, Baltimore, MD
      • BRITTANY L KMUSH, PHDAssistant Professor, Department of Public Health, Food, Studies and Nutrition, Falk College of Sport and Human Dynamics, Syracuse University, Syracuse, NY
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    • 13

      Viral Hepatitis C: Epidemiology, ­pathogenesis, Transmission, and ­natural History

      By Raymond T. Chung, MD; Anna Lidofsky, BS; Jacinta A Holmes, MBBS, PhD
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      Viral Hepatitis C: Epidemiology, ­pathogenesis, Transmission, and ­natural History

      • RAYMOND T. CHUNG, MDLiver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
      • ANNA LIDOFSKY, BSPredoctoral Research Fellow, Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA
      • JACINTA A HOLMES, MBBS, PHDPostdoctoral Research Fellow, Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Postdoctoral Research Fellow, Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Australia
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    • 14

      Malnutrition in Cirrhosis and Its Management

      By Shareef Syed, MD; Adrienne E Lebsack, MPH, MAS; Jennifer C Lai, MD, MBA
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      Malnutrition in Cirrhosis and Its Management

      • SHAREEF SYED, MDDepartment of Surgery, University of California San Francisco
      • ADRIENNE E LEBSACK, MPH, MASDepartment of Medicine, University of California, San Francisco
      • JENNIFER C LAI, MD, MBADepartment of Medicine, University of California, San Francisco

      The World Health Organization defines malnutrition as a term referring to deficiencies, excesses, or imbalances in a person’s intake or energy and/or nutrients. Malnutrition is a nearly universal complication of end-stage liver disease, with a prevalence of up to 90%. Given their hepatic synthetic dysfunction, patients with cirrhosis are at a particularly high risk for protein-calorie depletion, which has been reported in over half of patients with cirrhosis and worsens with disease severity. Undernutrition is a potent predictor of adverse outcomes in cirrhotic patients, including lower survival rates, hepatic decompensation, longer length of days in the hospital and intensive care unit (ICU), increased number of infection episodes, and higher resource utilization. On the other hand, excess energy intake, or overnutrition, is increasingly being recognized as an important determinant of long-term outcomes in this population, particularly those with nonalcoholic steatohepatitis. Nearly one quarter of patients with cirrhosis are overnourished and up to 72% show excessive daily intake of energy and protein. In this review, we will consider the full spectrum of malnutrition in patients with end-stage liver disease and highlight key areas in need of further investigation.

      This review contains 4 figures, 4 tables, and 54 references.

      Key Words: frailty, inflammation, nocturnal feeding, nutritional assessment, nutritional risk, nutritional screening, protein-energy malnutrition, sarcopenia

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    • 15

      Acute Liver Failure

      By Constantine J Karvellas, MD, SM, FRCPC; R. Todd Stravitz, MD, FACP, FACG, FAASLD
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      Acute Liver Failure

      • CONSTANTINE J KARVELLAS, MD, SM, FRCPCAssociate Professor of Medicine, Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine; Adjunct Professor, School of Public Health Sciences, University of Alberta, Edmonton, AB
      • R. TODD STRAVITZ, MD, FACP, FACG, FAASLDProfessor of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Medical Director of Liver Transplantation, Hume-Lee Transplant Center of Virginia Commonwealth University, Richmond, VA

      Acute liver failure (ALF) remains one of the most dramatic and highly mortal syndromes in modern medicine, with a poor outcome (death or need for emergency liver transplantation) in more than 50% of affected patients. However, prevention of specific etiologies of ALF, general improvements in intensive care medicine, and specific improvements in the management of the systemic complications of ALF, have markedly reduced mortality over the last 40 years. Specific ALF etiologies, including hepatitis A and B, appear to have decreased in developed nations along with improvements in sanitation and widespread vaccination. The management of specific complications—cerebral edema in particular—has lowered the proportion of ALF deaths due to intracranial hypertension, which was once the most dreaded systemic manifestation of ALF. A recent randomized, multicenter trial has documented the efficacy of high-volume plasma exchange in improving transplant-free and overall in-hospital survival. These and other advances have led to a speculation that ALF will be a “curable” clinical condition by the year 2024. Challenges persist, however, as acetaminophen (APAP) overdose continues to account for ~50% of cases of ALF in many developed nations. In the United Kingdom, legislation to limit access to the drug has led to a marked decrease in the incidence of ALF due to acetaminophen overdose: an important lesson for other governments to consider as they work to meet the goal of rendering ALF a “curable” condition.

      This review contains 6 figures, 19 tables and 54 references

      Key Words: acetaminophen, acute liver failure, cerebral edema, drug-induced liver injury, extracorporeal liver assist device, fulminant liver failure, hepatic encephalopathy, intracranial hypertension, liver transplantation

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    • 16

      Acute Liver Failure

      By Constantine J Karvellas, MD, SM, FRCPC; R. Todd Stravitz, MD, FACP, FACG, FAASLD
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      Acute Liver Failure

      • CONSTANTINE J KARVELLAS, MD, SM, FRCPCAssociate Professor of Medicine, Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine; Adjunct Professor, School of Public Health Sciences, University of Alberta, Edmonton, AB
      • R. TODD STRAVITZ, MD, FACP, FACG, FAASLDProfessor of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Medical Director of Liver Transplantation, Hume-Lee Transplant Center of Virginia Commonwealth University, Richmond, VA
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    • 17

      Nonalcoholic Fatty Liver Disease

      By Michael Fuchs, MD, PhD; Puneet Puri, MD
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      Nonalcoholic Fatty Liver Disease

      • MICHAEL FUCHS, MD, PHDAssociate Professor of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University Medical Center, Staff Physician, Hepatology Service, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA
      • PUNEET PURI, MDAssociate Professor of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University Medical Center and Gastrointestinal & Hepatology Service, Hunter Holmes McGuire Department of Veterans Affairs Med¬ical Center, Richmond, VA
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  • Human Genetics
    • 1

      Genomics Overview

      By W Gregory Feero, MD, PhD
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      Genomics Overview

      • W GREGORY FEERO, MD, PHDSpecial Advisor to the Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, Faculty, Maine-Dartmouth Family Medicine Residency, Augusta, ME

      New genomic applications are affecting internal medicine subspecialties and will soon affect the practices of all physicians. This chapter discusses the fields of genetics versus genomics and details the fundamentals of a genomic approach to health care. It includes special considerations such as the intersection between genomics and evidence-based medicine, genetic discrimination, the regulation of genetic testing, and the marketing of genetic testing directly to consumers. The chapter looks at genome-wide association studies and clinical care, as well as sequencing technologies. Tables offer examples of patterns of inheritance, clinical recommendations and red flags raised by family history, and intended uses for genetic tests. One figure shows an example pedigree obtained by using the US surgeon general's My Family Health Portrait family history tool, while the other shows the chromosomal locations of genetic markers associated with disease risk discovered in genome-wide association studies between 2005 and 2009. This chapter contains 41 references.

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    • 2

      Practice of Genetics in Clinical Medicine

      By Bruce R Korf, MD, PhD, FACMG; Carlos Gallego, MD
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      Practice of Genetics in Clinical Medicine

      • BRUCE R KORF, MD, PHD, FACMGProfessor and Chair, Department of Genetics, University of Alabama at Birmingham, Birmingham, AL
      • CARLOS GALLEGO, MDInternist Geneticist, Huntsville Hospital

      This review provides a general overview of the genetic approach in medical practice, discusses the principles of genetic testing, including interpretation of genetic tests and direct-to-consumer genomic testing, and looks at genetic counseling and approaches to treatment. The internist should become familiar with genetic disorders such as those associated with mutations in single genes or changes in chromosome number or structure. This is the traditional area of focus for medical geneticists and is likely to remain so. The internist should be familiar with basic principles of care for individuals with the more common of these conditions and needs to recognize clues that suggest the presence of these disorders, especially in family history. The section on genetics of common disorders focuses on pharmacogenetics, risk assessment, and prevention. Figures illustrate commonly used standard pedigree symbols and examples of autosomal recessive, autosomal dominant, X-linked recessive, and maternal inheritance. Tables offer different forms of genetic testing and types of gene mutations at genome and DNA levels.

      This review contains 2 figures, 2 tables, and 83 references.

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    • 3

      Heritable and Acquired Thrombophilias in Clinical Practice

      By Hanny Al-Samkari, MD; Nathan T. Connell, MD, MPH
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      Heritable and Acquired Thrombophilias in Clinical Practice

      • HANNY AL-SAMKARI, MDDivision of Hematology, Massachusetts General Hospital, Boston, MA
      • NATHAN T. CONNELL, MD, MPHHematology Division, Brigham & Women’s Hospital, Boston, MA; Harvard Medical School, Boston, MA

      Thrombosis is common in clinical practice. Venous thromboembolism in particular raises questions of a possible underlying hereditary or acquired thrombophilic state. Despite considerable data describing the impact of various thrombophilic states on risks of initial and recurrent thromboembolic events, thrombophilia testing is not standardized. An understanding of the utility and pitfalls of clinical thrombophilia testing is necessary to employ this testing properly. When utilized appropriately, thrombophilia testing can be vital in informing an individual patient’s thrombosis risk and pursuing optimal anticoagulant management. Hereditary thrombophilia testing involves investigation for factor V Leiden, the prothrombin G202010A gene mutation, and deficiencies of the natural anticoagulants protein C, protein S, and antithrombin. Assessment for acquired thrombophilias is perhaps even more important, recognizing the possibility for myeloproliferative neoplasms, antiphospholipid antibody syndrome, occult malignancy and other important acquired thrombotic predispositions. Timing of thrombophilia testing in relation to anticoagulation, acute thrombosis, and use of hormonal agents or pregnancy is critical to ensure accurate diagnosis. This review describes each of the most important hereditary and acquired thrombophilias, explains their relationship to venous and arterial thrombosis, delineates evidence-based indications for thrombophilia testing, identifies potential testing pitfalls, and synthesizes the key points in outlining algorithms for thrombophilia testing in clinical practice.

      This review contains 4 figures, 4 tables, and 48 references.

      Key words: thrombophilia, venous thromboembolism, pulmonary embolus, deep vein thrombosis, factor V Leiden, prothrombin gene mutation, protein C deficiency, protein S deficiency, antiphospholipid antibody syndrome, hypercoagulability of malignancy

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    • 4

      Achondroplasia and Hypochondroplasia

      By Catherine Gooch, MD; Akila Subramaniam, MD; Nathaniel Robin, MD
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      Achondroplasia and Hypochondroplasia

      • CATHERINE GOOCH, MDUniversity of Alabama at Birmingham, Birmingham, AL
      • AKILA SUBRAMANIAM, MDUniversity of Alabama at Birmingham Department of Obstetrics and Gynecology, Birmingham, AL
      • NATHANIEL ROBIN, MDUniversity of Alabama at Birmingham Department of Genetics, Birmingham, AL

      Many women with skeletal dysplasias, such as achondroplasia and hypochondroplasia, choose to become pregnant. These women and their partners should receive pre-conception genetic counseling. Once the woman becomes pregnant, a multidisciplinary team at a tertiary care hospital should mange her antepartum care and birth process. An anesthesia plan should be in place that addressed kyphosis, weight based medications and the possibility of a Cesarean Section. Patients should be monitored for respiratory compromise from the gravid uterus on a smaller body frame.  Neonatology must be available to help care for the infant. With a supportive antepartum and postpartum care plan, most women with skeletal dysplasia do well and resume routine OBGYN care after birth.

      This review contains 5 figures, and 21 references.

      Keywords: Maternal Achondroplasia, Maternal Hypochondroplasia, Inheritance patterns, short limb dwarfism, high risk pregnancy, autosomal dominant inheritance 

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  • Infectious Disease
    • 1

      General Principles of Antibiotic Therapy

      By Alyssa R. Letourneau, MD, MPH; Michael S. Calderwood, MD, MPH
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      General Principles of Antibiotic Therapy

      • ALYSSA R. LETOURNEAU, MD, MPHDepartment of Medicine , Harvard Medical School, Assistant Director, Antimicrobial Stewardship Program, Massachusetts General Hospital, Boston, MA
      • MICHAEL S. CALDERWOOD, MD, MPHAssistant Professor, Department of Medicine, Harvard Medical School, Assistant Hospital Epidemiologist/Associate Director, Antimicrobial Stewardship, Brigham and Women’s Hospital, Boston, MA

      The essential feature of effective antibiotic agents is the ability to inhibit the growth of microorganisms at concentrations tolerated by the host. Antibiotic agents generally target anatomic structures or biosynthetic pathways unique to bacteria. The appropriate choice of an antibiotic for an infection depends on the following: clinician’s level of suspicion; the infecting organism and its antibiotic susceptibilities; the type of infection; factors associated with specific antibiotic agents; host factors; and public health considerations. This review provides an overview of antibiotic therapy and covers identifying the cause of an infection, determination of bacterial susceptibility to specific drugs, site of infection and ancillary therapy, antibiotic drug targets, pharmacodynamic parameters, factors affecting dosage and route of administration, host factors, complications of antibiotic therapy, Clostridium difficile infection, and antimicrobial resistance. 

      This review contains 2 figures, 7 tables, and 45 references.

      Key words: Antimicrobial therapy, antibiotic, infection, microorganism, renal dosing, hepatic dosing, Clostridium difficile

       

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    • 2

      Specific Antibiotic Agents

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      Specific Antibiotic Agents

      The simultaneous use of multiple antibiotics in a shotgun fashion should be avoided because of the problems of drug toxicity and hypersensitivity reactions, microbial superinfections, and antagonisms between certain agents. Most bacterial infections can be treated satisfactorily with a single antibiotic agent. There are a limited number of situations, however, in which the simultaneous administration of different antibiotics is warranted. This review covers specific antimicrobial agents, including β-lactam antibiotics, aminoglycosides, polymyxins, tetracyclines, macrolides, clindamycin, nitroimidazoles, chloramphenicol, vancomycin, lipoglycopeptides, oxazolidinones, daptomycin, streptogramins, sulfonamides and trimethoprim, fluoroquinolones, nitrofurantoin, fosfomycin, rifamycins, and fidaxomicin, and provides empirical therapy recommendations. Figures show an overview of penicillin antibiotics, an overview of β-lactam/β-lactamase inhibitor combinations, and a positive D-zone test for inducible clindamycin resistance. Tables list antibacterial guidelines for initial inpatient empirical therapy and empirical sepsis guidelines.

       

      This review contains 3 figures, 5 tables, and 51 references.

      Keywords: β-Lactam Antibiotics ,penicillins,Cephalosporins, Carbapenems , monobactams, Gentamicin, Tobramycin, Polymyxins, Tetracyclines, Clarithromycin, Clindamycin

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    • 3

      Diverticulitis and Colitis

      By Joshua Rempell, MD, MPH
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      Diverticulitis and Colitis

      • JOSHUA REMPELL, MD, MPH

      Diverticulitis and colitis (which may be broadly grouped into inflammatory, infectious, and ischemic categories) are commonly encountered in the emergency department, and patients’ conditions can range from mild to severe. This review details the pathophysiology, stabilization and assessment, diagnosis and treatment, dispositions and outcomes of diverticulitis and colitis. Figures include a computed tomographic scan showing diverticulitis, a bedside sonogram of a patient with diverticulitis, an ultrasound showing bowel wall thickening, a plain abdominal film showing grossly dilated small and large bowel (as seen in toxic megacolon in a patient with inflammatory bowel disease), a computed tomographic image of a patient presenting with known Crohn disease showing thickening of the distal ileum and a small abscess formation, and a computed tomographic image of a patient with ischemic colitis showing air in the small bowel. Tables list the Hinchey classification and the modified Hinchey classification showing stages of diverticulitis, differential diagnosis of left lower quadrant pain, empirical coverage for diverticulitis, indications for surgical treatment for acute diverticulitis, and differential diagnosis of colitis.

      This review contains 6 highly rendered figures, 5 tables, and 105 references.

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    • 4

      Sepsis

      By Steven P LaRosa, MD; Steven M. Opal, MD
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      Sepsis

      • STEVEN P LAROSA, MDStaff Physician, Infectious Disease Division, Beverly Hospital/Lahey Health System, Beverly, MA
      • STEVEN M. OPAL, MDChief, Infectious Disease Division, Memorial Hospital of Rhode Island, Pawtucket, RI

      Sepsis, along with the multiorgan failure that often accompanies this condition, is a leading cause of mortality in the intensive care unit. Although modest improvements in the prognosis have been made over the past two decades and promising new therapies continue to be investigated, innovations in the management of septic shock are still required. This chapter discusses the definitions, epidemiology, and pathogenesis (including microbial factors, host-derived mediators, and organ dysfunction) relating to sepsis. Management of severe sepsis and septic shock is also described. 

      This review contains 5 figures, 11 tables, and 99 references

      Keywords:Organ dysfunction, sepsis, septic shock, infection, bacteremia, fluid resuscitation, vasopressor

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    • 5

      Septic Arthritis, Septic Bursitis, and Osteomyelitis

      By Cameron Ashbaugh, MD
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      Septic Arthritis, Septic Bursitis, and Osteomyelitis

      • CAMERON ASHBAUGH, MDAssistant Professor of Medicine, Harvard Medical School, Associate Physician, Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA

      Infections of joints and bones are important causes of morbidity due to the potential for permanent injury to structures necessary for mechanical support and useful motion. The spectrum of disease is broad, with host factors, pathogen, site of infection, and comorbidities all influencing outcome. In some cases of bone infection, cure may not be possible, and the therapeutic goal becomes control. This review details the epidemiology, pathogenesis, diagnosis, differential diagnosis, treatment, and prognosis of septic arthritis, septic bursitis, vertebral body osteomyelitis, pedal osteomyelitis in association with diabetes, and chronic posttraumatic osteomyelitis with union or malunion.

      This review contains 13 highly rendered figures, 16 tables, and 192 references.

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    • 6

      Acute Viral Meningitis

      By Karen L. Roos, MD; Jared R. Brosch, MD
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      Acute Viral Meningitis

      • KAREN L. ROOS, MDJohn and Nancy Nelson Professor of Neurology and Professor of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN
      • JARED R. BROSCH, MDDeptment of Neurology, Assistant Professor of Neurology, Indiana University School of Medicine, Indianapolis, IN

      Acute viral meningitis refers to inflammation of the meninges of the brain in response to a viral pathogen. Viruses cause meningitis, encephalitis, myelitis, or a combination of these, meningoencephalitis or encephalomyelitis. Viral meningitis is typically a self-limited disorder with no permanent neurologic sequelae. This chapter reviews the epidemiology, etiology, diagnosis, differential diagnosis, treatment, complications, and prognosis. Tables describe Wallgren’s criteria for aseptic meningitis, important arboviral infections found in North America, herpes family viruses and meningitis, classic cerebrospinal fluid (CSF) abnormalities with viral meningitis, Centers for Disease Control and Prevention criteria for confirming arboviral meningitis, basic CSF studies for viral meningitis, and etiology of CSF pleocytosis. Figures depict common causes of viral meningitis, nuchal rigidity, examination for Kernig sign, and Brudzinski sign for meningeal irritation.

      This chapter contains 4 figures, 12 tables, 19 references

      Keywords: Meningitis, viral infection, encephalitis, enterovirus, herpesvirus, lumbar puncture, arbovirus, aseptic meningitis, Kernig sign, Brudzinski sign

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    • 7

      Acute Bacterial Meningitis

      By Karen L. Roos, MD
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      Acute Bacterial Meningitis

      • KAREN L. ROOS, MDJohn and Nancy Nelson Professor of Neurology and Professor of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN

      Acute bacterial meningitis is a life-threatening infection. By definition, meningitis is an infection of the meninges and the subarachnoid space. Bacterial meningitis is associated with an inflammatory response that involves the meninges, the subarachnoid space, the brain parenchyma, and the cerebral arteries and veins. As such, bacterial meningoencephalitis is the more accurate descriptive term. This chapter discusses the epidemiology, etiology, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, complications, and prognosis of the disease. The discussion of diagnosis covers clinical manifestations, physical examination findings, laboratory tests, and imaging studies. The discussion of treatment covers empirical therapy, specific antimicrobial therapy, and dexamethasone therapy. Graphs compare causative organisms and clinical manifestations of community-acquired meningitis. Illustrations depict proper patient positioning for detecting nuchal rigidity, Kernig sign, Brudzinski sign, and lumbar puncture, as well as a sagittal view of a lumbar puncture needle as it is advanced into the subarachnoid space. An algorithm delineates the approach to the patient with symptoms and signs of bacterial meningitis. Tables outline bacterial pathogens based on predisposing and associated conditions, cerebrospinal fluid diagnostic studies for meningitis, the appearance of the organism on a Gram stain, empirical antimicrobial therapy based on predisposing and associated conditions, recommendations for specific antibiotic therapy in bacterial meningitis, and recommended doses for antibiotics commonly used in the treatment of bacterial meningitis.

       

      This chapter contains 8 figures, 13 tables, 78 references

      Keywords: Bacterial meningitis, antibiotics, Kernig sign, Brudzinski sign, nuchal rigidity, headache

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    • 8

      Infective Endocarditis

      By Patrick T. O'Gara, MD, FACC, FAHA, FACP
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      Infective Endocarditis

      • PATRICK T. O'GARA, MD, FACC, FAHA, FACPDirector, Clinical Cardiology, Brigham and Women’s Hospital, Professor of Medicine, Harvard Medical School, Boston, MA

      Infective endocarditis is a microbial infection of a cardiac valve or the mural endocardium caused by bacteria or fungi. Forms of this infection include subacute bacterial endocarditis (SBE) and acute bacterial endocarditis (ABE). Etiology and epidemiology are discussed. There is a section on pathogenesis followed by specific clinical presentations, including endocarditis associated with parenteral drug abuse as well as prosthetic valve endocarditis (PVE). Diagnosis and cardiac complications of endocarditis, treatment, recommendations for prophylaxis, and prognosis are addressed. There are several figures showing manifestations and anatomic relations from the infection. Tables describe microorganisms that cause native valve endocarditis, the etiology of PVE, the Duke criteria for diagnosis of infective endocarditis, antimicrobial therapy for endocarditis in adults, guidelines to prevent endocarditis, and recommendations and regimens for endocarditis prophylaxis. This chapter contains 99 references.

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    • 9

      Lyme Disease and Other Spirochetal Zoonoses

      By David C Tompkins, MD; Benjamin J Luft, MD, FACP
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      Lyme Disease and Other Spirochetal Zoonoses

      • DAVID C TOMPKINS, MDVice Chairman, Department of Medicine, Head, Division of Infectious Diseases, Lutheran Medical Center, Brooklyn, NY
      • BENJAMIN J LUFT, MD, FACPEdmund D. Pellegrino Professor, Division of Infectious Diseases, Department of Medicine, SUNY at Stony Brook, Stony Brook, NY

      This review discusses the epidemiology, pathology, clinical features, laboratory findings, and treatment for Lyme disease, leptospirosis, relapsing fever, and rat-bite fever. Lyme disease is a tick-borne illness caused by the spirochete Borrelia burgdorferi. Lyme disease is a progressive infectious disease with a wide array of clinical manifestations. In most persons, the initial sign of infection is the development of erythema migrans. In general, three stages of the illness can be distinguished: early localized disease, early disseminated disease, and persisting late disease. A photograph shows an erythema migrans lesion, and an algorithm for diagnosis of Lyme disease is provided. A table lists the antibiotic regimens used for the different stages and manifestations of Lyme disease. Leptospirosis is a worldwide zoonosis caused by spirochetes from the genus Leptospira; these spirochetes are shown in a photomicrograph. The disease is acquired by contact with infected animals or exposure to contaminated soil or freshwater and can cause illness ranging from asymptomatic infection to severe multisystem disease with a significant mortality. Relapsing fever is an acute louse-borne or tick-borne infection caused by spirochetes of the genus Borrelia and is characterized by recurrent febrile episodes separated by asymptomatic intervals. Rat-bite fever is infection caused by Streptobacillus moniliformis in the United States and Europe or by Spirillum minus in Asia. 

      This review 6 figures, 13 tables, and 95 references.

      Keywords: Spirochete, borreliosis, tick, Lyme disease, rat bite fever, leptospirosis, zoonosis, target rash, relapsing fever, louse

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    • 10

      Vaginitis and Sexually Transmitted Diseases

      By Joel T. Katz, MD, FACP
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      Vaginitis and Sexually Transmitted Diseases

      • JOEL T. KATZ, MD, FACPMedicine Education Office, Brigham and Woman’s Hospital, Boston, MA

      Sexually transmitted infections (STIs) are among the most common causes of infectious illness worldwide, and therefore, familiarity with the recognition and management of these infectious pathogens is critical for physicians. This chapter reviews the epidemiology and transmission of STIs and describes the principles of taking a sexual history, reporting STIs, and screening for them. Urethritis, vulvovaginitis, mucopurulent cervicitis, pelvic inflammatory disease (PID), and genital ulcer disease are discussed. STIs in men who have sex with men is discussed, as is anorectal STIs in women. One figure shows a Gram stain in gonorrhea; the other shows ectopic pregnancy and tubal infertility in PID. 

      This review contains 2 figures, 24 tables, and 89 references.

      Keywords Vulvovaginitis, sexually transmitted infection, herpes, gonorrhea, urethritis, human papilloma virus, syphilis, chlamydia, viral hepatitis, pelvic inflammatory disease

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    • 11

      Fungal, Bacterial, and Viral Infections of the Skin

      By Jan V. Hirschmann, MD
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      Fungal, Bacterial, and Viral Infections of the Skin

      • JAN V. HIRSCHMANN, MDProfessor of Medicine, University of Washington School of Medicine, Staff Physician, Puget Sound VA Medical Center, Seattle, WA

      The skin can become infected by viruses, fungi, and bacteria, including some that ordinarily are harmless colonizing organisms. The most common fungal infections are caused by dermatophytes, which can involve the hair, nails, and skin. Potassium hydroxide (KOH) preparations of specimens from affected areas typically demonstrate hyphae, and either topical or systemic antifungal therapy usually cures or controls the process. The most common bacterial pathogens are Staphylococcus aureus and group A streptococci, which, alone or together, can cause a wide variety of disorders, including impetigo, ecthyma, and cellulitis. Topical antibiotics may suffice for impetigo, but ecthyma and cellulitis require systemic treatment. S. aureus, including methicillin-resistant strains, can also cause furuncles, carbuncles, and cutaneous abscesses. For these infections, incision and drainage without antibiotics are usually curative. Warts are the most common cutaneous viral infection, and eradication can be difficult, especially where the skin is thick, such as the palms and soles, or the patient is immunocompromised. Most therapies consist of trying to destroy the viruses by mechanical, chemical, or immune mechanisms. This review covers dermatophyte infections, yeast infections, bacterial infections, and viral infections of the skin. Figures show the classic annular lesion of tinea corporis, a typical kerion presenting as a zoophilic Microsporum canis infection of the scalp (tinea capitis), tinea corporis, tinea barbae, tinea pedis between and under the toes and on the plantar surface, inflammatory tinea pedis, tinea unguium, tinea manuum, angular cheilitis, prominent satellite lesions of discrete vesicles associated with candidiasis, facial candidiasis, Candida paronychia, tinea versicolor, nonbullous impetigo, bullous impetigo, ecthyma, leg cellulitis, erythema and edema on the cheeks, eyelids, and nose, furuncle, carbuncle, nasal folliculitis, pitted keratolysis, trichomycosis axillaris, necrotizing fasciitis, Fournier gangrene, folliculitis, plantar wart, condyloma acuminatum, and benign lesions of bowenoid papulosis. Tables list dermatophyte species, terminology of dermatophyte infections, topical agents for dermatophyte infections, treatment options for impetigo (adult doses), and treatment options for erythrasma.

       

      This review contains 29 figures, 12 tables, and 36 references

      Keywords: Staphylococcus aureus, methicillin-resistant strains, furuncles, carbuncles, cutaneous abscesses, dermatophytes, zoophilic Microsporum canis, andidiasis, facial candidiasis, Candida paronychia, tinea versicolor, nonbullous impetigo, bullous impetigo, ecthyma, leg cellulitis, erythema

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    • 12

      Tuberculosis

      By Jonathan B. Parr, MD, MPH; Michael K Leonard Jr, MD; Henry M Blumberg, MD, FACP
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      Tuberculosis

      • JONATHAN B. PARR, MD, MPHClinical Instructor, Division of Global Health Equity, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
      • MICHAEL K LEONARD JR, MDID Consultants, Charlotte, NC
      • HENRY M BLUMBERG, MD, FACPProfessor of Medicine, Epidemiology, and Global Health, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA

      Tuberculosis (TB) is a bacterial disease caused by Mycobacterium tuberculosis, a relatively slow-growing, aerobic, acid-fast bacillus (AFB). Classically, TB is a pulmonary disease, but disseminated and extrapulmonary manifestations may also occur, especially in immunocompromised persons. TB is transmitted person to person and is usually contracted by inhalation of M. tuberculosis droplet nuclei generated by an infectious person. If infection occurs after M. tuberculosis enters the body, the host’s cell-mediated immunity may contain the organism but not eradicate all the bacilli, resulting in latent tuberculosis infection (LTBI). M. tuberculosis can remain dormant and persist (e.g., within macrophages); persons with LTBI are at risk for reactivation and development of active TB.

      This review contains 5 figures, 7 tables, and 75 references.

      Key Words: tuberculosis, pulmonary tuberculosis, extrapulmonary tuberculosis, tuberculosis in hiv-infected patients


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    • 13

      Viral Zoonoses

      By Lyle R Petersen, MD, MPH; Duane J. Gubler, ScD; Daniel R Kuritzkes, MD, FACP
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      Viral Zoonoses

      • LYLE R PETERSEN, MD, MPHDirector, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO
      • DUANE J. GUBLER, SCDProfessor, Program on Emerging Infectious Diseases, DUKE-NUS Graduate Medical School, Singapore
      • DANIEL R KURITZKES, MD, FACPChief, Division of Infectious Diseases, Brigham and Women's Hospital; Professor of Medicine, Harvard Medical School, Boston, MA

      Human infection by zoonotic viruses—pathogens that normally infect animals—may result in no obvious illness, a nonspecific viral syndrome, or more severe illness typically characterized by hemorrhagic fever, encephalitis, or rash arthralgia. Transmission usually occurs by direct contact with or a bite from an infected animal or arthropod. Viral families discussed include Flaviviridae, Bunyaviridae, Arenaviridae, Filoviridae, Togaviridae, Rhabdoviridae, Paramyxoviridae, and Reoviridae, with consideration given to the epidemiology, diagnosis, treatment, and prevention of specific viruses. Hemorrhagic fevers addressed include dengue fever, dengue hemorrhagic fever, yellow fever, Crimean-Congo hemorrhagic fever, and Rift Valley fever; hantavirus infections; and the Marburg and Ebola viruses. Encephalitic fever–causing viruses discussed include La Crosse; Japanese; Murray Valley; St. Louis; tick-borne; West Nile; Powassan; eastern, western, and Venezuelan equine; rabies; Nipah; Barmah Forest; and Colorado tick fever. Rash arthralgia may be caused by the Barmah Forest, Chikungunya, Mayaro, O’nyong-nyong, Ross River, and dengue viruses. Other viral zoonoses considered include monkey B virus, ruminant and primate poxvirus, Newcastle, and foot-and-mouth diseases, as well as vesicular stomatitis virus infection. A diagram depicts the generalized arbovirus maintenance cycle. Tables list the important viral zoonoses that cause human disease, the principal hantaviruses that cause human disease, the arenaviruses that cause significant human illness, and the viral zoonoses endemic in the United States. 

      This review contains 1 figure, 32 tables, and 80 references.

      Key words: dengue, diagnosis, encephalitis, epidemic, epidemiology, infection, rabies, virus, vaccine

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    • 14

      HIV and AIDS

      By Daniel R. Kuritzkes, MD, FACP
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      HIV and AIDS

      • DANIEL R. KURITZKES, MD, FACP

      In the quarter-century since the first report of AIDS in the United States, HIV infection has spread throughout the population, disproportionately affecting black women, Hispanic women, and men who have sex with men. The prognosis for persons infected with HIV has improved dramatically with the introduction and evolution of highly active antiretroviral therapy (HAART). The underlying principle of HAART is that a combination of potent antiretrovirals, each of which requires different mutations in the HIV genome for resistance to develop, can suppress replication sufficiently to prevent mutation and the emergence of resistance. The prospect that currently available antiretroviral therapy (ART) regimens may suppress HIV replication indefinitely provides the hope that infected patients will have life expectancies similar to those of age-matched uninfected individuals. For these patients, HIV care has shifted from an emphasis on treatment and prevention of the complications of HIV disease itself to a focus on suppression of HIV replication and management of short- and long-term complications of HIV, ART toxicities, and aging. This chapter describes the epidemiology, pathophysiology and pathogenesis, prevention, diagnosis, and management of acute and chronic HIV infection and AIDS, with figures and tables illustrating each chapter section.


      This review contains 9 figures, 32 tables, and 257 references

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    • 15

      Urinary Tract Infections

      By Sigal Yawetz, MD
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      Urinary Tract Infections

      • SIGAL YAWETZ, MDAssociate Physician, Brigham and Women’s Hospital, Boston, MA; Assistant Professor of Medicine, Harvard Medical School, Boston, MA

      Urinary tract infection (UTI) is the most common bacterial infection, affecting women far more than men. Aerobic gram-negative bacteria are the most common uropathogens causing UTI, with Escherichia coli remaining the most predominant organism in complicated infections. UTI can result in a variety of infections and inflammations, from asymptomatic bacteriuria to typical symptomatic cystitis to acute pyelonephritis, as well as bacterial prostatitis in men. In general, antimicrobial therapy is warranted for any symptomatic infection of the urinary tract. However, new consensus treatment guidelines for uncomplicated UTI in women, set by the Infectious Diseases Society of America and the European Society for Microbiology of Infection Diseases in 2010, account for the increasing antimicrobial resistance of pathogens and focus on first-line empirical treatment regimens. To reduce the use of antibiotics, treatment and prevention of recurrent UTI may involve several strategies on varying levels of effectiveness; some of the more well-tested options include probiotics, antiseptics, and topical estrogen. Antimicrobial approaches should be reserved for women in whom these options prove to be ineffective.

      This review contains 7 figures, 10 tables, and 122 references.

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    • 16

      Acute Pneumonia

      By John I Hogan, MD; Benjamin Davis, MD
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      Acute Pneumonia

      • JOHN I HOGAN, MD
      • BENJAMIN DAVIS, MD

      Acute pneumonia continues to represent a major source of morbidity, mortality, and healthcare expenditure in the U.S. It is imperative that clinicians at all levels of training have a firm understanding of this potentially deadly infection and its numerous complications. The current state of our diagnostic capabilities often dictates that clinicians will need to make important therapeutic decisions in patients presenting with acute pneumonia before identifying a culprit pathogen. Only after understanding the pathogenesis of pneumonia under different clinical circumstances can one devise rational empiric therapeutic regimens. In this practical review we offer a succinct description of the epidemiology and pathogenesis of acute pneumonia. We then proceed to discuss the evaluation and management of patients presenting with acute pneumonia with emphasis on the most valuable clinical trials and major guidelines that we use to inform our clinical decisions. Despite significant advances in the field of infectious disease over the past century, clinicians continue to recognize pneumonia, the infection of the pulmonary parenchyma, as a major source of morbidity and mortality. In this article we attempt to provide the general practitioner with a practical review of acute pneumonia and its complications. Prioritizing the needs of the general practitioner, we most thoroughly address community acquired pneumonia (CAP). Though we do not intend for this review to be completely comprehensive, in this article we also briefly discuss healthcare associated pneumonia (HCAP), hospital associated pneumonia (HAP), and ventilator associated pneumonia (VAP). Focusing much of our attention on the most important clinical trials and guidelines underpinning the diagnosis and management of this common problem, we hope that this publication will serve as a useful review to aid in clinical decision making.

      This review contains 1 figure, 6 tables and 65 references

      Key Words: Pneumonia, viral pneumonia, bacterial pneumonia, community-acquired pneumonia, ventilator-associated pneumonia, VAP, healthcare-associated pneumonia, hospital-acquired pneumonia

       

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    • 17

      Bacterial Infections of the Adult Upper Respiratory Tract

      By Laura K Certain, MD, PhD; Miriam B Barshak, MD, PhD
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      Bacterial Infections of the Adult Upper Respiratory Tract

      • LAURA K CERTAIN, MD, PHDInstructor, Harvard Medical School, Assistant in Medicine, Massachusetts General Hospital, Boston, MA
      • MIRIAM B BARSHAK, MD, PHDAssistant Professor, Harvard Medical School, Attending Physician, Massachusetts General Hospital, Clinical Associate, Massachusetts Eye and Ear Infirmary, Boston, MA

      Upper respiratory tract infections are the most common maladies experienced by humankind.1 The majority are caused by respiratory viruses. A Dutch case-controlled study of primary care patients with acute respiratory tract infections found that viruses accounted for 58% of cases; rhinovirus was the most common (24%), followed by influenza virus type A (11%) and corona­viruses (7%). Group A streptococcus (GAS) was responsible for 11%, and 3% of patients had mixed infections. Potential pathogens were detected in 30% of control patients who were free of acute respiratory symptoms; rhinovirus was the most common.2 Given the increasing problem of antibiotic resistance and the increasing awareness of the importance of a healthy microbiome, antibiotic use for upper respiratory infections should be reserved for those patients with clear indications for treatment. A recent study of adult outpatient visits in the United States found that respiratory complaints accounted for 150 antibiotic prescriptions per 1,000 population annually, yet the expected “appropriate” rate would be 45.3 In other words, most antibiotic prescriptions for these complaints are unnecessary. Similarly, a study in the United Kingdom found that general practitioners prescribed antibiotics to about half of all patients presenting with an upper respiratory infection, even though most of these infections are viral.4

      This review contains 5 figures, 16 tables, and 82 references.

      Keywords: infection, airway, sinusitis, otitis media, otitis externa, pharyngitis, epiglottitis, abscess

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    • 18

      Coronaviruses: Hcov, Sars-cov, Mers-cov, and COVID-19

      By Michael G. Ison, MD, MSc
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      Coronaviruses: Hcov, Sars-cov, Mers-cov, and COVID-19

      • MICHAEL G. ISON, MD, MSCAssociate Professor, Divisions of Infectious Diseases & Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL

      Coronaviruses (CoVs) are a group of viral pathogens that infect mammals and birds. The presentation in humans is typically that of a mild upper respiratory tract infection, similar to the common cold. However, in recent years, dramatic attention has arisen for more lethal members of this viral family (e.g., severe acute respiratory syndrome [SARS-CoV], Middle East respiratory syndrome [MERS-CoV], and coronavirus disease 2019 [COVID-19]). The epidemiology, clinical presentation, diagnosis, and management of these viruses are discussed in this review. Importantly, new guideline tables from the Centers for Disease Control and Prevention, as well as the World Health Organization are provided at the conclusion of the review.

      This review contains 12 tables, 3 figure and 48 references.

      Keywords: Coronavirus, severe acute respiratory distress syndrome (SARS), Middle East respiratory syndrome (MERS), COVID-19, respiratory infection, antiviral, real-time polymerase chain reaction

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    • 19

      Lyme Disease and Other Spirochetal Zoonoses

      By David C Tompkins, MD; Benjamin J Luft, MD, FACP
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      Lyme Disease and Other Spirochetal Zoonoses

      • DAVID C TOMPKINS, MDVice Chairman, Department of Medicine, Head, Division of Infectious Diseases, Lutheran Medical Center, Brooklyn, NY
      • BENJAMIN J LUFT, MD, FACPEdmund D. Pellegrino Professor, Division of Infectious Diseases, Department of Medicine, SUNY at Stony Brook, Stony Brook, NY
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    • 20

      Viral Zoonoses

      By Lyle R Petersen, MD, MPH; Duane J. Gubler, ScD; Daniel R Kuritzkes, MD, FACP
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      Viral Zoonoses

      • LYLE R PETERSEN, MD, MPHDirector, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO
      • DUANE J. GUBLER, SCDProfessor, Program on Emerging Infectious Diseases, DUKE-NUS Graduate Medical School, Singapore
      • DANIEL R KURITZKES, MD, FACPChief, Division of Infectious Diseases, Brigham and Women's Hospital; Professor of Medicine, Harvard Medical School, Boston, MA
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    • 21

      Vaginitis and Sexually Transmitted Diseases

      By Joel T. Katz, MD, FACP
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      Vaginitis and Sexually Transmitted Diseases

      • JOEL T. KATZ, MD, FACPMedicine Education Office, Brigham and Woman’s Hospital, Boston, MA
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    • 22

      Acute Pneumonia

      By John I Hogan, MD; Benjamin Davis, MD
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      Acute Pneumonia

      • JOHN I HOGAN, MD
      • BENJAMIN DAVIS, MD
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    • 23

      Urinary Tract Infections

      By Sigal Yawetz, MD
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      Urinary Tract Infections

      • SIGAL YAWETZ, MDAssociate Physician, Brigham and Women’s Hospital, Boston, MA; Assistant Professor of Medicine, Harvard Medical School, Boston, MA
      Purchase PDF
    • 24

      Vaccines and Vaccination

      By Lindsey Obradovich, PharmD, MSc; Nicholas C Issa, MD
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      Vaccines and Vaccination

      • LINDSEY OBRADOVICH, PHARMD, MSCSenior Research Pharmacist, Investigational Drug Service, Brigham and Women’s Hospital, Boston, MA
      • NICHOLAS C ISSA, MDAssistant Professor of Medicine, Harvard Medical School, Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA

      The advent of vaccination began a new era in the world and in medicine. From the eradication of smallpox and near-eradication of polio to the significant reduction in many childhood diseases, vaccination has saved countless lives. Progress continues today in the form of safer and more effective vaccines, along with new vaccines against old and emerging pathogens that threaten worldwide pandemics. Several vaccines have been approved recently by the Food and Drug Administration, including a more immunogenic pneumococcal vaccine, new meningococcal serotype B vaccines, a 9-valent HPV vaccine, and the first adjuvanted influenza vaccine. Additional advancement with improved vaccines against herpes zoster and novel vaccines against emerging pathogens (Ebola and Zika viruses) is on the horizon. In this review, we discuss the immune mechanisms by which vaccines induce protection, the different types of vaccines, and the most recent recommendations by the Advisory Committee on Immunization Practices for vaccination schedules in adults. Key information for the general practitioner is presented in a concise and easy-to-read format, summarized in tables whenever possible. Vaccination in special populations, such as pregnant women, immunocompromised patients, international travelers, and health care workers, is also included in this review. A list of guidelines is also included.

