A 67-year-old woman with a history of obesity, chronic low back pain, and recurrent episodes of major depression presents with mild depressive symptoms of more than 2 years’ duration, with worsening symptoms over the past 4 months. She was receiving sertraline at a stable dose of 100 mg per day until 3 months ago, when she initially presented for her worsening depressive symptoms. At that time, sertraline was tapered off, and treatment with extra-long extended-release bupropion (bupropion XL) was started at a dose of 150 mg daily and was increased to 300 mg daily 3 weeks later. Despite having taken the higher dose of bupropion XL for more than 2 months, the patient continues to have low mood, loss of interest in usual pleasurable activities, trouble falling asleep, wakefulness several times during the night, diminished energy, poor appetite, difficulty concentrating, and intrusive thoughts of being “better off dead,” but she does not have active suicidal thinking. Her nine-question Patient Health Questionnaire (PHQ-9) score is 17 (on a scale of 0 to 27, with higher scores indicating greater severity of depressive symptoms). How would you evaluate and treat this patient?

A 24-year-old woman is being seen for routine health care. She has not received any vaccinations against human papillomavirus (HPV). The patient initiated sexual activity at 18 years of age and has had three male sex partners. What would you recommend regarding HPV vaccination?

Since January 2022, there has been an increase in reports of cases of acute hepatitis of unknown cause in children. Although cases have been reported across multiple continents, most have been reported in the United Kingdom. Investigations are ongoing to identify the causative agent or agents.

SNAKE ENVENOMATION REPRESENTS AN IMPORTANT HEALTH PROBLEM IN much of the world. In 2009, it was recognized by the World Health Organization (WHO) as a neglected tropical disease, and in 2017, it was elevated into Category A of the Neglected Tropical Diseases list, further expanding access to funding for research and antivenoms. However, snake envenomation occurs in both tropical and temperate climates and on all continents except Antarctica. Worldwide, the estimated number of annual deaths due to snake envenomation (80,000 to 130,000) is similar to the estimate for drug-resistant tuberculosis and for multiple myeloma., In countries with adequate resources, deaths are infrequent (e.g., <6 deaths per year in the United States, despite the occurrence of 7000 to 8000 bites), but in countries without adequate resources, deaths may number in the tens of thousands. Venomous snakes kept as pets are not rare, and physicians anywhere might be called on to manage envenomation by a nonnative snake. Important advances have occurred in our understanding of the biology of venom and the management of snake envenomation since this topic was last addressed in the Journal two decades ago. For the general provider, it is important to understand the spectrum of snake envenomation effects and approaches to management and to obtain specific guidance, when needed.

A 78-year-old woman presents with vision changes in the right eye for one week. Specifically, she describes central blurring in her vision and bending or waviness in straight lines. She also reports increasing difficulty reading print and often feels that there are blind spots in her vision. How would you diagnose and treat this patient?

Large B-cell lymphomas, with an estimated 150,000 new cases annually worldwide, represent almost 30% of all cases of non-Hodgkin’s lymphoma. Patients typically present with progressive lymphadenopathy, extranodal disease, or both and require therapy. Despite the advanced stage at presentation in the majority of patients, more than 60% can be cured with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) immunochemotherapy (Fig. 1A). Patients with treatment failure after R-CHOP often have a poor outcome — in particular, those with disease that is refractory to frontline or subsequent therapies — although some patients can have a durable remission and be cured after secondary therapies. Over the past two decades, improved insights into large B-cell lymphomas, in terms of epidemiology, prognostic factors, and biologic heterogeneity, have led to a refinement of disease classification and the development of new therapeutic approaches.

Throughout the world, approximately 800,000 people die by suicide every year, accounting for 1.5% of all deaths. Suicide is the 10th leading cause of death in North America and the foremost cause of death worldwide among persons 15 to 24 years of age.

A 45-year-old woman with hypothyroidism that has been treated with a stable dose of levothyroxine presents to her primary care provider with depressed mood, negative feelings about herself, poor sleep, low appetite, poor concentration, and lack of energy. These symptoms began several months ago during a conflict with her partner. Although she has been able to continue with work and life responsibilities, she feels sadness most days and occasionally thinks that she would be better off dead. How would you evaluate and treat this patient?