      This review contains 7 figures, 13 tables, and 57 references.

      Key words: immunocompromised host, postexposure prophylaxis, travel, vaccination, vaccine

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    • 25

      Vaccines and Vaccination

      By Lindsey Obradovich, PharmD, MSc; Nicholas C Issa, MD
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      Vaccines and Vaccination

      • LINDSEY OBRADOVICH, PHARMD, MSCSenior Research Pharmacist, Investigational Drug Service, Brigham and Women’s Hospital, Boston, MA
      • NICHOLAS C ISSA, MDAssistant Professor of Medicine, Harvard Medical School, Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA
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    • 26

      Fungal, Bacterial, and Viral Infections of the Skin

      By Jan V. Hirschmann, MD
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      Fungal, Bacterial, and Viral Infections of the Skin

      • JAN V. HIRSCHMANN, MDProfessor of Medicine, University of Washington School of Medicine, Staff Physician, Puget Sound VA Medical Center, Seattle, WA
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    • 27

      HIV and AIDS

      By Daniel R. Kuritzkes, MD, FACP
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      HIV and AIDS

      • DANIEL R. KURITZKES, MD, FACP
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    • 28

      Acute Bacterial Meningitis

      By Karen L. Roos, MD
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      Acute Bacterial Meningitis

      • KAREN L. ROOS, MDJohn and Nancy Nelson Professor of Neurology and Professor of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN
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    • 29

      Acute Viral Meningitis

      By Karen L. Roos, MD; Jared R. Brosch, MD
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      Acute Viral Meningitis

      • KAREN L. ROOS, MDJohn and Nancy Nelson Professor of Neurology and Professor of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN
      • JARED R. BROSCH, MDDeptment of Neurology, Assistant Professor of Neurology, Indiana University School of Medicine, Indianapolis, IN
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  • Interdisciplinary (and Preventative) Medicine
    • 1

      Exercise

      By Elizabeth G Nabel, MD, FACP
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      Exercise

      • ELIZABETH G NABEL, MD, FACPPresident, Brigham and Women’s Hospital, Professor of Medicine, Harvard Medical School, Boston, MA

      Numerous observational studies have demonstrated an inverse relationship between physical activity and risk of many chronic illnesses. The protective effect of exercise is strongest against coronary artery disease, hypertension, stroke, type 2 diabetes mellitus, obesity, anxiety, depression, osteoporosis, and cancers of the colon and breast. Despite these proven benefits, only 25% of adults in the United States exercise at recommended levels. Globally, physical inactivity is the fourth leading risk factor for death, followed by overweight and obesity. This module describes exercise physiology, including cardiovascular response to dynamic exercise, pulmonary response, musculoskeletal response, metabolic effects, effects on blood lipid levels, hematologic effects, effects on vascular inflammation, effects on body fluids, and psychological effects. Exercise and the elderly and the relationship between exercise and longevity are reviewed. Prescribing exercise and complications of exercise are also discussed. Tables describe the categories of patients screened for possible coronary artery disease, exercise time required to consume 2,000 kcal, and exercise advice for patients. Figures include a graph showing the number of adults who met the federal physical activity guidelines criteria, the top 10 global risk factors for death in 2004, the process of providing energy for the muscle, and trends in physician prescriptions for exercise.

      This module contains 4 highly rendered figures, 3 tables, 35 references, and 5 MCQs.

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    • 2

      Diet

      By Elizabeth G Nabel, MD, FACP
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      Diet

      • ELIZABETH G NABEL, MD, FACPPresident, Brigham and Women’s Hospital, Professor of Medicine, Harvard Medical School, Boston, MA

      An unhealthy diet is a major risk factor for chronic diseases such as cardiovascular diseases, cancer, diabetes, and conditions related to obesity. In the 20th century, the average American diet shifted from one based on fresh, minimally processed vegetable foods to one based on animal products and highly refined, processed foods, leading to an increased consumption of calories, fat, cholesterol, refined sugar, animal protein, sodium, and alcohol and far less fiber and starch than was healthful. As a result, more than one third of US adults are obese, with an estimated medical cost of $147 billion. Physicians have an important role in educating patients about healthful nutrition and in providing dietary guidelines. This module discusses the role of energy in weight loss; the structure of fat and cholesterol, their effects on blood lipid levels and cardiovascular risk, and related dietary recommendations; carbohydrates; dietary fiber; proteins; vitamin and mineral consumption; water and food consumption; and the relationship between diet and health. Tables review the principles of a healthy diet; recommended daily intake of fat and other nutrients; types of dietary fiber and representative food sources; types of vitamins; essential minerals and trace elements; and dietary guidelines for healthy people. Figures include a graph showing the percentage of adults who are healthy weight, overweight, and obese and the structure of fat and cholesterol.

      This review contains 2 highly rendered figures, 6 tables, and 37 references.

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    • 3

      Adult Preventive Health Care

      By Jennifer S Haas, MD, MSc
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      Adult Preventive Health Care

      • JENNIFER S HAAS, MD, MSCProfessor of Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA

      Over the past quarter century, prevention has become a major activity in primary care. During a typical day, primary care clinicians spend much of their time managing asymptomatic conditions in which the main goal is to prevent death or complications (e.g., hypertension, hyperlipidemia, osteoporosis). This chapter focuses primarily on preventive screening recommendations from the United States Preventive Services Task Force (USPSTF). The rationale and evolution of preventive care guidelines are discussed. Advantages and disadvantages of cervical, colorectal, breast, prostate, ovarian and lung cancer screening are explained, along with recommendations regarding behavioral counseling, especially for smoking cessation and alcohol use. Graphs are included. Tables delineate major causes of death in the United States, criteria for evaluating a screening program, sample board examination questions about screening, government-sponsored preventive guidelines programs, the USPSTF grading system, strongly recommended noncancer preventive services in adults, the recommended adult immunization schedule, recommended and strongly recommended measures for cancer prevention, recommended preventive noncancer screening measures, and selected recommendations for counseling and patient education.

      This review contains 5 figures, 10 tables, and 77 references.

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    • 4

      Medical Evaluation of the Surgical Patient

      By Marie Gerhard-Herman, MD; Jonathan Gates, MD
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      Medical Evaluation of the Surgical Patient

      • MARIE GERHARD-HERMAN, MDDepartment of Medicine, Cardiovascular Division, Brigham and Womens Hospital, Boston, MA
      • JONATHAN GATES, MDDirector of the Burn and Trauma Unit, Department of Surgery, Brigham and Womens Hospital, Boston, MA

      Medical evaluation prior to surgery includes risk assessment and the institution of therapies to decrease perioperative morbidity and mortality to improve patient outcomes. The most effective medical consultation for surgical patients begins with an assessment of the individual patient and knowledge of the planned surgery and anesthesia followed by clear communication of a concise and specific recommended plan of perioperative care to the surgical team. This chapter describes anesthetic, cardiac, pulmonary, hepatic, nutritional, and endocrine risk assessment. Perioperative thrombotic management and postoperative care and complications, including fluid management; pulmonary, cardiac, renal complications; and delirium are discussed. Tables outline the American Society of Anesthesiologists class and perioperative mortality risk, a comparison of the Revised Cardiac Risk Index and National Surgery Quality Improvement Program, Duke Activity Status Index, high-risk stress test findings, markers for increased perioperative risk in pulmonary hypertension, aortic stenosis and nonemergent noncardiac surgery, risk factors for pulmonary complications in noncardiac surgery, the Model for End-Stage Liver Disease score to predict postoperative mortality, venous thromboembolism risk factors and options for pharmacologic prophylactic regimens, perioperative management of warfarin, and Brigham and Women’s Hospital guidelines for postoperative blood product replacement. Figures include a care algorithm for noncardiac surgery, an illustration of types of myocardial infarction, and an algorithm for the treatment of postoperative delirium.

      This chapter contains 3 highly rendered figures, 12 tables, 68 references, and 5 MCQs.

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    • 5

      Drugs of Abuse

      By Matthew D Zuckerman , MD; Kavita Babu, MD, FACEP, FACMT
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      Drugs of Abuse

      • MATTHEW D ZUCKERMAN , MDAssistant Professor, Department of Emergency Medicine, Medical Toxicology, University of Colorado Anschutz Medical Campus, Aurora, CO
      • KAVITA BABU, MD, FACEP, FACMTFellowship Director, Division of Medical Toxicology, Associate Professor, Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, MA

      The term “drugs of abuse” lacks a formal medical definition. Historically, discussions of drugs of abuse focused on “street drugs”; however, the adverse effects of the nonmedical use of prescription medications, such as opiates, benzodiazepines, and therapeutic amphetamines, are increasingly seen. The purpose of this review is to aid the clinician in identifying and treating a broad representation of drugs of abuse, which may include those illicitly produced in laboratories (e.g., methamphetamine), diverted pharmaceuticals (oxycodone), and herbal products (marijuana). This review covers stimulants, hallucinogens, cannabinoids, and sedative-hypnotics. Figures show substances ranked according to weighted harm score on a normalized scale from 0 being no harm to 100 being extreme harm to self and others, a treatment algorithm for sympathomimetic toxicity, a treatment algorithm for sedative-hypnotic overdose, and a treatment algorithm for opioid overdose. Tables list commonly abused sympathomimetic agents, modern novel drugs of abuse, commonly abused sedative-hypnotic agents, commonly abused opiates, and pitfalls of the drug screen.

      This review contains 4 highly rendered figures, 5 tables, and 89 references

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    • 6

      Opioid Therapy for Chronic Noncancer Pain: Safe, Effective, Appropriate?

      By Joseph V. Pergolizzi Jr, MD; Robert B. Raffa, PhD, Professor Emeritus; Robert Taylor, PhD; Jo Ann LeQuang, BA
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      Opioid Therapy for Chronic Noncancer Pain: Safe, Effective, Appropriate?

      • JOSEPH V. PERGOLIZZI JR, MDNEMA Research, Inc., Naples, FL
      • ROBERT B. RAFFA, PHD, PROFESSOR EMERITUSDepartment of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA Adjunct Professor, Department of Pharmacology and Toxicology, University of Arizona College of Pharmacy
      • ROBERT TAYLOR, PHDExecutive Director of Operations, NEMA Research, Inc., Bonita Springs, FL
      • JO ANN LEQUANG, BADirector of Scientific Communications, NEMA Research, Inc., Bonita Springs, FL

      In determining the appropriate role of opioids, two public health crises must be balanced: the opioid abuse epidemic and the “silent” crisis of unrelieved chronic pain. Opioids can be used safely and effectively in selected patients; however, clinicians must be aware of their abuse liability and individual risk factors for opioid misuse. A number of opioids are approved for use in the United States, and although there are class effects, there can be great variability among patients with regard to opioid response. In addition to the medication, prescribers must also determine the most appropriate dose and route of administration. Considerations must be made for special population, such as the renally impaired, those with hepatic dysfunction, and pediatric and elderly patients. Another factor is abuse-deterrent properties. Of particular interest as an opioid agent is buprenorphine, which is available in various routes of administration and because of its unique pharmacokinetics may be administered to renally compromised and elderly patients without dosing restrictions. Buprenorphine is also associated with a lower abuse liability than other opioids. Patients suffering moderate to severe pain syndromes should not be denied access to effective pain control, which in some cases may appropriately include opioid therapy.

      Key words:Buprenorphine, Chronic Pain, Opioid, Opioid Abuse, Opioid Prescribing, Risk Factors for Opioid Abuse

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    • 7

      Physicians' Role in Curbing the Worst Drug Crisis in America: Prescription Opioid Abuse

      By Sairam Atluri, MD, FIPP; Gururau Sudarshan, MD, FRCA
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      Physicians' Role in Curbing the Worst Drug Crisis in America: Prescription Opioid Abuse

      • SAIRAM ATLURI, MD, FIPPDirector, Tristate Pain Management Institute, Cincinnati, OH
      • GURURAU SUDARSHAN, MD, FRCADirector, Cincinnati Pain Physicians, Cincinnati, OH

      Opioids have an important role in the management of acute, cancer, and chronic pain. However, their indiscriminate use in chronic pain has led, in part, to the epidemic of prescription drug abuse, resulting in a dramatic increase in morbidity and mortality in America. Most of this abuse originates from legitimate prescriptions by physicians. Prescribing opioids to chronic pain patients while restricting them to those who abuse them is very challenging, and physicians seek appropriate and unbiased prescribing guidelines. Our review, based on analysis of the available literature, focuses on striking a balance between overprescribing and underprescribing. The core concept of this strategy relies in using screening tools to identify patients who are at high risk for opioid abuse along with diligent monitoring using prescription monitoring programs and urine drug screens, while also limiting opioid doses. Hopefully, using these principles, physicians can more confidently prescribe opioids to those who would benefit from these powerful drugs and at the same time keep opioids away from those who could potentially be harmed.

      Key Words: abuse, addiction, chronic pain, dose limitation, misuse, monitoring, opioids, overdose, screening

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    • 8

      Toxic Gases

      By Stephanie T Weiss, MD, PhD; Kathryn W Weibrecht, MD
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      Toxic Gases

      • STEPHANIE T WEISS, MD, PHDAssociate Director, Emergency Medicine, Morton Hospital and Medical Center, Taunton, MA
      • KATHRYN W WEIBRECHT, MDAssociate Director, Emergency Medicine, Morton Hospital, Taunton, MA

      This review looks at the potential causes, diagnoses, and possible treatments for three asphyxiant gases: carbon monoxide, hydrogen cyanide, and hydrogen sulfide, Exposure to these gases can lead to central nervous system depression, unconsciousness, and death due to tissue hypoxia. These gases are among the most common causes of fatalities related to toxic gas poisoning, with carbon monoxide responsible for 36% and hydrogen sulfide 7.7%. It is necessary to remove victims affected by poisoning immediately from the source of the toxic gas, administer oxygen, and assess their stability. As symptoms of these gases can differ widely, ranging from broad and unspecific to highly morbid, and may require different levels of care, the correct diagnosis should also rely on inferences from the patient history and the context of the admission, including evidence of fire and chemical reactions. Normobaric oxygen and hyperbaric oxygen are the two main treatments for carbon monoxide, although studies have been inconclusive in regards to the effectiveness of hyperbaric oxygen. The Cyanokit (containing hydroxocobalamin) is considered to be more effective for hydrogen cyanide when compared with the Cyanide Antidote Kit due to the former’s low toxicity and high effectiveness. Hydrogen sulfide is often used as a suicide agent, the mortality of which is close to 100%. Figures show the mechanisms by which the asphyxiant gases carry out their negative effects on the human body. Tables show the half-life of carboxyhemoglobin with oxygen therapy and a comparison between the Cyanide Antidote Kit and the Cyanokit.

      This review contains 3 figures, 13 tables, and 44 references. 

      Keywords: Inhalation, poisoning, carbon monoxide, cyanide, methemoglobin, carboxyhemoglobin, hydrogen sulfide, smoke


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    • 9

      Complementary, Alternative, and Integrative Medicine

      By Helene M. Langevin, MD
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      Complementary, Alternative, and Integrative Medicine

      • HELENE M. LANGEVIN, MDDirector, Osher Center for Integrative Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

      Complementary and alternative medicine (CAM) refers to a group of diverse medical and health care systems, practices, and products that are not considered to be part of conventional or allopathic medicine. Common CAM practices (e.g., acupuncture, meditation, and therapeutic massage) are gradually becoming incorporated into conventional care in response to patients looking to alternative sources for information and advice about health matters and increased understanding of various CAM methods through evidence-based testing. However, although the claims of some methods are supported with academic research, well-founded concerns remain in many popularized CAM practices regarding the lack of evidence and placebo effects. It is thus imperative for physicians to be comfortable in discussing CAM-related topics with patients and be able to appropriately and informatively guide them in a way that harnesses potential benefits and avoids potential harm. In this review, the major CAM therapies in the United States are examined, including the settings in which they are being used, evidence base status, and efficacy of some of the most commonly used modalities. 

      This review contains 5 figures, 21 tables, and 123 references.

      Keywords: Alternative medicine, complementary medicine, acupuncture, homeopathy, osteopathy, chiropractic, massage therapy, naturopathy

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    • 10

      Oral Health and Nutrition

      By Carole. A. Palmer, Ed.D., RD, LDN; Zhangmuge Cheng, MS, RD, CNSC, LDN
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      Oral Health and Nutrition

      • CAROLE. A. PALMER, ED.D., RD, LDNProfessor Emerita and Former Head, Division of Nutrition and Oral Health Promotion, Department of Comprehensive Care, Tufts University School of Dental Medicine Professor Emerita and Former Master’s Program Director - Dietetic Internship/Master’s Program Tufts’ Friedman School of Nutrition Science and Policy Adjunct Professor (retired), Program in Public Health, Tufts University School of Medicine
      • ZHANGMUGE CHENG, MS, RD, CNSC, LDNRegistered Dietitian II, Sodexo Kent Hospital, Warwick, RI

      Oral diseases are among the most prevalent diseases affecting global health. In his report on the crisis in oral disease in America, the Surgeon General warned that one cannot be truly healthy without oral health. Oral health means freedom from all oral health problems; tooth decay (dental caries), periodontal diseases, tooth loss, oral-facial pain, oral cancer and the effects of its treatment, oral infections, craniofacial birth defects and more. The relationships between oral conditions and systemic health and disease are many and synergistic, and most involve dietary and/or systemic nutritional factors. Diet and nutrition can play important roles in the etiology, prevention, and/or management of oral conditions, as they do in overall health and disease. Today, all health professionals and educators need to be aware of and consider oral issues and their possible diet/nutritional implications as a component of optimal health care and education. This review article provides a brief overview of how diet and nutrition impact and are impacted by oral conditions, and offers general guidelines and resources for providing meaningful interventions throughout the life cycle.

      This review contains 3 figures, 3 tables, and 57 references

      Keywords: biofilm, cariogenic, dental caries, dental plaque, ECC-early childhood caries, lactobacillus, mucositis, non-cariogenic, periodontal disease, Streptococcus mutans

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  • Integrative Medicine
    • 1

      Peripheral Nerve Blocks for the Lower Extremity

      By Candace Shavit, MD; Monica W. Harbell, MD
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      Peripheral Nerve Blocks for the Lower Extremity

      • CANDACE SHAVIT, MD
      • MONICA W. HARBELL, MD

      Lower extremity peripheral nerve blocks (PNBs) are often used for surgical anesthesia and postoperative pain management. The use of PNB provides improved analgesia, reduced opioid consumption, and improved patient satisfaction and can facilitate earlier rehabilitation and discharge. As the number of lower extremity total joint arthroplasties is projected to increase significantly, the role of peripheral nerve blocks can be expected to grow in similar fashion. With the growing number of procedures and the increasing focus on patient experience and expeditious hospital discharge, PNBs are increasingly recognized as a powerful tool to improve patient care and facilitate recovery after lower extremity surgery. We provide a basic review of regional anesthesia for lower extremity surgical procedures. The widespread availability of ultrasonography has improved the performance and efficacy of PNBs; thus, we focus on ultrasonography-guided procedures. In this review, we discuss pertinent lower extremity anatomy and sonoanatomy, indications, patient outcome measures, techniques, and complications of the most commonly used blocks.

      This review contains 35 figures, 11 tables, 5 videos, and 103 references

      Key words: adductor canal block, analgesia, ankle block, clinical applications of peripheral nerve blocks, complications of peripheral nerve blocks, continuous peripheral nerve catheter, early ambulation, fascia iliaca compartment block, femoral nerve block, lower extremity nerve blocks, lower extremity regional anesthesia, lumbar plexus block, obturator nerve block, peripheral nerve block, peripheral nerve catheter, popliteal block, psoas compartment block, regional anesthesia, regional anesthesia techniques, saphenous nerve block, sciatic nerve block, ultrasonography guided

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    • 2

      Clinical Trial Design and Statistics

      By Julie Ann Sosa, MA, MD, FACS; Samantha M. Thomas, MS; April K.S. Salama, MD
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      Clinical Trial Design and Statistics

      • JULIE ANN SOSA, MA, MD, FACSAssociate Professor of Surgery, Divisions of Endocrine Surgery and Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, CT
      • SAMANTHA M. THOMAS, MSBiostatistician, Department of Biostatistics & Bioinformatics, Duke Cancer Institute, Durham, NC
      • APRIL K.S. SALAMA, MDAssistant Professor of Medicine, Division of Medical Oncology, Duke University School of Medicine, Durham, NC

      A clinical trial is a planned experiment designed to prospectively measure the efficacy or effectiveness of an intervention by comparing outcomes in a group of subjects treated with the test intervention with those observed in one or more comparable group(s) of subjects receiving another intervention.  Historically, the gold standard for a clinical trial has been a prospective, randomized, double-blind study, but it is sometimes impractical or unethical to conduct such in clinical medicine and surgery. Conventional outcomes have traditionally been clinical end points; with the rise of new technologies, however, they are increasingly being supplemented and/or replaced by surrogate end points, such as serum biomarkers. Because patients are involved, safety considerations and ethical principles must be incorporated into all phases of clinical trial design, conduct, data analysis, and presentation. This review covers the history of clinical trials, clinical trial phases, ethical issues, implementing the study, basic biostatistics for data analysis, and other resources. Figures show drug development and clinical trial process, and type I and II error. Tables list Food and Drug Administration new drug application types, and types of missing data in clinical trials.

      This review contains 2 figures, 3 tables, and 38 references

      Keywords: Clinical trial, study design, type I error, type II error, double-blind study, ethics

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    • 3

      Complementary, Alternative, and Integrative Medicine

      By Helene M. Langevin, MD
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      Complementary, Alternative, and Integrative Medicine

      • HELENE M. LANGEVIN, MDDirector, Osher Center for Integrative Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

      Complementary and alternative medicine (CAM) refers to a group of diverse medical and health care systems, practices, and products that are not considered to be part of conventional or allopathic medicine. Common CAM practices (e.g., acupuncture, meditation, and therapeutic massage) are gradually becoming incorporated into conventional care in response to patients looking to alternative sources for information and advice about health matters and increased understanding of various CAM methods through evidence-based testing. However, although the claims of some methods are supported with academic research, well-founded concerns remain in many popularized CAM practices regarding the lack of evidence and placebo effects. It is thus imperative for physicians to be comfortable in discussing CAM-related topics with patients and be able to appropriately and informatively guide them in a way that harnesses potential benefits and avoids potential harm. In this review, the major CAM therapies in the United States are examined, including the settings in which they are being used, evidence base status, and efficacy of some of the most commonly used modalities. 

      This review contains 5 figures, 21 tables, and 123 references.

      Keywords: Alternative medicine, complementary medicine, acupuncture, homeopathy, osteopathy, chiropractic, massage therapy, naturopathy

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    • 4

      Clinical Trial Design and Statistics

      By Julie Ann Sosa, MA, MD, FACS; Samantha M. Thomas, MS; April K.S. Salama, MD
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      Clinical Trial Design and Statistics

      • JULIE ANN SOSA, MA, MD, FACSAssociate Professor of Surgery, Divisions of Endocrine Surgery and Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, CT
      • SAMANTHA M. THOMAS, MSBiostatistician, Department of Biostatistics & Bioinformatics, Duke Cancer Institute, Durham, NC
      • APRIL K.S. SALAMA, MDAssistant Professor of Medicine, Division of Medical Oncology, Duke University School of Medicine, Durham, NC
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  • Nephrology and Urology
    • 1

      Approach to Acid-base Disorders

      By Horacio J Adrogué, MD; Nicolaos E Madias, MD
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      Approach to Acid-base Disorders

      • HORACIO J ADROGUÉ, MD
      • NICOLAOS E MADIAS, MD

      This review on the approach to acid-base disorders uses the physiologic approach to assessing acid-base status, namely that based on the H2CO3/[HCO3] buffer pair. A simple acid-base disorder is characterized by a primary abnormality in either carbon dioxide tension (Pco2) or serum [HCO3] accompanied by the appropriate secondary response in the other component. The four cardinal, simple acid-base disorders are categorized into respiratory disorders and metabolic disorders. Respiratory disorders are expressed as primary changes in Pco2 and include respiratory acidosis or primary hypercapnia (primary increase in Pco2) and respiratory alkalosis or primary hypocapnia (primary decrease in Pco2). Metabolic disorders are expressed as primary changes in serum [HCO3]) and include metabolic acidosis (primary decrease in serum [HCO3]) and metabolic alkalosis (primary increase in serum [HCO3]). A mixed acid-base disorder denotes the simultaneous occurrence of two or more simple acid-base disorders. Arriving at an accurate acid-base diagnosis rests with assessment of the accuracy of the acid-base variables, calculation of the serum anion gap, and identification of the dominant acid-base disorder and whether a simple or mixed disorder is present. Identifying the cause of the acid-base disorder depends on a detailed history and physical examination as well as obtaining additional testing, as appropriate.  

      Key words: acid-base disorders; simple disorders; mixed disorders; anion gap; physiologic approach; physicochemical approach; base-excess approach

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    • 2

      Acute Kidney Injury - Part I

      By Paul W Sanders, MD, FACP; Anupam Agarwal, MD, FASN
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      Acute Kidney Injury - Part I

      • PAUL W SANDERS, MD, FACPProfessor and Director, Nephrology Research and Training Center, University of Alabama at Birmingham, Chief, Renal Section, Birmingham Veterans Affairs Medical Center, Birmingham, AL
      • ANUPAM AGARWAL, MD, FASNProfessor and Director, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL

      Acute renal failure (ARF) has been defined as a syndrome in which an abrupt decrease in renal function produces retention of nitrogenous waste products. Translating this abstract description into a clinically useful, accurate, and widely accepted definition has been challenging, in large part because of the focus on serum creatinine concentration, which is easily obtained but has the inherent limitation of poor detection of rapid or subtle, but clinically important, changes in the glomerular filtration rate (GFR). In recent years, therefore, the term acute kidney injury (AKI) has replaced ARF because AKI denotes the entire clinical spectrum from mild increases in serum creatinine to overt renal failure. AKI is defined by the Risk-Injury-Failure-Loss-ESRD (RIFLE) criteria, based on serum creatinine concentration and urine flow rate. The Acute Kidney Injury Network (AKIN) subsequently modified the definition further and divided AKI into three stages. This chapter includes discussions of the etiology and diagnosis of AKI in hospitalized patients and community-acquired AKI. The specific causes, management, and complications of AKI are also discussed. Figures illustrate the pathophysiologic classification of AKI and the effect of hyperkalemia on cardiac conduction—electrocardiogram (ECG) changes. A worksheet for following patients with AKI is provided. 

      This review contains 3 figures, 21 tables, and 46 references

      Keywords: Acute kidney injury, dialysis, contrast, rhabdomyolysis, nephropathy, urinalysis, multiple myeloma, ethylene glycol, sepsis, hepatorenal syndrome

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    • 3

      Acute Kidney Injury - Part II: Special Situations

      By Paul W Sanders, MD, FACP; Anupam Agarwal, MD, FASN
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      Acute Kidney Injury - Part II: Special Situations

      • PAUL W SANDERS, MD, FACPProfessor and Director, Nephrology Research and Training Center, University of Alabama at Birmingham, Chief, Renal Section, Birmingham Veterans Affairs Medical Center, Birmingham, AL
      • ANUPAM AGARWAL, MD, FASNProfessor and Director, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL

      Acute renal failure (ARF) has been defined as a syndrome in which an abrupt decrease in renal function produces retention of nitrogenous waste products. Translating this abstract description into a clinically useful, accurate, and widely accepted definition has been challenging, in large part because of the focus on serum creatinine concentration, which is easily obtained but has the inherent limitation of poor detection of rapid or subtle, but clinically important, changes in the glomerular filtration rate (GFR). In recent years, therefore, the term acute kidney injury (AKI) has replaced ARF because AKI denotes the entire clinical spectrum from mild increases in serum creatinine to overt renal failure. AKI is defined by the Risk-Injury-Failure-Loss-ESRD (RIFLE) criteria, based on serum creatinine concentration and urine flow rate. The Acute Kidney Injury Network (AKIN) subsequently modified the definition further and divided AKI into three stages. This part of the AKI review specifically discusses special situations: rhabdomyolysis, aristolochic acid nephropathy, acute urate nephropathy, acute phosphate nephropathy, AKI in multiple myeloma, ehytlene glycol poisoning, contrast-induced nephropathy, AKI in sepsis, hepatorenal syndrome, and AKI in pregnancy.

      This review contains 10 tables, and 47 references.

      Keywords:Acute kidney injury, dialysis, contrast, rhabdomyolysis, nephropathy, urinalysis, multiple myeloma, ethylene glycol, sepsis, hepatorenal syndrome

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    • 4

      Vascular Diseases of the Kidney

      By Ronald J. Falk, MD, FACP; Julieanne G McGregor, MD; Vimal K Derebail, MD, MPH; Abhijit V. Kshirsagar, MD, MPH
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      Vascular Diseases of the Kidney

      • RONALD J. FALK, MD, FACPAllan Brewster Distinguished Professor of Medicine; Chief, Division of Nephrology and Hypertension; Director, UNC Kidney Center, Department of Medicine, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC
      • JULIEANNE G MCGREGOR, MDAssistant Professor, Department of Medicine, Division of Nephrologyand Hypertension, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC
      • VIMAL K DEREBAIL, MD, MPHAssistant Professor, Department of Medicine, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC
      • ABHIJIT V. KSHIRSAGAR, MD, MPHAssociate Professor, Department of Medicine, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC

      A number of local and systemic disease processes affect the renal vascular tree. Although the underlying mechanisms may differ, vascular diseases of the kidney all characteristically cause varying degrees of vessel obstruction, eventually leading to an impairment of renal blood flow. Acute impairment in renal function occurs in most vascular diseases of the kidney. This chapter discusses the major vascular diseases of the kidney, categorized according to the size of the affected vessel. Large-vessel diseases described are renal artery stenosis from atherosclerosis and fibromuscular dysplasia, Takayasu arteritis, and renal vein thrombosis. Medium-size-vessel diseases described are polyarteritis nodosa and Kawasaki disease. Small-vessel diseases described are those traditionally associated with glomerulopathy, including rapidly progressive glomerulonephritis and Henoch-Schönlein purpura; thrombotic microangiopathy, including thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, preeclampsia, antiphospholipid syndrome, systemic sclerosis, and malignant hypertension; sickle cell disease; and atheroembolic disease. Tables describe the American College of Rheumatology classification criteria for Takayasu arteritis and induction therapy for rapidly progressive glomerulonephritis. Figures show an overview of vascular disease of the kidney; an arteriogram of renal artery stenosis demonstrating an ostial lesion; light microscopy showing typical crescentic glomerulonephritis; purpuric eruptions in small vessel vasculitides, Henoch-Schönlein purpura, hypersensitivity vasculitis, and antineutrophil cytoplasmic autoantibody–associated disease; light microscopy showing the characteristic onion-skin lesion in scleroderma renal crisis; electron microscopy showing a glomerular capillary with thrombotic thrombocytopenic purpura; injection microradioangiograms comparing the vasa recta of a normal kidney with that in a patient with sickle cell disease; and a light microscopy that reveals an atheroembolus lodged in a small renal artery and occlusion of the vascular lumen. This chapter contains 151 references.

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    • 5

      Urinalysis

      By Gautam Kishore Valecha , MBBS; Rafeel Syed, MD; Amina Rehman, MBBS; Suzanne El-Sayegh, MD
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      Urinalysis

      • GAUTAM KISHORE VALECHA , MBBSResident, Department of Medicine, Staten Island University Hospital, Staten Island, NY
      • RAFEEL SYED, MDFellow, Department of Nephrology, Staten Island University Hospital, Staten Island, NY
      • AMINA REHMAN, MBBSClinical Research Volunteer, Department of Medicine, Staten Island University Hospital, Staten Island, NY
      • SUZANNE EL-SAYEGH, MDProgram Director, Department of Medicine, Staten Island University Hospital, Staten Island, NY

      Urinalysis comprises physical, chemical, and microscopic examination of urine. Although widely available, this test is often underused and misinterpreted. Urinalysis can provide helpful clues in the assessment of a variety of clinical conditions, but one must be aware of their limitations. On proper collection, the sample must be analyzed ideally within 2 hours. Dipstick urinalysis is convenient and commonly performed but provides qualitative or semiquantitative assessment only, and its results can be affected by urine discoloration and the presence of various other substances. Finally, urine microscopy is an important component of urinalysis used to identify various structures such as crystals, cells, microorganisms, and casts, which in turn helps in the assessment of the underlying disease. In this review, we discuss the clinical implications of various findings on urinalysis. Additionally, we also highlight the importance of proper sample collection and examination techniques to optimize the diagnostic yield of this invaluable test.

      This review contains 1 highly rendered figure, 5 tables, and 53 references.

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    • 6

      Urinary Incontinence and Overactive Bladder Syndrome

      By Kristie A. Greene, MD; Lennox Hoyte, MD, MSEECS
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      Urinary Incontinence and Overactive Bladder Syndrome

      • KRISTIE A. GREENE, MDFellow, Female Pelvic Medicine and Reconstructive Surgery, University of South Florida College of Medicine, Tampa General Hospital, Tampa, FL
      • LENNOX HOYTE, MD, MSEECSAssociate Professor and Director, Female Pelvic Medicine and Reconstructive Surgery, University of South Florida College of Medicine, Director, Urogynecology, and TGH-Pelvic Floor Disorders Group, Tampa General Hospital, Tampa, FL

      Urinary incontinence falls into two broad categories: stress incontinence and urge incontinence. Stress urinary incontinence occurs when urethral closure pressure cannot increase sufficiently to compensate for a sudden increase in intra-abdominal pressure, as from a cough or Valsalva maneuver. Urge urinary incontinence occurs when an unintended bladder contraction creates an insuppressible urge to void, leading to urinary leakage. When women have signs and/or symptoms of both stress and urge incontinence, it is referred to as mixed urinary incontinence. Overactive bladder syndrome is defined by the Standardization Subcommittee of the International Continence Society (ICS) as urinary urgency, with or without urge incontinence and usually with frequency and nocturia. Nocturia, which is often associated with urinary frequency, is defined as a need to urinate that awakens the person during the night. This chapter discusses the epidemiology and physiology of urinary incontinence and overactive bladder syndrome in women, as well as diagnosis and treatment. Tables list foods and beverages that may cause urinary frequency and urgency; features of urge incontinence, stress incontinence, and mixed incontinence; American Urologic Association (AUA) guidelines regarding level of evidence and indications for adult urodynamics; and currently available antimuscarinic drugs and their dosages, selectivity, efficacy, and side effects. Figures depict the journal of someone with mixed incontinence, a typical urodynamics suite, a urodynamic study of someone with detrusor overactivity, incontinence pessaries, and transobturator and retropubic slings.

      This review contains 5 figures, 5 tables, and 44 references.

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    • 7

      Chronic Kidney Failure and Dialysis

      By Raghu V Durvasula, MD; Jonathan Himmelfarb, MD
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      Chronic Kidney Failure and Dialysis

      • RAGHU V DURVASULA, MDAssistant Professor of Medicine, Department of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA
      • JONATHAN HIMMELFARB, MDDepartment of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA

      Chronic kidney disease (CKD) is a clinical syndrome arising from progressive kidney injury, formerly known as chronic renal failure, chronic renal disease, and chronic renal insufficiency. It is classified into five stages based primarily on glomerular filtration rate (GFR). This article discusses the epidemiology of CKD and end-stage renal disease (ESRD), as well as etiology and genetics, pathophysiology, and pathogenesis. The section on diagnosis looks at clinical manifestations and physical findings, laboratory (and other) tests, imaging studies, and biopsy. A short section on differential diagnosis is followed by a discussion of treatment, including hemodialysis and peritoneal dialysis. Long-term complications of patients on dialysis include cardiovascular disease, renal osteodystrophy, dialysis-related amyloidosis, and acquired cystic disease (renal cell carcinoma). The final section addresses prognosis and socioeconomic burden. Figures include the classification system for CKD, prevalence of CKD in the United States, rising prevalence, risk of, and leading causes of ESRD in the United States, plus the changing prevalence of ESRD over time, clinical manifestations of uremia, and an overview of hemodialysis circuit. Tables look at the burden of CKD relative to other chronic disorders, the specific hereditary causes of kidney disease, and situations when serum creatinine does not accurately predict GFR. Other tables list equations for estimating GFR, the causes of CKD without shrunken kidneys, and clinical features distinguishing chronic kidney disease from acute kidney injury. ESRD and indications for initiation of dialysis are presented, as well as typical composition of dialysate and reasons for failure of peritoneal dialysis.

      This review contains 8 figures, 17 tables and 77 references

      Keywords: Renal disease, chronic kidney disease, hemodialysis, peritoneal dialysis, end-stage renal disease, glomerular filtration rate, mineral bone disease

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    • 8

      Nephrolithiasis

      By José Luiz Nishiura, MD, PhD; Ita Pfeferman Heilberg, MD, PhD
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      Nephrolithiasis

      • JOSÉ LUIZ NISHIURA, MD, PHDAssociate Researcher, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.
      • ITA PFEFERMAN HEILBERG, MD, PHDAssociate Professor, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.

      Nephrolithiasis is a highly prevalent condition, but its incidence varies depending on race, gender, and geographic location. Approximately half of patients form at least one recurrent stone within 10 years of the first episode. Renal stones are usually composed of calcium salts (calcium oxalate monohydrate or dihydrate, calcium phosphate), uric acid, or, less frequently, cystine and struvite (magnesium, ammonium, and phosphate). Calcium oxalate stones, the most commonly encountered ones, may result from urinary calcium oxalate precipitation on the Randall plaque, which is a hydroxyapatite deposit in the interstitium of the kidney medulla. Uric acid nephrolithiasis, which is common among patients with metabolic syndrome or diabetes mellitus, is caused by an excessively acidic urinary pH as a renal manifestation of insulin resistance. The medical evaluation of the kidney stone patient must be focused on identifying anatomic abnormalities of the urinary tract, associated systemic diseases, use of lithogenic drugs or supplements, and, mostly, urinary risk factors such as low urine volume, hypercalciuria, hyperuricosuria, hypocitraturia, hyperoxaluria, and abnormalities in urine pH that can be affected by dietary habits, environmental factors, and genetic traits. Metabolic evaluation requires a urinalysis, stone analysis (if available), serum chemistry, and urinary parameters, preferably obtained by two nonconsecutive 24-hour urine collections under a random diet. Targeted medication and dietary advice are effective to reduce the risk of recurrence. Clinical, radiologic, and laboratory follow-ups are needed to prevent stone growth and new stone formation, to assess treatment adherence or effectiveness to dietary recommendations, and to allow adjustment of pharmacologic treatment.

      This review contains 5 figures, 3 tables, and 107 references.

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    • 9

      Management of Chronic Kidney Disease and Its Complications

      By Joshua S. Hundert, MD; Ajay K Singh, MBBS, FRCP (UK), MBA
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      Management of Chronic Kidney Disease and Its Complications

      • JOSHUA S. HUNDERT, MDClinical Fellow, Department of Medicine, Division of Nephrology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
      • AJAY K SINGH, MBBS, FRCP (UK), MBAAssociate Professor of Medicine, Associate Dean for Global Education and Continuing Education, Harvard Medical School, Director, Continuing Medical Education, Department of Medicine and Renal Division, Brigham and Women’s Hospital, Boston, MA

      Management of early renal failure helps in the reduction or prevention of end-stage renal disease. The monitoring of renal function is discussed, and the chapter includes a table that shows commonly used methods for monitoring. Risk factors for chronic renal failure include stroke and cardiac disease. Risk factors for renal disease progression are diabetes mellitus, hypertension, proteinuria, smoking, protein intake, and hyperlipidemia. Complications of chronic renal failure that are addressed include sodium and water imbalance, potassium imbalance, acidosis, calcium and phosphorus imbalance, and anemia. There is also a section that discusses the case for early referral to a nephrologist. Tables present the equations used to estimate the glomerular filtration rate (GFR); stages of chronic kidney disease and the appropriate steps in their management; risk factors for chronic kidney disease in which the testing of proteinuria and estimation of GFR are indicated; appropriate diet for patients who have chronic kidney disease; and guidelines for diagnosing and treating anemia resulting from chronic kidney disease. An algorithm outlines the steps in management of calcium and phosphate in patients with kidney disease.

      This review contains 3 figures, 10 tables and 50 references

      Key Words End-stage renal disease, chronic kidney disease, glomerular filtration rate, Modification of Diet in Renal Disease, Proteinuric renal disease, Hyperuricemia

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    • 10

      Benign Prostatic Hyperplasia

      By Michael J Barry, MD, FACP
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      Benign Prostatic Hyperplasia

      • MICHAEL J BARRY, MD, FACPPhysician Medical Services, Massachusetts General Hospital, Clinical Professor of Medicine, Harvard Medical School, Boston, MA

      Benign prostatic hyperplasia (BPH) is a common cause of morbidity in older men in developed countries. BPH causes lower urinary tract symptoms (LUTS) and occasionally results in such complications as acute urinary retention (AUR), urinary tract infection, and even obstructive uropathy. Although the development of medical treatments has reduced the role of surgery, prostatectomy remains a widely performed procedure. Epidemiology, risk factors, and pathophysiology are discussed. Diagnosis includes clinical features, history, physical examination, and laboratory testing. Management can include watchful waiting, medical treatment, surgery, and minimally invasive treatment. Management of AUR is also addressed. 

      This review contains 4 figures, 10 tables, and 58 references.

      Keywords: Benign prostatic hyperplasia, lower urinary tract symptoms, urinary retention, incontinence, alpha blocker, 5α-reductase inhibitor, cystoscopy, transurethral intervention

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    • 11

      Pharmacologic Approach to Renal Insufficiency

      By Ali J. Olyaei, PharmD; William M. Bennett, MD
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      Pharmacologic Approach to Renal Insufficiency

      • ALI J. OLYAEI, PHARMD
      • WILLIAM M. BENNETT, MDMedical Director, Legacy Transplant Services, Professor of Pharmacy Practice, Legacy Good Samaritan Medical Center, Oregon State University, Portland, OR

      Prescribing drugs in patients with kidney disease is complex: drug dosing needs to be adjusted by the stage of kidney disease (whether chronic kidney disease [CKD] stages 1 through 5 or acute kidney injury [AKI] stages 1 through 3); because potential interactions with other agents that are being used need to be considered; and because of the possibility of extracorporeal treatment that might need to be used (e.g., continuous renal replacement therapy [CRRT], peritoneal dialysis [PD], or hemodialysis [HD]). Besides this complexity, there has been an explosion in the classes of new agents and the routes of delivery of these agents. The purpose of this chapter is to review the basic pharmacokinetic and pharmacologic principles that should guide therapy and to summarize basic recommendations for patients with CKD and AKI. The general principles for drug dosing in CKD and AKI include pharmacokinetics in renal failure; bioavailability; volume of distribution; protein binding; and biotransformation. A stepwise approach to dosage adjustment is described and created as an algorithmic approach. Drug dosing considerations in dialysis patients and in AKI patients are covered as well.
      This chapter contains 2 algorithms, 7 tables, 25 references, 5 Board-styled MCQs, and 1 Teaching Slide Set.

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    • 12

      Disorders of Water and Sodium Balance: Hyponatremia

      By Danilea M. Carmona Matos, MS; Herbert Chen, MD, FACS
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      Disorders of Water and Sodium Balance: Hyponatremia

      • DANILEA M. CARMONA MATOS, MSMedical Student, San Juan Bautista School of Medicine, Caguas, PR
      • HERBERT CHEN, MD, FACSChairman, Department of Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, AL

      Disorders of water and sodium balance are common in clinical practice. To better assess them, we must have a clear understanding of water-electrolyte homeostasis and renal function. The following review goes over practical equations necessary for electrolyte balance analysis as well as the foundations of renal physiology. Emphasis is placed on the understanding of sodium transport and its physiologic and pharmacologic regulation. In addition, we explore the most common electrolyte imbalance affecting up to 28% of hospitalized patients: hyponatremia (ie, low sodium concentration). Hyponatremia has been found in several acute and chronic clinical scenarios including postoperative, drug-induced, and exercise-associated hyponatremia. However, it is not uncommon to find this disorder coexisting with other diseases such as syndrome of inappropriate secretion of antidiuretic hormone (SIADH), acquired immunodeficiency syndrome (AIDS), cancer, and in rare cases, hypothyroidism. To better understand this disorder, the etiology, diagnosis with clinical manifestations and laboratory values, and treatment options are explored.

      This review contains 9 figures, 9 tables, and 53 references

      Keywords: aldosterone, antidiuretic hormone, body fluids, electrolyte balance, hyponatremia, hypovolemia, osmolality, sodium transport, vasopressin

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    • 13

      Disorders of Water and Sodium Balance: Hypernatremia

      By Danilea M. Carmona Matos, MS; Herbert Chen, MD, FACS
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      Disorders of Water and Sodium Balance: Hypernatremia

      • DANILEA M. CARMONA MATOS, MSMedical Student, San Juan Bautista School of Medicine, Caguas, PR
      • HERBERT CHEN, MD, FACSChairman, Department of Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, AL

      Hypernatremia is an electrolyte disorder most prevalent in the elderly and the critically ill, with over 60% of cases developing over the course of an inpatient stay. Characterized by elevated serum sodium concentrations, this disorder is manifested either by pure-water loss without replacement, or excessive sodium intake without appropriate water balance. Left untreated it may lead to seizures and coma. General treatment in the case of severe hypernatremia is infusion of isotonic saline followed by pure-water after the patient is stabilized. Further treatment of the underlying cause may involve diuretics, thiazides, and a variety of other medications in conjunction with dietary and lifestyle modifications. This review offers an overview of various disorders of water balance: diabetes insipidus, nephrotic syndrome, cirrhosis, idiopathic edema, and volume depletion, as well as their clinical presentations, lab tests, and management.

      This review contains 1 figure, 5 tables, and 26 references

      Keywords: Hypernatremia, Edematous States , Diabetes insipidus, Volume Depletion, Cirrhosis, Diuretics

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    • 14

      Peritoneal Dialysis

      By Karlien François, MD; Joanne M. Bargman, MD, FRCPC
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      Peritoneal Dialysis

      • KARLIEN FRANÇOIS, MDDivision of Nephrology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium
      • JOANNE M. BARGMAN, MD, FRCPCDivision of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada

      In peritoneal dialysis (PD), the peritoneum serves as a biological dialyzing membrane. The endothelium of the vast capillary network perfusing the peritoneum functions as a semipermeable membrane and allows bidirectional solute and water transfer between the intravascular space and dialysate fluid dwelling in the peritoneal cavity. PD is a renal replacement strategy for patients presenting with end-stage renal disease. It can also be offered for ultrafiltration in patients with diuretic-resistant fluid overload even in those without advanced renal failure. PD can also be used for patients with acute kidney injury, although in the developed world this occurs rarely compared to the use of extracorporeal therapies.

      This review contains 9 videos,  8 figures, 4 tables, and 73 references. 

      Keywords: peritoneal dialysis, peritoneal cavity, catheter, dialysis fluid, ultrafiltration, tunnel infection, osmotic pressure, renal failure

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    • 15

      Nephrolithiasis

      By José Luiz Nishiura, MD, PhD; Ita Pfeferman Heilberg, MD, PhD
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      Nephrolithiasis

      • JOSÉ LUIZ NISHIURA, MD, PHDAssociate Researcher, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.
      • ITA PFEFERMAN HEILBERG, MD, PHDAssociate Professor, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.
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    • 16

      Acute Kidney Injury - Part I

      By Paul W Sanders, MD, FACP; Anupam Agarwal, MD, FASN
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      Acute Kidney Injury - Part I

      • PAUL W SANDERS, MD, FACPProfessor and Director, Nephrology Research and Training Center, University of Alabama at Birmingham, Chief, Renal Section, Birmingham Veterans Affairs Medical Center, Birmingham, AL
      • ANUPAM AGARWAL, MD, FASNProfessor and Director, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL
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    • 17

      Disorders of Acid-base and Potassium Balance

      By Stuart L Linas, MD, FACP
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      Disorders of Acid-base and Potassium Balance

      • STUART L LINAS, MD, FACPProfessor of Medicine, University of Colorado Denver, Denver, CO

      Water accounts for approximately half of an adult human's body weight. Two thirds of body water is intracellular, and the remaining one third is contained in the extracellular fluid compartment, which includes intravascular (plasma) and interstitial fluid. Small amounts of water are also contained in bone, dense connective tissue, digestive secretions, and cerebrospinal fluid. To maintain stability of the internal milieu, body fluids are processed by the kidney, guided by intricate physiologic control systems that regulate fluid volume and composition. This chapter reviews the principles of body fluid hemostasis and discusses disorders of water excess (hyponatremia), water deficiency (hypernatremia), water conservation (diabetes insipidus), saltwater excess (edematous states), and saltwater deficiency (volume depletion). Figures illustrate the relation between the plasma hydrogen ion concentration and the blood pH, proximal tubular bicarbonate reabsorption, renal secretion of hydrogen ions, renal glutamine metabolism and ammonia diffusion, metabolic alkalosis, and the electrocardiographic changes in and approach to causes of hypokalemia and hyperkalemia. Tables describe causes of metabolic acidosis with a high and a normal ion gap; causes of type 1 renal tubular acidosis; causes of type 4 renal tubular acidosis and aldosterone resistance; causes of metabolic alkalosis, respiratory acidosis, and respiratory alkalosis; evaluation of the renal defect in hyperkalemia; and treatment of hyperkalemia.

      This chapter contains 10 figures, 12 tables, and 53 references.

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    • 18

      Disorders of Acid-base and Potassium Balance

      By Stuart L Linas, MD, FACP
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      Disorders of Acid-base and Potassium Balance

      • STUART L LINAS, MD, FACPProfessor of Medicine, University of Colorado Denver, Denver, CO
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    • 19

      Chronic Kidney Failure and Dialysis

      By Raghu V Durvasula, MD; Jonathan Himmelfarb, MD
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      Chronic Kidney Failure and Dialysis

      • RAGHU V DURVASULA, MDAssistant Professor of Medicine, Department of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA
      • JONATHAN HIMMELFARB, MDDepartment of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA
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    • 20

      Disorders of Water and Sodium Balance: Hyponatremia

      By Danilea M. Carmona Matos, MS; Herbert Chen, MD, FACS
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      Disorders of Water and Sodium Balance: Hyponatremia

      • DANILEA M. CARMONA MATOS, MSMedical Student, San Juan Bautista School of Medicine, Caguas, PR
      • HERBERT CHEN, MD, FACSChairman, Department of Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, AL
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    • 21

      Disorders of Water and Sodium Balance: Hypernatremia

      By Danilea M. Carmona Matos, MS; Herbert Chen, MD, FACS
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      Disorders of Water and Sodium Balance: Hypernatremia

      • DANILEA M. CARMONA MATOS, MSMedical Student, San Juan Bautista School of Medicine, Caguas, PR
      • HERBERT CHEN, MD, FACSChairman, Department of Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, AL
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  • Neurology
    • 1

      Pain Syndromes Other Than Headache

      By Edgar L. Ross, MD
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      Pain Syndromes Other Than Headache

      • EDGAR L. ROSS, MD

      Pain is experienced within a complex biologic, emotional, psychological, and social context that may defy physical examination, diagnostic procedures, and laboratory tests. This chapter aims to empower internists to improve their medical practices in pain management. It provides a scientific background that covers nociception and how sensory processing occurs at multiple levels in the body. Clinical assessment is detailed, as well as diagnostic categories that include mixed or uncertain chronic pain syndromes (back pain, fibromyalgia, postamputation pain, pain from cancer and bone) and neuropathic pain syndromes (polyneuropathy, mononeuropathy multiplex, ganglionopathy, genetic disorders, focal and regional syndromes). Treatment of chronic pain can be surgical or interventional. Pharmacologic treatment for acute and chronic nociceptive pain includes special considerations for geriatric and terminal patients. For treatment of neuropathic pain, medications are the major component. One tables lists iatrogenic nerve injuries that can cause posttraumatic neuralgia and complex regional pain syndrome. Other tables detail stepwise pharmacologic management of neuropathic pain and cite recommendations on opioid use from the Centers for Disease Control and Prevention. One figure illustrates how pain transducers monitor and influence tissue conditions. Other figures show sensory processing in the spinal cord dorsal horn, physical findings in the feet of patients with bilateral foot pain from small-fiber polyneuropathy, illustrate how examination can identify specific nerve injuries causing chronic pain, and provide classification of chronic pain syndromes. This chapter contains 82 references.

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    • 2

      Difficult to Treat (refractory) Chronic Migraine: Outpatient Approaches

      By Lawrence Robbins, MD, (retired)
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      Difficult to Treat (refractory) Chronic Migraine: Outpatient Approaches

      • LAWRENCE ROBBINS, MD, (RETIRED) Assistant Professor of Neurology, Dept. of Neurology, University of Illinois; (retired) Assistant Professor of Neurology, Dept. of Neurology, Rush Medical College, Chicago, Il

      This comprehensive review addresses the many challenges in treating refractory migraine. Issues relating to pathophysiology are covered. A unique “refractory scale for migraine patients” is introduced. The definition and role of medication overuse headache are presented with a much different perspective than is usually found. Issues outside of medication that are covered include active coping, acceptance, resilience, and catastrophizing. A number of outpatient treatments are thoroughly discussed. These include the role of onabotulinum toxin, the application of polypharmacy, when to employ sphenopalatine ganglion  blocks, the role of occipital and trigger-point injections, the implementation of long-acting opioids, the advantages of stimulants, and the possible use of monoamine oxidase inhibitors. Miscellaneous approaches include muscle relaxants, nasal or intravenous ketamine, transcranial magnetic stimulation, memantine, and ergonovine. Finally, many cutting-edge “refractory clinical pearls” are listed. 

      This review contains 8 highly rendered figures, 4 tables, and 25 references.

      Key Words: Headache, migraine, chronic, refractory, medication overuse, alternative, treatments

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    • 3

      Clinical Aspects of Non-alzheimer Disease Dementias

      By David Knopman, MD
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      Clinical Aspects of Non-alzheimer Disease Dementias

      • DAVID KNOPMAN, MDProfessor of Neurology, Department of Neurology, Mayo Clinic, Rochester, MN

      There are a relatively small number of disorders that account for the majority of dementia in the elderly that is not Alzheimer disease (AD): cerebrovascular disease, Lewy body disease (α-synucleinopathies), and the frontotemporal lobar degenerations. Cerebrovascular disease and Lewy body disease account for most non-AD dementia among persons in the eighth decade of life and beyond. These two frequently co-occur with AD but can occur in their pure forms rarely (in the case of dementia associated with cerebrovascular disease) or more commonly (in the case of Lewy body disease). There is no one cognitive or behavioral syndrome associated with cerebrovascular disease; however, attempts to isolate a common theme suggest that cognitive slowing is typical of cerebrovascular contributions to cognitive impairment. Cerebrovascular pathology relevant to cognitive impairment accumulates subclinically more commonly than it causes acute, strokelike declines in cognition. Dementia with Lewy bodies is a multidimensional disorder that includes a nonamnestic dementia, Parkinson disease or at least some parkinsonian features, a disorder of sleep and wakefulness, autonomic disturbances, and depression. The disorders of sleep prominently include rapid eye movement sleep behavior disorder, excessive daytime sleepiness, visual hallucinations, and marked fluctuations in level of alertness. The frontotemporal lobar degenerations are nearly as common as causes of dementia in persons under age 65 as is AD. The group of disorders includes two cognitive syndromes (primary progressive aphasia and behavior variant frontotemporal dementia) and two neuropathologic subtypes (tauopathy and TDP43 proteinopathy) and is associated with three major autosomal dominant genetic mutations (in MAPT, GRN,and C9ORF72).

      Key words: dementia with Lewy bodies, frontotemporal lobar degenerations, vascular cognitive impairment

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    • 4

      Neuromuscular Junction Disorders

      By Anthony A Amato, MD; Mohammad Kian Salajegheh, MD
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      Neuromuscular Junction Disorders

      • ANTHONY A AMATO, MDChief, Division of Neuromuscular Disease, Department of Neurology, Brigham and Women’s Hospital, Professor of Neurology, Harvard Medical School, Boston, MA
      • MOHAMMAD KIAN SALAJEGHEH, MDDirector, Peripheral Nerve Clinic, Associate Neurologist, Department of Neurology, Brigham and Women’s Hospital, Assistant Professor of Neurology, Harvard Medical School, Boston, MA

      The three main components of the neuromuscular junction (NMJ) include the presynaptic region, the synaptic cleft, and the postsynaptic region. The NMJ acts as an interface between the motor nerve and muscle by converting the motor nerve electric currents into chemical signals and then back into electric currents in the muscle. This chapter reviews electrodiagnostic testing in NMJ disorders, including repetitive nerve stimulation and single-fiber electromyography. Myasthenia gravis, congenital myasthenic syndromes, Lambert-Eaton myasthenic syndrome, botulism, and organophosphate poisoning and other toxins are discussed, including epidemiology, etiology/genetics, pathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis. Tables include an overview of neuromuscular disorders, drugs with adverse effects on the NMJ, common immunomodulatory agents used for treatment of myasthenia gravis, congenital myasthenic syndromes, and toxins and venoms. Figures illustrate the NMJ structure and function, structure of the presynaptic and postsynaptic regions, electrodiagnostic studies in NMJ disorders, and dysfunction of the NMJ in acetylcholine receptor myasthenia gravis.

      This review contains 5 highly rendered figures, 5 tables, and 65 references.

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    • 5

      Multiple Sclerosis and Related Disorders

      By J William Lindsey, MD
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      Multiple Sclerosis and Related Disorders

      • J WILLIAM LINDSEY, MDProfessor, Department of Neurology, University of Texas Health Science Center at Houston, Houston, TX

      Multiple sclerosis (MS) is a relatively common cause of neurologic symptoms and disability in young adults. The distinguishing pathologic features of MS are loss of myelin and inflammation in the central nervous system (CNS). The myelin sheath is essential for rapid conduction of nerve signals along large-diameter axons. Oligodendrocytes produce and maintain myelin in the CNS, and Schwann cells produce and maintain myelin in the peripheral nerves. In addition to MS, there are a number of related disorders causing demyelination, inflammation, or both in the CNS. This chapter discusses MS and related disorders, including neuromyelitis optica, optic neuritis, acute disseminated encephalomyelitis, transverse myelitis, Behçet syndrome, neurosarcoidosis, inherited demyelinating diseases (leukodystrophies, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]), and virus-induced demyelination (progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis). The section on MS covers epidemiology, etiology/genetics, pathogenesis, diagnosis, differential diagnosis, management, and prognosis. Figures include organization of the microenvironment of larger-diameter axons, typical magnetic resonance imaging findings in MS and neuromyelitis optica, postgadolinium images of the cervical spine in MS, and an approach to treatment of relapsing-remitting MS. Tables list MS and related disorders, distribution of neurologic deficits at the onset of MS, differential diagnosis of MS, disease-modifying therapies for relapsing-remitting MS, and selected leukodystrophies, as well as diagnostic criteria and selected symptomatic therapies for MS.

      This review contains 3 highly rendered figures, 7 tables, and 82 references.

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    • 6

      Motor Neuron Diseases

      By Elena Ratti, MD; Merit E. Cudkowicz, MD, MSc; James D Berry, MD, MPH
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      Motor Neuron Diseases

      • ELENA RATTI, MDClinical Research Fellow, Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, MA
      • MERIT E. CUDKOWICZ, MD, MSCChief of Neurology, Massachusetts General Hospital, Julieanne Dorn Professor of Neurology Harvard Medical School, Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, MA
      • JAMES D BERRY, MD, MPHAssistant Professor of Neurology, Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, MA

      The motor neuron diseases (MNDs) are a family of diseases commonly categorized by their propensity to affect upper or lower motor neurons and by their mode of inheritance. The chapter provides some content on infectious MNDs caused by viral infections affecting the motor neurons in the anterior horn of the spinal cord. However, the chapter devotes most of its attention to the inherited and sporadically occurring MNDs. The majority of research into adult MND focuses on amyotrophic lateral sclerosis (ALS) due to its high prevalence, rapid progression, and phenotypical similarities between its inherited form and its sporadic form. As our knowledge of genetic mechanisms underlying ALS pathology has grown, common themes have emerged. These include abnormalities in RNA biology, axonal transport, protein folding, and inflammatory responses. These themes currently drive much of the direction in ALS experimental therapy development. It is clear that MND is complex and involves several different molecular pathways. Given this complexity, ALS might not be a single disease entity, and if this is the case, treatment approaches may need to be targeted to specific pathologies rather than all ALS patients on a broad scale. Chapter content is enhanced by tables outlining the types of MNDs, criteria for supporting a diagnosis, first-line workup, the genes associated with ALS, ALS efficacy outcome measures, symptom management of ALS, and spinal muscular atrophy classification. Mechanisms of ALS are illustrated, and clinical photographs demonstrate symptoms.

      This review contains 5 figures, 14 tables and 253 references

      Keywords: motor neuron disease, amyotrophic lateral sclerosis, electromyography, Guillain-Barré syndrome

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    • 7

      Parkinsonism and Related Disorders

      By Elizabeth J. Slow, MD, PhD; Anthony E. Lang, MD
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      Parkinsonism and Related Disorders

      • ELIZABETH J. SLOW, MD, PHDAssistant Professor, Morton and Gloria Shulman Movement Disorders Clinic and The Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University of Toronto, Toronto, ON
      • ANTHONY E. LANG, MDProfessor, Morton and Gloria Shulman Movement Disorders Clinic and The Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University of Toronto, Toronto, ON

      Parkinsonism describes the core clinical criteria of tremor, bradykinesia, rigidity, and postural instability. There is a large differential diagnosis, but the most common cause of parkinsonism is due to Parkinson disease. This review details the epidemiology, etiology/genetics, pathogenesis, diagnosis and differential diagnosis, management, and prognosis of Parkinson disease, dementia with Lewy bodies, progressive supranuclear palsy, corticobasal degeneration, vascular parkinsonism, normal pressure hydrocephalus, and drug-induced parkinsonism. 

      This review contains 8 figures, 32 tables, and 73 references.

      Keywords: Parkinson disease, parkinsonism, levodopa, cogwheel ridigity, multiple system atrophy, dementia, substantia nigra, palsy, neurodegenerative disease, hydrocephalus, Lewy body, Lewy neurite

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    • 8

      Dizziness

      By Kevin A. Kerber, MD, MS; Robert W. Baloh, MD
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      Dizziness

      • KEVIN A. KERBER, MD, MSAssistant Professor, Department of Neurology, University of Michigan, Ann Arbor, MI
      • ROBERT W. BALOH, MDProfessor, Departments of Neurology and Surgery (Head and Neck), UCLA Medical Center, Reed Neurological Research Center, Los Angeles, CA

      Dizziness is the quintessential symptom presentation in all of clinical medicine. It is a common reason that patients present to a physician. This chapter provides background information about the vestibular system, then reviews key aspects of history-taking and examination of the patient, then discusses specific disorders and common presentation types. Throughout the chapter the focus is on neurologic and vestibular disorders. Normal vestibular anatomy and physiology are discussed, followed by recommendations for history-taking and the physical examination. Specific disorders that cause dizziness are explored, along with common causes of non-specific dizziness. Common presentations are discussed, including acute severe dizziness, recurrent attacks, and recurrent positional vertigo. Finally, the chapter looks at laboratory investigations in diagnosis and management. Figures include population prevalence of dizziness symptoms, the anatomy of inner structures, primary afferent vestibular nerve activity, the head thrust test, the Dix-Hallpike maneuver, the supine positional test, the canalith repositioning procedure, and the barbecue roll maneuver. Tables list physiologic properties and clinical features of the components of the peripheral vestibular system, information to be acquired from history of the present illness, common symptoms patients report as dizziness, examination components, distinguishing among common peripheral and central vertigo syndromes, common causes of nonspecific dizziness, types of dizziness presentations, relevant imaging abnormalities on neuroimaging studies, vestibular testing components, and medical therapy for symptomatic dizziness.

      This review contains 8 highly rendered figures, 11 tables, and 69 references.

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    • 9

      Acute Ischemic Stroke and Transient Ischemic Attack

      By Lauren M. Nentwich, MD
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      Acute Ischemic Stroke and Transient Ischemic Attack

      • LAUREN M. NENTWICH, MDAssistant Professor, Department of Emergency Medicine, Boston University School of Medicine, Boston, MA

      Stroke is a sudden neurologic deficit attributed to an acute focal injury of the central nervous system (CNS) by a vascular cause, including either ischemia (87%) or hemorrhage (13%). Specifically, acute ischemic stroke (AIS) is an episode of neurologic dysfunction caused by focal cerebral, spinal, or retinal infarction, where infarction is defined as pathologic, imaging, clinical, or other objective evidence of focal ischemic cell death and injury in a defined vascular distribution. Conversely, a transient ischemic attack (TIA) is defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. A TIA is not a separate entity from AIS, but rather both AIS and TIA are on the spectrum of serious conditions caused by CNS ischemia. This review covers the pathophysiology, stabilization and assessment, diagnosis and treatment, and  disposition and outcomes of AIS and TIA. Figures show potential sources of cardioembolism, cerebrovascular anatomy and common sites of atherosclerosis, early computed tomographic (CT) findings in AIS and noncontrast head CT scan of a right putamenal intracerebral hemorrhage, magnetic resonance image (MRI) showing perfusion-diffusion mismatch in AIS, and intra-arterial thrombolysis for AIS.

      This review contains 5 figures, 11 tables, and 65 references.

      Key words Acute ischemic stroke, atheroembolism, cardioembolism, stroke, transient ischemic attack

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    • 10

      Intracerebral Hemorrhage

      By Natalie P. Kreitzer, MD; Opeolu Adeoye, MD, MS
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      Intracerebral Hemorrhage

      • NATALIE P. KREITZER, MDNeurocritical Care Fellow in Training, Department of Emergency Medicine, University of Cincinnati, Cincinnati, OH
      • OPEOLU ADEOYE, MD, MSAssociate Professor of Emergency Medicine and Neurocritical Care, University of Cincinnati, Cincinnati, OH

      Intracerebral hemorrhage can be classified as either secondary (due to trauma, vascular malformations, aneurysms, tumors, or hemorrhagic transformation of ischemic stroke) or primary (without a clear secondary cause). Intracerebral hemorrhage is a neurologic emergency, and leads to significant death and disability each year; care should be expedited and emergency departments should be equipped to appropriately care for and manage these patients. This review covers the risk factors, natural history, pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes for patients with intracerebral hemorrhage. Figures show head computed tomographic scans demonstrating a left basal ganglia intracerebral hemorrhage, and an algorithm of management of intracerebral hemorrhage in the emergency department. Tables list some common causes of intracerebral hemorrhage, Boston criteria for diagnosis of cerebral amyloid angiopathy, mechanism of action of common anticoagulants, and suggested reversal agents.


      This review contains 2 figures, 6 tables, and 59 references.

      Key words: Intracerebral hemorrhage; intracranial hemorrhage; intraparenchymal hemorrhage; hemorrhagic stroke; hypertensive hemorrhage; spontaneous intracerebral hemorrhage; ICH; cerebral bleeds


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    • 11

      Coma and Disorders of Consciousness

      By Jonathan A. Edlow, MD, FACEP; Nicole M Dubosh, MD
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      Coma and Disorders of Consciousness

      • JONATHAN A. EDLOW, MD, FACEPVice-Chairman of Emergency Medicine, Beth Israel Deaconess Medical Center, Professor of Medicine and Emergency Medicine, Harvard Medical School, Boston, MA
      • NICOLE M DUBOSH, MD

      There are many causes of disorders of consciousness, including toxic/metabolic, infectious, and traumatic disorders, as well as other causes that may be more difficult to diagnose. Following stabilization, a thorough history taking involving discussion with family members, witnesses, friends, or police can often help disclose the likely cause of coma, although the resulting information may be limited. In the emergency department, physicians should be extremely cautious about making an early prognosis or diagnosis of brain death because all relevant information may not yet be available. This review examines the pathophysiology, stabilization and assessment, diagnosis and treatment, prognosis, and disposition and outcomes for coma and disorders of consciousness. Figures show anatomic structures and dorsal and ventral pathways involved with the maintenance of consciousness, the Full Outline of Unresponsiveness (FOUR) scale, and the spectrum of pupil abnormalities and causes. Tables list the Glasgow Coma Scale, blood gas abnormalities due to toxins, and a computed tomography checklist for comatose patients. 

      This review contains 3 figures, 7 tables, and 65 references.

      Keywords: coma, altered level of consciousness, reticular activating system, basilar artery stroke, posterior circulation stroke, stupor, brain herniation, brainstem compression, non-convulsive status epilepticus

       

       

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    • 12

      Headache

      By Benjamin W Friedman, MD, MS
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      Headache

      • BENJAMIN W FRIEDMAN, MD, MSProfessor of Emergency Medicine, Department of Emergency Medicine,Albert Einstein College of Medicine, Montefi ore Medical Center, Bronx, NY

      Headaches are one of the most common complaints of patients seen by emergency physicians. They can be classified as primary headaches, which have no identifiable underlying cause, and secondary headaches, which are classified according to their cause. The majority of headaches are benign in origin, and most patients with headache can be treated successfully in the emergency department and discharged home; however, some have potentially life-threatening causes, and consideration of a broad differential diagnosis for all patients is essential. This review covers the primary headache disorders, pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes. The figure shows areas of the brain sensitive to pain. Tables review differential diagnosis of headache, International Headache Society primary headache criteria, clinical characteristics of secondary headaches, high-risk clinical characteristics among patients with a headache peaking in intensity within 1 hour, drugs associated with headache, and parenteral treatment of acute migraine.

      This review contains 1 figure, 9 tables, and 58 references.


      Key words: migraine, calcitonin gene related peptide, greater occipital nerve block, venous sinus thrombosis, reversible cerebral vasoconstriction syndrome, Ottawa, subarachnoid, cluster headache, trigeminal autonomic cephalalgias, post-traumatic headache

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    • 13

      Principles of Neurologic Ethics

      By Matthew S. Siket, MD; Jay M. Baruch, MD
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      Principles of Neurologic Ethics

      • MATTHEW S. SIKET, MDAssistant Professor, Department of Emergency Medicine, Alpert Medical School of Brown University, Providence, RI
      • JAY M. BARUCH, MDAssociate Professor, Department of Emergency Medicine, Alpert Medical School of Brown University, Providence, RI

      Neuroethics refers to the branch of applied bioethics pertaining to the neurosciences and emerging technologies that impact our ability to understand or enhance a human mind. In the setting of emergency medicine, the clinician will encounter neuroethical dilemmas pertaining to the acutely brain injured or impaired; similar to other ethical decisions encountered in emergency medicine, such neuroethical dilemmas are often complicated by insufficient information regarding the patient’s wishes and preferences and a short time frame in which to obtain this information. This review examines the basis of neuroethics in emergency medicine; neuroethical inquiry; the neuroscience of ethics and intuition; issues regarding autonomy, informed consent, paternalism, and persuasion; shared decision making; situations in which decision-making capacity is in question; beneficence/nonmaleficence; incidental findings and their implications; risk predictions; and issues of justice. The figure shows the use of tissue plasminogen activator (t-PA) for cerebral ischemia within 3 hours of onset and changes in outcome due to treatment. Tables list common ethical theories, virtues/values of an acute care provider, components of informed consent discussion unique to t-PA in acute ischemic stroke, models of the physician-patient relationship, eight ways to promote effective shared decision making, components of capacity assessment, and emergency department assessment of futility.

      This review contains 1 figure, 9 tables, and 90 references.

      Keywords: Ethics, autonomy, shared decision-making, moral dilemmas, framing, decision-making capacity, beneficence and nonmaleficence

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    • 14

      Epilepsy and Related Disorders

      By Barbara Dworetzky, MD; Jong Woo Lee, MD, PhD
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      Epilepsy and Related Disorders

      • BARBARA DWORETZKY, MDAssociate Professor of Neurology, Harvard Medical School, Chief, Division of Epilepsy, EEG, and Sleep Neurology, Director, The Edward B. Bromfield Epilepsy Program, Brigham and Women’s Hospital, Boston, MA
      • JONG WOO LEE, MD, PHDAssistant Professor of Neurology, Harvard Medical School, Director, ICU EEG Monitoring, The Edward B. Bromfield Epilepsy Program, Brigham and Women’s Hospital, Boston, MA

      Epilepsy is a chronic disorder of the brain characterized by recurrent unprovoked seizures. A seizure is a sudden change in behavior that is accompanied by electrical discharges in the brain. Many patients presenting with a first-ever seizure are surprised to find that it is a very common event. A reversible or avoidable seizure precipitant, such as alcohol, argues against underlying epilepsy and therefore against treatment with medication. This chapter discusses the epidemiology, etiology, and classification of epilepsy and provides detailed descriptions of neonatal syndromes, syndromes of infancy and early childhood, and syndromes of late childhood and adolescence. The pathophysiology, diagnosis, and differential diagnosis are described, as are syncope, migraine, and psychogenic nonepileptic seizures. Two case histories are provided, as are sections on treatment (polytherapy, brand-name versus generic drugs, surgery, stimulation therapy, dietary treatments), complications of epilepsy and related disorders, prognosis, and quality measures. Special topics discussed are women?s issues and the elderly. Figures illustrate a left midtemporal epileptic discharge, wave activity during drowsiness, cortical dysplasias, convulsive syncope, rhythmic theta activity, right hippocamal sclerosis, and right temporal hypometabolism. Tables describe international classifications of epileptic seizures and of epilepsies, epilepsy syndromes and related seizure disorders, differential diagnosis of seizure, differentiating epileptic versus nonepileptic seizures, antiepileptic drugs, status epilepticus protocol for treatment, when to consider referral to a specialist, and quality measures in epilepsy. 

      This review contains 7 figures, 17 tables and 38 references

      Keywords: Seizures, focal (partial)seizure, generalized seizures, Myoclonic seizures, Atonic seizures, Concurrent electromyographyTonic-clonic (grand mal) seizures

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    • 15

      Stroke and Other Cerebrovascular Diseases

      By Scott E. Kasner, MD, MSCE, FAHA, FAAN; Christina A Wilson, MD, PhD
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      Stroke and Other Cerebrovascular Diseases

      • SCOTT E. KASNER, MD, MSCE, FAHA, FAANProfessor, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Director, Comprehensive Stroke Center, University of Pennsylvania Health System, Philadelphia, PA
      • CHRISTINA A WILSON, MD, PHDAssistant Professor, Department of Neurology, University of Florida, Gainesville, FL

      Stroke is a leading cause of neurologic morbidity and mortality, and rapid treatment is key for a good outcome. This review addresses the epidemiology, common presenting symptoms, causes, and treatment of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Current recommendations for the emergent evaluation and treatment of an acute ischemic stroke are highlighted, including recently updated indications and contraindications for intravenous recombinant tissue plasminogen activator administration and recent guidelines for the expanded role of endovascular mechanical embolectomy for stroke due to acute large vessel occlusion. An algorithm of diagnostic evaluations to assist with identification of the cause of ischemic stroke is offered. Evidence-based primary and secondary stroke prevention is discussed, including the ideal choice of antithrombotic based on identified stroke mechanism and optimal risk factor management. Best practice supportive measures for the post-stroke patient are highlighted, including recent guidelines for the management of elevated intracranial pressure. Management of uncommon causes of ischemic stroke is also addressed. 

      This review contains 7 figures, 9 tables, and 84 references.

      Key Words:Intracerebral hemorrhage, ischemic stroke, recombinant tissue plasminogen activator, subarachnoid hemorrhage, antiplatelet therapy, endovascular therapy

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    • 16

      Management and Therapeutic Issues in the Dementias

      By David Knopman, MD
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      Management and Therapeutic Issues in the Dementias

      • DAVID KNOPMAN, MDProfessor of Neurology, Department of Neurology, Mayo Clinic, Rochester, MN

      As of 2016, treatment of Alzheimer disease (AD) dementia and the principal non-AD dementias is entirely palliative. Although there are several drugs approved for the treatment of mild to moderate AD dementia, these drugs—the cholinesterase inhibitors and memantine—have rather modest benefits. In general, nonpharmacologic approaches to the management of patients with dementia emphasize support for the caregiver, attention to safety, and providing a supportive and socially enriched environment for the patient. Depression is common in dementias of diverse etiology; lower doses of later-generation antidepressants are effective in controlling depressive symptoms in patients with dementia. Agitation is not a ubiquitous occurrence in patients with dementia, but physically aggressive behavior, hallucinations, and delusions affect a sizable fraction of patients with dementia. There is much controversy regarding the appropriate medication classes to use in cases of agitation, but the antipsychotic agent quetiapine is often effective and unique among its class in not causing parkinsonism or tardive dyskinesia.

      Key words: antidepressants, antipsychotic agents, caregiver support, cholinesterase inhibitors

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    • 17

      Stroke and Other Cerebrovascular Diseases

      By Scott E. Kasner, MD, MSCE, FAHA, FAAN; Christina A Wilson, MD, PhD
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      Stroke and Other Cerebrovascular Diseases

      • SCOTT E. KASNER, MD, MSCE, FAHA, FAANProfessor, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Director, Comprehensive Stroke Center, University of Pennsylvania Health System, Philadelphia, PA
      • CHRISTINA A WILSON, MD, PHDAssistant Professor, Department of Neurology, University of Florida, Gainesville, FL
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    • 18

      Acute Ischemic Stroke and Transient Ischemic Attack

      By Lauren M. Nentwich, MD
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      Acute Ischemic Stroke and Transient Ischemic Attack

      • LAUREN M. NENTWICH, MDAssistant Professor, Department of Emergency Medicine, Boston University School of Medicine, Boston, MA
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    • 19

      Coma and Disorders of Consciousness

      By Jonathan A. Edlow, MD, FACEP; Nicole M Dubosh, MD
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      Coma and Disorders of Consciousness

      • JONATHAN A. EDLOW, MD, FACEPVice-Chairman of Emergency Medicine, Beth Israel Deaconess Medical Center, Professor of Medicine and Emergency Medicine, Harvard Medical School, Boston, MA
      • NICOLE M DUBOSH, MD
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    • 20

      Epilepsy and Related Disorders

      By Barbara Dworetzky, MD; Jong Woo Lee, MD, PhD
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      Epilepsy and Related Disorders

      • BARBARA DWORETZKY, MDAssociate Professor of Neurology, Harvard Medical School, Chief, Division of Epilepsy, EEG, and Sleep Neurology, Director, The Edward B. Bromfield Epilepsy Program, Brigham and Women’s Hospital, Boston, MA
      • JONG WOO LEE, MD, PHDAssistant Professor of Neurology, Harvard Medical School, Director, ICU EEG Monitoring, The Edward B. Bromfield Epilepsy Program, Brigham and Women’s Hospital, Boston, MA
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  • Oncology
    • 1

      Pancreatic, Gastric, and Other Gastrointestinal Cancers

      By Davendra Sohal, MD, MPH; Weijing Sun, MD; Daniel Haller, MD, FACP
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      Pancreatic, Gastric, and Other Gastrointestinal Cancers

      • DAVENDRA SOHAL, MD, MPHFellow, Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Abramson Cancer Center, Philadelphia, PA
      • WEIJING SUN, MDAssociate Professor of Medicine, Division of Hematology-Oncology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
      • DANIEL HALLER, MD, FACPProfessor of Medicine, Division of Hematology-Oncology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA

      According to 2009 estimates from the American Cancer Society, cancers originating in the gastrointestinal tract rank second in both incidence and cancer-related deaths. One in four deaths in the United States is caused by cancer, with 25% of cancer-related deaths caused by gastrointestinal (GI) malignancies; more than 50% of these deaths are caused by cancer of the pancreas, stomach, esophagus, liver, or biliary tract. Recent advances in molecular biology, medical genetics, and imaging and endoscopic techniques, as well as the development of antitumor agents, have significantly altered the approaches to the prevention, diagnosis, and treatment of GI cancers. The chapter covers esophageal, gastric, pancreatic, hepatocellular, biliary tract, and anal cancers, as well as GI stromal tumors and gastric lymphoma. Coverage of all cancers includes diagnosis and treatment; various sections include information on epidemiology, etiology, risk factors, screening and prevention, molecular mutations, pathogenesis, and/or metastatic disease. Figures depict a barium esophagogram showing squamous cell carcinoma; imaging of esophageal cancer, gastric cancer, and pancreatic cancer; a pedigree of a family with inactivation of germline mutation of E-cadherin; hereditary gastric cancer; gastric cancer survival rates after gastrectomy; axial T1-weighted magnetic resonance imaging (MRI) showing cancer of the pancreatic head; and T1- and T2-weighted MRIs of intrahepatic bile duct carcinoma. Tables provide information on new cases and mortality from GI cancer in 2009; guidelines for diagnosis and surveillance of Barrett esophagus; the declining incidence of gastric cancer in Japan, Slovenia, and the United States; TNM staging of gastric cancer, pancreatic cancer, and hepatocellular carcinoma; the incidence of familial pancreatic carcinoma; molecular mutations involved in pancreatic cancer; staging of pancreatic intraepithelial neoplasia; and the Chinese University Prognostic Index.

      This review contains 9 figures, 39 tables, and 173 references.

      Keywords: biliary cancer, carcinoma, endoscopic, esophageal, gastric, hepatic, lesions, lymphoma, malignant, mutations

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    • 2

      Gynecologic Cancer

      By Stephen A Cannistra, MD; Christina I Herold, MD
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      Gynecologic Cancer

      • STEPHEN A CANNISTRA, MDProfessor of Medicine, Harvard Medical School, Director, Gynecologic Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA
      • CHRISTINA I HEROLD, MDInstructor of Medicine, Harvard Medical School, Gynecologic Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA

      This chapter focuses on the three types of gynecologic cancer—epithelial cancer of the ovary, cancer of the uterine cervix, and cancer of the endometrium (uterine cancer)—and reviews their epidemiology, diagnosis, differential diagnosis, surgical features, and staging, as well as their risk factors and clinical features. Also discussed are methods of treatment and the management of relapse. Epithelial ovarian cancer occurs at a mean age of 60 years in the United States and is the most lethal of gynecologic tract tumors. However, a recent trial has demonstrated a survival advantage through the use of intraperitoneal chemotherapy for appropriate patients with optimally debulked ovarian cancer.

      Invasive cervical cancer is uncommon in developed countries, partly because of the effectiveness of Pap smear screening. Nevertheless, cancer of the uterine cervix is the third most common gynecologic cancer diagnosis and cause of death among gynecologic cancers in the United States. However, for women with early-stage cervical cancer, data from several randomized trials indicate an improvement in response rate and survival through the use of combination platinum-based regimens for platinum-sensitive relapse. Also noted is an improvement in survival using combined-modality chemoradiation in appropriate patients with locally advanced cervical cancer.

      Endometrial cancer is the most frequent tumor of the gynecologic tract; it is estimated that it occurred in over 46,000 women and caused more than 8,000 deaths in the United States in 2011. Recent data indicate improvement in survival using adjuvant platinum-based chemotherapy in appropriate patients with high-risk endometrial cancer.

      Tables in this chapter review the common histologic types of epithelial ovarian cancer, selected signs and symptoms of ovarian cancer, the International Federation of Gynecology and Obstetrics (FIGO) staging system for epithelial ovarian cancer, differential diagnosis of a complex cyst detected by transvaginal sonography, selected adverse prognostic factors in epithelial ovarian cancer, common chemotherapy agents used in the treatment of epithelial ovarian cancer, the FIGO surgical staging of endometrial cancer, and postoperative management considerations for patients with uterine cancer. Figures illustrate the four histologic subtypes of epithelial ovarian cancer, the intraoperative appearance of stage III epithelial ovarian cancer, and FIGO staging of cervical cancer.

      This review contains 6 highly rendered figures, 8 tables, and 150 references.

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    • 3

      Prostate Cancer

      By Jonathan E. Rosenberg, MD; Philip W Kantoff, MD
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      Prostate Cancer

      • JONATHAN E. ROSENBERG, MDAssistant Professor of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
      • PHILIP W KANTOFF, MDProfessor of Medicine, Dana-Faber Cancer Institute, Harvard Medical School, Boston, MA

      Prostate cancer is the most commonly diagnosed noncutaneous malignancy in men in the United States. This chapter discusses the epidemiology, pathogenesis, and diagnosis of prostate cancer, as well as risk factors, the use of digital rectal examination and prostate-specific antigen measurement for screening, and staging for the disease. Also reviewed are the natural history of untreated prostate cancer; the treatment of localized and advanced prostate cancer, including prostatectomy, radiation therapy, and androgen deprivation therapy; and the prevention of prostate cancer. Figures illustrate the incidence rates of prostate cancer by race, age-adjusted and/or age-specific cancer of the prostate, the risk of a diagnosis in 20 years (based on being cancer free at certain ages), the 5-year survival rate, and the overall survival in patients with early prostate cancer treated with observation or radical prostatectomy. Tables in this chapter review the clinical staging definitions and the combined-modality staging approach to prostate cancer.

      This chapter contains 6 figures, 8 tables and 104 references

      Keywords: Prostate cancer, digital rectal exam, PSA, prostatectomy, men's health, prostate cancer screening

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    • 4

      Management of Bladder Cancer

      By Joaquim Bellmunt, MD, PhD; Rosa Nadal, MD, PhD
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      Management of Bladder Cancer

      • JOAQUIM BELLMUNT, MD, PHDAssociate Professor of Medicine, Harvard Medical School, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute/Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
      • ROSA NADAL, MD, PHDClinical Fellow Genitourinary Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD

      Bladder cancer is the fourth most common cancer in men and the tenth most common in women. Patients commonly present with painless hematuria. Urinary frequency, urinary tract infection, upper tract obstruction, and pain are also possible; however, the physical examination of the patients is often unremarkable. Clinical diagnosis depends on urine cytology, bladder ultrasonography, and office cystoscopy. This review describes the epidemiology, pathology and natural history, clinical presentation and workup, staging and grading, non–muscle-invasive bladder cancer, bladder preservation strategies, nontraditional approaches, chemotherapy for metastatic disease, immunotherapy, and predictive factors of response to chemotherapy for bladder cancer. Figures show representative images of urothelial cell carcinoma, diagrams showing a cystoscopy for a man and bladder cancer staging, urinary diversion, and computed tomographic scans of a patient with hepatic metastases from bladder cancer before and after treatment with gemcitabine-cisplatin. Tables list the tumor-node-metastasis staging system for bladder cancer, the histologic classification of tumors of the urinary tract (WHO 1973 versus WHO 2004), risk group stratification based on the European Organization for Research and Treatment of Cancer Scoring System, types of bacillus Calmette-Guérin failure/recurrence and treatment recommendations, unfavorable factors for bladder preservation chemoradiation, consensus criteria for patients unfit for cisplatin-based regimens, and first-line combination chemotherapy regimens.

      This review contains 5 highly rendered figures, 7 tables, and 80 references.

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    • 5

      Sarcomas of the Soft Tissue and Bone

      By Adam Lerner, MD; Huihong Xu, MD; Karen H Antman, MD
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      Sarcomas of the Soft Tissue and Bone

      • ADAM LERNER, MDProfessor of Medicine and Pathology, Boston University School of Medicine, Boston, MA
      • HUIHONG XU, MDAssistant Professor of Pathology, Boston University School of Medicine, Boston, MA
      • KAREN H ANTMAN, MDDean, Boston University School of Medicine, Provost, Boston University Medical School Campus, Boston, MA

      Sarcomas originate from bone or soft tissue. The most common bone sarcomas are osteosarcomas, Ewing sarcomas, and chondrosarcomas. Soft tissue sarcomas develop in fibrous tissue, fat, muscle, blood vessels, and nerves. Historically, soft tissue sarcomas of the trunk and extremities were reported separately from those of visceral organs (e.g., gastrointestinal and gynecologic sarcomas). This chapter discusses the classification, epidemiology, diagnosis, staging, and treatment of sarcomas of bone and cartilage, and classic soft tissue sarcomas. Management of Kaposi sarcoma, gastrointestinal stromal tumors (GISTs), mesothelioma, and rhabdomyosarcoma is also described. Figures include images of patients with osteosarcoma, liposarcoma, uterine leiomyosarcoma, GIST, and osteosarcoma in a patient with Paget disease of bone. Tables list epidemiologic features of sarcomas, a summary of sarcomas by histology, familial syndromes associated with increased risk of sarcoma, survival rates in sarcoma patients, staging of soft tissue sarcomas, and results of a meta-analysis of doxorubicin-based adjuvant chemotherapy for localized resectable soft tissue sarcoma. This chapter contains 126 references.

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    • 6

      Colorectal Cancer

      By Cathy Eng, MD, FACP
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      Colorectal Cancer

      • CATHY ENG, MD, FACPAssociate Professor, Associate Director of the Colorectal Center, The University of Texas M.D. Anderson Cancer Center, Houston, TX

      Colorectal cancer is the third most common cancer and the second leading cause of cancer death in the United States. Although environmental factors, including diet and lifestyle, clearly play a role in the etiology of colorectal cancer, as many as 25% of patients with colorectal cancer have a family history of the disease, which suggests the involvement of a genetic factor. Inherited colon cancers can be divided into two main types: the well-studied but rare familial adenomatous polyposis (FAP) syndrome, and the increasingly well-characterized, more common hereditary nonpolyposis colorectal cancer (HNPCC, a.k.a. Lynch Syndrome). The prevention, screening, diagnosis, and treatment of cancers of the colon and rectum are covered in this chapter. Figures illustrate various forms of adenomatous polyps, the tumor, node, metastasis (TNM) staging system for colorectal cancer, and the five-year survival rate in patients with colorectal carcinoma. Tables describe risk factors; possible chemopreventive agents; evidence supporting the effectiveness of screening tests; features and usage issues with different fecal occult blood tests; recommendations for early detection, screening, and surveillance for patients at different levels of risk; colorectal cancer staging systems; indicators of poor prognosis; and chemotherapeutic and biologic agents in the treatment of colorectal cancer. This chapter contains 197 references.

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    • 7

      Breast Cancer

      By Nancy E Davidson, MD
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      Breast Cancer

      • NANCY E DAVIDSON, MDDirector, University of Pittsburgh Cancer Institute and UPMC Cancer Center, Hillman Professor of Oncology, University of Pittsburgh, Pittsburgh, PA

      Invasive breast cancer, the most common nonskin cancer in women in the United States, will be diagnosed in 266,120 In 2018, along with 63,960 new cases of non-invasive (in situ) breast cancer. Incidence and mortality reached a plateau and appear to be dropping in both the United States and parts of western Europe. This decline has been attributed to several factors, such as early detection through the use of screening mammography and appropriate use of systemic adjuvant therapy, as well as decreased use of hormone replacement therapy. However, the global burden of breast cancer remains great, and global breast cancer incidence increased from 641,000 in 1980 to 1,643,000 in 2010, an annual rate of increase of 3.1%. This chapter examines the etiology, epidemiology, prevention, screening, staging, and prognosis of breast cancer. The diagnoses and treatments of the four stages of breast cancer are also included. Figures include algorithms used for the systemic treatment of stage IV breast cancer and hormone therapy for women with stage IV breast cancer. Tables describe selected outcomes from the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 and P-2 chemoprevention trials, tamoxifen chemoprevention trials for breast cancer, the TNM staging system and stage groupings for breast cancer, some commonly used adjuvant chemotherapy regimens, an algorithm for suggested treatment for patients with operable breast cancer from the 2011 St. Gallen consensus conference, guidelines for surveillance of asymptomatic early breast cancer survivors from the American Society of Clinical Oncology, and newer agents for metastatic breast cancer commercially available in the United States.

      This review contains 2 highly rendered figures, 8 tables, and 108 references.

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    • 8

      Cervical Cancer Prevention and Screening

      By Andrew Quinn, MD; Carolyn D Runowicz, MD
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      Cervical Cancer Prevention and Screening

      • ANDREW QUINN, MDResident, PGY-1, Department of Obstetrics and Gynecology, New York Hospital, New York, NY
      • CAROLYN D RUNOWICZ, MDExecutive Associate Dean for Academic Affairs, Professor of Obstetrics and Gynecology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL

      With the advent of HPV DNA testing and the availability of HPV vaccinations, the recommendations and rationale for screening and prevention of cervical cancer and its precursors have undergone revision, reflecting this new knowledge and understanding of cervical intra-epithelial neoplasia and the role of HPV. This review incorporates the new guidelines and rationale for current screening guidelines for cervical cancer and in the management of patients with atypical or unsatisfactory cervical cytology.

      This review contains 4 figures, 4 tables, and 71 references

      Keywords: Cervical cancer, Gynecological cancer, HPV, HPV testing, HPV vaccine, Pap smear, HPV DNA, Human papillomavirus

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    • 9

      Late Stage Prostate Cancer

      By Karthik Giridhar, MD; Manish Kohli, MD
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      Late Stage Prostate Cancer

      • KARTHIK GIRIDHAR, MDOncology Fellow, Mayo Clinic, Division of Medical Oncology, Rochester, MN
      • MANISH KOHLI, MDProfessor of Oncology, Mayo Clinic, Division of Medical Oncology, Rochester, MN

      Prostate cancer remains the second leading cause of cancer death in men and encapsulates a wide spectrum of disease. This review describes recent advances in genomic sciences and summarizes the impact of emerging molecular profiling–based clinical applications in the diagnosis and management of early and advanced prostate cancer. It addresses the controversial guidelines surrounding prostate-specific antigen–based screening for prostate cancer and summarizes the recommendations from six different agencies. This review highlights landmark clinical trials in metastatic prostate cancer, focusing on developments within the last 5 years. It also summarizes the rationale for earlier use of chemotherapy for newly diagnosed prostate cancer (chemohormonal therapy) and gives an overview of ongoing research into the development of novel genome-based therapeutics.

      This review contains 4 figures, 7 tables, and 53 references.

      Key words: castration resistant, molecular profiling, prostate cancer, screening guidelines, treatment options

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    • 10

      Lung Cancer - Part I

      By Jeffrey Crawford, MD; John Strickler, MD
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      Lung Cancer - Part I

      • JEFFREY CRAWFORD, MDGeorge Barth Geller Professor for Research in Cancer, Chief, Division of Medical Oncology, Department of Medicine, Duke University Medical Center, NC 27710
      • JOHN STRICKLER, MDFellow, Divisions of Hematology, Medical Oncology, and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC 27710

      In the United States, lung cancer is the second most common cancer, surpassed only by prostate cancer in men and breast cancer in women. But lung cancer is the leading cause of cancer deaths, accounting for 29% and 26% of all cancer-related deaths in men and women, respectively. The four major pathologic cell types of lung cancer are small cell carcinoma, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Because they have overlapping clinical behaviors and responses to treatment, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma are generally grouped together in the category of non–small cell lung cancer (NSCLC). This review discusses both NSCLC and small cell lung cancer (SCLC), including lung cancer in those who have never smoked, prevention of lung cancer, with sections on diagnosis, biomarkers, treatment, and supportive care. 

      This review contains 7 figures, 10 tables, and 81 references.

      Keywords: lung cancer, mediastinoscopy, chemoradiotherapy, TNM staging system, pulmonary parenchyma, segmentectomy

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    • 11

      Lung Cancer Part II

      By Jeffrey Crawford, MD
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      Lung Cancer Part II

      • JEFFREY CRAWFORD, MDGeorge Barth Geller Professor for Research in Cancer, Chief, Division of Medical Oncology, Department of Medicine, Duke University Medical Center, NC 27710

      In the United States, lung cancer is the second most common cancer, surpassed only by prostate cancer in men and breast cancer in women. But lung cancer is the leading cause of cancer deaths, accounting for 29% and 26% of all cancer-related deaths in men and women, respectively. The four major pathologic cell types of lung cancer are small cell carcinoma, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Because they have overlapping clinical behaviors and responses to treatment, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma are generally grouped together in the category of non–small cell lung cancer (NSCLC). This review discusses treatment of both NSCLC and small cell lung cancer (SCLC).

      This review contains 2 figures, 20 tables, and 95 references.

      Keywords: lung cancer, mediastinoscopy, chemoradiotherapy, TNM staging system, pulmonary parenchyma, segmentectomy

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    • 12

      Head and Neck Cancer

      By Everett E Vokes, MD; Kevin C. Wood, MD
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      Head and Neck Cancer

      • EVERETT E VOKES, MDChairman, Department of Medicine, Deputy Director, Cancer Research Center, John E. Ultmann Professor of Medicine Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois
      • KEVIN C. WOOD, MDFellow, Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL

      The most common histology of non-thyroid head and neck cancer is squamous cell carcinoma.  Common risk factors for head and neck malignancies include tobacco and alcohol abuse and viruses, including Epstein-Barr Virus (EBV) and Human Papillomavirus (HPV). Early stage disease is often treated with surgery or radiation therapy alone, while more advanced disease often requires a multi-modality approach including systemic chemotherapy, radiation, and surgical resection.  In the curative setting, current clinical trials are evaluating the de-escalation of therapy in HPV-releated head and neck cancer.  In the metastatic setting, clinical trials have focused on using immunotherapy agents to improve outcomes. This review chapter will discuss the etiology and common presentations of head and neck cancer, and also analyze recent advancements in the treatment of the disease.       

       

      Key words: chemoradiation, head and neck cancer, human papillomavirus, immunotherapy, oropharynx, squamous cell carcinoma, treatment deescalation

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    • 13

      Pancreatic, Gastric, and Other Gastrointestinal Cancers

      By Davendra Sohal, MD, MPH; Weijing Sun, MD; Daniel Haller, MD, FACP
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      Pancreatic, Gastric, and Other Gastrointestinal Cancers

      • DAVENDRA SOHAL, MD, MPHFellow, Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Abramson Cancer Center, Philadelphia, PA
      • WEIJING SUN, MDAssociate Professor of Medicine, Division of Hematology-Oncology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
      • DANIEL HALLER, MD, FACPProfessor of Medicine, Division of Hematology-Oncology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
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    • 14

      Prostate Cancer

      By Jonathan E. Rosenberg, MD; Philip W Kantoff, MD
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      Prostate Cancer

      • JONATHAN E. ROSENBERG, MDAssistant Professor of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
      • PHILIP W KANTOFF, MDProfessor of Medicine, Dana-Faber Cancer Institute, Harvard Medical School, Boston, MA
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    • 15

      Cervical Cancer Prevention and Screening

      By Carolyn D. Runowicz, MD; Andrew Quinn, MD
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      Cervical Cancer Prevention and Screening

      • CAROLYN D. RUNOWICZ, MDAssociate Dean for Women’s Affairs, Professor of Obstetrics and Gynecology, Florida International University, Herbert Wertheim College of Medicine, 11200 S.W. 8 Street, AHC2 693, Miami, FL
      • ANDREW QUINN, MDResident, PGY-1, Department of Obstetrics and Gynecology, New York Hospital, New York, NY
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  • Palliative Medicine
    • 1

      Symptom Management in Palliative Medicine

      By Kathy J Selvaggi, MD; Janet L Abrahm, MD
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      Symptom Management in Palliative Medicine

      • KATHY J SELVAGGI, MDAssistant Professor of Medicine, Harvard Medical School, Director, Intensive Palliative Care Unit, Brigham and Women’s Hospital, Boston, MA
      • JANET L ABRAHM, MDProfessor of Medicine, Harvard Medical School, Division Chief, Adult Palliative Care, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, MA

      Palliative care is an interdisciplinary specialty focused on providing comfort, communication, and support for patients, families, and professional caregivers throughout the course of a life-limiting illness. This chapter discusses assessment and treatment of symptoms and disorders that commonly contribute to patient distress during these illnesses: pain, disorders of the respiratory and gastrointestinal systems, skin disorders, hot flashes, fatigue, pruritis, insomnia, and delirium. This chapter reviews care of the imminently dying patient, discusses methods for assessing patients' symptoms, and provides two examples of valid and reliable symptom measurement systems: the Edmonton Symptom Assessment Scale and the Memorial Symptom Assessment Scale. Achieving symptom control requires the physician to assess patient suffering in all dimensions: physical, psychological, social, and spiritual. The extent of the assessment may be modified, however, based on patients’ prognosis as well as their goals and the burden and benefit of the diagnostic intervention. A 10-step protocol for terminal wean is presented. Signs that patients are entering their final days and symptom management in the last hours of a patient's life are discussed. Tables list the modified Edmonton Symptom Assessment Scale; the Memorial Symptom Assessment Scale; the DOLOPLUS-2 scale (behavioral pain assessment in the elderly); relative potencies of commonly used opioids; conversions between the transdermal fentanyl patch and morphine; symptomatic treatment for dyspnea, cough, and hiccups; pharmacologic treatment of nausea and vomiting; a progressive bowel regimen for patients receiving opioid therapy; treatments for constipation; etiology-based treatment for oral problems; risk factors for pressure ulcers; and applicable medications for physical and psychological sources of distress near the end of life. This chapter contains 12 tables, 120 references, 5 MCQs.

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    • 2

      Management of Psychosocial Issues in Terminal Illness

      By Jane DeLima Thomas, MD; Eva Reitschuler-Cross, MD; Susan D Block, MD
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      Management of Psychosocial Issues in Terminal Illness

      • JANE DELIMA THOMAS, MDAttending Physician, Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Instructor in Medicine, Harvard Medical School, Boston, MA
      • EVA REITSCHULER-CROSS, MDClinical Assistant Professor of Medicine, University of Pittsburgh, Section of Palliative Care and Medical Ethics, University of Pittsburgh Medical Center, Pittsburgh, PA
      • SUSAN D BLOCK, MDChair, Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute and Brigham and Women’s Hospital Co-Director, HMS Center for Palliative Care, Professor of Psychiatry and Medicine, Harvard Medical School, Boston, MA

      Patients facing serious or life-threatening illness experience challenges to their psychological, social, and spiritual lives as well as to their physical function and comfort. Physicians may be accustomed to focusing on the biomedical aspects of illness, but they have a critical role in assessing the patient's psychosocial issues to identify sources of distress and help implement a plan for mitigating them. An appropriate psychosocial assessment requires a methodical and rigorous approach and includes assessment of any psychosocial issue affected by or affecting a patient's experience of illness. This chapter outlines a structured approach to addressing psychosocial issues by discussing (1) the doctor-patient relationship; (2) coping with illness; (3) family dynamics and caregiving; (4) ethnic and cultural issues; (5) religious, spiritual, and existential issues; (6) mental health issues, including adjustment disorder, depression, anxiety, personality disorders, aberrant drug behaviors, and major mental health issues; and (7) grief and bereavement. Tables outline psychosocial assessment questions, factors predisposing patients with serious illness to depression, risk factors for suicide in patients with terminal illness, and classes of antidepressants, anxiolytics, and sedatives. The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire is provided, as well as a list of Web sites with further resources about psychosocial issues in serious illness.

      This review contains 1 highly rendered figure, 6 tables, and 216 references.

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    • 3

      Communication of Bad News

      By Paul K Mohabir, MD; Preethi Balakrishnan, MD
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      Communication of Bad News

      • PAUL K MOHABIR, MDClinical Professor, Pulmonary and Critical Care Medicine
      • PREETHI BALAKRISHNAN, MDCritical Care Medicine Fellow, Stanford Hospital, Stanford, CA

      Delivering bad news is a critical part of the patient-physician relationship. Historically, physicians have withheld or incompletely related the diagnosis and prognosis of a patient’s disease. However, the trajectory of medical practice and patient expectations mandates a change in communicating bad news. Poor communication of bad news also affects physician job satisfaction and increases burnout. Empathy is crucial to communicating bad news well. It is a very complex emotion that requires the physician to identify the patient’s reaction to the news being delivered and to react to the patient in a supportive manner. Patients do not find it helpful when the physician underplays the bad part of the news. Emerging research shows that patients prefer pairing of bad news with hope to provide anchors in the overwhelming conversation but not to take away from the gravity of the news. Family and friends can help ameliorate or, unfortunately, augment patient anxiety. Physicians have to be cognizant of the dynamics family and friends bring to the interaction as well. A patient-centered approach—a combination of evidence-based medicine and patient goal-oriented medicine—to delivering bad news is most likely to benefit the patient-physician relationship and decision-making process. The SPIKES and the Expanded Four Habits Model can be used as guidelines for communicating bad news.

      This review contains 1 figure and 38 references.

      Key words: communicating bad news, empathy, Expanded Four Habits Model, patient-centered care, SPIKES

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    • 4

      Principles and Practice of Palliative Care

      By Kristen G Schaefer, MD; Rachelle E Bernacki, MD, MS
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      Principles and Practice of Palliative Care

      • KRISTEN G SCHAEFER, MDDirector of Medical Student and Resident Education, Division of Adult Palliative Care, Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Center for Palliative Care, Harvard Medical School, Division of General Internal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA
      • RACHELLE E BERNACKI, MD, MSDirector of Quality Initiatives, Division of Adult Palliative Care, Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Center for Palliative Care, Harvard Medical School, Division of Aging, Department of Medicine, Brigham and Women’s Hospital, Boston, MA

      The trajectories of serious illness and dying have changed in the last century; in the past, patients lived shorter lives and often died quickly of infectious disease, whereas patients in the 21st century live longer and often with prolonged debility in the advanced stages of illness. As a result, patients with serious illness can suffer undertreated symptoms and often feel poorly prepared for the final stages of disease. With more options for advanced life support and other aggressive interventions at the end of life, patients and families face increasingly complex medical decisions in the terminal phase of illness, and the treatments they receive do not always align with their goals and values. Emerging evidence suggests that integrating palliative care into the treatment of advanced illness can improve outcomes, decrease costs, and improve both patient and family satisfaction. Consequently, patient access to high-quality specialty-level palliative care is becoming standard of care at most academic cancer centers and more available in the community. This chapter describes the practice and principles of specialty-level palliative care and outlines specific "generalist" palliative care competencies essential for all physicians caring for patients with serious illness, including prognostication, patient-centered communication, and the navigation of ethical dilemmas in the field of palliative care. Tables outline the philosophy of palliative care, domains of suffering, location of death of hospice patients, the palliative performance scale, median survival times for cancer syndromes, indicators associated with a poorer prognosis in congestive heart failure, the NURSE mnemonic for accepting and responding to emotion, palliative care communication competencies in the intensive care unit, and the SPIKES mnemonic for breaking bad news. Figures depict causes of death in 1900 versus 2010, palliative care through the trajectory of serious illness, theoretical trajectories of disease, life expectancies for women and men, mortality at 1 year post discharge, and a model for patient-centered communication.

      This review contains 6 highly rendered figures, 9 tables, and 169 references.

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  • Psychiatry
    • 1

      Adjustment Disorder and Its Clinical Management

      By Mauro Giovanni Carta, MD; Antonio Preti, MD
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      Adjustment Disorder and Its Clinical Management

      • MAURO GIOVANNI CARTA, MDProfessor and Chair of Quality of Care, University of Cagliari, Head, Liaison Psychiatry and Psychosomatics Unit, University Hospital, University of Cagliari, Cagliari, Italy
      • ANTONIO PRETI, MDConsultant in Psychiatry, Liaison Psychiatry and Psychosomatics Unit, University Hospital, University of Cagliari, Cagliari, Italy

      Adjustment disorder is a condition of subjective emotional distress triggered as a consequence of a meaningful change in life. The diagnosis of adjustment disorder is hindered by the difficult operational definition of stress and of its related concept of “vulnerability,” by the problem of disentangling symptoms of adjustment disorder from those attributable to comorbid anxiety and mood disorders, and by the poor boundaries of the disorder with other stress-related conditions on the one hand and with common adaptation to life events on the other. Despite the high frequency of its diagnosis in clinical settings, there has been relatively little research on the adjustment disorder and, consequently, very few hints about its treatments. Several psychotherapies have been developed to deal with patients diagnosed with adjustment disorder, with inconclusive evidence on their effectiveness. Antidepressants may abate the symptoms and help patients reacquire occupational and social functioning. The medium-term outcome of adjustment disorder is good, with 70 to 80% of those diagnosed with it showing no evidence of psychopathology when reassessed 5 years from the episode. However, when comorbid with a personality disorder or a substance use disorder, the short-term risk of suicide may be increased. The long-term outcome of adjustment disorder seems to be worse in children and adolescents than in adults. In particular, adolescents diagnosed with adjustment disorder were more likely than adults to have received a diagnosis of a severe mental disorder at the 5-year follow-up, including schizophrenia, schizoaffective disorder, and bipolar disorder.

      This review contains 1 figure, 6 tables, and 52 references.

      Key words: adaptation, adjustment disorder, anxiety, depression, stress, trauma, treatment, vulnerability

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    • 2

      Sleep Disorders

      By Sudhansu Chokroverty, MD, FRCP, FACP
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      Sleep Disorders

      • SUDHANSU CHOKROVERTY, MD, FRCP, FACPProfessor and Director of Sleep Research, Medical Director of Devry Technology Training Program, Co-Chair Emeritus of Neurology, Department of Neurology, JFK Neuroscience Institute, Edison, NJ, Professor of Neuroscience, Seton Hall University, South Orange, NJ, Clinical Professor of Neurology, Robert Wood Johnson Medical School, New Brunswick, NJ

      Recent research has generated an enormous fund of knowledge about the neurobiology of sleep and wakefulness. Sleeping and waking brain circuits can now be studied by sophisticated neuroimaging techniques that map different areas of the brain during different sleep states and stages. Although the exact biologic functions of sleep are not known, sleep is essential, and sleep deprivation leads to impaired attention and decreased performance. Sleep is also believed to have restorative, conservative, adaptive, thermoregulatory, and consolidative functions. This review discusses the physiology of sleep, including its two independent states, rapid eye movement (REM) and non–rapid eye movement (NREM) sleep, as well as functional neuroanatomy, physiologic changes during sleep, and circadian rhythms. The classification and diagnosis of sleep disorders are discussed generally. The diagnosis and treatment of the following disorders are described: obstructive sleep apnea syndrome, narcolepsy-cataplexy sydrome, idiopathic hypersomnia, restless legs syndrome (RLS) and periodic limb movements in sleep, circadian rhythm sleep disorders, insomnias, nocturnal frontal lobe epilepsy, and parasomnias. Sleep-related movement disorders and the relationship between sleep and psychiatric disorders are also discussed. Tables describe behavioral and physiologic characteristics of states of awareness, the international classification of sleep disorders, common sleep complaints, comorbid insomnia disorders, causes of excessive daytime somnolence, laboratory tests to assess sleep disorders, essential diagnostic criteria for RLS and Willis-Ekbom disease, and drug therapy for insomnia. Figures include polysomnographic recording showing wakefulness in an adult; stage 1, 2, and 3 NREM sleep in an adult; REM sleep in an adult; a patient with sleep apnea syndrome; a patient with Cheyne-Stokes breathing; a patient with RLS; and a patient with dream-enacting behavior; schematic sagittal section of the brainstem of the cat; schematic diagram of the McCarley-Hobson model of REM sleep mechanism; the Lu-Saper “flip-flop” model; the Luppi model to explain REM sleep mechanism; and a wrist actigraph from a man with bipolar disorder.

      This review contains 14 figures, 20 tables, 124 references

      Keywords: sleep disorder, rapid eye movement, non-rapid eye movement, insomnia, narcolepsy, circardian rhythm sleep disorder, restless legs syndrome, parasomnia

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    • 3

      Acute Psychosis

      By James Kimo Takayesu, MD, MS; Suzanne Bird, MD
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      Acute Psychosis

      • JAMES KIMO TAKAYESU, MD, MSAssistant Residency Director, Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA
      • SUZANNE BIRD, MDAcute Psychiatric Service, Massachusetts General Hospital, Boston, MA

      Acute psychosis can be a true emergency, and the primary goal in the evaluation of an acutely psychotic patient should be to maintain safety and prevent harm to the patient and staff. The defining symptoms of psychosis include hallucinations, delusions, disorganized thought or speech, abnormal motor behavior, and negative symptoms. This review covers the approach to the patient, and definitive treatment, disposition and outcomes for patients experiencing acute psychosis. The figure shows an interview setting in a triangular arrangement, allowing for safe egress. Tables list goals in the evaluation of the acutely psychotic patient; causes of secondary psychosis; common medication classes causing mental status change; four key questions for assessing psychotic behavior; screening assessment for psychosis; clinical features of dementia, delirium, and psychiatric illness; brief mental status examination; common medications for the treatment of acute psychosis and chemical sedation; QT-prolonging effects of commonly used antipsychotic medications; and documentation required in the use of chemical and/or physical restraints.

      This review contains 1 highly rendered figure, 10 tables, and 57 references.

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    • 4

      Overview of Anxiety Disorders

      By Jon E Grant, JD, MD, MPH
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      Overview of Anxiety Disorders

      • JON E GRANT, JD, MD, MPH

      Anxiety disorders are the most common psychiatric disorders among adults in the United States. Although anxiety disorders generally result in significant psychosocial impairment, most adults do not seek treatment until many years after the onset of the anxiety disorder. The treatment literature for anxiety disorder has grown tremendously since the 1980s, and both psychotherapy and medications may prove beneficial for people with anxiety disorders. This review presents a general overview of the anxiety disorders.

      This review contains 10 tables, and 36 references.

      Key words: agoraphobia, anxiety disorder, generalized anxiety disorder, panic disorder, separation anxiety disorder, social anxiety disorder, specific phobia, treatment of anxiety

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    • 5

      Overview of Posttraumatic Stress Disorder

      By Dana Downs, MA, MSW; Carol North, MD, MPE
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      Overview of Posttraumatic Stress Disorder

      • DANA DOWNS, MA, MSWClinical Research Manager (Retired), Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX
      • CAROL NORTH, MD, MPEMedical Director, The Altshuler Center for Education & Research at Metrocare Services, The Nancy and Ray L. Hunt Chair in Crisis Psychiatry and Professor of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX

      Posttraumatic stress disorder (PTSD) is a psychiatric disorder that may follow exposure to trauma. The experience of trauma has potential personal implications. Some individuals develop PTSD after trauma; others may be more resilient, experiencing distress but not succumbing to psychopathology; and yet others may emerge from the experience with new strength and direction.

      This review contains 1 figure, 7 tables, and 48 references

      Keyword: Posttraumatic stress disorder, transcranial magnetic stimulation (TMS), deep brain stimulation, vagal nerve stimulation, transcranial direct current stimulation, Diagnostic and Statistical Manual of Mental Disorders, hypothalamic-pituitary-adrenal (HPA) axis

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    • 6

      Management of Somatic Symptoms

      By Andreas Schröder, MD, PhD; Joel E Dimsdale, MD
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      Management of Somatic Symptoms

      • ANDREAS SCHRÖDER, MD, PHDConsultant in Psychiatry, The Research Clinic for Functional Disorders, Aarhus University Hospital, Aarhus, Denmark
      • JOEL E DIMSDALE, MDDistinguished Professor of Psychiatry Emeritus, Department of Psychiatry, University of California, San Diego, La Jolla, CA

      Somatic symptoms that cannot be attributed to organic disease account for 15 to 20% of primary care consultations and up to 50% in specialized settings. About 6% of the general population has chronic somatic symptoms that affect functioning and quality of life. This chapter focuses on the recognition and effective management of patients with excessive and disabling somatic symptoms. The clinical presentation of somatic symptoms is categorized into three groups of patients: those with multiple somatic symptoms, those with health anxiety, and those with conversion disorder. The chapter provides information to assist with making a diagnosis and differential diagnosis. Management includes ways to improve the physician–patient interaction that will benefit the patient, a step-care model based on illness severity and complexity, and psychological and pharmacologic treatment. The chapter is enhanced by figures and tables that summarize health anxiety, symptoms, differential diagnoses, and management strategies, as well as by case studies and examples.

      This review contains  5 highly rendered figures, 10 tables, and 235 references.

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    • 7

      Depressive Disorders: Update on Diagnosis, Etiology, and Treatment

      By Isabelle E. Bauer, PhD; Antonio L Teixeira, MD, PhD; Marsal Sanches, MD, PhD; Jair C. Soares, MD
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      Depressive Disorders: Update on Diagnosis, Etiology, and Treatment

      • ISABELLE E. BAUER, PHDDepartment of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX
      • ANTONIO L TEIXEIRA, MD, PHDDepartment of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX
      • MARSAL SANCHES, MD, PHDDepartment of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX
      • JAIR C. SOARES, MDDepartment of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX

      This review discusses the changes in the diagnostic criteria for depressive disorders as outlined in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), and recent findings exploring the etiology of and treatment strategies for these disorders. Depressive disorders are typically characterized by depression in the absence of a lifetime history of mania or hypomania. New developments in the DSM-5 include the recognition of new types of depressive disorders, such as disruptive mood dysregulation disorder, persistent depressive disorder, premenstrual dysphoric disorder, and the addition of catatonic features as a specifier for persistent depressive disorder. These diagnostic changes have important implications for the prognosis and treatment of this condition. A thorough understanding of both the clinical phenotype and the biosignature of these conditions is essential to provide individualized, long-term, effective treatments to affected individuals. 

      This review contains 6 table and 53 references

      Key words: brain volumes, depressive disorders, DSM-5, hormones, inflammation, neuropeptides, somatic therapy, stress

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    • 8

      Personality Disorders

      By Yosefa A. Ehrlich, BS; Amir Garakani, MD; Stephanie R Pavlos, MA; Larry Siever, MD
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      Personality Disorders

      • YOSEFA A. EHRLICH, BSDoctoral Student in Clinical Psychology, City University of New York Graduate Center, New York, NY
      • AMIR GARAKANI, MDAssistant Clinical Professor of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY
      • STEPHANIE R PAVLOS, MADoctoral Student in Clinical Psychology, St. Johns University, Queens, NY
      • LARRY SIEVER, MDProfessor of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY

      Personality can be defined as an organizational system of self that shapes the manner in which a person interacts with his or her environment. Personality traits develop in adolescence or early adulthood and are thought to be shaped by early childhood experiences and enduring throughout a lifetime. Personality traits that prevent an individual from being able to function in society or that cause significant distress are diagnosed as personality disorders. A thorough history is needed to rule out other psychiatric and medical disorders. This chapter reviews the diagnostic criteria, differential diagnosis, comorbidity, prevalence, etiology (including genetics and neurobiology), prognosis, and treatment of paranoid, schizoid, schizotypal, borderline, antisocial, narcissistic, histrionic, avoidant, obsessive-compulsive, and dependent personality disorders. A discussion of the relevance of personality disorders to primary care practices and approaches to managing such patients is also included. Tables describe the diagnostic criteria of each personality disorder. Figures illustrate the prevalence of personality disorders in the general and psychiatric populations; schizotypal personality disorder in the community, general population, and clinical population; childhood trauma in individuals with personality disorder; and comorbid disorders in individuals with borderline personality disorder. A model of brain processing in borderline personality disorder is also featured.

      This chapter contains 5 highly rendered figures, 10 tables, 230 references, and 5 MCQs.

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    • 9

      Overview of Schizophrenia and Other Psychotic Disorders

      By James A. Wilcox, MD, PhD; Donald W. Black, MD
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      Overview of Schizophrenia and Other Psychotic Disorders

      • JAMES A. WILCOX, MD, PHD
      • DONALD W. BLACK, MD

      Psychotic disorders are among the most disabling conditions and constitute a major public health problem. Described throughout recorded time, they affect as many as 5% of the population and cause a disproportionate amount of suffering and loss to society. In the chapter on schizophrenia spectrum and other psychotic disorders, the DSM-5 lists delusional disorder, brief psychotic disorder, schizophreniform disorder, schizophrenia, and schizoaffective disorder, as well as categories for substance- or medically induced psychotic disorders. The term psychosis indicates that the individual has a severe inability to interpret the surrounding environment in a realistic way. Symptoms include hallucinations, delusions, and bizarre behavior. Psychotic disorders are associated with premature death, mostly attributable to suicide. The pathophysiology and etiology of psychotic disorders are only now beginning to be understood, and treatment for these conditions remains suboptimal. Researchers are currently refining the cause of these symptoms and developing more effective treatments.  

      This review contains 6 tables, and 37 references

      Key words: Brief psychotic disorder, delusions, hallucinations, psychosis, schizoaffective disorder, schizophrenia, schizophreniform disorder

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    • 10

      Overview of Substance Use Disorders

      By Alexander W Thompson, MD, MBA, MPH; Timothy Ando, MD; Emily Morse, DO
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      Overview of Substance Use Disorders

      • ALEXANDER W THOMPSON, MD, MBA, MPHClinical associate professor, Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA.
      • TIMOTHY ANDO, MDPsychiatry Resident, Department of Psychiatry, Stanford University School of Medicine, Stanford, CA
      • EMILY MORSE, DOChief Resident in Psychiatry, Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA

      Substance use disorders are a major source of morbidity and mortality, contributing to a significant proportion of deaths in the United States and worldwide each year. A substantial rise in deaths related to drug overdoses in recent decades has drawn increasing public attention to this issue. However, the majority of individuals struggling with substance use disorders remain untreated. The financial costs and health burden are substantial. This review provides a broad overview of substance-related and addictive disorders. The evolution of the classification system is described, and the diagnostic criteria for the various substance use disorders are reviewed. Epidemiology and etiologic considerations, including neurobiological pathways, genetics, environmental influences, and dimensional risk factors, are examined. Finally, individual substances and their related disorders are reviewed, including alcohol, caffeine, cannabis, hallucinogens, inhalants, opioids, sedative/hypnotics, stimulants, tobacco, and other or unknown substances. Intoxication and withdrawal syndromes are described where applicable, and clinical management concepts are discussed. 

      This review contains 6 figures, 5 tables, and 71 references.

      Key words: abuse, addiction, alcohol, caffeine, cannabis, dependence, diagnosis, DSM-5, epidemiology, hallucinogen, hypnotic, inhalant, intoxication, methamphetamine, nicotine, opioid, sedative, stimulant, substance use disorders, tobacco, tolerance, withdrawal

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    • 11

      Bipolar Disorders and Their Clinical Management, Part I: Epidemiology, Etiology, Genetics, and Neurobiology

      By Vladimir Maletic, MD; Bernadette DeMuri-Maletic, MD
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      Bipolar Disorders and Their Clinical Management, Part I: Epidemiology, Etiology, Genetics, and Neurobiology

      • VLADIMIR MALETIC, MD
      • BERNADETTE DEMURI-MALETIC, MDClinical Assistant Professor of Psychiatry and Mental Health Sciences, Medical College of Wisconsin, Milwaukee, WI

      The concept of bipolar disorders has undergone a substantial evolution over the course of the past two decades. Emerging scientific research no longer supports the notion of bipolar disorder as a discrete neurobiologic entity. Most likely, there are a number of different biotypes with similar phenotypical manifestations. Advancements in genetic research suggest that bipolar disorders have a polygenetic pattern of inheritance, sharing common genetic underpinnings with a number of other psychiatric disorders, including schizophrenia, autistic spectrum disorder, and major depressive disorder. Contemporary etiological theories are discussed in some detail, inclusive of the role of immune disturbances, oxidative stress, and changes in neuroplasticity and neurotransmission, which underpin functional and structural brain changes associated with bipolar disorders. Contemporary epidemiologic research and understanding of disease evolution are discussed from the perspective of its clinical relevance. Our review provides a succinct summary of relevant literature.

      This review contains 4 figures, 2 tables, and 80 references.

      Key Words: bipolar disorders, endocrine disturbances, epidemiology, genetics, glia, immunity, neurobiology, neuroplasticity, neurotransmitters

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    • 12

      Bipolar Disorders and Their Clinical Management, Part II: Diagnosis, Differential Diagnosis, and Treatment

      By Bernadette DeMuri-Maletic, MD; Vladimir Maletic, MD, MS
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      Bipolar Disorders and Their Clinical Management, Part II: Diagnosis, Differential Diagnosis, and Treatment

      • BERNADETTE DEMURI-MALETIC, MDClinical Assistant Professor of Psychiatry and Mental Health Sciences, Medical College of Wisconsin, Milwaukee, WI
      • VLADIMIR MALETIC, MD, MSClinical Professor of Psychiatry and Behavioral Sciences, University of South Carolina School of Medicine, Greenville, SC

      Bipolar disorder is a biologically and phenotypically diverse disorder and its diagnosis and treatment provides a significant challenge to even the most seasoned clinician. We provide an update on the diagnosis and differential diagnosis of bipolar disorder, reflecting recent changes in DSM-5. Our review provides a succinct summary of the treatment literature, encompassing pharmacologic and psychosocial interventions for bipolar depression, mania/hypomania, mixed states, and prevention of disease recurrence. We provide a brief critical review of emerging treatment modalities, including those used in treatment resistance. Challenges involved in maintaining adherence are further discussed. Additionally, we review common treatment adverse effects and provide recommendations for proper side effect monitoring. There is evidence of significant functional impairment in patients with bipolar disorder and we conclude with a discussion of the impact of impairment on prognosis and quality of life.

      This review contains 4 figures, 7 tables, and 45 references.

      Key Words: bipolar disorders, differential diagnosis, maintenance pharmacotherapy, prognosis, psychosocial interventions, treatment, quality of life

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    • 13

      Unhealthy Alcohol Use

      By Stephen R Holt, MD, MSc; Joseph H. Donroe, MD, MPH
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      Unhealthy Alcohol Use

      • STEPHEN R HOLT, MD, MSCAssistant Professor of Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT
      • JOSEPH H. DONROE, MD, MPH Assistant Professor of Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT

      Unhealthy alcohol use refers to a spectrum of alcohol consumption ranging from at-risk drinking to alcohol use disorder. It is associated with both a high cost to society and to individuals. Globally, alcohol is a leading cause of death and disability, and despite the high prevalence of unhealthy alcohol use, diagnosis, and treatment of alcohol use disorder remains disproportionately low. Risk for unhealthy alcohol use and alcohol related harms is multifactorial and includes genetic factors, gender, age, socioeconomic status, cultural and societal norms, and policies regulating alcohol consumption among others. Excessive alcohol use is associated with a myriad of poor physical and mental health outcomes, and screening for unhealthy alcohol use is universally recommended and effective.

      This review contains 1 figures, 2 tables, and 76 references. 


      Key Words: addiction, alcohol, cancer, diagnosis, drinking, liver disease, screening, stigma, use disorder
      Important Advances

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    • 14

      Treatment of Unhealthy Alcohol Use

      By Stephen R Holt, MD, MSc; David A Fiellin, MD
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      Treatment of Unhealthy Alcohol Use

      • STEPHEN R HOLT, MD, MSCAssistant Professor of Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT
      • DAVID A FIELLIN, MDProfessor of Medicine, Investigative Medicine and Public Health, Department of Medicine, Yale University School of Medicine, New Haven, CT

      Unhealthy alcohol use represents the fifth leading cause of morbidity and mortality globally, and the first leading cause among persons 18 to 45 years of age. Despite the global impact of unhealthy alcohol use, the adoption of evidence-based treatments has been sluggish. Behavioral strategies for lower level drinking include the brief motivational interview, designed to be within the scope of any healthcare provider, and more specialist-driven approaches for those with alcohol use disorder (AUD) such as cognitive behavioral therapy and motivational enhancement therapy. Benzodiazepines remain the mainstay treatment for inpatient alcohol withdrawal treatment, whereas other medications have similar efficacy in managing patients in the outpatient setting with milder forms of withdrawal. For maintenance treatment of AUD, four FDA-approved medications exist, with efficacy in treating AUD, as well as several non–FDA-approved medications that have been found to be effective in promoting abstinence and reducing drinking. The use of medication to treat many patients with AUD falls within the scope of primary care providers.

      This review contains 6 tables and 54 references.

      Key Words: addiction, alcohol, counseling, drinking, pharmacotherapy, primary care, psychotherapy, relapse, treatment

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    • 15

      Intimate Partner Violence

      By Jane S. Sillman, MD
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      Intimate Partner Violence

      • JANE S. SILLMAN, MDAssistant Professor of Medicine, Department of Medicine, Harvard Medical School, Senior Physician, Brigham and Women’s Hospital, Boston, MA

      Intimate-partner violence describes relationships characterized by intentional controlling or violent behavior by someone who is in an intimate relationship with the victim. The abuser’s controlling behavior may take many forms, including psychological abuse, physical abuse, sexual abuse, economic control, and social isolation. Abuse may ultimately lead to the death of the victim from homicide or suicide. Typically, an abusive relationship goes through cycles of violence. There are periods of calm, followed by increasing tension in the abuser, outbursts of violence, and return to periods of calm. These cycles often spiral toward increasing violence over time. The victims of intimate-partner violence are usually women, but intimate-partner violence is also a significant problem for gay couples and for the disabled and elderly of both sexes. This review discusses the epidemiology, diagnosis, treatment, outcomes, and prevention of intimate-partner violence. Risk factors for experiencing violence, risk factors for perpetrating violence, and consequences of abuse are also analyzed.

      This review contains 5 figures, 14 tables, and 30 references.

      Keywords: Domestic abuse, intimate-partner violence, elder abuse, child abuse, batterer, sexual abuse, physical abuse

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    • 16

      Alcohol and Drug Withdrawal Syndromes and Their Clinical Management

      By Alexander Thompson, MD, MBA, MPH; Andrea Weber, MD, MME
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      Alcohol and Drug Withdrawal Syndromes and Their Clinical Management

      • ALEXANDER THOMPSON, MD, MBA, MPH
      • ANDREA WEBER, MD, MMEFifth-Year Medicine-Psychiatry Resident, Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA

      Withdrawal syndromes are clusters of signs and symptoms that occur with cessation or decrease in use of a substance. All substance withdrawal syndromes are classified and diagnosed based on criteria published in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). All withdrawal syndromes range in their ability to cause significant medical and/or psychiatric consequences. Alcohol withdrawal remains a medically serious syndrome that can occur within hours to days of decreased use and result in hallucinations, delirium, seizures, and death. Despite increasing research into the type, frequency, dose, and route of administration, benzodiazepines remain the first-line treatment in preventing alcohol withdrawal complications. Although typically not medically severe, opioid withdrawal is often associated with relapse even after successful detoxification. Opioid-agonist therapy, including methadone and buprenorphine, remains the treatment of choice for both opioid withdrawal and relapse prevention. Stimulant withdrawal from cocaine or amphetamines can cause significant psychiatric symptoms within minutes to hours of cessation and may require psychiatric hospitalization for suicidal ideation or attempts. There are no current medications approved by the Food and Drug Administration (FDA) for treatment of stimulant withdrawal. Cannabis withdrawal, although not medically dangerous, has recently been adopted as a discrete syndrome in the DSM-5. Its severity correlates significantly with the amount of cannabis used, functional impairment, and ability to achieve sustained remission. There are no current medications approved by the FDA for treatment of cannabis withdrawal.

      This review contains 6 figures, 13 tables, and 101 references.

      Key words: alcohol, amphetamine, benzodiazepines, buprenorphine, cannabis, clonidine, cocaine, dexmedetomidine, methadone, opioid, phenobarbital, stimulant, withdrawal 

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    • 17

      Male Sexual Dysfunction

      By Michael Eisenberg, MD; Kathleen Hwang, MD
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      Male Sexual Dysfunction

      • MICHAEL EISENBERG, MDDirector, Male Reproductive Medicine and Surgery, Assistant Professor, Departments of Urology and Obstetrics & Gynecology, Stanford University, Stanford, California
      • KATHLEEN HWANG, MDDepartment of Urology, Brown University, Providence, Rhode Island

      Normal male sexual function requires complex interactions among psychological, neurologic, hormonal, and vascular systems. Under the influence of proper stimulation, the acquisition and maintenance of a penile erection occur. Male sexual dysfunction includes erectile dysfunction (ED), impaired libido, and abnormal ejaculation, which occur due to aberrations in normal male sexual response. Estimates suggest a prevalence of approximately 10 to 20% in the adult male population. Thus, sexual dysfunction is a common problem in this country. This chapter focuses on several key, common components of male sexual dysfunction: namely, ED, premature ejaculation (PE), and Peyronie disease (PD). Figures include management algorithms, a graph depicting distribution of intravaginal ejaculation latency time values in a random cohort of men, and a Sexual Health Inventory for Men (SHIM). Tables list medications associated with ED, oral therapies for the treatment of PD, intralesional therapies for PD, indications for surgical correction of PD, recommended questions to establish the diagnosis of PE, treatment options for PE, and causes of delayed ejaculation, anejaculation, and anorgasmia.
      This chapter contains 5 highly rendered figures, 8 tables, 116 references, 1 teaching slide set, and 5 MCQs.

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    • 18

      Mood Disorders

      By Hasan A Baloch, MD; Jair C. Soares, MD
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      Mood Disorders

      • HASAN A BALOCH, MDAssistant Professor, Department of Psychiatry, Medical Director, Pediatric Bipolar Program, CERT-BD, UNC School of Medicine, Chapel Hill, NC
      • JAIR C. SOARES, MDDepartment of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX

      Affective disorders are among the most common disorders in psychiatry. They are generally classified according to the persistence and extent of symptoms and by the polarity of these symptoms. The two poles of the affective spectrum are mania and depression. Bipolar disorder is characterized by the presence of the mania or hypomania and often depression. Unipolar depression is defined by depression in the absence of a lifetime history of mania or hypomania. These differences are not merely categorical but have important implications for the prognosis and treatment of these conditions. Bipolar disorder, for example, is better treated using mood-stabilizing medication, whereas unipolar depression responds optimally to antidepressant medications. In addition, prognostically, unipolar depression may sometimes be limited to one episode in a lifetime, whereas bipolar disorder is typically a lifelong condition. The course of both conditions, however, is often chronic, and frequently patients can present with unipolar depression only to later develop manic symptoms. A thorough understanding of both conditions is therefore required to treat patients presenting with affective symptomatology. This chapter discusses the epidemiology, etiology and genetics, pathogenesis, diagnosis, and treatment of unipolar depression and bipolar disorder. Figures illustrate gray matter differences with lithium use and the bipolar spectrum. Tables list the pharmacokinetics of commonly used antidepressants and medications commonly used in the treatment of bipolar disorder.

      This review contains 2 figures, 2 tables, and 136 references.

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    • 19

      Attention-deficit/hyperactivity Disorder in Children and Adolescents

      By Sergio Delgado, MD
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      Attention-deficit/hyperactivity Disorder in Children and Adolescents

      • SERGIO DELGADO, MDCincinatti Children's Hospital

      Attention-deficit/hyperactivity disorder (ADHD) is the most common and thoroughly researched neuropsychiatric disorder affecting children and adolescents. The prevalence of ADHD ranges from 8 to 12% in school-age children, and 70% of these individuals continue to meet DSM-5 criteria for the disorder in adolescence. ADHD is more commonly diagnosed in boys compared with girls. ADHD is chronic, with prominent symptoms and impairment in family, social, and academic functioning. ADHD is often associated with comorbid disorders, including disruptive, mood, and anxiety disorders, and can increase the risk of developing substance use disorders. The diagnosis of ADHD requires a comprehensive clinical assessment, including a detailed history, clinical interview, and collateral information, and is clinically established by review of symptoms and impairment and having established a developmental history of the symptoms. The biological underpinning of the disorder is supported by genetic, neuroimaging, neurochemistry, and neuropsychological data. Treatment should attend to developmental milestones of the child and include family and individual psychosocial interventions. Psychosocial interventions in combination with medication are helpful for ADHD and comorbid problems. Pharmacotherapy, including psychostimulants, noradrenergic agents, alpha agonists, and antidepressants, plays a fundamental role in the treatment and management of ADHD.

      This review contains 2 figures, 9 tables, and 114 references.

      Key words: attention, attention-deficit/hyperactivity disorder, comorbidity, hyperactivity, impulsivity, learning, nonstimulants, psychosocial, psychostimulants, treatment

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    • 20

      Clinical Management of Feeding and Eating Disorders

      By Patricia Westmoreland, MD; Anne Marie O’Melia , MD
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      Clinical Management of Feeding and Eating Disorders

      • PATRICIA WESTMORELAND, MDAttending Psychiatrist, Eating Recovery Center, Denver, CO Consultant, ACUTE, Denver Health, Denver CO Adjunct Assistant Professor, University of Colorado, Denver, CO Forensic Psychiatrist, Denver, CO
      • ANNE MARIE O’MELIA , MD

      Eating disorders are diverse in etiology and presentation and are best treated by a multidisciplinary treatment team (physicians, nurses, dietitians, and psychotherapists). Effective treatment includes combinations of behavioral management, psychotherapy, and psychiatric medication. Pica and rumination disorder are typically treated with behavioral management. Treatment of avoidant/restrictive food intake disorder and restricting or binge/purge anorexia nervosa usually requires nutritional and medical management before patients are able to benefit from psychotherapy or psychiatric medication management. There are currently only two medications FDA approved for treatment in eating disorders. Fluoxetine is FDA approved for the treatment of bulimia. Lisdexamfetamine was recently approved for the treatment of binge eating disorder. Novel therapies, such as deep brain stimulation, repetitive transcranial magnetic stimulation, and transcranial direct current stimulation, are being studied for the treatment of severe and enduring forms of anorexia nervosa.


      This review contains 5 tables and 58 references

       Key words: behavioral management, diversity, FDA approval, fluoxetine, lisdexamfetamine, multidisciplinary team, novel therapies, psychotherapy, psychotropics

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    • 21

      Feeding and Eating Disorders

      By Patricia Westmoreland, MD; Phillip S Mehler, MD
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      Feeding and Eating Disorders

      • PATRICIA WESTMORELAND, MDAttending Psychiatrist, Eating Recovery Center, Denver, CO Consultant, ACUTE, Denver Health, Denver CO Adjunct Assistant Professor, University of Colorado, Denver, CO Forensic Psychiatrist, Denver, CO
      • PHILLIP S MEHLER, MD

      Feeding and eating disorders are defined by persistent disturbance of eating (or behaviors related to eating) with subsequent changes in consumption or absorption of nutrition that are detrimental to physical health and social functioning. The following eating disorders are described in the DSM-5: anorexia nervosa, bulimia nervosa, binge eating disorder, pica, rumination disorder, avoidant/restrictive food intake disorder (ARFID), other specified feeding or eating disorder (OSFED), and unspecified feeding or eating disorder (USFED). ARFID, OSFED, USFED, rumination disorder, and binge eating disorder are new additions to the manual and are first described in the DSM-5. The DSM-5 also provides severity specifiers—mild, moderate, severe, and extreme—for the diagnoses of bulimia nervosa and anorexia nervosa. This review describes the eating disorders enumerated in the DSM-5 and provides information regarding their genesis and course.

      This review contains 11 tables and 82 references

      Key words: avoidant/restrictive eating disorder, binge eating disorder, DSM-5, eating disorder, other specified feeding or eating disorder, pharmacotherapy, pica rumination, psychotherapy, unspecified feeding or eating disorder

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    • 22

      Overview of Posttraumatic Stress Disorder

      By Dana Downs, MA, MSW; Carol North, MD, MPE
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      Overview of Posttraumatic Stress Disorder

      • DANA DOWNS, MA, MSWClinical Research Manager (Retired), Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX
      • CAROL NORTH, MD, MPEMedical Director, The Altshuler Center for Education & Research at Metrocare Services, The Nancy and Ray L. Hunt Chair in Crisis Psychiatry and Professor of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX
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    • 23

      Feeding and Eating Disorders

      By Patricia Westmoreland, MD; Phillip S Mehler, MD
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      Feeding and Eating Disorders

      • PATRICIA WESTMORELAND, MDAttending Psychiatrist, Eating Recovery Center, Denver, CO Consultant, ACUTE, Denver Health, Denver CO Adjunct Assistant Professor, University of Colorado, Denver, CO Forensic Psychiatrist, Denver, CO
      • PHILLIP S MEHLER, MD
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    • 24

      Clinical Management of Drug Use Disorders

      By Alexander Thompson, MD, MBA, MPH; Timothy Ando, MD; James Jackson, MD
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      Clinical Management of Drug Use Disorders

      • ALEXANDER THOMPSON, MD, MBA, MPH
      • TIMOTHY ANDO, MDPsychiatry Resident, Department of Psychiatry, Stanford University School of Medicine, Stanford, CA
      • JAMES JACKSON, MD

      Despite mammoth efforts toward the treatment and prevention of substance use disorders in the United States over the past 30 years, they remain a significant public health concern and an all-too-common comorbidity among people with other forms of mental illness. Continued research into genetics, pharmacotherapies, psychotherapies, and epidemiology for substance use disorders results in huge amounts of new information for clinicians to assimilate each year. This review summarizes current diagnostic and categorical standards in substance use disorders, epidemiology, genetic and physiologic factors in addiction for each class, clinically relevant laboratory testing, evidence-based treatments, and prognostic considerations in substance use disorders. Specifically, sections cover cannabinoids, hallucinogens, opioids, sedatives, and stimulants.

      This review contains 3 figures, 6 tables and 60 references

      Key words: benzodiazepines, cannabis, drug dependence, hallucinogens, MDMA, substance abuse, substance dependence, synthetic cannabinoids

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    • 25

      Sleep Disorders

      By Sudhansu Chokroverty, MD, FRCP, FACP
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      Sleep Disorders

      • SUDHANSU CHOKROVERTY, MD, FRCP, FACPProfessor and Director of Sleep Research, Medical Director of Devry Technology Training Program, Co-Chair Emeritus of Neurology, Department of Neurology, JFK Neuroscience Institute, Edison, NJ, Professor of Neuroscience, Seton Hall University, South Orange, NJ, Clinical Professor of Neurology, Robert Wood Johnson Medical School, New Brunswick, NJ
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  • Pulmonary
    • 1

      Asthma

      By Haitham Nsour, MBBS; Anne E. Dixon, MA, BMBCH
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      Asthma

      • HAITHAM NSOUR, MBBSAssistant Professor, Department of Medicine, University of Vermont College of Medicine, Fletcher Allen Health Care, Burlington, VT
      • ANNE E. DIXON, MA, BMBCHProfessor, Department of Medicine, University of Vermont College of Medicine, Fletcher Allen Health Care, Burlington, VT

      Asthma is one of the most common diseases in developed nations. A pathognomonic feature of asthma is episodic aggravations of the disease; these exacerbations can be life-threatening and contribute to a significant proportion of the public health burden of asthma. In the emergency department, successful management of asthma exacerbations requires early recognition and intervention before they become severe and potentially fatal. This review summarizes the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes for asthma. Figures show the management of asthma exacerbations in the emergency department and hospital, pooled odds ratio comparing inhaled corticosteroids and oral corticosteroids with oral corticosteroids alone following emergency department discharge, and an asthma discharge plan at the emergency department. Tables list current asthma prevalence among selected demographic groups in the United States, risk factors for fatal asthma exacerbations, differential diagnosis of asthma exacerbations, and dosages of drugs for asthma exacerbations.

      This review contains 3 figures, 16 tables, and 88 references.

      Key Words: Asthma, allergic bronchopulmonary aspergillosis, gastroesophageal reflux disease, sinus disease, breathlessness, shortness of breath

       

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    • 2

      Pulmonary Function Testing

      By Maryl Kreider, MD, MS
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      Pulmonary Function Testing

      • MARYL KREIDER, MD, MSAssistant Professor of Medicine, University of Pennsylvania School of Medicine, Medical Director, Pulmonary Diagnostics Laboratory, Hospital of the University of Pennsylvania, Philadelphia, PA

      Intelligent management of pulmonary disease requires a fundamental understanding of the complex interrelationships between multiple elements that interact to maintain homeostasis in the respiratory system. This chapter discusses the physiologic basis for pulmonary function testing and the use of these tests to diagnose disease, quantitate functional impairments, and follow the effects of treatment. Figures illustrate the relationships between lung volume, airway conductance, and airway resistance; the relationship between forced expiratory volume and time (spirogram); the relationship between spirometry and maximum expiratory flow volume; dynamic airway compression; patterns of abnormalities seen on flow-volume curves; lung volumes and capacities; pressure-volume relationships in health and disease; and the clinical assessment of lung function. Tables list the capacities and volumes of gas contained in the lungs during various breathing maneuvers, conditions associated with alterations in diffusing capacity, and recommendations for tests for various clinical scenarios.

      This review contains 7 highly rendered figures, 3 tables, and 86 references.

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    • 3

      Sarcoidosis

      By Robert P Baughman, MD; Mary Beth Scholand, MD
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      Sarcoidosis

      • ROBERT P BAUGHMAN, MDProfessor of Medicine, Department of Medicine, University of Cincinnati Medical Center Cincinnati, OH
      • MARY BETH SCHOLAND, MDAssociate Professor of Medicine, Department of Medicine, University of Utah, Salt Lake City, UT

      Sarcoidosis is a systemic disease characterized by the presence of noncaseating granulomas, which accumulate in affected organs. The incidence, organ involvement, and disease severity depend on environmental exposures and host factors. The cause of sarcoidosis remains unknown. Any organ can be affected; however, involvement of the lung, heart, and nervous system contributes most to morbidity and mortality. This review discusses the epidemiology, etiology, genetics, pathogenesis, diagnosis (including clinical manifestations), differential diagnosis, management, complications, and prognosis of sarcoidosis. Figures depict the pathogenesis of sarcoidosis, radiographic stages of sarcoidosis, contrast-enhanced magnetic resonance imaging of a patient with neurosarcoidosis, noncaseating granuloma from a tissue biopsy of a patient with sarcoidosis, various manifestations of sarcoidosis, approach to the use of anti-inflammatory therapy for sarcoidosis, and an algorithm for symptomatic disease. 

      This review contains 7 highly rendered figures, 3 tables, and 126 references

      Keywords: cardiac sarcoidosis, hilar lymphadenopathy, Löfgren syndrome, neurosarcoidosis, noncaseating granuloma, sarcoidosis, uveitis 

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    • 4

      Idiopathic Lung Diseases Other Than Pulmonary Fibrosis

      By Lawrence A Ho, MD; Bridget F Collins, MD; Ganesh Raghu, MD
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      Idiopathic Lung Diseases Other Than Pulmonary Fibrosis

      • LAWRENCE A HO, MDClinical Assistant Professor, Center for Interstitial Lung Disease, Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA
      • BRIDGET F COLLINS, MDClinical Assistant Professor, Center for Interstitial Lung Disease, Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA
      • GANESH RAGHU, MDProfessor of Medicine & Lab Medicine, Center for Interstitial Lung Disease, Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA

      Idiopathic lung diseases are diffuse parenchymal lung diseases that are grouped under the term interstitial lung disease (ILD). The term interstitial (or interstitium) is, however, misleading as the term interstitium refers to the microscopic anatomic space between the basement membranes of the endothelial and epithelial cells. The pathologic processes involved in these diseases, however, are not limited to the interstitium and can affect other elements of the gas exchange units as well as bronchiolar lumen, terminal bronchioles, pulmonary parenchyma, and pleural and vascular spaces. Since there are potentially hundreds of agents and clinical situations that are associated with ILD, a simplified grouping scheme includes seven main entities: ILD associated with (1) occupational and environmental factors (inhalation cause), (2) collagen vascular diseases, (3) granulomatous lung disease of known and unknown causes (eg, hypersensitivity pneumonitis [HP], sarcoidosis), (4) inherited diseases, (5) iatrogenic/drug induced, (6) certain specific entities (eg, pulmonary Langerhans cell histiocytosis [PLCH], lymphangioleimyomatosis, and (7) idiopathic interstitial pneumonia (IIP). As idiopathic pulmonary fibrosis (IPF) is a subgroup of IIP, this review focuses on the clinical features and management of the major IIPs, and IPF is discussed more in the review, “Idiopathic Pulmonary Fibrosis,” found elsewhere in this publication. This review also focuses on HP as it is a key disease in the differential diagnosis of the IIPs. Figures depict chest radiographs, high resolution computed topography (HRCT) scans, and histopathologic features of various ILDs. Tables list the American Thoracic Society (ATS) and the European Respiratory Society (ERS) classification of IIPs, and common antigens associated with HP and their potential sources.

      This review contains 22 highly rendered figures, 2 tables, and 156 references.

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    • 5

      Chronic Obstructive Pulmonary Disease

      By Andrew J Schissler, MD; George Washko, MD; Carolyn E. Come, MD, MPH
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      Chronic Obstructive Pulmonary Disease

      • ANDREW J SCHISSLER, MDClinical and Research Fellow, Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
      • GEORGE WASHKO, MDAssociate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
      • CAROLYN E. COME, MD, MPHInstructor in Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

      Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and death worldwide. This edition reviews the epidemiology and etiologies of COPD, including the gender effects, racial differences, and more recently identified genetic factors associated with this condition. It details the many pathogenetic mechanisms thought to be associated with this disease state, such as increased airway inflammation and turnover of extracellular matrix. There is a detailed discussion about diagnosis, classification, and the therapeutic options available for both stable disease and acute exacerbations. The recent evidence supporting various treatments, such as vaccinations, inhaled bronchodilators, inhaled corticosteroids, oral corticosteroids, antibiotics, supplemental oxygen, pulmonary rehabilitation, and surgery, is reviewed in depth. There is further evaluation of experimental approaches, such as bronchoscopic lung reduction procedures and the use of extracorporeal carbon dioxide removal for hypercapnic respiratory failure. The many complications associated with COPD are described, acknowledging that evidence continues to suggest that COPD has a significant systemic component associated with increased rates of psychiatric illness, cardiovascular disease, osteoporosis, and skeletal muscle dysfunction along with lung cancer. Overall this text serves as an excellent evidence-based guide to better understand, diagnose, and manage COPD and its array of associated complications.

      This review contains 6 highly rendered figures, 6 tables, and 241 references

      Key words: chronic obstructive pulmonary disease (COPD), COPD complications, COPD diagnosis, COPD management, COPD pathophysiology, Global Initiative for Chronic Obstructive Lung Disease (GOLD)

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    • 6

      Approach to the Patient With Dyspnea

      By Roza Badr Eslam, MD; Aaron B Waxman, MD, PhD
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      Approach to the Patient With Dyspnea

      • ROZA BADR ESLAM, MDPulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
      • AARON B WAXMAN, MD, PHDPulmonary and Critical Care Medicine, Director, Pulmonary Vascular Disease Program, Executive Director, Center for Pulmonary-Heart Diseases, Brigham and Women’s Hospital Heart and Vascular Center, Associate Professor of Medicine/Harvard Medical School, Boston, MA

      Dyspnea is a common, distressing symptom of cardiopulmonary and neuromuscular disease. In a consensus statement, the American Thoracic Society defined dyspnea as “a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.” Dyspnea is a nonspecific complaint and is one of the most frequent patient complaints. This review discusses the definition, epidemiology, etiology, pathophysiology, peripheral mechanisms, and evaluation of dyspnea. Figures depict cellular metabolism and exercise physiology, and an invasive cardiopulmonary exercise testing (iCPET) flow diagram. Tables list the common causes of dyspnea, invasive cardiopulmonary exercise testing (iCPET) diagnosis, and iCPET characteristics of pulmonary hypertension.

      This review contains 2 highly rendered figures, 3 tables, and 51 references.

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    • 7

      Approach to the Patient With Cough

      By Christopher H. Fanta, MD
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      Approach to the Patient With Cough

      • CHRISTOPHER H. FANTA, MDDirector, Partners Asthma Center; Member, Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women’s Hospital; and Professor of Medicine, Harvard Medical School, Boston, MA

      The cough reflex is critically important in the clearance of abnormal airway secretions and protection of the lower respiratory tract from aspirated foreign matter. A weak or ineffective cough can lead to respiratory compromise from even a relatively minor bronchial infection. Persistent cough is often one of a constellation of symptoms indicative of respiratory disease—a potential clue in the differential diagnosis of the patient’s illness. Given the widespread distribution of sensory nerve endings of the cough reflex throughout the upper and lower respiratory tract, it is not surprising that myriad respiratory diseases, involving lung parenchyma and airways, can manifest with cough. Sometimes cough is the sole or predominant symptom in a patient who is otherwise well. Evaluating and treating the patient with persistent cough who has few, if any, other respiratory symptoms is a common challenge for the practicing physician. This review covers the normal cough mechanism, impaired cough, pathologic cough, cough suppressant therapy, and new developments. Figures show a flow-volume loop during cough, a posteroanterior chest x-ray in a patient presenting with chronic cough, flow-volume curves and spirograms documenting expiratory airflow obstruction, and the approach to the patient with chronic cough. The table lists selected examples of extrapulmonary physical findings of potential importance in the assessment of cough.

      This review contains 4 highly rendered figures, 1 table, and 94 references.

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    • 8

      Upper Airway Disorders

      By Lawrence Proano, MD, DTMH ; Seth Gemme, MD; Robert Partridge, MD, MPH, DTMH
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      Upper Airway Disorders

      • LAWRENCE PROANO, MD, DTMH Clinical Professor of Emergency Medicine, The Alpert Medical School of Brown University, Providence, RI
      • SETH GEMME, MDRhode Island Hospital; Chief Resident, The Alpert Medical School of Brown University, Providence, RI
      • ROBERT PARTRIDGE, MD, MPH, DTMH Adjunct Associate Professor of Emergency Medicine, he Alpert Medical School of Brown University, Providence, RI

      Upper airway disorders are frequently encountered in the primary care setting and present in both adults and children.  This review covers earache, sinusitis, sore throat, peritonsillar abscess, sialolithiasis and sialadenitis, parotitis, epiglottitis, epistaxis, foreign body in the ear, nose, or throat, and Ludwig angina. Figures show right-sided peritonsillar abscess demonstrating swelling and distortion of the anterior and posterior tonsillar pillars and uvular deviation, peritonsillar abscess demonstrated by an ultrasound image of a hypoechoic fluid collection, ultrasound imaging of sagittal view of the tonsillar pillars, lateral radiograph of the neck demonstrating a swollen epiglottis and widened vallecula, photographs of brawny swelling of the submandibular region of the neck in Ludwig angina, and a patient with peritonsillar abscess with extension to the base of the tongue. Tables list criteria for diagnosing acute sinusitis, and clinical presentations that best identify patients with acute bacterial versus viral rhinosinusitis.

       

      This review contains 7 figures, 17 tables, and 66 references

      Keywords: Epiglottitis, epistaxis, parotitis, peritonsillar abscess, pharyngitis, sialolithiasis, sinusitis

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    • 9

      Respiratory Viral Infections

      By Michael G. Ison, MD, MSc
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      Respiratory Viral Infections

      • MICHAEL G. ISON, MD, MSCAssociate Professor, Divisions of Infectious Diseases & Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL

      The respiratory tract can be infected by a diverse group of viruses that produce syndromes ranging in severity from mild colds to fulminant pneumonias. Respiratory viral infections are a leading cause of morbidity, hospitalization, and mortality throughout the world; influenza and pneumonia were the most prevalent infectious causes of death during the 20th century in the United States.

      This review contains 8 figures, 26 tables and 87 references.

      Keywords: Virus, infection, respiratory tract, antiviral, pneumonia, croup, pharyngitis, epidemic, pandemic, outbreak

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    • 10

      The Respiratory System: Physiology

      By John Yerxa, MD; Cory J Vatsaas, MD; Suresh Agarwal, MD, FACS, FCCM
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      The Respiratory System: Physiology

      • JOHN YERXA, MDResident in General Surgery, Department of Surgery, Duke University, Durham, NC
      • CORY J VATSAAS, MDAssistant Professor, Department of Surgery, Duke University, Durham, NC
      • SURESH AGARWAL, MD, FACS, FCCMChief, Division of Trauma and Critical Care Surgery, Professor, Department of Surgery, Duke University, Durham, NC

      Respiratory system uses an elegant physiologic mechanism to support the metabolic demands of the body through oxygenation and ventilation. Oxygen must be absorbed and delivered to the tissues to sustain oxidative metabolism, whereas carbon dioxide must be expelled in a delicate balance to maintain an acid-base equilibrium. Complete understanding of oxygen content, delivery, consumption, and carbon dioxide elimination is essential as a provider caring for the critically ill patient.

      This review contains 13 figures and 25 references.

      Key Words: oxygenation, respiratory system, ventilation, gas exchange, haemoglobin, respiratory physiology, respiratory anatomy, oxidative metabolism, dead space.

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    • 11

      The Respiratory System: Physiologic Assessment and Real-world Application

      By Joshua Watson, MD; Cory Vatsaas, MD; Suresh Agarwal, MD, FACS, FCCM
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      The Respiratory System: Physiologic Assessment and Real-world Application

      • JOSHUA WATSON, MDResident in General Surgery, Department of Surgery, Duke University, Durham, NC
      • CORY VATSAAS, MDAssistant Professor, Department of Surgery, Duke University, Durham, NC
      • SURESH AGARWAL, MD, FACS, FCCMChief, Division of Trauma and Critical Care Surgery, Professor, Department of Surgery, Duke University, Durham, NC

      The respiratory system is an elegant physiologic mechanism that provides the most basic support of the body, oxygenation and ventilation. Oxygen must be absorbed and delivered to the tissues to continue with oxidative metabolism while the byproduct of carbon dioxide must be expelled in a delicate balance to maintain an acid/base equilibrium. Complete understanding of oxygen content, delivery, and consumption is essential as a provider caring for the critically ill patient. The respiratory system can be closely monitored through a variety of helpful adjuncts including pulse oximetry, capnometry, and pulmonary function testing. These additional data points are useful for assessing a patient’s clinical condition in conjunction with the patient’s overall pulmonary status, underlying pathology, and environmental factors. A thorough understanding of the respiratory system guided by diagnostic testing and an assessment of patient factors are helpful in mitigating risk of pulmonary complications in the perioperative environment.

      This review contains 2 figures, 2 tables, and 54 references.

      Key Words: capnometry, pulse oximetry, respiratory system, oxygenation, ventilation pulmonary, pulmonary function testing, pulmonary complications, preoperative pulmonary optimization, smoking cessation

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    • 12

      Respiratory System: Physiology of Mechanical Ventilation

      By John Yerxa, MD; Cory J Vatsaas, MD; Suresh Agarwal, MD, FACS, FCCM
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      Respiratory System: Physiology of Mechanical Ventilation

      • JOHN YERXA, MDResident in General Surgery, Department of Surgery, Duke University, Durham, NC
      • CORY J VATSAAS, MDAssistant Professor, Department of Surgery, Duke University, Durham, NC
      • SURESH AGARWAL, MD, FACS, FCCMChief, Division of Trauma and Critical Care Surgery, Professor, Department of Surgery, Duke University, Durham, NC

      Airway and ventilatory management are mandatory skills for the critical care surgeon. Identifying and correctly managing a patient’s airway is the first step followed by correcting any oxygenation or ventilation deliver deficits. Mechanical ventilation with positive pressure has multiple physiologic effects that must be completely understood in a complex critically ill patient. Invasive and non-invasive modalities may be used to aid in achieving these goals. Further strategies such as using low tidal volume, adequate PEEP, and rescue strategies are important in patients with ARDS. Weaning from the ventilator as soon as able is an important consideration to improve outcomes,  The subsequent chapter reviews airway management and the physiologic aspects of mechanical ventilation to aid in decision-making when caring for the critically ill patient with deficits in oxygenation or ventilation.

      This review 5 figures, 2 tables, and 41 references.

      Key Words: airway management, mechanical ventilation, invasive ventilation, non-invasive ventilation, tracheostomy, Acute Respiratory Distress Syndrome (ARDS), positive pressure ventilation, oxygenation

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    • 13

      Disorders of the Pleura, Mediastinum, and Hilum

      By Andrew D Lerner, MD; David Feller-Kopman, MD
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      Disorders of the Pleura, Mediastinum, and Hilum

      • ANDREW D LERNER, MDAssistant in Medicine, Interventional Pulmonology, Division of Pulmonary and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, MD
      • DAVID FELLER-KOPMAN, MDDirector, Bronchoscopy and Interventional Pulmonology, Associate Professor of Medicine, Otolaryngology–Head and Neck Surgery, Interventional Pulmonology, Division of Pulmonary and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, MD

      The pleura are a composition of two serous membranes: the visceral pleura lining the lungs and the parietal pleura lining the inner chest wall, diaphragm, and mediastinum. The pulmonary hilum is composed of blood vessels, airways, nerves, and lymph nodes and denotes the meeting point between the mediastinum and the pleural cavities. This review covers disorders of the pleura, mediastinum, and hilum. Figures show a schematic diagram of normal filtration/resorption of fluid in the pleural space; comparison of a simultaneously obtained chest x-ray (CXR) and a chest computed tomographic (CT) scan of the same patient; an algorithm for evaluation of patients with pleural effusion (PE); a three-compartment model of mediastinal anatomy; photographs of a resected, well-encapsulated thymoma and a benign, multiloculated thymic cyst that were completely removed by sternotomy, a resected esophageal duplication cyst, and an esophageal leiomyoma being removed by means of a right thoracotomy; CT scans demonstrating the characteristic appearance of an invasive thymoma, an extragonadal germ cell tumor, a primary mediastinal B cell lymphoma, a goiter with extension behind the trachea, right paratracheal adenopathy in the middle mediastinal compartment, a middle mediastinal cystic mass, a large subcarinal bronchogenic cyst, a tracheal chondrosarcoma, gas in the mediastinum due to esophageal perforation, and mediastinal fibrosis; coronal imaging showing a large, smooth muscle tumor associated with the distal esophagus; a barium swallow showing a large esophageal perforation that resulted in soilage of the middle mediastinum; and posteroanterior and lateral CXRs of a posterior mediastinal neurogenic tumor accompanied by a CT scan showing the posterior mediastinal neurogenic tumor visualized in the posteroanterior radiograph. 

      This review contains 19 figures, 51 tables, and 83 references.

      Keywords:  Mediastinum, mediastinitis, pleural effusion, empyema, congestive heart failure, adenopathy, thymoma, esophageal perforation

       

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    • 14

      Occupational and Environmental Lung Diseases Selected Pneumoconiosis

      By Cora S Sack, MD ; Sverre Vedal, MSc, MD; Joel D Kaufman, MPH, MD
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      Occupational and Environmental Lung Diseases Selected Pneumoconiosis

      • CORA S SACK, MD Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, Department of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA
      • SVERRE VEDAL, MSC, MDDepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA
      • JOEL D KAUFMAN, MPH, MDDepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, Department of Medicine, University of Washington, Seattle, WA, Department of Epidemiology, University of Washington, Seattle, WA

      Environmental and occupational lung diseases encompass a diverse group of lung diseases caused by the inhalation of potentially harmful substances. This review provides an in-depth discussion of the pneumoconioses, hypersensitivity pneumonitis, chronic beryllium disease, and other occupational lung diseases that affect the parenchyma. For each disease, the review presents the epidemiology, biologic mechanisms when known, diagnosis, and clinical care. The review includes tables with different pneumoconioses, occupations and industries associated with silicosis and asbestosis, and some selected causes of hypersensitivity pneumonitis, as well as chest radiographs, computed tomographic scans, and/or pathologic slides of some selected diseases.

      This review contains 9 figures, 4 tables, and 68 references.

      Key words: asbestosis, asbestos-related pleural plaque, coal worker’s pneumoconiosis, chronic beryllium disease, hard metal pneumoconiosis, hypersensitivity pneumonitis, pneumoconiosis, progressive massive fibrosis, silicosis

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    • 15

      Cystic Fibrosis and Non-cystic Fibrosis Bronchiectasis

      By Michael J Stephen, MD
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      Cystic Fibrosis and Non-cystic Fibrosis Bronchiectasis

      • MICHAEL J STEPHEN, MDAssistant Professor of Medicine, Drexel University School of Medicine, Philadelphia, PA

      Cystic fibrosis (CF) is an autosomal recessive disease characterized by an elevated sweat chloride level, diffuse bronchiectasis, and pancreatic exocrine deficiency. It is the most common lethal inherited disease in whites. Most patients present at birth or early childhood, although later diagnoses are not infrequent. Once CF was uniformly fatal at an early age, but advances in nutrition, airway clearance, and infection management have led to an average survival of 37 years. The newest aspect of care is the advent of protein modulators, which may increase life expectancy even further. This chapter discusses the epidemiology, genetics, pathophysiology and pathogenesis, diagnosis, differential diagnosis, and treatment of CF. The definition, epidemiology, etiology, pathogenesis, diagnosis, management, and prognosis of non-CF bronchiectasis are also covered. Figures illustrate normal and abnormal CF transmembrane conductance regulators, the vicious cycle hypothesis of lung injury, rates of respiratory germs by age, the diagnosis of CF, the therapeutics pipeline for CF, forced expiratory volume in 1 second lung function percent predicted versus body mass index, and the median predicted survival age of patients with CF. A chest x-ray and chest computed tomographic scan of CF are also provided. Tables outline the most common CF mutations in 2011, class mutations of CF, a mnemonic for acute exacerbations of CF, the diagnosis of CF-related diabetes in a stable patient, sweat test values, and the differential diagnosis of bronchiectasis.
      This chapter contains 9 highly rendered figures, 6 tables, 143 references, 1 teaching slide set, and 5 MCQs.

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    • 16

      Pulmonary Edema I: Cardiogenic Pulmonary Edema

      By Annette Esper, MD; Greg S Martin, MD, MSc, FACP; Gerald W. Staton Jr, MD, FACP
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      Pulmonary Edema I: Cardiogenic Pulmonary Edema

      • ANNETTE ESPER, MDAssistant Professor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, 615 Michael Street, Whitehead Building 205, Atlanta, GA 30322
      • GREG S MARTIN, MD, MSC, FACPAssociate Professor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, 615 Michael Street, Whitehead Building 205, Atlanta, GA 30322
      • GERALD W. STATON JR, MD, FACPProfessor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, Atlanta, GA

      There are two categories of pulmonary edema: edema caused by increased capillary pressure (hydrostatic or cardiogenic edema) and edema caused by increased capillary permeability (noncardiogenic pulmonary edema, or acute respiratory distress syndrome). This review focuses on cardiogenic pulmonary edema and describes the general approach to patients with suspected cardiogenic pulmonary edema. The pathogenesis, diagnosis, treatment, and outcome of cardiogenic pulmonary edema are reviewed. Figures include chest scans showing pulmonary edema and noncardiogenic pulmonary edema, an illustration of the differences between cardiogenic and noncardiogenic edema, and a chart comparing lung mechanics and other variables in experimental models of cardiogenic pulmonary edema and noncardiogenic edema. Tables show clinical characteristics of patients with cardiogenic pulmonary edema and treatment options.

      This review contains 3 figures, 4 tables, and 29 references

      Keywords: cardiogenic pulmonary edema, congestive heart failure, pulmonary edema, Starling’s law

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    • 17

      Occupational and Environmental Lung Diseases: Diagnosis and Prevention

      By Cora S Sack, MD ; Sverre Vedal, MSc, MD; Joel D Kaufman, MPH, MD
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      Occupational and Environmental Lung Diseases: Diagnosis and Prevention

      • CORA S SACK, MD Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, Department of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA
      • SVERRE VEDAL, MSC, MDDepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA
      • JOEL D KAUFMAN, MPH, MDDepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, Department of Medicine, University of Washington, Seattle, WA, Department of Epidemiology, University of Washington, Seattle, WA

      Environmental and occupational lung diseases encompass a diverse group of lung diseases caused by the inhalation of potentially harmful substances. Although workplace regulations and the changing economy in the United States have significantly decreased incidence, these diseases remain both common and associated with significant morbidity. In addition, novel exposures continue to be recognized as new causes of disease. This review provides the medical student and clinician with a framework for approaching and categorizing environmental and occupational lung disease. It also presents an in-depth discussion of the epidemiology, biological mechanisms, diagnosis, and clinical care of some of the more commonly encountered diseases. Occupational lung diseases that affect the airways, such as work-related asthma and chronic obstructive pulmonary disease, and malignant neoplasms are covered. This review concludes with general strategies to help prevent disease incidence and progression.    

      This review contains 1 figure, 5 tables, and 56 references.

      Key words: bronchiolitis obliterans, chronic obstructive pulmonary disease, irritant-induced occupational asthma, mesothelioma, occupational asthma, occupational lung disease, occupational lung neoplasm, work-related asthma

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    • 18

      Pulmonary Edema II: Noncardiogenic Pulmonary Edema

      By Annette Esper, MD; Greg S Martin, MD, MSc, FACP; Gerald W. Staton Jr, MD, FACP
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      Pulmonary Edema II: Noncardiogenic Pulmonary Edema

      • ANNETTE ESPER, MDAssistant Professor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, 615 Michael Street, Whitehead Building 205, Atlanta, GA 30322
      • GREG S MARTIN, MD, MSC, FACPAssociate Professor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, 615 Michael Street, Whitehead Building 205, Atlanta, GA 30322
      • GERALD W. STATON JR, MD, FACPProfessor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, Atlanta, GA

      There are two categories of pulmonary edema: edema caused by increased capillary pressure (hydrostatic or cardiogenic edema) and edema caused by increased capillary permeability (noncardiogenic pulmonary edema, or acute respiratory distress syndrome [ARDS]). This review focuses on noncardiogenic pulmonary edema and describes the general approach to patients with suspected pulmonary edema. The pathogenesis, diagnosis, treatment, and outcome of noncardiogenic pulmonary edema are reviewed. Miscellaneous causes of pulmonary edema are discussed, including neurologic insults, exposure to high altitude, reexpansion of a collapsed lung, lung transplantation, upper airway obstruction, drugs, and lung resection. Figures include chest scans showing pulmonary edema and noncardiogenic pulmonary edema, an illustration of the differences between cardiogenic and noncardiogenic edema, and a chart comparing lung mechanics and other variables in experimental models of cardiogenic pulmonary edema and noncardiogenic edema. Tables show clinical characteristics of patients with noncardiogenic pulmonary edema, the definition of ARDS, causes of ARDS, and treatments for ARDS that do not involve ventilation.

      This review contains 3 figures, 9 tables, and 64 references

      Keywords: acute respiratory distress syndrome, diffuse alveolar damage, noncardiogenic pulmonary edema, pulmonary edema

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    • 19

      Invasive Diagnostic and Therapeutic Techniques in Lung Disease

      By Raphael Bueno, MD; Abby White, DO
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      Invasive Diagnostic and Therapeutic Techniques in Lung Disease

      • RAPHAEL BUENO, MDAssociate Chief, Division of Thoracic Surgery, Brigham and Women’s Hospital, Boston, MA
      • ABBY WHITE, DOInstructor, Department of Surgery, Harvard Medical School, Associate Surgeon, Division of Thoracic Surgery, Brigham and Women’s Hospital, Consultant Surgeon, Dana-Farber Cancer Institute, Boston, MA

      This review encompasses the diagnosis and management of primary lung diseases. Although every encounter with a patient with suspected primary lung disease begins with a history and physical examination, many patients present with imaging abnormalities. It is therefore essential to have a thorough understanding of chest radiography, computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonography (US). Many patients are simply followed with chest CT to monitor disease progression, stability, or regression before proceeding with invasive methods, the subject of this review. This review discusses flexible and rigid bronchoscopies, and open and video-assisted surgeries.

      This review contains 21 figures, 9 tables, and 40 references. 

      Keywords: Lung, transplant, bronchoscopy, thoracotomy, video-assisted thoracoscopic surgery, ablation, electrocautery, cryotherapy, stent, thoracentesis, mediastinoscopy

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    • 20

      Invasive Diagnostic and Therapeutic Techniques in Lung Disease

      By Raphael Bueno, MD; Abby White, DO
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      Invasive Diagnostic and Therapeutic Techniques in Lung Disease

      • RAPHAEL BUENO, MDAssociate Chief, Division of Thoracic Surgery, Brigham and Women’s Hospital, Boston, MA
      • ABBY WHITE, DOInstructor, Department of Surgery, Harvard Medical School, Associate Surgeon, Division of Thoracic Surgery, Brigham and Women’s Hospital, Consultant Surgeon, Dana-Farber Cancer Institute, Boston, MA
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    • 21

      Sarcoidosis

      By Robert P Baughman, MD; Mary Beth Scholand, MD
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      Sarcoidosis

      • ROBERT P BAUGHMAN, MDProfessor of Medicine, Department of Medicine, University of Cincinnati Medical Center Cincinnati, OH
      • MARY BETH SCHOLAND, MDAssociate Professor of Medicine, Department of Medicine, University of Utah, Salt Lake City, UT
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    • 22

      Asthma

      By Haitham Nsour, MBBS; Anne E. Dixon, MA, BMBCH
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      Asthma

      • HAITHAM NSOUR, MBBSAssistant Professor, Department of Medicine, University of Vermont College of Medicine, Fletcher Allen Health Care, Burlington, VT
      • ANNE E. DIXON, MA, BMBCHProfessor, Department of Medicine, University of Vermont College of Medicine, Fletcher Allen Health Care, Burlington, VT
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    • 23

      Lung Transplantation 2: Care of the Lung Transplant Recipient

      By Hilary J Goldberg, MD, MPH
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      Lung Transplantation 2: Care of the Lung Transplant Recipient

      • HILARY J GOLDBERG, MD, MPHProfessor of Medicine, Harvard Medical School, Boston, MA

      Lung transplantation is a potential therapeutic option for select candidates with advanced lung disease who have exhausted other therapeutic interventions and in whom survival and/or quality of life are threatened by the progression of disease. Although lung transplantation may confer substantial benefits on recipients, the median survival after lung transplantation according to the most recent registry data is only 5.7 years,1 substantially shorter than that for other solid-organ transplant cohort. This review discusses posttransplantation management, transplantation outcomes, and posttransplanation complications. 

      This review contains 5 figures, 6 tables, and 38 references. 

      Keywords: Lung transplant, postoperative period, immunosuppression, survival, complications, allograft rejection, infection, bronchiolitis obliterans syndrome, lung infection

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    • 24

      Lung Transplantation 2: Care of the Lung Transplant Recipient

      By Hilary J Goldberg, MD, MPH
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      Lung Transplantation 2: Care of the Lung Transplant Recipient

      • HILARY J GOLDBERG, MD, MPHProfessor of Medicine, Harvard Medical School, Boston, MA
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    • 25

      Obstructive Sleep Apnea: Epidemiology, Causes, and Consequences

      By Diane C Lim, MD, MTR; Richard J Schwab, MD
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      Obstructive Sleep Apnea: Epidemiology, Causes, and Consequences

      • DIANE C LIM, MD, MTRAssistant Professor, Medicine, University of Pennsylvania, Philadelphia, PA
      • RICHARD J SCHWAB, MDProfessor, Medicine University of Pennsylvania, Philadelphia, PA

      As part one of the three chapters on sleep-disordered breathing, this chapter reviews obstructive sleep apnea (OSA) epidemiology, causes, and consequences. When comparing OSA prevalence between 1988 to 1994 and 2007 to 2010, we observe that OSA is rapidly on the rise, paralleling increasing rates in obesity. Global epidemiologic studies indicate that there are differences specific to ethnicity with Asians presenting with OSA at a lower body mass index than Caucasians. We have learned that structural and physiologic factors increase the risk of OSA and both can be influenced by genetics. Structural risk factors include craniofacial bony restriction, changes in fat distribution, and the size of the upper airway muscles. Physiologic risk factors include airway collapsibility, loop gain, pharyngeal muscle responsiveness, and arousal threshold. The consequences of OSA include daytime sleepiness and exacerbation of many underlying diseases. OSA has been associated with cardiovascular diseases including hypertension, coronary heart disease, stroke, atrial fibrillation, and other cardiac arrhythmias; pulmonary hypertension; metabolic disorders such as type 2 diabetes, hypothyroidism, acromegaly, Cushing syndrome, and polycystic ovarian syndrome; mild cognitive impairment or dementia; and cancer.

      This review contains 4 figures, 1 table and 48 references.

      Key Words: cardiac consequences, craniofacial bony restriction, epidemiology, fat distribution, metabolic disease, neurodegeneration, obesity, obstructive sleep apnea

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    • 26

      Pulmonary Edema I: Cardiogenic Pulmonary Edema

      By Annette Esper, MD; Greg S Martin, MD, MSc, FACP; Gerald W. Staton Jr, MD, FACP
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      Pulmonary Edema I: Cardiogenic Pulmonary Edema

      • ANNETTE ESPER, MDAssistant Professor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, 615 Michael Street, Whitehead Building 205, Atlanta, GA 30322
      • GREG S MARTIN, MD, MSC, FACPAssociate Professor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, 615 Michael Street, Whitehead Building 205, Atlanta, GA 30322
      • GERALD W. STATON JR, MD, FACPProfessor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, Atlanta, GA
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    • 27

      Pulmonary Edema II: Noncardiogenic Pulmonary Edema

      By Annette Esper, MD; Greg S Martin, MD, MSc, FACP; Gerald W. Staton Jr, MD, FACP
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      Pulmonary Edema II: Noncardiogenic Pulmonary Edema

      • ANNETTE ESPER, MDAssistant Professor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, 615 Michael Street, Whitehead Building 205, Atlanta, GA 30322
      • GREG S MARTIN, MD, MSC, FACPAssociate Professor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, 615 Michael Street, Whitehead Building 205, Atlanta, GA 30322
      • GERALD W. STATON JR, MD, FACPProfessor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, Atlanta, GA
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    • 28

      Pulmonary Edema II: Noncardiogenic Pulmonary Edema

      By Annette Esper, MD; Greg S Martin, MD, MSc, FACP; Gerald W. Staton Jr, MD, FACP
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      Pulmonary Edema II: Noncardiogenic Pulmonary Edema

      • ANNETTE ESPER, MDAssistant Professor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, 615 Michael Street, Whitehead Building 205, Atlanta, GA 30322
      • GREG S MARTIN, MD, MSC, FACPAssociate Professor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, 615 Michael Street, Whitehead Building 205, Atlanta, GA 30322
      • GERALD W. STATON JR, MD, FACPProfessor of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, Atlanta, GA
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    • 29

      Upper Airway Disorders

      By Lawrence Proano, MD, DTMH ; Seth Gemme, MD; Robert Partridge, MD, MPH, DTMH
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      Upper Airway Disorders

      • LAWRENCE PROANO, MD, DTMH Clinical Professor of Emergency Medicine, The Alpert Medical School of Brown University, Providence, RI
      • SETH GEMME, MDRhode Island Hospital; Chief Resident, The Alpert Medical School of Brown University, Providence, RI
      • ROBERT PARTRIDGE, MD, MPH, DTMH Adjunct Associate Professor of Emergency Medicine, he Alpert Medical School of Brown University, Providence, RI
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  • Rheumatology
    • 1

      Idiopathic Inflammatory Myopathies

      By Frederick W Miller, MD, PhD; Adam Schiffenbauer, MD
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      Idiopathic Inflammatory Myopathies

      • FREDERICK W MILLER, MD, PHDChief, Environmental Autoimmunity Group, Office of Clinical Research, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD
      • ADAM SCHIFFENBAUER, MDStaff Clinician, Environmental Autoimmunity Group, Office of Clinical Research, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD

      The idiopathic inflammatory myopathies (IIMs), also known as myositis syndromes, are a collection of heterogeneous disorders that share the common feature of chronic muscle inflammation of unknown cause. These disorders may occur in adults or children and are sometimes associated with other connective tissue disorders and a variety of cancers. A combined clinical, laboratory, and pathologic evaluation is needed to establish the diagnosis of these acquired systemic connective tissue diseases to rule out the many disorders that mimic IIMs. This module reviews the classification of IIMs, including polymyositis, dermatomyositis, inclusion body myositis, myositis associated with other connective tissue diseases and cancer, and antisynthetase syndrome. The epidemiology; etiology, genetics, and environmental factors; pathophysiology and pathogenesis; diagnosis; differential diagnosis; treatment; and prognosis of IIMs are discussed. Tables describe the criteria for polymyositis, dermatomyositis, and inclusion body myositis; well-characterized subgroups of the IIMs in adults and children; presentation of polymyositis; differential diagnosis of muscle weakness or pain; features that assist in discriminating IIMs from other myopathies; goals for managing IIMs; and key factors for achieving adequate corticosteroid response in IIMs. Figures demonstrate skin findings in IIMs, muscle pathology of IIMs, magnetic resonance imaging of three patients with different IIMs, and treatment approaches to the management of myositis patients.

      This review contains 4 highly rendered figures, 8 tables, and 80 references.

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    • 2

      Systemic Vasculitis Syndromes

      By Alexandra Villa-Forte, MD, MPH; Brian F Mandell, MD, PhD, FACP
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      Systemic Vasculitis Syndromes

      • ALEXANDRA VILLA-FORTE, MD, MPHStaff Physician, Center for Vasculitis Care and Research, Orthopedic and Rheumatologic Institute, Cleveland Clinic, Cleveland, OH
      • BRIAN F MANDELL, MD, PHD, FACPProfessor of Medicine, Department of Rheumatic Immunologic Disease, Vice Chairman of Medicine, Cleveland Clinic, Lerner College of Medicine, Case Western Reserve University, Cleveland, OH

      Vasculitis is defined by histologic evidence of inflammation that involves the blood vessels. The diagnosis of a specific primary vasculitic disorder depends on the pattern of organ involvement, the histopathology, the size of affected blood vessels, and the exclusion of diseases that can cause “secondary” vasculitis. This review presents an approach to the patient suspected of having vasculitis, and goes on to discuss small vessel vasculitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa, Kawasaki disease, large vessel arteritis, and Behçet disease. Figures show classification of the systemic vasculitis syndromes, the relationships among the causes of small vessel (“hypersensitivity”) vasculitis, palpable purpura of the distal extremities, saddle nose deformity, the nodular infiltrates of the lung in granulomatosis with polyangiitis shown on plain radiograph as well as computed tomography, necrotizing scleritis, livedo reticularis, and angiograms of a patient with Takayasu arteritis. Tables list selected laboratory tests for patients with multisystem disease and possible vasculitis, practical comments on immunosuppressive therapies for vasculitis, features of vasculitis, diagnostic criteria for Kawasaki disease, and giant cell arteritis.

      This review contains 8 figures, 15 tables, and 65 references

      Keywords: Vasculitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, giant cell arteritis, Takayasu arteritis, polyarteritis nodosa, Kawasaki disease, Behçet disease, hypersensitivity

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    • 3

      The Patient With Complex Regional Pain Syndrome

      By George C Chang Chien, DO; Charles A Odonkor, MD; Robert Norman Harden, MD
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      The Patient With Complex Regional Pain Syndrome

      • GEORGE C CHANG CHIEN, DOMedical Director, Pain Management, Ventura County Medical Center, Director, Center for Regenerative Medicine, University of Southern California, CA
      • CHARLES A ODONKOR, MDJohn Hopkins Medicine, Baltimore, MD
      • ROBERT NORMAN HARDEN, MDProfessor Emeritus of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL

      Complex regional pain syndrome (CRPS) is a multisymptom syndrome involving aberrant pathophysiology of the peripheral, autonomic, and/or central nervous systems. The central feature is severe, often debilitating pain. This is accompanied by a collection of sensory, motor, autonomic, skin, and/or bone abnormalities. A key feature is allodynia, where otherwise innocuous stimulation will cause pain and hyperalgesia. The patient will present with varying degrees of pain, allodynia, hyperalgesia, swelling, and color and temperature changes. There are often changes in motor function, such as muscle stiffness or even involuntary movements. Regional osteopenia, changes to hair and nail growth, and dystrophic cutaneous changes may occur. The Budapest criteria have been twice validated and are used to diagnose CRPS. A patient-centric clinical approach is important in the treatment of CRPS. Key domains to be addressed in the management of CRPS include rehabilitation and pain management with adjunct psychological therapy. It is important that these interventions happen concurrently within the continuum of care. With the guidance of a physician, physical therapist, occupational therapist, and neuropsychologist, rehabilitative training programs are designed to address motor, sensory, and cognitive deficits.

      This review contains 2 highly rendered figures, 4 tables, and 110 references.

      Key Words: Budapest criteria, complex regional pain syndrome, reflex sympathetic dystrophy, sympathetically mediated pain

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    • 4

      Osteoarthritis

      By Christopher Wise, MD, FACP
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      Osteoarthritis

      • CHRISTOPHER WISE, MD, FACPRobert Irby Professor of Medicine, Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA

      Osteoarthritis is a common form of arthritis characterized by degeneration of articular cartilage and pathologic changes in surrounding bone and periarticular tissue. The disease process results in pain and dysfunction of affected joints and is a major cause of disability in the general population. Prognosis is variable; greater muscle strength, mental health, self-efficacy, social support, and aerobic exercise are associated with better outcomes. This review outlines the classification of osteoarthritis (primary and secondary) and its epidemiology and etiologic factors, including risk factors, normal articular cartilage, and pathologic changes. Diagnosis is reviewed in terms of general considerations and specific joint involvement and related complications. The differential diagnosis is discussed. Management of osteoarthritis includes nonpharmacologic measures, pharmacologic therapy, surgery, and disease-modifying or chondroprotective therapy. 

      This review contains 6 figures, 8 tables, and 84 references.

      Keywords: Knee, hand, hip, osteoarthritis, joint pain, synovial fluid, inflammation, weight-bearing

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    • 5

      Rheumatoid Arthritis: Treatment

      By Gary S. Firestein, MD; Anna-Karin H. Ekwall, MD, PhD
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      Rheumatoid Arthritis: Treatment

      • GARY S. FIRESTEIN, MDProfessor of Medicine, Dean and Associate Vice Chancellor of Translational Medicine, UC San Diego School of Medicine, La Jolla, California
      • ANNA-KARIN H. EKWALL, MD, PHDSpecialist in Rheumatology, University of California San Diego School of Medicine, La Jolla, CA, Researcher/Postdoc, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden

      The main goal of treatment of rheumatoid arthritis (RA) has evolved from modest improvement to low disease activity and will soon be complete remission. To reach this goal, the rheumatologist and patient should define the goal and treatment strategy together. Disease activity should be measured regularly using validated composite measures such as disease activity score, simple disease activity index, and clinical disease activity index. Management involves efforts to relieve pain and discomfort, preserve strength and joint function, and prevent structural deformities. Surgical intervention is important for replacing destroyed joints and for restoring function and preventing further damage. This review discusses the role of drug therapy, including nonsteroidal antiinflammatory drugs, methotrexate, antimalarial drugs, sulfasalazine, leflunomide, tofacitinib, biologic drugs, T cell– and B cell–targeted therapy, glucocorticoids, and other immunosuppressive agents. Nonmedical therapy, surgery, and prognosis are also detailed. 

      This review contains 2 figures, 16 tables, and 40 references.

      Keywords: Autoimmune, rheumatoid arthritis, T cell therapy, B cell therapy, methotrexate, joint disease, tofacitinib

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    • 6

      Fibromyalgia

      By Daniel Joseph Clauw, MD
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      Fibromyalgia

      • DANIEL JOSEPH CLAUW, MDProfessor of Anesthesiology, Medicine and Psychiatry, Director, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, MI

      Clinicians often encounter individuals who present with pain that they cannot adequately explain based on the degree of damage or inflammation noted in peripheral tissues. This typically prompts an evaluation looking for a cause of the pain. If no cause is found, these individuals are often given a diagnostic label that merely connotes that the patient has chronic pain in a region of the body, without an underlying mechanistic cause. Fibromyalgia (FM) is merely the current term for widespread musculoskeletal pain for which no alternative cause can be identified. This review covers the epidemiology, etiology/genetics, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, and complications and prognosis of FM. Figures show underlying mechanisms that can cause chronic pain; an individual’s “set point” or “volume control setting” for pain as set by a variety of factors, including the levels of neurotransmitters that either facilitate pain or reduce pain transmission; the 2011 Fibromyalgia Survey Criteria; symptoms and syndromes frequently seen in individuals with FM; the distribution of the 2011 Fibromyalgia Survey scores in a large cohort of individuals undergoing joint replacement surgery; and an algorithm showing the importance of dually focused treatment for FM and other chronic pain conditions. Tables list clinical characteristics of centralized pain, pharmacologic therapies for FM, and nonpharmacologic therapies for FM.

      This review contains 6 figures, 9 tables, and 78 references.

      Keywords: Fibromyalgia, chronic low back pain, headache, temporomandibular joint disorder, gastrointestinal disorder, irritable bowel syndrome (IBS), nonulcer dyspepsia, or esophageal dysmotility,  interstitial cystitis, chronic prostatitis, vulvodynia, vulvar vestibulitis, and endometriosis

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    • 7

      Seronegative Spondyloarthritis: Epidemiology, Pathogenesis, and Pathology

      By Walter P Maksymowych, MB, ChB, FRCP (UK), FRCPC, FACP
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      Seronegative Spondyloarthritis: Epidemiology, Pathogenesis, and Pathology

      • WALTER P MAKSYMOWYCH, MB, CHB, FRCP (UK), FRCPC, FACPProfessor of Medicine, Department of Medicine, University of Alberta, Medical Scientist, Alberta Innovates-Health Solutions, Edmonton, AB

      Classification of spondyloarthritis (SpA) is aimed at including patients with radiographic evidence of sacroiliitis and those with early disease who do not yet meet radiographic criteria but have positive features on magnetic resonance imaging (MRI). Most studies report a prevalence of SpA of 0.1 to 0.6%. Human leukocyte antigen (HLA)-B27 contributes approximately 20% of the heritability of SpA, and non–major histocompatibility complex loci identified to date (n = 113) contribute another approximately 10%. To date, 160 subtypes of HLA-B*27 have been reported, although population-based disease association studies are limited to only a few subtypes. Subtypes HLA-B*27:05 and HLA-B*27:04 are examples of subtypes associated with disease, whereas HLA-B*27:06 and HLA-B*27:09 are nonassociated. Properties of the B27 molecule relevant to pathogenesis include antigen presentation, propensity to misfold, and formation of homodimers. Key pathways identified by genetic studies include the interleukin (IL)-23 and M1-aminopeptidase pathways. The latter pathway is involved in peptide trimming in the endoplasmic reticulum, changing both the length and amino acid composition of peptides available for HLA class I presentation. IL-23 is a key cytokine regulating expression of IL-17 in a specific T helper cell phenotype, Th17, and also a variety of cells of the innate immune system. The IL-23–IL-17 pathway has been directly implicated in inflammation at sites that are inflamed in SpA. Increasing evidence based on prospective clinical and imaging data supports a link between inflammation and ankylosis, especially if the resolution of inflammation is followed by the appearance of a particular type of reparative tissue, namely, fat metaplasia, on T1-weighted MRI.

      This review contains 8 figures, 5 tables and 33 references

      Key words: association, classification, genetics, heritability, innate immunity, prevalence, spondyloarthritis

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    • 8

      Seronegative Spondyloarthritis: Diagnosis and Management

      By Walter P Maksymowych, MB, ChB, FRCP (UK), FRCPC, FACP
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      Seronegative Spondyloarthritis: Diagnosis and Management

      • WALTER P MAKSYMOWYCH, MB, CHB, FRCP (UK), FRCPC, FACPProfessor of Medicine, Department of Medicine, University of Alberta, Medical Scientist, Alberta Innovates-Health Solutions, Edmonton, AB

      Diagnosis of spondyloarthritis is challenging in its early stages due to a lack of sensitivity and specificity of clinical and laboratory features. The advent of magnetic resonance imaging (MRI) has been transformational for diagnosis due to its ability to detect inflammation, reparative changes, and structural lesions far sooner than plain radiography. New guidelines for diagnostic evaluation now call for the early use of MRI in the setting of suspicious clinical features and where radiography of the sacroiliac joints is normal or equivocal rather than additional radiography or isotopic scanning. Standardized MRI evaluation should include a T1-weighted sequence to assess structural lesions and a water-sensitive sequence to detect inflammation. Earlier diagnosis has facilitated clinical trials of tumor necrosis factor inhibitors (TNFIs) in patients who have not yet developed full-blown radiographic sacroiliitis, and these have shown comparable efficacy to trials with TNFI agents in patients meeting the criteria for radiographic sacroiliitis. New treatment guidelines call for the use of these agents in patients with early, nonradiographic, axial disease after having failed at least two nonsteroidal antiinflammatory agents, especially in those with objective features of inflammation. Monoclonal antibody TNFIs are also beneficial for acute anterior uveitis, psoriasis, and colitis. Advances in the understanding of pathophysiology have also led to a successful trial of a biologic, secukinumab, targeting interleukin-17. Despite profound benefits for the signs and symptoms, it remains unclear whether any of these agents can prevent structural progression of disease. 

      This review contains 9 figures, 9 tables and 37 references 

      Key words: diagnosis, guidelines, magnetic resonance imaging, radiography, spondyloarthritis, treatment

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    • 9

      Systemic Lupus Erythematosus

      By Kyriakos A. Kirou, MD; Michael D. Lockshin , MD
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      Systemic Lupus Erythematosus

      • KYRIAKOS A. KIROU, MDAssistant Professor of Clinical Medicine, Weill Medical College of Cornell University, Co-director, Mary Kirkland Center for Lupus Care, Hospital for Special Surgery
      • MICHAEL D. LOCKSHIN , MDProfessor of Medicine and Obstetrics-Gynecology, Weill Medical College of Cornell University, Director, Barbara Volcker Center, Hospital for Special Surgery

      Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune illness characterized by autoantibodies directed at nuclear antigens that cause clinical and laboratory abnormalities, such as rash, arthritis, leukopenia and thrombocytopenia, alopecia, fever, nephritis, and neurologic disease. Most or all of the symptoms of acute lupus are attributable to immunologic attack on the affected organs. Many complications of long-term disease are attributable to both the disease and its treatment. Intense sun exposure, drug reactions, and infections are circumstances that induce flare; the aim of treatment is to induce remission. This chapter is divided into sections dealing with SLE’s definitions; epidemiology; pathogenesis; disease classification, diagnosis, and differential diagnosis; and treatment.

      This review contains 10 figures, 12 tables, and 97 references.

      Key Words: Systemic lupus erythematosus, Dermatomyositis, Sjögren syndrome, rheumatoid arthritis, systemic sclerosis, Discoid lupus erythematosus, truncal psoriasiform, annular polycyclic rash

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    • 10

      Introduction to the Patient With Rheumatic Disease

      By David A. Fox, MD
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      Introduction to the Patient With Rheumatic Disease

      • DAVID A. FOX, MDProfessor, Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School and Health System, Ann Arbor, MI

      The rheumatic diseases encompass a broad spectrum of conditions that include inflammatory, metabolic, and structural diseases of the joints and adjacent musculoskeletal structures, chronic musculoskeletal pain syndromes, and a wide range of systemic autoimmune and autoinflammatory diseases that may or may not have articular manifestations.

      This review contains 4 figures, 13 tables, and 28 references.

      Key Words osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus, fibromyalgia, acute monoarthritis, Ankylosing spondylitis, nonradiographic axial spondyloarthritis, gouty arthritis, lupus nephritis

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    • 11

      Back Pain and Common Musculoskeletal Problems

      By Christopher M. Wise, MD; Huzaefah Syed, MD
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      Back Pain and Common Musculoskeletal Problems

      • CHRISTOPHER M. WISE, MDW. Robert Irby Professor of Medicine, Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Virginia Commonwealth University Health System, Richmond, VA
      • HUZAEFAH SYED, MDAssistant Professor of Medicine, Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Virginia Commonwealth University Health System, Richmond, VA

      Knowledge of the common nonarticular regional rheumatic disorders is important because of their high prevalence in primary care practice, the dependence on clinical findings for diagnosis, and the high cost that can result from unnecessary laboratory evaluations. The ability to recognize important patterns of pain and associated physical signs is essential to making a correct diagnosis; in most cases, radiographic and laboratory studies are not needed. This review covers the common causes of pain in the neck, back, shoulder, chest wall, elbow, hand and wrist, hip girdle, knee and lower leg, and ankle and foot.

      This review contains 5 figures, 11 tables, and 96 references.

      Key words Acute back pain, Chronic back pain, Lumbar stenosis, Shoulder pain, Chest wall pain, Elbow pain, Hand and wrist pain, Carpal Tunnel Syndrome, Hip girdle pain, Knee and lower leg pain, Ankle and foot pain

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    • 12

      Crystal-induced Joint Disease

      By N Lawrence Edwards, MD, FACP, FACR
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      Crystal-induced Joint Disease

      • N LAWRENCE EDWARDS, MD, FACP, FACRProfessor and Program Director, Vice Chairman, Department of Medicine, University of Florida College of Medicine, Gainesville, FL

      The destructive potential of intracellular crystals has been recognized for over a century. The mechanisms by which crystals induce inflammation and bone and cartilage destruction have been elucidated over the past decade. The three most common crystal-induced arthropathies are caused by precipitation of monosodium urate monohydrate, calcium pyrophosphate dihydrate (CPP) and basic calcium phosphate. The definition, epidemiology, pathogenesis and etiology, diagnosis, and treatment of gout and CPP crystal deposition are reviewed, as well as the clinical stages of gout (i.e., acute gouty arthritis, intercritical gout, advanced gout, nonclassic presentations of gout, and other conditions associated with gout). Also reviewed are the clinical manifestations of calcium pyrophosphate dihydrate deposition disease (CPPD), such as asymptomatic CPPD, osteoarthritis with CPPD, acute CPP crystal arthritis, and chronic CPP crystal inflammatory arthritis. Figures illustrate renal transport of urate, monosodium urate crystals, acute gouty flare, advanced gouty arthritis, gouty synovial fluid, radiographic changes of advanced gout, ultrasound appearance of the femoral intercondylar cartilage, pharmacologic management of gout, the effect of gender and age on knee chondrocalcinosis, radiographs of chondrocalcinosis, and compensated polarized microscopy of CPPD. Tables present the major factors responsible for hyperuricemia, characteristics of classic gouty flares, antiinflammatory therapy for gout, and urate-lowering therapy. This chapter contains 90 references.

      This review contains 11 figures, 12 tables, and 88 references.

      Keywords: acute gouty arthritis, intercritical gout, advanced gout, asymptomatic CPPD, osteoarthritis with CPPD, acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis

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    • 13

      Scleroderma and Related Disorders

      By Kristine Phillips, MD, PhD
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      Scleroderma and Related Disorders

      • KRISTINE PHILLIPS, MD, PHDScleroderma Program, Division of Rheumatology, University of Michigan, Ann Arbor, MI

      Scleroderma spectrum diseases are a heterogeneous group of disorders that are distinguished by abnormalities of the connective tissue in the skin and, in some cases, other organs. Each disorder may be characterized by the extent of cutaneous and internal involvement, as well as histopathologic features of skin biopsy. Scleroderma spectrum diseases include systemic scleroderma, localized scleroderma, and eosinophilic fasciitis. This chapter reviews the classification, epidemiology, etiology, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, outcome measures, management, and clinical course of scleroderma as well as the definition and classification, etiology/genetics, differential diagnosis, and treatment of localized scleroderma. Also discussed are the definition and classification, epidemiology, etiology/genetics/pathogenesis, diagnosis, differential diagnosis, and treatment of eosinophilic fasciitis. Tables review the classification of—and antinuclear antibodies in—scleroderma as well as the key assessments and interventions in scleroderma management. Figures illustrate the disease's presentation and clinical manifestations, including several images of scleroderma of the hands; face, palmar, and buccal telangiectasias in a patient with scleroderma; a radiograph demonstrating calcinosis of the elbow; Raynaud’s phenomenon; high-resolution computed tomographic images of diffuse cutaneous scleroderma, scleroderma and severe pulmonary hypertension, and limited cutaneous scleroderma; plus an esophagram demonstrating hypomotility.

      This review contains 11 highly rendered figures, 3 tables, and 72 references.

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    • 14

      Osteoarthritis

      By Christopher Wise, MD, FACP
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      Osteoarthritis

      • CHRISTOPHER WISE, MD, FACPRobert Irby Professor of Medicine, Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA
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    • 15

      Introduction to the Patient With Rheumatic Disease

      By David A. Fox, MD
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      Introduction to the Patient With Rheumatic Disease

      • DAVID A. FOX, MDProfessor, Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School and Health System, Ann Arbor, MI
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    • 16

      Systemic Lupus Erythematosus

      By Kyriakos A. Kirou, MD; Michael D. Lockshin, MD
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      Systemic Lupus Erythematosus

      • KYRIAKOS A. KIROU, MDAssistant Professor of Clinical Medicine, Weill Medical College of Cornell University, Co-director, Mary Kirkland Center for Lupus Care, Hospital for Special Surgery, 535 E 70th street, New York, NY 10021, Tel: 212-606-1728; Fax: 212-606-1012
      • MICHAEL D. LOCKSHIN, MDProfessor of Medicine and Obstetrics-Gynecology, Weill Medical College of Cornell University, Director, Barbara Volcker Center, Hospital for Special Surgery, 535 E 70th St, New York, NY 10021, Tel 212-606-1461; Fax 212-774-2374
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    • 17

      Seronegative Spondyloarthritis: Diagnosis and Management

      By Walter P Maksymowych, MB, ChB, FRCP (UK), FRCPC, FACP
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      Seronegative Spondyloarthritis: Diagnosis and Management

      • WALTER P MAKSYMOWYCH, MB, CHB, FRCP (UK), FRCPC, FACPProfessor of Medicine, Department of Medicine, University of Alberta, Medical Scientist, Alberta Innovates-Health Solutions, Edmonton, AB
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    • 18

      Rheumatoid Arthritis: Treatment

      By Gary S. Firestein, MD; Anna-Karin H. Ekwall, MD, PhD
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      Rheumatoid Arthritis: Treatment

      • GARY S. FIRESTEIN, MDProfessor of Medicine, Dean and Associate Vice Chancellor of Translational Medicine, UC San Diego School of Medicine, La Jolla, California
      • ANNA-KARIN H. EKWALL, MD, PHDSpecialist in Rheumatology, University of California San Diego School of Medicine, La Jolla, CA, Researcher/Postdoc, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden
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    • 19

      Axial Neck Pain

      By Vikram B Patel, MD, FIPP, DABIPP
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      Axial Neck Pain

      • VIKRAM B PATEL, MD, FIPP, DABIPPDirector, Phoenix Interventional Center for Advanced Learning Algonquin, IL

      Neck pain is one of the most common symptoms that we see in patients presenting to a pain center for treatment. The complex nature of pain generated by various elements in the neck as well as their radiation patterns sometimes makes it difficult to diagnose and treat a patient’s pain. A proper diagnosis is important for providing optimal management of neck pain. Axial neck pain mainly refers to the pain generated by the osseous elements and the intervertebral disks in the vertebral column. Neurologic pain presents differently from axial pain, exhibiting different characteristics and radiation patterns. The following review discusses the causes of axial neck pain, diagnoses, and available treatments. 

      This review contains 7 figures, 4 tables, and 26 references.

      Keywords: Neck pain, range of motion, whiplash, subluxation, cervical spine, facet joints

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    • 20

      Axial Neck Pain

      By Vikram B Patel, MD, FIPP, DABIPP
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      Axial Neck Pain

      • VIKRAM B PATEL, MD, FIPP, DABIPPDirector, Phoenix Interventional Center for Advanced Learning Algonquin, IL
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    • 21

      Systemic Vasculitis Syndromes

      By Alexandra Villa-Forte, MD, MPH; Brian F Mandell, MD, PhD, FACP
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      Systemic Vasculitis Syndromes

      • ALEXANDRA VILLA-FORTE, MD, MPHStaff Physician, Center for Vasculitis Care and Research, Orthopedic and Rheumatologic Institute, Cleveland Clinic, Cleveland, OH
      • BRIAN F MANDELL, MD, PHD, FACPProfessor of Medicine, Department of Rheumatic Immunologic Disease, Vice Chairman of Medicine, Cleveland Clinic, Lerner College of Medicine, Case Western Reserve University, Cleveland, OH
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  • Women's Health
    • 1

      Normal and Abnormal Menstruation

      By Janet E. Hall, MD
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      Normal and Abnormal Menstruation

      • JANET E. HALL, MDProfessor of Medicine, Harvard Medical School, Associate Chief, Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA

      Normal reproductive function requires precise integration of hormonal events involving the hypothalamus, the pituitary, and the ovary, with the uterus, vagina, and breast acting as key end organs for ovarian steroid effects. This chapter discusses the physiology of the reproductive system in women; the assessment of reproductive function; and the epidemiology, etiology, diagnosis, and treatment of primary and secondary amenorrhea, abnormal vaginal bleeding—including menorrhagia, menometrorrhagia, and hypomenorrhea—and dysmenorrhea. Figures illustrate the relationship between the hypothalamus, pituitary, and ovaries in reproductive function and normal menstrual cycle function; an algorithm depicts the evaluation of amenorrhea. Tables list the relative frequency of the causes of amenorrhea and the neuroanatomic causes of hypogonadotropic hypogonadism. This chapter has 42 references.

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    • 2

      Endometriosis

      By Valerie A Flores, MD; Hugh S Taylor, MD
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      Endometriosis

      • VALERIE A FLORES, MDFellow, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT
      • HUGH S TAYLOR, MDAnita O’Keeffe Young Professor and Chair, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, Chief, Department of Obstetrics and Gynecology, Yale-New Haven Hospital, New Haven, CT

      Endometriosis is a chronic, gynecologic disease affecting 6 to 10% of reproductive age women. Pelvic pain, dyspareunia, and infertility are the most common symptoms of endometriosis that can have a significant impact on patients’ lives. Although the etiology remains largely unknown, the role of estrogens in the development and growth of endometriosis is well characterized. Medical and surgical therapies are the two cornerstones of endometriosis management. Following diagnosis of endometriosis, treatment options will be dependent on patient preference (ie, seeking pain relief versus fertility treatment). Future research aimed at targeting altered molecular pathways in patients with endometriosis will hopefully help mitigate the burden of this debilitating disease.

      This review contains 5 figures, 7 tables, and 75 references.

      Key Words: aberrant gene expression, altered immunity, endometriosis, infertility, medical and surgical therapy, pelvic pain, retrograde menstruation, stem cells

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    • 3

      Stress Fractures and the Reproductive System in the Female Athlete

      By Irfan M Asif, MD; Kimberly Harmon, MD; Mallory Shasteen, MD
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      Stress Fractures and the Reproductive System in the Female Athlete

      • IRFAN M ASIF, MDDirector, Primary Care Sports Medicine Fellowship, Assistant Professor, Department of Family Medicine, University of Tennessee, Knoxville, TN
      • KIMBERLY HARMON, MDDirector, Primary Care Sports Medicine Fellowship, Professor, Departments of Family Medicine and Orthopaedics and Sports Medicine, Team Physician, University of Washington, Seattle, WA
      • MALLORY SHASTEEN, MDEmergency Physician, Department of Emergency Medicine, Greenville Health System/University of South Carolina School of Medicine Greenville, Greenville, SC

      Stress fractures are more common in the female athlete. Stress fractures of the pubic ramus and femoral neck are particularly more common in females than in males. Rib stress fractures are an important injury to consider in the female rower, whereas spondylolysis is a common cause of low back pain in female athletes who hyperextend their spines. The higher incidence of stress fractures in females is mainly due to the higher prevalence of disordered eating and subsequent energy imbalance, which leads to detrimental effects on bone. This review discusses stress fractures and unique issues related to exercise and the female reproductive system.

      This review contains 6 figures, 5 tables and 49 references

      Key words: amenorrhea, bone mineral density, disordered eating, female athlete triad, femoral neck, pregnancy, pubic ramus, rib, spondylolysis, stress fracture

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    • 4

      Pelvic Organ Prolapse

      By Lennox Hoyte, MD, MSEECS; Renee Bassaly, DO; Stuart Hart, MD; Mona McCullough, MD, ME; Elisha Jackson, MD
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      Pelvic Organ Prolapse

      • LENNOX HOYTE, MD, MSEECSAssociate Professor and Director, Female Pelvic Medicine and Reconstructive Surgery, University of South Florida College of Medicine, Director, Urogynecology, and TGH-Pelvic Floor Disorders Group, Tampa General Hospital, Tampa, FL
      • RENEE BASSALY, DOAssistant Professor, Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, College of Medicine, University of South Florida, Tampa, FL
      • STUART HART, MDAssistant Professor, Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, College of Medicine, University of South Florida, Tampa, FL
      • MONA MCCULLOUGH, MD, MEClinical Instructor, Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, College of Medicine, University of South Florida, Tampa, FL
      • ELISHA JACKSON, MD

      Pelvic organ prolapse (POP) is the descent of one of more aspects of the vagina and/or uterus. Evaluation of POP always begins with a thorough history and physical examination. Management choices include observation, conservative options, and surgical options. Surgical management is divided into two categories, which are restorative and obliterative. It is important to counsel patients that although POP may affect quality of life, it is not life-threatening. This chapter is designed to guide the healthcare provider with a review of epidemiology, anatomy, evaluation, and management of POP. The chapter contains 14 figures that illustrate examples of common examination findings, devices, and treatment options. Also, there are 5 tables that provide concise reference materials to help guide the healthcare provider.

      This review contains 91 references, 14 figures, and 6 tables.

      Key Words: constipation, mesh, pain, pelvic floor, pessary, POP-Q, risk factors, surgery, vaginal wall

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    • 5

      Primary and Preventive Care of Women

      By Janet B. Henrich, MD
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      Primary and Preventive Care of Women

      • JANET B. HENRICH, MDAssociate Professor of Medicine and Obstetrics and Gynecology, Yale University, New Haven, CT

      Women’s health can be defined as diseases or conditions that are unique to women or that involve gender differences that are particularly important to women. This definition acknowledges the increasing scientific evidence supporting a focus on sex and gender and expands the concept of women’s health beyond the traditional focus on reproductive organs and their function. Over time, the definition has come to include an appreciation of wellness and prevention, the interdisciplinary and holistic nature of women’s health, the diversity of women and their health needs over the life span, and the central role of women as patients and as active participants in their health care. This broader interdisciplinary perspective has important implications for clinicians providing care to women. In addition to understanding basic female physiology and reproductive biology, clinicians need to appreciate the complex interaction between the environment and the biology and psychosocial development of women. When dealing with conditions that are not specific to women, clinicians need to be aware of those aspects of disease that are different in women or have important gender implications. The ability to apply this information requires that clinicians adopt attitudes and behavior that are culturally and gender sensitive. Figures visualize female life expectancy, age-adjusted death rates, female breast cancer incidence and death rates, trends in female cigarette smoking, and the U.S. Preventive Services Task Force guidelines for preventive primary care in women. 


      This review contains 5 figures, 6 tables and 56 references.

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    • 6

      Contraception

      By Siripanth Nippita, MD, MS; Eva Luo, MD, MBA
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      Contraception

      • SIRIPANTH NIPPITA, MD, MSBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
      • EVA LUO, MD, MBABeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

      Most individuals will wish to avoid pregnancy for some part of their reproductive years. A variety of hormonal and nonhormonal contraceptive methods are available, which have different characteristics related to systemic effects, bleeding patterns, and effort required on the user’s part. The goal of contraceptive counseling is to identify a method that is safe and compatible with the individual’s preferences. Clinicians may often be able to help patients initiate contraception on the day of the initial office visit. They should remain available and supportive to patients who wish to switch methods and provide comprehensive counseling for all available contraceptive methods as well as emergency contraception options.

      This review contains 8 figures, 7 tables and 51 references

      Keywords: birth control, contraception, emergency contraception, Essure, hysteroscopy, interval, laparoscopy, microinserts, postpartum, salpingectomy, sterilization

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    • 7

      Infertility

      By Eric D. Levens, MD; Katherine A Green, MD; Alan H. DeCherney, MD
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      Infertility

      • ERIC D. LEVENS, MDShady Grove Fertility Reproductive Science Center, Rockville, MD
      • KATHERINE A GREEN, MDClinical Fellow, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD
      • ALAN H. DECHERNEY, MDChief, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD

      Infertility affects 12 to 18% of couples in the United States and may be due to female factors, male factors, or both. A systematic evaluation of the common causes of infertility can identify conditions that may be treated by the obstetrician-gynecologist to help the couple achieve their family-building goals or those that require referral to a subspecialist. This review discusses current recommendations regarding the workup and treatment of the common causes of infertility, including tubal and pelvic factors, ovulatory disorders, and male factors. Advances in assisted reproductive technology are also discussed, including the use of genetic screening in in vitro fertilization and fertility preservation options for individuals facing gonadotoxic therapy.

      This review contains 6 figures, 8 tables, and 53 references

      Key words: anovulation, assisted reproductive technology, clomiphene citrate, infertility, letrozole, oocyte cryopreservation, ovulation induction, semen analysis, tubal factor, uterine factor

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    • 8

      Menopause

      By Susan D. Reed, MD, MPH; Eliza L. Sutton, MD, FACP
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      Menopause

      • SUSAN D. REED, MD, MPHProfessor, Department of Obstetrics and Gynecology, Department of Epidemiology, Director, Women’s Reproductive Health Research Program, University of Washington School of Medicine, Chief of Service, Obstetrics and Gynecology, Harborview Medical Center, Seattle, WA
      • ELIZA L. SUTTON, MD, FACPAssociate Professor, Department of Medicine, University of Washington School of Medicine Medical Director, Women's Health Care Center, University of Washington Medical Center Seattle Washington

      The female reproductive system matures in a continuous, natural process from menarche to menopause as the finite numbers of oocytes produced during fetal development are gradually lost to ovulation and senescence. Menopause is defined as the permanent cessation of menses; by convention, the diagnosis of menopause is not made until the individual has had 12 months of amenorrhea. Menopause is thus characterized by the menstrual changes that reflect oocyte depletion and subsequent changes in ovarian hormone production. However, hormonal changes, rather than the cessation of menstruation itself, cause the manifestations that occur around the time of menopause. Therefore, a woman who has undergone a hysterectomy but who retains her ovaries can experience normal menopausal symptoms as oocyte depletion leads to changes in estrogen levels, even though cessation of menstruation occurred with surgery. This review covers definitions, natural menopause, menopausal transition and postmenopausal symptom management, and premature ovarian insufficiency. Figures show stages of reproductive aging, serum concentrations of hormones during menopausal transition and postmenopause, hormonal changes associated with reproductive aging, symptoms of menopausal transition and menopause, treatment algorithm(s), and Women’s Health Initiative findings: risks and benefits of estrogen alone and estrogen plus progestin by age group: 50 to 59, 60 to 69, and 70 to 79 years. Tables list target tissues, physical manifestations, and menopausal symptoms; selective estrogen receptor modulators used in postmenopausal women; differential diagnosis and evaluation of common menopausal symptoms; estrogen doses; progestogen dosing for endometrial protection; nonhormonal pharmaceutical hot flash therapies; and pharmacologic therapy for genitourinary atrophy.

      This review contains 6 figures, 8 tables, and 122 references.

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    • 9

      Premenstrual Syndrome

      By Sarah L Berga, MD; Jessica B Spencer, MD, MSc
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      Premenstrual Syndrome

      • SARAH L BERGA, MDJames Robert McCord Professor and Chairman, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA
      • JESSICA B SPENCER, MD, MSCAssistant Professor, Department of Gynecology and Obstetrics, Emory University School of Medicine, Altlanta, GA

      Premenstrual syndrome (PMS) is a recurrent constellation of affective and physical symptoms that begin during the luteal phase of the menstrual cycle and resolve completely or almost completely during the follicular phase. Symptoms range in severity from mild to severe. The pathophysiology of PMS is discussed in this chapter, and potential causes are listed in a table. The diagnosis and differential diagnosis are reviewed. To warrant medical attention, evaluation, and intervention, premenstrual symptoms must be recurrent and sufficiently severe to interfere with daily work and social activities. Mild cases of PMS can be treated with lifestyle modification (e.g., good sleep patterns, regular exercise) and nonpharmacologic therapy (e.g., bright-light therapy, stress management, behavioral therapy). More severe cases warrant aggressive intervention, with pharmacologic therapy and even surgery in women who respond very well to a gonadotropin-releasing hormone (GnRH) agonist and have completed childbearing.

      This review contains 1 figure, 5 tables and 51 references

      Key Words: Premenstrual syndrome, premenstrual dysphoric disorder, selective serotonin reuptake inhibitors, anxiogenic progesterone metabolites, estrogen, progesterone.

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    • 10

      Prenatal Screening and Diagnosis

      By Barbara O’Brien, MD; Emily Willner, MD
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      Prenatal Screening and Diagnosis

      • BARBARA O’BRIEN, MDAssociate Professor of Obstetrics, Gynecology & Reproductive Biology, Harvard Medical School; Director, Maternal Fetal Medicine Fellowship, Beth Israel Deaconess Medical Center, Boston, MA
      • EMILY WILLNER, MDClinical Fellow of Obstetrics, Gynecology & Reproductive Biology, Harvard Medical School; Chief Resident, Obstetrics & Gynecology, Beth Israel Deaconess Medical Center, Boston, MA

      Prenatal genetic testing offers patients and providers the opportunity to screen for aneuploidy, genetic syndromes, and congenital malformations during pregnancy. Screening options include taking a clinical history, evaluation of maternal serum markers or noninvasive cell-free DNA, and ultrasound evaluation during the first and second trimesters. Invasive diagnostic testing such as amniocentesis or chorionic villus sampling allows for further investigation of positive screening results and a directed test to identify aneuploidy as well as specific gene mutations and gain, loss, or rearrangement of genetic information. Laboratory methods for testing fetal samples differ by types of genetic abnormalities that can be detected and turnaround time for results; these methods include karyotype, fluorescence in situ hybridization, and microarray.

      This review contains 5 figures, 5 tables and 43 references

      Key words: amniocentesis, aneuploidy, cell-free DNA, chorionic villus sampling, karyotype, microarray, prenatal genetic screening, ultrasonography

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    • 11

      Cervical Cancer Prevention and Screening

      By Andrew Quinn, MD; Carolyn D Runowicz, MD
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      Cervical Cancer Prevention and Screening

      • ANDREW QUINN, MDResident, PGY-1, Department of Obstetrics and Gynecology, New York Hospital, New York, NY
      • CAROLYN D RUNOWICZ, MDExecutive Associate Dean for Academic Affairs, Professor of Obstetrics and Gynecology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL

      With the advent of HPV DNA testing and the availability of HPV vaccinations, the recommendations and rationale for screening and prevention of cervical cancer and its precursors have undergone revision, reflecting this new knowledge and understanding of cervical intra-epithelial neoplasia and the role of HPV. This review incorporates the new guidelines and rationale for current screening guidelines for cervical cancer and in the management of patients with atypical or unsatisfactory cervical cytology.

      This review contains 4 figures, 4 tables, and 71 references

      Keywords: Cervical cancer, Gynecological cancer, HPV, HPV testing, HPV vaccine, Pap smear, HPV DNA, Human papillomavirus

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    • 12

      Approach to the Patient With a Breast Mass

      By George Plitas, MD; Monica Morrow, MD, FACS; Brandon R Bruns, MD
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      Approach to the Patient With a Breast Mass

      • GEORGE PLITAS, MDAssistant Attending, Breast Service, Memorial Sloan-Kettering Cancer Center, New York, NY, Assistant Professor of Surgery, Weill Cornell Medical College, New York, NY
      • MONICA MORROW, MD, FACSChief, Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, Anne Burnett Windfohr Chair of Clinical Oncology, Professor of Surgery, Weill Cornell Medical College, New York, NY
      • BRANDON R BRUNS, MDAssociate Professor of Surgery, R Adams Cowley Shock Trauma Center at the University of Maryland Medical Center, Baltimore, MD

      A breast mass is the most common presenting symptom among patients in a breast clinic. The presence of a breast mass can cause a great deal of anxiety in women, as well as their physicians. The differential diagnosis of a palpable breast abnormality is broad, although the majority of breast masses are benign. The responsibility of the physician who is evaluating a breast mass is to exclude the presence of malignancy. Once cancer is ruled out, the physician should then attempt to provide an accurate diagnosis, appropriate treatment, and reassurance to the patient. This chapter discusses the assessment of normal breast physiology, identification of a breast mass, evaluation of the various classifications of breast mass (e.g., dominant mass with clinically benign features and dominant mass with suspicious features), differential diagnosis and management of common benign breast masses (e.g., cysts, fibroadenomas, phyllodes tumors, hamartomas, fat necrosis), and the risk of breast cancer associated with benign breast lesions. The chapter also discusses the diagnosis and management of a breast mass in male patients. Tables outline breast lesions that may present as a palpable abnormality, factors used for the assessment of breast cancer risk, physical characteristics of benign and malignant breast masses, the accuracy of fine-needle aspiration, and benign breast lesions by category. Figures illustrate diagnostic procedures, the anatomy of the human breast, visual inspection of the breasts, physical examination of the breasts, breast palpation technique, the evaluation and management of a new breast mass, and the identification of cysts.

      This review contains 10 figures, 14 tables, and 64 references.

      Keywords: breast mass, lobuloalveolar development, subareolar nodularity, parenchyma (glandular elements), stromal tissue, ovarian graafian follicles

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    • 13

      Diseases of the Vulva

      By Huma Farid, MD; Catherine Nosal, MD
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      Diseases of the Vulva

      • HUMA FARID, MDClinical Instructor, Department of Obstetrics/Gynecology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA
      • CATHERINE NOSAL, MDPGY-4, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

      Vulvar symptoms are a common reason for a gynecologic visit. A variety of conditions impact the vulva, including dermatologic conditions, hormonal changes, vulvar pain, and sexually transmitted or other infections. History and physical exam, focused on the symptoms and the vulvovaginal area, are crucial to identifying the etiology of the symptoms. A full evaluation may include vulvar biopsies and testing for infections. The treatment of the symptoms depends on the etiology; therefore, an accurate and thorough determination of the cause of the patient’s symptoms is of primary importance. Treatment can include antibiotics, antifungals, steroids, antidepressants, hormones, and pelvic floor physical therapy. In this chapter, we summarize common conditions affecting the vulvar, their evaluation, and their treatment.

      This review contains 7 figures, 10 tables, and 40 references.

      Key Words: Bartholin gland, candidiasis, dermatitis, eczema, hidradenitis suppurativa, lichen planus, lichen sclerosus, sexually transmitted infections, vulva, vulvodynia, vulvovaginal atrophy

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    • 14

      Approach to the Patient With a Pelvic Mass

      By Carolyn D. Runowicz, MD; Mary I. Fatehi, MD; Joseph T Chambers, MD, PhD
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      Approach to the Patient With a Pelvic Mass

      • CAROLYN D. RUNOWICZ, MDAssociate Dean for Women’s Affairs, Professor of Obstetrics and Gynecology, Florida International University, Herbert Wertheim College of Medicine, 11200 S.W. 8 Street, AHC2 693, Miami, FL
      • MARY I. FATEHI, MDDirector, Gynecologic Oncology at Long Island College Hospital, Associate Professor, State University of New York at Downstate
      • JOSEPH T CHAMBERS, MD, PHDChairman, The Mary Polak Oenslager Department of Obstetrics and Gynecology, Long Island College Hospital, Professor, State University of New York at Downstate

      Every year, between 5% and 10% of women in the United States undergo surgery for a suspected ovarian neoplasm; however, only 13% to 21% of these women prove to have an ovarian malignant neoplasm. A pelvic mass may be identified in symptomatic or asymptomatic women during an abdominal or pelvic examination or on imaging studies. The differential diagnosis is extensive, because a pelvic mass may be of gynecologic or nongynecologic origin and may be associated with congenital, functional, neoplastic (either benign or malignant), obstructive, or inflammatory processes. The underlying cause and potential risk of cancer varies with age. The first section of the chapter provides an overview of diagnostic evaluation. This is followed by a section that discusses diagnostic considerations in patients of specific age groups-namely, prepubertal girls, adolescents, women of reproductive age, and postmenopausal women. The specific presentations discussed for these patients include cystic adnexal masses, cystic teratomas, leiomyomas, endometriomas, malignant neoplasms, anatomic abnormalities, and ectopic pregnancy. 

      This review contains 15 tables, and 45 references.

      Keywords: Pelvic mass, adnexal mass, ovarian tumor, fibroid, endometriosis, leiomyoma, endometrioma, ectopic pregnancy, cyst

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    • 15

      Cardiovascular Disease in Women

      By JoAnne Micale Foody, MD, FAHA, FACC; Fatima Rodriguez, MD, MPH
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      Cardiovascular Disease in Women

      • JOANNE MICALE FOODY, MD, FAHA, FACCMedical Director Cardiovascular Wellness Program, Brigham and Women’s Hospital, Boston, MA
      • FATIMA RODRIGUEZ, MD, MPHResident Physician, Department of Internal Medicine, Brigham and Women’s Hospital, Boston, MA

      Heart disease is the leading cause of death and disability in women in the United States. In 2007, almost half a million women died of cardiovascular disease (CVD). Almost one out of every two women in the United States will die from some cardiovascular event—most likely myocardial infarction (MI), hypertensive heart disease, or stroke. In addition, CVD claims more lives than cancer, Alzheimer’s disease, chronic lower respiratory diseases, and accidents combined. Heart failure now represents a growing epidemic in women—particularly older women. Despite its importance for women, CVD has traditionally been viewed as a disease of middle-aged men, and most clinical data come from studies in middle-aged men. Yet there is increasing evidence that significant gender differences exist. Moreover, although mortality associated with coronary artery disease (CAD) in men has dramatically declined over the years, the mortality gap between men and women persists. This chapter reviews those uniquely female attributes that are associated with differences in cardiovascular disease presentation and discusses ways to reduce risk and improve clinical outcomes. 

      This review contains 2 figures, 9 tables, and 100 references. 

      Keywords: Women's health, cardiovascular risk, coronary artery disease, coronary heart disease, acute coronary syndrome, heart failure, prevention, cardiovascular disease

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    • 16

      Musculoskeletal Problems in the Female Athlete

      By Irfan M Asif, MD; Emily Edwards, DO; Kimberly Harmon, MD
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      Musculoskeletal Problems in the Female Athlete

      • IRFAN M ASIF, MDDirector, Primary Care Sports Medicine Fellowship, Assistant Professor, Department of Family Medicine, University of Tennessee, Knoxville, TN
      • EMILY EDWARDS, DODepartment of Family Medicine, University of Tennessee, Knoxville, TN
      • KIMBERLY HARMON, MDDirector, Primary Care Sports Medicine Fellowship, Professor, Departments of Family Medicine and Orthopaedics and Sports Medicine, Team Physician, University of Washington, Seattle, WA

      Musculoskeletal injuries in the female athlete are, for the most part, similar to those in the male athlete. However, there are differences in the incidence of these injuries and in the sports in which they tend to occur. Female athletes have a higher rate of noncontact anterior cruciate ligament injuries than male athletes. Other musculoskeletal problems are also more common in females, such as multidirectional instability of the shoulder, adhesive capsulitis, and patellofemoral pain. This review addresses injuries that are seen commonly in female athletes and outlines current diagnosis and treatment options.

      This review contains 3 figures and 32 references

      Key words: ACL tear, adhesive capsulitis, atraumatic, female athlete, injection, knee, patellofemoral pain, shoulder

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    • 17

      Women With Disabilities

      By Lisa I. Iezzoni, MD, MSc
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      Women With Disabilities

      • LISA I. IEZZONI, MD, MSCProfessor of Medicine, Department of Medicine, Harvard Medical School, Director, Mongan Institute for Health Policy, Massachusetts General Hospital, Boston, MA

      Women with disabilities face substantial barriers to obtaining health care services. They are more likely than nondisabled women to smoke cigarettes, to be obese or overweight, to be physically inactive, and to report depressive symptoms, anxiety, and fears. Women with disabilities are often stigmatized as being asexual and experience higher rates of domestic partner and in-home abuse. Physical, communication, and attitudinal barriers within the health care system may prevent women with disabilities from receiving the care they need. This module discusses the definition of disability, prevalence and demographics of disability among US women, health conditions and risk factors, and general considerations in caring for women with disabilities. Selected health issues in caring for women with disabilities, including reproductive and parental rights, menstruation and fertility, contraception, preconception counseling, and menopause, are also discussed. Tables review components of the International Classification of Functioning, Health and Disability, examples of disability definitions, disability indicators using National Health Interview Survey data, health conditions causing chronic mobility disability for women ages 18 to 49, comorbid health conditions reported among women with and without disability, mental health conditions reported by women with and without disability, examples of women’s experiences with inaccessible medical equipment, examples of communication accommodations, and accessible labeling of prescription drug containers. Figures include the International Classification of Functioning, Health and Disability model of disability and graphs showing the percentage of women with basic action difficulties (BADs); with one or more BADs; with complex action limitations; with BADs by racial and ethnic groups; with indicated level of education and income among women with and without BADs; with indicated level of self-reported overall health among women with BADs; by smoking status among women with and without BADs; in body mass index category among women with and without BADs; with indicated physical activity level among women with and without BADs; with indicated heath care service use and lacking health insurance among women with and without BADs; and receiving Pap smears, mammography screening, and colon cancer screening among women with and without BADs.

      This review contains 12 highly rendered figures, 9 tables, and 86 references.

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    • 18

      Pulmonary Edema in Pregnancy

      By Sarah Rae Easter, MD; Nicole A. Smith, MD, MPH
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      Pulmonary Edema in Pregnancy

      • SARAH RAE EASTER, MDDivision of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA Division of Critical Care Medicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
      • NICOLE A. SMITH, MD, MPHDivision of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

      Pulmonary edema is characterized by the movement of excess fluid into the alveoli of the lungs.  Although the alterations of cardiovascular and pulmonary physiology in pregnancy may predispose patients to pulmonary edema, it is never normal and constitutes severe maternal morbidity.  The etiologies of pulmonary edema are diverse, ranging from disease processes independent of pregnancy to pathophysiology unique to the gravid state.  The causes of pulmonary edema can be broadly classified as either cardiogenic or noncardiogenic, which constitutes the first important branch point in the diagnosis and management of the disease.  The treatment of pulmonary edema in pregnancy parallels that in the nonpregnant population with an emphasis on maintaining the physiologic alterations of pregnancy through supportive care, including mechanical ventilation if needed.  In all cases of pulmonary edema, the decision to proceed with delivery to improve the maternal status should be considered within the context of the etiology and anticipated disease course, the gestational age, and the goals of care.

      This review contains  3 figures, 4 tables, and 60 references.

      Key Words:  Pulmonary edema, respiratory alkalosis, acute respiratory distress syndrome (ARDS), cardiogenic pulmonary edema, transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), mechanical ventilation, extra corporeal membrane oxygenation (ECMO).

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    • 19

      Ectopic Pregnancy and Spontaneous Abortion

      By Eric D. Levens, MD; Alan H. DeCherney, MD
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      Ectopic Pregnancy and Spontaneous Abortion

      • ERIC D. LEVENS, MDShady Grove Fertility Reproductive Science Center, Rockville, MD
      • ALAN H. DECHERNEY, MDChief, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD

      Ectopic pregnancy, the implantation of an embryo outside the endometrial cavity, is the leading cause of morbidity and mortality in the first trimester. The embryo may be implanted in the fallopian tubes, ovaries, abdomen, or cervix, with the fallopian tubes being the site of implantation in 95% of cases. If left untreated, ectopic pregnancy can result in rupture of the fallopian tube, which can lead to hemorrhagic shock and death. The signs and symptoms of ectopic pregnancy and diagnosis and treatment are detailed in the chapter. Spontaneous abortion, defined as a natural termination of a pregnancy before 20 weeks’ gestation, occurs in almost 30% of known pregnancies and an estimated 50% of all conceptions. Causes include genetic, environmental, endocrine, and immunologic factors; anatomic abnormalities; antiphospholipid syndrome; and polycystic ovary syndrome. 

      This review contains 6 figures, 7 tables, and 42 references.

      Keywords: Ectopic pregnancy, miscarriage, spontaneous abortion, early pregnancy loss, vaginal spotting

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    • 20

      Female Sexuality: Assessing Satisfaction and Addressing Problems

      By Jennifer Potter, MD
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      Female Sexuality: Assessing Satisfaction and Addressing Problems

      • JENNIFER POTTER, MDAssociate Professor of Medicine, Department of Medicine, Harvard Medical School, Director, Women’s Health Center, Beth Israel Deaconess Medical Center, Boston, MA

      Sexuality is important to women of all ages. Although changes in sexual function occur with aging, hormonal transitions, illness, the use of medications, and disability, many women can maintain a satisfying sex life by making appropriate adaptations. Clinicians who take the time to obtain a complete and careful sexual history and perform a pertinent physical examination can help the majority of women who present with sexual complaints. Effective treatment must address the contribution of psychological, relationship, and biologic factors and often requires the collaboration of physicians and psychotherapists, as well as sex and physical therapists in many circumstances. Simply initiating a discussion about sexual concerns is frequently the most valuable aspect of treatment for women and their partners. Also useful are provision of basic education about normal female genital anatomy and sexual function across the lifespan; permission to explore masturbation, erotica, and versatile sexual techniques, as well as nongenital pleasuring; information about lubricants; and the prescription of estrogen in the setting of vulvovaginal atrophy. There are as yet no approved agents to treat the biologic component of hypoactive sexual desire. However, it may be appropriate to consider using androgen supplementation in patients with surgical menopause, as well as the addition of bupropion in patients taking selective serotonin reuptake inhibitors (SSRIs). This review discusses the epidemiology of female sexual disorders, the female sexual response and sexual behavior, and the diagnosis and management of specific sexual disorders, including desire, arousal, orgasm, and sexual-pain problems. 

      This review contains 4 figures, 41 tables, and 96 references.

      Keywords: Sexual dysfunction disorder, arousal, orgasm, desire, dyspareunia, vulvodynia, vestibulitis, vaginismus

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    • 21

      Delayed Puberty

      By Amanda French, MD
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      Delayed Puberty

      • AMANDA FRENCH, MDBoston Children’s Hospital, Boston MA

      Although common, delayed puberty can be distressing to patients and families.   Careful assessment is necessary to ensure appropriate physical and social development in patients that require intervention to reach pubertal milestones and achieve optimal growth.  Most pubertal delay is from lack of activation of the hypothalamic-pituitary-gonadal axis which then results in a functional or physiologic GnRH deficiency.  The delay may be temporary or permanent.  Constitutional delay (CDGP), also referred to as self-limited delayed puberty (DP), describes children on the extreme end of normal pubertal timing and is the most common cause of delayed puberty, representing about one third of cases.  Hypergonadotropic hypogonadism (primary hypogonadism) results from a failure of the gonad itself, and hypogonadotropic hypogonadism (secondary hypogonadism) results from a failure of the hypothalamic-pituitary axis, which is usually caused by another process, often systemic.  Diagnosis is based on history and examination.  Treatment is based on the underlying cause of pubertal delay and may include hormone replacement.  Involving a pediatric endocrinologist should be considered.  Appropriate counseling and ongoing support are important for all patients and families, regardless of underlying disease process.  

      This review contains 4 figures, 4 tables, and 32 references.

      Keywords: puberty, delayed puberty, hypogonadism, hypogonadotropic hypogonadism, hypergonadotropic hypogonadism, menarche, thelarche, constitutional delay and growth in puberty, Turner syndrome

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    • 22

      Cardiovascular Disease in Women

      By JoAnne Micale Foody, MD, FAHA, FACC; Fatima Rodriguez, MD, MPH
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      Cardiovascular Disease in Women

      • JOANNE MICALE FOODY, MD, FAHA, FACCMedical Director Cardiovascular Wellness Program, Brigham and Women’s Hospital, Boston, MA
      • FATIMA RODRIGUEZ, MD, MPHResident Physician, Department of Internal Medicine, Brigham and Women’s Hospital, Boston, MA
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    • 23

      Approach to the Patient With a Pelvic Mass

      By Carolyn D. Runowicz, MD; Mary I. Fatehi, MD; Joseph T Chambers, MD, PhD
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      Approach to the Patient With a Pelvic Mass

      • CAROLYN D. RUNOWICZ, MDAssociate Dean for Women’s Affairs, Professor of Obstetrics and Gynecology, Florida International University, Herbert Wertheim College of Medicine, 11200 S.W. 8 Street, AHC2 693, Miami, FL
      • MARY I. FATEHI, MDDirector, Gynecologic Oncology at Long Island College Hospital, Associate Professor, State University of New York at Downstate
      • JOSEPH T CHAMBERS, MD, PHDChairman, The Mary Polak Oenslager Department of Obstetrics and Gynecology, Long Island College Hospital, Professor, State University of New York at Downstate
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    • 24

      Menopause

      By Susan D. Reed, MD, MPH; Eliza L. Sutton, MD, FACP
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      Menopause

      • SUSAN D. REED, MD, MPHProfessor, Department of Obstetrics and Gynecology, Department of Epidemiology, Director, Women’s Reproductive Health Research Program, University of Washington School of Medicine, Chief of Service, Obstetrics and Gynecology, Harborview Medical Center, Seattle, WA
      • ELIZA L. SUTTON, MD, FACPAssociate Professor, Department of Medicine, University of Washington School of Medicine Medical Director, Women's Health Care Center, University of Washington Medical Center Seattle Washington
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    • 25

      Primary and Preventive Care of Women

      By Janet B. Henrich, MD
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      Primary and Preventive Care of Women

      • JANET B. HENRICH, MDAssociate Professor of Medicine and Obstetrics and Gynecology, Yale University, New Haven, CT
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    • 26

      Infertility

      By Eric D. Levens, MD; Katherine A Green, MD; Alan H. DeCherney, MD
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      Infertility

      • ERIC D. LEVENS, MDShady Grove Fertility Reproductive Science Center, Rockville, MD
      • KATHERINE A GREEN, MDClinical Fellow, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD
      • ALAN H. DECHERNEY, MDChief, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD
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    • 27

      Approach to the Patient With a Breast Mass

      By George Plitas, MD; Monica Morrow, MD, FACS; Brandon R Bruns, MD
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      Approach to the Patient With a Breast Mass

      • GEORGE PLITAS, MDAssistant Attending, Breast Service, Memorial Sloan-Kettering Cancer Center, New York, NY, Assistant Professor of Surgery, Weill Cornell Medical College, New York, NY
      • MONICA MORROW, MD, FACSChief, Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, Anne Burnett Windfohr Chair of Clinical Oncology, Professor of Surgery, Weill Cornell Medical College, New York, NY
      • BRANDON R BRUNS, MDAssociate Professor of Surgery, R Adams Cowley Shock Trauma Center at the University of Maryland Medical Center, Baltimore, MD
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    • 28

      Contraception

      By Siripanth Nippita, MD, MS; Eva Luo, MD, MBA
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      Contraception

      • SIRIPANTH NIPPITA, MD, MSBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
      • EVA LUO, MD, MBABeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
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  • Pediatrics
    • 1

      Pediatric Minor Head Injury and Concussion

      By Chad Scarboro, MD; Simone Lawson, MD
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      Pediatric Minor Head Injury and Concussion

      • CHAD SCARBORO, MDAssistant Professor, Department of Emergency Medicine/Pediatric Emergency Medicine, Carolinas Medical Center, Charlotte, NC
      • SIMONE LAWSON, MDPediatric Emergency Medicine Fellow, Department of Emergency Medicine/Pediatric Emergency Medicine, Carolinas Medical Center, Charlotte, NC

      Head injury is one of the most common reasons children present to the emergency department (ED) and the leading cause of pediatric death and disability. Head injuries can range from having no neurologic deficits to death. Management in the ED centers on determining if there is a serious brain injury and preventing secondary brain injury. In most cases of mild traumatic brain injury, serious injuries can be ruled out based on the history of the injury, associated symptoms, and clinical assessment. Concussion is a common presentation of head injury and encompasses a wide range of symptoms. Computed tomography should be used judiciously, and extensive research has led to algorithms to aid in this decision. Prior to discharge from the ED, parents will often have questions about when their child may resume normal activity. This is a decision that most often will involve the patient’s primary care provider or a concussion specialist as the ED provider is unable to follow progression or resolution of symptoms. However, the ED provider should be able to provide anticipatory guidance.

      This review contains 5 figures, 7 tables, and 48 references.

      Keywords: computed tomography, concussion, head injury, mild traumatic brain injury, traumatic brain injury

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    • 2

      Pediatric Rashes

      By Summer Stears-Ellis, MD
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      Pediatric Rashes

      • SUMMER STEARS-ELLIS, MDClinical Instructor, Emergency Ultrasound Fellow, Department of Emergency Medicine, The University of Arizona, Tucson, AZ

      Pediatric rashes are a common chief complaint in the emergency department (ED) and a source of anxiety for both parents and providers. Many of these rashes will not require intervention aside from symptomatic relief and parental reassurance. However, there is a subset of rashes that are the result of underlying life-threatening conditions that will warrant immediate intervention and treatment to prevent further deterioration and possible death. This review focuses on outlining the pathology of seven potentially deadly pediatric rashes that ED physicians are likely to encounter, how they present, and how to treat and manage them according to the most recent available guidelines. Figures show primary lesions, pattern of lesions, and distribution of rash associated with bacterial meningitis, toxic shock syndrome (TSS), Rocky Mountain spotted fever, Stevens-Johnson syndrome/toxic epidermal necrolysis, erythema multiforme minor and major, necrotizing fasciitis, and Henoch-Schönlein purpura. Tables list bacterial meningitis antibiotic treatment, Centers for Disease Control and Prevention clinical and laboratory criteria for TSS, TSS antibiotic treatment regimens, scoring systems for toxic epidermal necrolysis and necrotizing fasciitis, and the latest guidelines as of June 2017.

      This review contains 9 figures, 17 tables, and 58 references

      Keywords: Pediatric rash, toxic shock syndrome, skin rash, rash distribution, Rocky Mountain spotted fever, Stevens-Johnson syndrome, toxic epidermal necrolysis,  necrotizing fasciitis, Henoch-Schönlein purpura

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    • 3

      Pediatric Fever

      By Clifford C. Ellingson, MD; Dale P. Woolridge, MD, PhD
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      Pediatric Fever

      • CLIFFORD C. ELLINGSON, MDDepartment of Pediatric and Emergency Medicine, University of Arizona and Banner University Medical Center, Tucson, AZ
      • DALE P. WOOLRIDGE, MD, PHDProfessor, Department of Pediatric and Emergency Medicine, University of Arizona, Tucson, AZ

      Fever is one of the most common chief complaints among pediatric emergency departments. The evaluation and approach to a pediatric fever can be challenging. Although most cases of fever are viral in origin, the potential for a deadly bacterial infection would make even the most seasoned practitioner attentive. This review discusses the initial assessment of the pediatric patient and both necessary and recommended workups for pediatric fevers among various age groups. Common infections of bacterial and viral causes for fever are discussed and treatment recommendations offered. 

      This review contains 3 figures, 9 tables and 57 references

      Keywords: Pediatric fever, otitis media, pneumonia, urinary tract infection, neonatal sepsis, bacteremia, meningitis, serious bacterial infection, viral illness

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    • 4

      Pediatric Upper Airway Obstruction

      By Michael W. Chan, MD; Suzanne M. Schmidt, MD
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      Pediatric Upper Airway Obstruction

      • MICHAEL W. CHAN, MDFellow, Pediatric Emergency Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
      • SUZANNE M. SCHMIDT, MD Attending Physician, Pediatric Emergency Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Assistant Professor, Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL

      Upper airway obstruction is a common reason that children present for emergency care, and causes range from simple and benign etiologies to life-threatening conditions requiring emergent intervention. Both congenital and acquired conditions can result in airway obstruction at various levels, and due to the high risk of acute decompensation associated with some of these conditions, rapid diagnosis and treatment are essential. This review covers assessment and stabilization, diagnosis, and treatment of foreign-body aspiration, croup, bacterial tracheitis, epiglottitis, peritonsillar abscess, and retropharyngeal abscess. Figures show a diagram of the pediatric airway, an anteroposterior radiograph of the neck demonstrating the characteristic “steeple sign” in croup, an algorithm for the treatment of croup, lateral radiographs demonstrating a thickened epiglottis, consistent with a diagnosis of epiglottitis,  and a widening of the prevertebral soft tissues of the neck, consistent with a diagnosis of retropharyngeal abscess. Tables list causes of upper airway obstruction by anatomic location, symptoms of upper airway obstruction by anatomic location, severity of croup, and microbiology of deep neck abscesses.

       

      This review contains 5 figures, 13 tables, and 32 references

      Key words: Upper airway obstruction; Pediatric upper airway obstruction, Foreign-body aspiration, Croup, Bacterial tracheitis, Epiglottitis, Peritonsillar abscess, Retropharyngeal abscess, Stridor

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    • 5

      Pediatric Hematologic and Oncologic Emergencies

      By Rebecca Milligan, MD; Jenny Mendelson, MD
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      Pediatric Hematologic and Oncologic Emergencies

      • REBECCA MILLIGAN, MD
      • JENNY MENDELSON, MD

      Hematologic and oncologic emergencies that afflict children and adolescents are important for emergency medicine physicians to recognize. Pediatric patients can present with a previous formal diagnosis and have a complication related to their disease or with new symptoms that suggest a hematologic or oncologic process. Oncologic treatments can also lead to life-threatening complications. Recognizing these emergencies is very important for emergency physicians to prevent further morbidity. This review covers common patient presentations, diagnosis, and treatments for hematologic and oncologic emergencies.

       This review contains 6 figures, 9 tables and 66 references

      Keywords: hematology, oncology, tumor lysis syndrome, hemophilia, pediatrics, von Willebrand Disease, sickle cell disease

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    • 6

      Pediatric Abdominal Emergencies

      By Jeffrey Bullard-Berent, MD, FAAP, FACEP; Aaron Kornblith, MD
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      Pediatric Abdominal Emergencies

      • JEFFREY BULLARD-BERENT, MD, FAAP, FACEPVice Chair, Emergency Medicine, Medical Director, Child Ready Virtual Pediatric Emergency Department, Professor of Emergency Medicine and Pediatrics, University of New Mexico School of Medicine, Albuquerque, NM
      • AARON KORNBLITH, MDAssistant Professor, Emergency Medicine and Pediatrics, Benioff Children’s Hospital, San Francisco, University of California, San Francisco, San Francisco, CA

      Pediatric abdominal emergencies represent a diverse group of conditions affecting children of all ages and are a common cause of emergency department visits. The challenge for emergency physicians is discerning which child presenting with the common complaints of abdominal pain, nausea, vomiting, and diarrhea has an abdominal emergency. The emergency physician must use a thorough history, developmentally appropriate examination skills, and integration of his or her knowledge base to arrive at the correct diagnosis. This review evaluates the most common pediatric abdominal emergencies organized by chronicity from birth to adolescents: midgut volvulus, infantile hypertrophic pyloric stenosis, incarcerated inguinal hernia, ileocecal intussusception, Meckel diverticulum, and appendicitis. Readers will understand common presentations as well as the evaluation and treatment options for each diagnosis.  

      This review contains 7 figures, 9 tables and 64 references

      Key words: abdominal pain, appendicitis, hernia, hypertrophic pyloric stenosis, intussusception, Meckel diverticulum, midgut volvulus

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    • 7

      Pediatric Orthopedic Emergencies

      By Priya Gopwani, MD; Joy Koopmans, MD
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      Pediatric Orthopedic Emergencies

      • PRIYA GOPWANI, MDAttending Physician, Assistant Professor of Pediatric Emergency Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
      • JOY KOOPMANS, MDAttending Physician, Department of Pediatric Emergency Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago at Central DuPage Hospital, Health Systems Clinician, Northwestern University Feinberg School of Medicine, Winfield, IL

      Proper care of orthopedic injuries and emergencies in children and adolescents requires knowledge of the altered bone and ligament characteristics, varying stages of skeletal development, and potential for congenital or developmental abnormalities. Pediatric fractures affecting the growth plate require unique management to maintain optimal growth. Whereas some specific fractures in these skeletally immature patients require urgent surgical repair, other fractures remodel extremely well and can be managed with a simple splint. Particular dislocations are common in this population and may have concomitant fractures. There are several overuse injuries seen primarily in children, and treatment aims to keep the patient active while allowing the injury to heal. Potentially devastating osteoarticular infections occur in the pediatric population and must be differentiated from more benign causes of joint pain, such as transient synovitis or congenital abnormalities. Children are also at risk for abnormalities such as slipped capital femoral epiphysis or Legg-Calvé-Perthes disease, which are rarely diagnosed in the adult population. It is imperative for a clinician to be aware of these and other nuances to optimally care for orthopedic injuries and emergencies in the pediatric population.

      This review contains 9 figures, 19 tables and 51 references

      Keywords: bone, musculoskeletal, orthopedic, skeletal, osteomyelitis, pediatrics, fracture, Legg-Calvé-Perthes disease

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    • 8

      Child Abuse and Nonaccidental Trauma

      By S Terez Malka, MD
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      Child Abuse and Nonaccidental Trauma

      • S TEREZ MALKA, MDAssistant Professor, Department of Emergency Medicine, Department of Pediatric Emergency Medicine, Massachusetts General Hospital, Boston, MA.

      Child abuse accounts for over 1% of visits to pediatric emergency departments (EDs), and injuries related to abuse have higher morbidity and mortality than accidental injuries. Recognizing child abuse and neglect in the ED is challenging but critical to prevent recurrent episodes of abuse and long-term physical and emotional sequelae. This review defines child abuse and neglect and explores historical and physical examination findings, assessment and diagnosis, treatment, disposition, and outcomes for victims of child abuse. Figures show x-rays demonstrating common fracture patterns associated with abusive injury and an algorithm for evaluation of nonaccidental trauma in the ED. Tables list key historical elements in the evaluation for abuse or neglect, bruising characteristics suggestive of abuse, fractures that are specific for abuse, and recommended laboratory evaluation for suspected abuse. 

      This review contains 4 figures, 5 tables, and 36 references.

      Key words: child abuse, child neglect, nonaccidental trauma, sexual abuse

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    • 9

      Failure to Thrive in Infants and Toddlers

      By Madhura Y Phadke, MD; Anthony F Porto, MD, MPH
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      Failure to Thrive in Infants and Toddlers

      • MADHURA Y PHADKE, MDFellow, Pediatric Gastroenterology, Yale University School of Medicine, New Haven, CT
      • ANTHONY F PORTO, MD, MPHAssistant Professor of Pediatrics, Associate Clinical Chief, Pediatric Gastroenterology, Yale University School of Medicine, New Haven, CT

      Failure to thrive (FTT) is a broad term that is used to document an abnormal pattern of weight gain over time. There is no single definition for FTT, but all proposed definitions use anthropometric parameters such as weight gain or weight for length. The term FTT has been falling out of favor, and the term weight/growth faltering is becoming more common to describe this clinical entity. The underlying problem in FTT is inadequate usable calories. The primary mechanisms leading to FTT are impaired absorption, increased metabolic demands, and inadequate caloric intake. Inadequate caloric intake is the most common of these mechanisms, although FTT is often a combination of the three. The diagnostic evaluation of FTT must take into account the multifactorial nature of this clinical sign. A comprehensive history is essential for diagnosis and should include specific questions about the child’s living situation and feeding habits. The physical examination must include accurate weight and length measurements. Clinicians should look for signs of abuse or neglect, dysmorphic features, abnormal skin or nail findings, digital clubbing, or other signs of chronic disease. Laboratory investigations are rarely revealing in FTT but should be considered if there is a high index of suspicion for underlying disease. Treatment in FTT favors a multidisciplinary approach. The primary goal of treatment is restoration of normal growth velocity. Children with FTT are at increased risk for growth and cognitive problems in later childhood, although the clinical significance of these findings is not well understood. The mainstay of treatment is increasing calories in the diet. Enteral feeding, orally or via a tube, is always preferred over parenteral feeding due to a better safety profile, ease of feeding, and lower cost. Parenteral nutrition is an acceptable way to meet caloric needs in infants and children when enteral nutrition is not possible. Children with FTT and malnutrition should be monitored closely for refeeding syndrome, which results from fluid and electrolyte shifts in malnourished children. In general, FTT can be treated on an outpatient basis with close follow-up. Indications for hospitalization include severe malnutrition/dehydration and concern for child endangerment.

      This review contains 7 figures, 8 tables and 26 references

      Key words: enteral feeding, failure to thrive, growth charts, nutrition, parenteral nutrition, poor weight gain, tube feeding, weight loss

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    • 10

      Pediatric Infectious Diarrhea and Dehydration

      By John W. Martel, MD, PhD; Scott McCorvey, MD, MS
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      Pediatric Infectious Diarrhea and Dehydration

      • JOHN W. MARTEL, MD, PHDAssistant Professor, Department of Emergency Medicine, Tufts University School of Medicine, Maine Medical Center, Portland, ME
      • SCOTT MCCORVEY, MD, MSResident, Department of Emergency Medicine, Maine Medical Center, Portland, ME

      Diarrhea is a common emergency department (ED) complaint, leading to more than 1.5 million outpatient visits and 200,000 hospital admissions in the United States alone. Although concomitant dehydration also exists in some cases, there are no standard clinical criteria to aid in identifying those children who merit intravenous resuscitation. Current pediatric volume repletion guidelines are based primarily on the estimated degree of volume depletion per the World Health Organization, Centers for Disease Control and Prevention, and American Academy of Pediatrics criteria. These practice guidelines stratify patients into mild (3 to 5% volume depletion), moderate (5 to 10% volume depletion), and severe (> 10% volume depletion). 

      This review contains 5 figures, 9 tables, and 64 references.

      Key Words: Clostridium difficile, dehydration, diarrhea, gastroenteritis, hemolytic-uremic syndrome, pediatrics

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    • 11

      Evaluation and Treatment of Pediatric Obesity

      By Nirav K Desai; Samir Softic
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      Evaluation and Treatment of Pediatric Obesity

      • NIRAV K DESAIInstructor in Pediatrics, Harvard Medical School, Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Boston, MA
      • SAMIR SOFTICInstructor in Pediatrics, Harvard Medical School, Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Boston, MA

      Obesity is one of the most significant health problems facing children and adolescents. The definition of overweight in children is a body mass index between the 85th and less than 95th percentile, whereas obesity is greater than or equal to the 95th percentile for age and sex. There are multiple comorbidities associated with obesity, including dyslipidemia, hypertension, type 2 diabetes, sleep apnea, and nonalcoholic fatty liver disease, as well as psychosocial issues. 


      This review contains 3 figures, 4 tables and 63 references.

      Key Words bariatric surgery, metabolic syndrome, obesity treatment, pediatric obesity, weight loss surgery

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    • 12

      Pediatric Seizures and Status Epilepticus

      By Lindsey Retterath, MD ; Dale Woolridge, MD
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      Pediatric Seizures and Status Epilepticus

      • LINDSEY RETTERATH, MD Banner University Medical Center – Tucson, Resident Physician, Department of Emergency Medicine and Department of Pediatrics
      • DALE WOOLRIDGE, MD Banner University Medical Center – Tucson, Program Director, Emergency Medicine and Pediatrics Combined Residency Program

      Seizures represent a common neurologic complaint among pediatric patients in the emergency department (ED). They can be classified as generalized or focal. In terms of etiology, seizures are most basically broken down into “acute symptomatic” seizures, which are due to another primary medical cause, and unprovoked seizures which occur as a primary pathology. Febrile seizures are the most common types of seizures in children, which themselves can be simple or complex. The most concerning seizures are those which associate with meningismus, encephalitis, metabolic derangements, intracranial mass, and, of course those which progress to status epilepticus. Significantly, it is appropriate and even critical to assume status epilepticus and intervene accordingly whenever a child arrives to the ED seizing for an unspecified period of time. This review covers the initial evaluation, resuscitation, management, work-up, and disposition of pediatric patients who present to the emergency room with seizures. Figures in this chapter illustrate stepwise and algorithmic approaches to initial management, expanded differential, systematic diagnostic approach, and disposition for pediatric patients presenting with seizures and status epilepticus. Tables list important physical exam components for evaluating children with seizures, classifications of seizures, common seizure look-alikes in children, features of febrile seizures, etiologies of pediatric seizures.

      Key Words: Pediatric seizures, febrile seizures, pediatric neurologic emergencies, pediatric emergency medicine, status epilepticus 

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    • 13

      Cystic Fibrosis in Childhood and Adolescence

      By Sabina Sabharwal, MD, MPH
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      Cystic Fibrosis in Childhood and Adolescence

      • SABINA SABHARWAL, MD, MPHInstructor, Harvard Medical School, Boston Children’s Hospital, Boston, MA

      Although cystic fibrosis (CF) has historically been considered a pulmonary disease, with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Moreover, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This review discusses gastrointestinal (including nutritional, pancreatic, and hepatobiliary) manifestations of CF and their management. It also discusses studies that have been critical to our understanding of these manifestations of CF.

      This review contains 1 figure, 1 table, and 36 references.

      Key words: body mass index, constipation, cystic fibrosis transmembrane regulator, distal intestinal obstruction syndrome, pancreatic insufficiency

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    • 14

      Abnormalities of the Fetal Chest

      By Karen M. Davidson, MD
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      Abnormalities of the Fetal Chest

      • KAREN M. DAVIDSON, MDAssistant Professor Harvard Medical School Brigham and Women’s Hospital Department of Obstetrics and Gynecology Division of Maternal Fetal Medicine

      The normal and abnormal development of the organs lying within the fetal thorax is discussed.  The abnormalities reviewed include more common findings of pulmonary hypoplasia, congenital diaphragmatic hernia, congenital pulmonary airway malformation, bronchopulmonary sequestration, as well as the rarer conditions of congenital fetal hydrothorax, congenital high airway obstruction syndrome, bronchogenic cysts, neurenteric cysts, and lung agenesis.  With each abnormality, the clinical implications for the fetus, best methods for prenatal diagnosis, as well as possible additional anomalies, syndromes, and aneuploidies are described.  In utero and postnatal treatments are also reviewed.  

      This review contains 10 figures, and 37 references.

      Key Words: Pulmonary hypoplasia, lung-head ratio, congenital diaphragmatic hernia, congenital pulmonary airway malformation, congenital fetal hydrothorax, bronchopulmonary sequestration, congenital high airway obstruction syndrome, bronchogenic cyst, neurenteric cyst, lung agenesis

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    • 15

      Abnormalities of the Fetal Head and Neck

      By Ann McHugh, MB, BCh, BAO, MA, MRCPI, MRCOG; Fergal D. Malone, MD, FACO, FRCOG, FRCPI
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      Abnormalities of the Fetal Head and Neck

      • ANN MCHUGH, MB, BCH, BAO, MA, MRCPI, MRCOGRotunda Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland
      • FERGAL D. MALONE, MD, FACO, FRCOG, FRCPIRotunda Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland

      Fetal head and neck abnormalities can be reliably assessed using a combination of 2D and 3D ultrasound. The accuracy of imaging depends to a large extent on gestational age. Magnetic resonance imaging (MRI) has evolved as a useful adjunct to ultrasound particularly for prenatal diagnosis of fetal head and neck anomalies. Intrauterine MRI improves diagnostic accuracy for fetal brain abnormalities and often leads to changes in management. MRI can be used to refine diagnoses in complex cases where ultrasound imaging is unclear or cannot determine the precise diagnosis. Some fetal neck masses can result in neonatal respiratory compromise. An ex utero intrapartum treatment (EXIT) procedure may be required if a neck mass is causing tracheal occlusion. Polyhydramnios can occur if there is oesophageal compression. When a fetal head and neck abnormality is detected, appropriate counselling regarding diagnosis, prognosis, and treatment options is crucial in allowing the patient to make an informed and timely decision in relation to pregnancy management.

      This review contains 14 figures, 3 tables, and 68 references.

      Key words: Intracranial abnormality, anencephaly, encephalocele, cystic hygroma, fetal neck mass, ventriculomegaly, fetal goiter, Craniosynostosis, Agenesis of the corpus callosum, Holoprosencephaly, EXIT

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    • 16

      Comprehensive Overview of Pediatric Airway Management

      By Dale Woolridge, MD ; Lisa Goldberg , MD; Garrett S. Pacheco, MD
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      Comprehensive Overview of Pediatric Airway Management

      • DALE WOOLRIDGE, MD Banner University Medical Center – Tucson, Program Director, Emergency Medicine and Pediatrics Combined Residency Program
      • LISA GOLDBERG , MDResident Physician, Department of Emergency Medicine, University of Arizona at South Campus, Tucson, AZ
      • GARRETT S. PACHECO, MDAssistant Professor, Departments of Emergency Medicine and Pediatrics, University of Arizona, Tucson, AZ

      Pediatric endotracheal intubation is a procedure that can be stress provoking to the emergency physician. Although the need for this core skill is rare, when confronted with this situation, the emergency physician must have knowledge of the anatomic, physiologic, and pathologic components unique to the pediatric airway to optimize success. Furthermore, the emergency physician should be well versed in the various equipment and adjuncts as well as techniques developed to effectively manage the pediatric airway. This review covers the pathophysiology and practice of endotracheal intubation. Figures show a gum elastic bougie; the Mallampati classification; appropriate oropharyngeal, laryngeal, and tracheal axes; advancing the laryngoscope to lift the epiglottis; endotracheal tube position in neonates; and synchronized intermittent mandatory ventilation pressure-regulated volume control mechanical ventilation. Tables list endotracheal tube sizes, neonatal endotracheal tube sizes, pediatric laryngeal mask airway sizes, commonly used induction agents, and endotracheal tube insertion depth guidelines.

      This review contains 6 figures, 8 tables, and 77 references.

      Key words: emergent tracheal intubation; endotracheal tube; laryngoscopy; pediatric airway; pediatric airway management; pediatric endotracheal intubation; pediatric laryngeal mask; video laryngoscopy

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    • 17

      Attention-deficit/hyperactivity Disorder in Children and Adolescents

      By Sergio Delgado, MD
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      Attention-deficit/hyperactivity Disorder in Children and Adolescents

      • SERGIO DELGADO, MDCincinatti Children's Hospital

      Attention-deficit/hyperactivity disorder (ADHD) is the most common and thoroughly researched neuropsychiatric disorder affecting children and adolescents. The prevalence of ADHD ranges from 8 to 12% in school-age children, and 70% of these individuals continue to meet DSM-5 criteria for the disorder in adolescence. ADHD is more commonly diagnosed in boys compared with girls. ADHD is chronic, with prominent symptoms and impairment in family, social, and academic functioning. ADHD is often associated with comorbid disorders, including disruptive, mood, and anxiety disorders, and can increase the risk of developing substance use disorders. The diagnosis of ADHD requires a comprehensive clinical assessment, including a detailed history, clinical interview, and collateral information, and is clinically established by review of symptoms and impairment and having established a developmental history of the symptoms. The biological underpinning of the disorder is supported by genetic, neuroimaging, neurochemistry, and neuropsychological data. Treatment should attend to developmental milestones of the child and include family and individual psychosocial interventions. Psychosocial interventions in combination with medication are helpful for ADHD and comorbid problems. Pharmacotherapy, including psychostimulants, noradrenergic agents, alpha agonists, and antidepressants, plays a fundamental role in the treatment and management of ADHD.

      This review contains 2 figures, 9 tables, and 114 references.

      Key words: attention, attention-deficit/hyperactivity disorder, comorbidity, hyperactivity, impulsivity, learning, nonstimulants, psychosocial, psychostimulants, treatment

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    • 18

      Common Maternal Genetic Syndromes II: Marfan Syndrome

      By Ali Said Al-Beshri, MD; Nathaniel H. Robin, MD
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      Common Maternal Genetic Syndromes II: Marfan Syndrome

      • ALI SAID AL-BESHRI, MDResident- Medical Genetics, Department of Genetics, University of Alabama at Birmingham, Birmingham, AL
      • NATHANIEL H. ROBIN, MDProfessor, Department of Genetics, Director of Clinical Genetics Services, Residency Director, Genetics, University of Alabama at Birmingham, Birmingham, AL

      Marfan syndrome is an autosomal dominant syndrome that affects various connective tissues including the aorta and skeletal system. It represent a major cause of aortic dissection in individuals with seemingly unremarkable past medical history, and is the most common cause of aortic dissection in pregnancy. Prompt and accurate diagnosis can be lifesaving. Careful physical examination and detailed personal and family history is vital for clinical evaluation. Genetic testing is often needed for accurate diagnosis but result interpretation might be challenging and genetic counseling is always required. Established guidelines can help navigate the challenges in obstetric management, which may include major surgical interventions during or after pregnancy.

      This review contains 6 figures, 4 tables, and 40 references.

      Keywords: Marfan syndrome, FBN1, aortic dissection, dilatation, connective tissue, ectopia lentis, pectus, systemic score, Ghent diagnostic criteria, genetic testing.

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    • 19

      Vulvar Lesions in the Pediatric Patient

      By Michele Troutman, MD; Hong-Thao Thieu, MD
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      Vulvar Lesions in the Pediatric Patient

      • MICHELE TROUTMAN, MDResident, Beth Israel Deaconess Medical Center, Boston, MA
      • HONG-THAO THIEU, MDObstetrician-Gynecologist, Tufts Medical Center, Boston, MA

      Vulvar lesions are a common complaint for which pediatric patients seek medical attention. Please refer to the chapter on Prepubertal Vulvovaginitis for more details. A careful history and physical exam, including full skin exam should be performed when pediatric and adolescent patients present with vulvar complaints. The chief complaint and chronicity of the symptoms can narrow the differential. The chronicity and areas of dermatologic involvement can also be key to diagnosing a systemic condition versus a primary vulvar dermatosis. When the latter is assumed, a referral to an appropriate specialist such as a Pediatric and Adolescent Gynecologist or Dermatologist should be considered. Treatment for vulvar dermatoses should be etiology dependent with consideration of systemic treatment as appropriately indicated. Vulvar hygiene should be considered in all patients as restoring the skin barrier and removing potential irritants is imperative to healing and preventing further irritation.

      This review contains 1 figure, 2 tables, and 25 references.

      Keywords: vulva, vulva dermatosis, vulvovaginitis, lichen sclerosus, atopic dermatitis, psoriasis, streptococcus vulvovaginitis, irritant dermatitis, contact dermatitis

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    • 20

      Pediatric Fever

      By Clifford C. Ellingson, MD; Dale P. Woolridge, MD, PhD
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      Pediatric Fever

      • CLIFFORD C. ELLINGSON, MDDepartment of Pediatric and Emergency Medicine, University of Arizona and Banner University Medical Center, Tucson, AZ
      • DALE P. WOOLRIDGE, MD, PHDProfessor, Department of Pediatric and Emergency Medicine, University of Arizona, Tucson, AZ
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    • 21

      Pediatric Orthopedic Emergencies

      By Priya Gopwani, MD; Joy Koopmans, MD
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      Pediatric Orthopedic Emergencies

      • PRIYA GOPWANI, MDAttending Physician, Assistant Professor of Pediatric Emergency Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
      • JOY KOOPMANS, MDAttending Physician, Department of Pediatric Emergency Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago at Central DuPage Hospital, Health Systems Clinician, Northwestern University Feinberg School of Medicine, Winfield, IL
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    • 22

      Pediatric Rashes

      By Summer Stears-Ellis, MD
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      Pediatric Rashes

      • SUMMER STEARS-ELLIS, MDClinical Instructor, Emergency Ultrasound Fellow, Department of Emergency Medicine, The University of Arizona, Tucson, AZ
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    • 23

      Pediatric Hematologic and Oncologic Emergencies

      By Rebecca Milligan, MD; Jenny Mendelson, MD
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      Pediatric Hematologic and Oncologic Emergencies

      • REBECCA MILLIGAN, MD
      • JENNY MENDELSON, MD
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  • Obstetrics
    • 1

      Medical Complications in Pregnancy

      By Ellen W. Seely, MD; Jeffrey L. Ecker, MD
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      Medical Complications in Pregnancy

      • ELLEN W. SEELY, MDDirector of Clinical Research, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
      • JEFFREY L. ECKER, MDDirector, Fellowship in Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Professor, Harvard Medical School, Boston, MA

      Medical complications and intercurrent disease have long presented challenges to obstetricians and other medical providers caring for pregnant women. Contemporary medical practice and treatments have only added to these challenges. Advances in disease management mean that patients with some conditions (e.g., cystic fibrosis) whose life expectancies in the past would have precluded pregnancy are now living to reproductive age. Furthermore, treatments to restore fertility allow the barrier of age, as well as anatomic and genetic barriers, to be surmounted. All of these advances emphasize the need for careful and considered collaboration between clinicians caring for women of reproductive age who are not pregnant and those who care for them during pregnancy. This review discusses pregnancy planning and counseling, principles of teratogenesis, physiologic changes in pregnancy, cardiovascular disease, diabetes mellitus, thyroid disease, thrombophilia, asthma, infectious diseases, renal disease, autoimmune diseases, cancer, neurologic diseases, substance use, intrahepatic cholestasis, and pregnancy-specific conditions. Tables list elements of preconception care and counseling, the Food and Drug Administration drug classification system for pregnancy, selected drugs with suspected or known teratogenic potential, and physiologic changes of pregnancy.

      This review contains 15 tables and 83 references.

      Key Words: Headache, maternal mortality, obstetric medicine, pregnancy, pulmonary embolism

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    • 2

      Polycystic Ovary Syndrome

      By Snigdha Alur-Gupta, MD; Anuja Dokras, MD, PhD
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      Polycystic Ovary Syndrome

      • SNIGDHA ALUR-GUPTA, MDDivision of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA
      • ANUJA DOKRAS, MD, PHDDivision of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA

      Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine disorder in women of reproductive age. In this review, the pathophysiology and current diagnostic criteria for PCOS are reviewed. Treatment options for symptoms commonly associated with PCOS such as hirsutism, acne, and menstrual irregularity are reviewed. Combined hormonal contraceptives are the first line of therapy in women not attempting pregnancy. The metabolic complications commonly associated with PCOS are impaired glucose tolerance and dyslipidemia. A summary of the current guidelines on screening and prevention of these complications is presented. In addition, PCOS is associated with an increased risk of depressive symptoms and anxiety disorders for which patients should be monitored.

      This review contains 7 tables and 59 references. 

      Keywords: Polycystic ovary syndrome, PCOS 

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    • 3

      Hypertensive Disorders in Pregnancy

      By Kavitha Vellanki, MD; Susan Hou, MD
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      Hypertensive Disorders in Pregnancy

      • KAVITHA VELLANKI, MDAssociate Professor of Medicine, Division of Nephrology and Hypertension, Loyola University Medical Center, Maywood, IL.
      • SUSAN HOU, MDProfessor of Medicine, Division of Nephrology and Hypertension, Department of Nephrology and Hypertension, Loyola University Medical Center, Maywood, IL.

      Hypertensive disorders are the second leading cause of maternal mortality in the United States. Hypertension in pregnancy is defined as blood pressure greater than or equal to 140 mm Hg systolic or greater than or equal to 90 mm Hg diastolic, measured on at least two separate occasions. Preeclampsia, as per the new guidelines, is characterized by the new onset of hypertension and either proteinuria or other end-organ dysfunction, more often after 20 weeks of gestation in a previously normotensive pregnant woman. New-onset proteinuria is not required for diagnosis of preeclampsia if there is evidence of other end-organ damage—a change from previous classifications. Although no screening test has yet proven accurate enough to predict preeclampsia, the use of a combination of the serologic factors seems promising. There are few data to support any specific blood pressure target in pregnancy. Although there is a general consensus on treating severe hypertension in pregnancy, there is a difference of opinion on treating mild to moderate hypertension in pregnancy. Avoiding uteroplacental ischemia and minimizing fetal exposure to adverse effects of medications are as important as avoiding maternal complications from high blood pressure during pregnancy.

      This review contains 2 figures, 4 tables, and 73 references.

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    • 4

      Bacterial Infections in Pregnancy

      By Patrick Duff, MD; Jessica Jackson, MD, MSBS
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      Bacterial Infections in Pregnancy

      • PATRICK DUFF, MDDepartment of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, FL, United States
      • JESSICA JACKSON, MD, MSBSDepartment of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, FL, United States

      All pregnant women should be screened on the first prenatal visit for chlamydia infection and gonorrhea. High-risk patients should be rescreened in the third trimester. Patients with symptomatic bacterial vaginosis should be treated with metronidazole to prevent complications such as preterm delivery, chorioamnionitis, and puerperal endometritis. All patients should be screened for GBS infection at 35 to 37 weeks and treated intrapartum with prophylactic antibiotics if they test positive. Prompt diagnosis and treatment of chorioamnionitis are essential to prevent neonatal and maternal complications. The treatment of choice intrapartum is ampicillin plus gentamicin. Patients who require cesarean delivery should also receive either clindamycin or metronidazole postpartum to strengthen coverage against anaerobes. Two highly effective treatment regimens for puerperal endometritis are clindamycin plus gentamicin or metronidazole plus ampicillin plus gentamicin.

      This review contains 5 figures, 7 tables and 43 references.

      Key Words: bacterial vaginosis, chorioamnionitis, lower genital tract infection, puerperal infection, urinary tract infection

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    • 5

      Infections Caused by Spirochetes: Syphilis, Lyme Disease, Leptospirosis

      By Patrick Duff, MD
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      Infections Caused by Spirochetes: Syphilis, Lyme Disease, Leptospirosis

      • PATRICK DUFF, MDDepartment of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, FL, United States

      Syphilis is caused by the spirochete Treponema pallidum. It is classified as primary, secondary, tertiary, and latent infection. If left untreated, syphilis can cause devastating injury to the fetus. The drug of choice for treatment of syphilis in pregnancy is penicillin. Lyme disease is caused by Borrelia burgdorferi and is transmitted by the Ixodes scapularis tick. The principal clinical manifestation of Lyme disease is erythema migrans, but patients may also develop arthritis and cardiac and neurologic abnormalities. Congenital Lyme disease has not been reported. The drug of choice for treatment of Lyme disease in pregnancy is amoxicillin. Leptospirosis is usually acquired from direct contact with urine of infected animals or through contaminated water, soil, or vegetation. Pregnant women with mild disease should be treated with oral amoxicillin. Patients with severe disease should be hospitalized and treated with intravenous penicillin or ampicillin.

      This review contains 5 figures, 5 tables, and 19 references.

      Key Words: clinical infection, congenital syphilis, latent infection, leptospirosis, Lyme disease, syphilis

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    • 6

      Viral Infections in Pregnancy – Part 1: CMV, Ebola Virus, Viral Hepatitis, HSV, and HIV

      By Patrick Duff, MD
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      Viral Infections in Pregnancy – Part 1: CMV, Ebola Virus, Viral Hepatitis, HSV, and HIV

      • PATRICK DUFF, MDDepartment of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, FL, United States

      A number of viral etiologies contribute to morbidity and mortality in pregnancy and the perinatal period. Here we discuss some of the major viral infections that occur in pregnancy. This review focuses on infections of cytomegalovirus (CMV), viral hepatitis, herpes simplex virus (HSV), and human immunodeficiency virus (HIV); other viral etiologies are discussed in part 2 of this topic. It is imperative to understand the risks, clinical course, diagnostic methodology, and management of these illnesses.


      This review contains 1 figure, 12 tables, and 71 references

      Keywords: viral infection, pregnancy, prenatal, perinatal, cytomegalovirus, Ebola virus, viral hepatitis, herpes simplex virus, HIV, management

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    • 7

      Preconception Care

      By Laura Bookman, MD; Tariro Mupombwa, MD
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      Preconception Care

      • LAURA BOOKMAN, MDStaff Physician, Department of Obstetrics and GynecologyBeth Israel Deaconess Medical Center, Assistant Professor of Obstetrics, Gynecology and Reproductive BiologyHarvard Medical School, Boston, MA
      • TARIRO MUPOMBWA, MDChief OBGYN Resident, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Clinical Fellow, Harvard Medical School, Boston, MA

      The goal of preconception care is to optimize the health and knowledge of every woman prior to pregnancy. Inquiring about plans for pregnancy can occur at any patient encounter, not just at a scheduled preconception care visit, because many women do not present for care until they are already pregnant. Identifying medical, social, environmental, and psychological risks prior to pregnancy can lead to interventions that may enhance the health of both mother and baby. Relevant preconception issues discussed in this review include medications; medical, surgical, mental health, and social history, including substance use and intimate partner violence; immunization recommendations; nutrition; genetic screening; and infectious disease.

      This review contains 2 figures, 5 tables and 52 references

      Keywords: depression, diabetes, exercise, hypertension, immunizations, intimate partner violence, nutrition, preconception care, reproductive life plan, thyroid disease

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    • 8

      Nausea and Vomiting of Pregnancy

      By Elizabeth Roberts, MD; Brett C Young, MD
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      Nausea and Vomiting of Pregnancy

      • ELIZABETH ROBERTS, MDDepartment of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA
      • BRETT C YOUNG, MDDepartment of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA

      In pregnancy, the majority of women experience at least some nausea and vomiting. For many women, these symptoms are mild and self-limiting and resolve by the second trimester. A minority of women experience severe symptoms of hyperemesis gravidarum with persistent vomiting, weight loss, and electrolyte derangements. The diagnosis of hyperemesis gravidarum is based on clinical history and exclusion of other etiologies of nausea and vomiting. First-line pharmacologic treatment is with pyridoxine and doxylamine. Other medical treatments include metoclopramide, phenothiazines, antacids, and ondansetron. In refractory cases, corticosteroids and enteral or parenteral nutrition may be considered.

      This review contains 3 figures, 2 tables and 83 references

      Key words: enteral feeding, hyperemesis gravidarum, maternal outcomes, nausea and vomiting of pregnancy, neonatal outcomes, nonpharmacologic antiemetics, pharmacologic antiemetics

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    • 9

      Perinatal Depression

      By Tiffany A. Moore Simas, MD, MPH, MEd (Corresponding Author); Bailey McGuiness, MD; Valerie Valant, MD; Nancy Byatt, DO, MS, MBA
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      Perinatal Depression

      • TIFFANY A. MOORE SIMAS, MD, MPH, MED (CORRESPONDING AUTHOR) Associate Professor of Obstetrics & Gynecology, Pediatrics, and Psychiatry University of Massachusetts Medical School/UMass Memorial Health Care Department of Obstetrics & Gynecology Memorial Campus – 119 Belmont Street – Jaquith 2.008 Worcester, MA 01568
      • BAILEY MCGUINESS, MDNYU Winthrop Hospital Ob/Gyn Residency, Mineola, NY
      • VALERIE VALANT, MDDartmouth-Hitchcock Ob/Gyn Residency, Lebanon, NH
      • NANCY BYATT, DO, MS, MBAAssociate Professor of Psychiatry and Obstetrics & Gynecology University of Massachusetts Medical School/UMassMemorial Health Care, Worcester, MA

      Perinatal depression includes major and minor depression occurring in pregnancy and one year postpartum. Affecting one in seven women, it is one of the most common pregnancy complications; however, it is often under recognized and undertreated. A personal history of perinatal or non-perinatal depression significantly increases risk. Screening using a validated instrument is recommended in the context of systems to ensure effective diagnosis, treatment, and follow-up. Evidence-based treatment includes psychotherapy and pharmacotherapy. Selective serotonin reuptake inhibitors are well-studied in pregnancy, are associated with low overall absolute risk, and are differentially secreted into breast milk. If left untreated, perinatal depression is associated with significant short- and long-term negative maternal-child consequences including, among many others things, poor bonding. Of note, maternal suicide exceeds hemorrhage and hypertensive disorders as a cause of maternal mortality. It is critical to recognize that one in five women who screen positive for perinatal depression will have bipolar disorder and are at highest risk for postpartum psychosis, suicide, and infanticide, especially if prescribed unopposed anti-depressant monotherapy. Women who screen positive for having bipolar disorder should be referred for psychiatric evaluation.

      This review contains 6 figures, 13 tables and 54 references

      Keywords: Pregnancy, Postpartum, Perinatal, depression, Mood disorder, Baby blues, Bipolar disorder, Psychosis, Psychotherapy, Psychopharmacology

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    • 10

      Breastfeeding

      By Marcie Richardson, MD
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      Breastfeeding

      • MARCIE RICHARDSON, MD

      Breastfeeding is endorsed by the medical community as the optimal nutrition for infants during the first 6-12 months of life.1,2,3  Breastfeeding rates in the US and worldwide have varied over time and still vary geographically.4 There is robust literature addressing the physiology of lactation, composition of breast milk, and health advantages of breastfeeding for both the mother and infant as well as strategies for clinicians to promote and support breastfeeding. This chapter reviews breastfeeding history, how milk is made, why breastfeeding matters, and the somewhat controversial the World Health Organization’s Baby Friendly Hospital Initiative (BFHI)5 for successful initiation of lactation as well as some special situations.   

      Key words:  breastfeeding, infant nutrition, human milk composition, breastfeeding advantages, lactation, lactation support, Baby Friendly Hospital Initiative, skin to skin contact

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    • 11

      Preconception Care

      By Laura Bookman, MD; Tariro Mupombwa, MD
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      Preconception Care

      • LAURA BOOKMAN, MDStaff Physician, Department of Obstetrics and GynecologyBeth Israel Deaconess Medical Center, Assistant Professor of Obstetrics, Gynecology and Reproductive BiologyHarvard Medical School, Boston, MA
      • TARIRO MUPOMBWA, MDChief OBGYN Resident, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Clinical Fellow, Harvard Medical School, Boston, MA
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  • Sports Medicine
    • 1

      Stress Fractures and the Reproductive System in the Female Athlete

      By Irfan M Asif, MD; Kimberly Harmon, MD; Mallory Shasteen, MD
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      Stress Fractures and the Reproductive System in the Female Athlete

      • IRFAN M ASIF, MDDirector, Primary Care Sports Medicine Fellowship, Assistant Professor, Department of Family Medicine, University of Tennessee, Knoxville, TN
      • KIMBERLY HARMON, MDDirector, Primary Care Sports Medicine Fellowship, Professor, Departments of Family Medicine and Orthopaedics and Sports Medicine, Team Physician, University of Washington, Seattle, WA
      • MALLORY SHASTEEN, MDEmergency Physician, Department of Emergency Medicine, Greenville Health System/University of South Carolina School of Medicine Greenville, Greenville, SC

      Stress fractures are more common in the female athlete. Stress fractures of the pubic ramus and femoral neck are particularly more common in females than in males. Rib stress fractures are an important injury to consider in the female rower, whereas spondylolysis is a common cause of low back pain in female athletes who hyperextend their spines. The higher incidence of stress fractures in females is mainly due to the higher prevalence of disordered eating and subsequent energy imbalance, which leads to detrimental effects on bone. This review discusses stress fractures and unique issues related to exercise and the female reproductive system.

      This review contains 6 figures, 5 tables and 49 references

      Key words: amenorrhea, bone mineral density, disordered eating, female athlete triad, femoral neck, pregnancy, pubic ramus, rib, spondylolysis, stress fracture

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    • 2

      Musculoskeletal Problems in the Female Athlete

      By Irfan M Asif, MD; Emily Edwards, DO; Kimberly Harmon, MD
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      Musculoskeletal Problems in the Female Athlete

      • IRFAN M ASIF, MDDirector, Primary Care Sports Medicine Fellowship, Assistant Professor, Department of Family Medicine, University of Tennessee, Knoxville, TN
      • EMILY EDWARDS, DODepartment of Family Medicine, University of Tennessee, Knoxville, TN
      • KIMBERLY HARMON, MDDirector, Primary Care Sports Medicine Fellowship, Professor, Departments of Family Medicine and Orthopaedics and Sports Medicine, Team Physician, University of Washington, Seattle, WA

      Musculoskeletal injuries in the female athlete are, for the most part, similar to those in the male athlete. However, there are differences in the incidence of these injuries and in the sports in which they tend to occur. Female athletes have a higher rate of noncontact anterior cruciate ligament injuries than male athletes. Other musculoskeletal problems are also more common in females, such as multidirectional instability of the shoulder, adhesive capsulitis, and patellofemoral pain. This review addresses injuries that are seen commonly in female athletes and outlines current diagnosis and treatment options.

      This review contains 3 figures and 32 references

      Key words: ACL tear, adhesive capsulitis, atraumatic, female athlete, injection, knee, patellofemoral pain, shoulder

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    • 3

      Injuries to the Face and Jaw

      By Mark E. Engelstad, DDS, MD; Richard A. Hopper, MD, MS
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      Injuries to the Face and Jaw

      • MARK E. ENGELSTAD, DDS, MDChief, Oral and Maxillofacial Surgery, Harborview Medical Center, University of Washington
      • RICHARD A. HOPPER, MD, MSService Chief, Craniofacial Plastic Surgery, Harborview Medical Center, Chief, Plastic Surgery, Surgical Director, Craniofacial Center, Seattle Children’s Hospital, Associate Professor, University of Washington, Seattle, WA

      Facial injuries occur most often through violence or vehicular accident. The main priorities after injury are to assess the airway and check for hemorrhage, followed by assessment of vision, a check for bony trauma or malocclusion, followed by assessment for soft tissue injuries. Most facial injury survey will be done via inspection, palpation, or diagnostic imaging, which includes plain radiography, CT scan, or MRI. Injuries to the face and jaw can be of the soft tissue variety. These include injuries to the facial and trigeminal nerve, parotid duct, scalp, eyelid, lacrimal duct, eyebrow, external ear, nasal passages, or lips. Treatment of maxillofacial fractures include dentoalveolar injuries, mandibular fractures, maxillary fractures, zygomatic fractures, orbital fractures, nasal fractures, nasoorbitoethmoid fractures, and frontal sinus fractures. Figures show common injuries and fractures. This chapter includes 28 references.

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    • Shoulder Pain
    • Knee Pain
    • Foot and Ankle Pain
    • Elbow Pain
    • Wrist and Hand Pain
    • Disease of the Hip and Pelvis
    • Back and Neck
  • Wellness in Training
    • 1

      Sleep Well to Be Well: Importance of Healthy Sleep During Medical Training

      By Ilia Kritikou, MD
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      Sleep Well to Be Well: Importance of Healthy Sleep During Medical Training

      • ILIA KRITIKOU, MDDivision of Sleep Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA

      Sleep is vital for our survival and wellness; lack of sleep is associated with significant cognitive, behavioral and physical health consequences, including increased mortality. In resident physicians and other health care providers, scheduled in-house calls, frequent pager/phone calls, and work required during nights are the norm. These phenomena along with the normal pull for work/life balance lead to acute and chronic partial sleep restriction, sleep disruption and circadian misalignment. As is true for the general population, residents are not immune to sleepiness and performance deficits associated with curtailed sleep. Residents are also at risk for metabolic dysregulation, including increased risk of obesity, cardiovascular disease, and mood disturbances that accompany disrupted sleep and circadian misalignment. Initial data suggesting worse patient outcomes when residents work >80 hours weekly, pushed Accreditation Council for Graduate Medical Education (ACGME) to limit resident duty-hours to 80 weekly, 30 per shift; newer data fail to show improved patient outcomes under the new limited work schedule. Nevertheless, recent studies suggest extended work schedules and circadian misalignment negatively affect well-being of resident physicians, increase risk of motor vehicle accidents. Long-term effects are yet to be determined.Implementing educational programs that foster programmatic, individual responsibility for fatigue management, GME programs and their leadership may mitigate negative consequences on safety and wellness.

      This review contains 2 figures, 3 tables, and 36 references.

      Keywords: sleep, sleep deprivation, sleepiness, circadian rhythms, residency, health care, patient outcomes, ACGME, wellness

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    • 2

      A Wellness Roadmap for Medical Trainees: What a Program Director Should Know

      By Richard Joseph, MD MBA; Lori Berkowitz, MD
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      A Wellness Roadmap for Medical Trainees: What a Program Director Should Know

      • RICHARD JOSEPH, MD MBABrigham and Women’s Hospital, Division of General Internal Medicine and Primary Care, Boston, MA
      • LORI BERKOWITZ, MDObstetrics & Gynecology, Massachusetts General Hospital, Boston, MA

      This review contains 2 figures, and 25 references.

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    • 3

      Self-compassion During GME Training

      By Rebecca M. Reimers, MD, MPH
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      Self-compassion During GME Training

      • REBECCA M. REIMERS, MD, MPHDepartment of Obstetrics and Gynecology, Brigham and Women’s Hospital, Boston, Massachusetts, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts

      Self-compassion is a positive psychology concept that is related to resilience, improved coping, and reduced stress. The three key components are self-kindness, mindfulness, and understanding that we are all part of a common humanity. Self-compassion is in opposition of harsh self-judgment or self-criticism, which have been linked to stress, emotional dysregularion, and avoidance of negative feedback.  Self-compassion can be useful during individual times of crisis and on a daily basis for improved resilience and coping. Exercises for acute events, suggestions for daily living, and a review of self-compassion research in healthcare settings are reviewed and explained in the following article.

      This review contains 1 table and 16 references.

      Keywords: mindfulness; resilience; self-compassion; well-being; residency; burnout; graduate medical education

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    • 4

      Creating a Culture of Wellness - No Jerks Allowed

      By Hope A Ricciotti, MD
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      Creating a Culture of Wellness - No Jerks Allowed

      • HOPE A RICCIOTTI, MDChair, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

      The culture of a health care system influences physician wellness; in turn, physician wellness is an indicator of the health care system quality. A career as a physician was traditionally viewed as a calling where patients came first, even to the personal detriment of the physician. Organizational cultures that support work-life integration allow flexibility and cooperative scheduling for the activities of work, home, family, community and self. Today’s health care challenges require collaboration, teamwork and the collective intelligence to get to the solutions that our complex environment requires. Open workspace is one method that can transform culture; academic medicine is following the model of the business world with spaces that flatten hierarchy, enhance communication among faculty and trainees, and foster a culture of civility and greater attachment to the organization. Top-down hierarchical leadership is outdated and counterproductive. Organizations with a flat structure are nimble, innovative and tend to outperform those with more traditional hierarchies. Adopting the humble attitude of a servant leader is essential to building positive department and organizational culture. Effective leaders have self-awareness, self-regulation, motivation, empathy and social skills, qualities collectively known as emotional intelligence. We need to move away from a physician centric culture and replace it with a new brand of department or health care organization that is just and collaborative, that promotes innovation and teamwork, iterates quickly and nurtures individuals at all levels to voice ideas and demonstrate leadership. These same ingredients promote joy in work and align with safe care models.

      This review contains 27 references.

      Keywords: Culture change, emotional intelligence, flattened hierarchy, innovation, leadership, servant leader, work-life integration

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    • 5

      Mindfulness

      By Alice D. Domar, Ph.D
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      Mindfulness

      • ALICE D. DOMAR, PH.DExecutive Director, Domar Centers for Mind/Body Health, Director of Integrative Care, Boston IVF, Senior Staff Psychologist, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Associate Professor of Obstetrics, Gynecology and Reproductive Biology, part-time, Harvard Medical School

      Most if not all physicians in training report feelings of exhaustion, burnout and inadequacy. Although many of these are normal reactions to an intense and rigorous period in their lives, it is possible to learn behaviors which can counter some of the physical and psychological impact. Mindfulness has been shown to be an effective antidote, and it is possible to incorporate mindfulness into one’s daily routine in a practical and efficient manner. Practicing mindfulness can ease the consequences of stress while simultaneously improving patient care. The key is the amount of practice one engages in; the more times one can practice mindfulness on a daily basis, the more benefits one receives. Physicians are encouraged to learn basic mindfulness skills and incorporate them into their personal and professional lives.

      This review contains 11 references.

      Keywords: mindfulness, meditation, residents, medical training, stress, depression, anxiety, symptom reduction

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    • 6

      Embracing Uncertainty

      By Arabella L. Simpkin, MD, MMSc
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      Embracing Uncertainty

      • ARABELLA L. SIMPKIN, MD, MMSCMassachusetts General Hospital Department of Medicine 100 Cambridge Street, 16th Floor, Boston, MA 02114

      We are constantly faced with uncertainty, which can instill a sense of vulnerability and fear. Prior studies link intolerance of uncertainty to burnout, ineffective communication strategies, cognitive biases and inappropriate resource use. Paradoxically, uncertainty is the driver of curiosity and progress, and is an important part of the practice of medicine. Indeed, the only certainty is in uncertainty. Unfortunately, we Western culture too often equates uncertainty with ignorance or failure, viewing it as a threat rather than a surmountable challenge, thus encouraging denial of this fundamental state for both physicians and patients. The time is ripe for a renewed perspective. Changing our culture to acknowledge, celebrate and embrace uncertainty could have positive downstream ramifications: decreasing physician burnout by reducing stress from uncertainty and altering our perspective on this state; and lightening physician’s burdens by absolving responsibility for implicitly having promised more than a physician or even medicine can deliver. Indeed, understanding and embracing uncertainty could be the most significant contribution of 21st century science to the human intellect.

      This review contains 29 references.

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    • 7

      Perfectionism

      By Alice D. Domar, PhD
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      Perfectionism

      • ALICE D. DOMAR, PHDExecutive Director, Domar Centers for Mind/Body Health, Director of Integrative Care, Boston IVF, Senior Staff Psychologist, Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Associate Professor of Obstetrics, Gynecology and Reproductive Biology, part-time, Harvard Medical School

      Perfectionism is common and even encouraged in medicine. Acceptance to medical school is predicated on academic excellence; those who commence being schooled in medicine and their perfectionistic tendencies may be rewarded. Residency and fellowship years are a time where teamwork, appropriate social behavior and flexibility may be as important as academic knowledge.  This can be threatening to the physician who has succeeded through perfectionistic academic self-induced pressure. Committing a mistake, although expected by all in this field, can feel overwhelming and unacceptable to a perfectionist: it can lead to symptoms of stress, depression and even suicide. Solutions to maladaptive perfectionism include cognitive-behavior therapy and coaching.

      This review contains 14 references.

      Key words: perfectionism, adaptive, maladaptive, physician burnout, suicide, CBT, coaching

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    • 8

      Substance Use Disorders

      By Erik A. Levinsohn, MD; Kevin P. Hill, MD, MHS
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      Substance Use Disorders

      • ERIK A. LEVINSOHN, MDBeth Israel Deaconess Medical Center
      • KEVIN P. HILL, MD, MHSDirector of Addiction Psychiatry, Beth Israel Deaconess Medical Center, Assistant Professor of Psychiatry, Harvard Medical School

      Given the incredible scope of substance use disorders, this chapter will primarily focus on alcohol and opioid use disorders, while also discussing substance use broadly. Furthermore, this chapter does not provide detailed guidelines for managing patients with a substance use disorder. Instead, this review aims to provide the reader with conceptual background of the biology of addiction as well as a general framework for its diagnosis and management. While this chapter primarily focuses on physicians in the role of caregiver, it is important to note that physicians also struggle with SUDs, at a rate near that of the general population.25

      This review contains 3 tables and 25 references.

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