Sequence analysis of cell-free DNA (cfDNA) fragments that circulate in the blood of pregnant women, along with the translation of this method into screening for fetal chromosome abnormalities, is a success story of modern genomic medicine. In less than a decade, prenatal cfDNA testing has gone from small, proof-of-principle studies to a global transformation of prenatal care. As of late 2017, a total of 4 million to 6 million pregnant women had had DNA from their plasma analyzed to screen for fetal aneuploidy. The exponential growth of the test has been a function of the role of the biotechnology industry in its development and marketing. Here we review what has been learned from the wide-scale implementation of this testing, how it has changed prenatal clinical care, and what ethical concerns have arisen, and we speculate about what lies ahead.

Clusters of cases of pneumocystis pneumonia and Kaposi’s sarcoma in New York and California in men who had sex with men were early harbingers of the acquired immunodeficiency syndrome (AIDS) epidemic. The syndrome was also soon noted to be associated with a high incidence of aggressive B-cell lymphomas. As the AIDS definition crystallized, Kaposi’s sarcoma, aggressive B-cell lymphomas, and invasive cervical cancer were considered to be AIDS-defining cancers when they developed in patients with human immunodeficiency virus (HIV) infection. Additional cancers are now known to be associated with HIV (Table 1). The term HIV-associated cancer is used here to describe this larger group of cancers (both AIDS-defining and non–AIDS-defining cancers) that have an increased incidence among patients with HIV infection. In addition, incidental cancers also may develop in patients with HIV infection.

A 75-year-old man is admitted for scheduled major abdominal surgery. He is functionally independent, with mild forgetfulness. His intraoperative course is uneventful, but on postoperative day 2, severe confusion and agitation develop. What is going on? How would you manage this patient’s care? Could his condition have been prevented?

A 17-year-old high school student who has never been pregnant presents for advice regarding contraception. She has an unremarkable medical history and is planning to become sexually active with her boyfriend in the near future. Her primary concern is an unintended pregnancy, and she inquires about methods of contraception that are highly effective. How would you counsel her about options for contraception?

A 22-year-old woman reports having hirsutism and irregular menses. She describes unpredictable and infrequent menses (five or six per year) since menarche at 11 years of age. Dark, coarse facial hair began to develop at 13 years of age. The symptoms worsened after she gained weight in college. The physical examination includes a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 29, blood pressure of 135/85 mm Hg, and moderate hirsutism without virilization. Laboratory tests reveal a total testosterone level of 65 ng per deciliter (2.3 nmol per liter) (assay reference range, 14 to 53 ng per deciliter [0.5 to 1.8 nmol per liter]), calculated free testosterone level of 15.3 pg per milliliter (53.1 pmol per liter) (assay reference range, 0.6 to 6.8 pg per milliliter [2.1 to 23.6 pmol per liter]), and glycated hemoglobin level of 5.7% (normal value, ≤5.6%). How should this case be evaluated and managed?

Key Clinical Points Postmenopausal Osteoporosis Fractures and osteoporosis are common, particularly among older women, and hip fractures can be devastating. Treatment is generally recommended in postmenopausal women who have a bone mineral density T score of -2.5 or less, a history of spine or hip fracture, or a Fracture Risk Assessment Tool (FRAX) score indicating increased fracture risk. Bisphosphonates (generic) and denosumab reduce the risk of hip, nonvertebral, and vertebral fractures; bisphosphonates are commonly used as first-line treatment in women who do not have contraindications. Teriparatide reduces the risk of nonvertebral and vertebral fractures. Osteonecrosis of the jaw and atypical femur fractures have been reported with treatment but are rare. The benefit-to-risk ratio for osteoporosis treatment is strongly positive for most women with osteoporosis. Because benefits are retained after discontinuation of alendronate or zoledronic acid, drug holidays after 5 years of alendronate therapy or 3 years of zoledronic acid therapy may be considered for patients at lower risk for fracture.

Because older victims of abuse tend to be isolated, their interactions with physicians are important opportunities to recognize abuse and intervene. This review explores the manifestations of elder abuse and the role of multidisciplinary teams in its assessment and management.

Once considered a rare condition, eosinophilic esophagitis is now one of the most common conditions diagnosed during the assessment of feeding problems in children and during the evaluation of dysphagia and food impaction in adults. The entity exists worldwide but has been most extensively studied in Western countries, where its prevalence has been estimated to be 0.4% among all children and adults. Whether eosinophilic esophagitis is truly a new disease or simply a recently recognized one is uncertain. In this review, we consider the diagnostic criteria, pathophysiological and clinical features, and treatment of this increasingly prevalent disease.

Although in textbooks asthma and chronic obstructive pulmonary disease (COPD) are viewed as distinct disorders, there is increasing awareness that many patients have features of both. This article reviews the asthma-COPD overlap syndrome.

Palliative care is the interdisciplinary specialty focused on improving quality of life for persons with serious illness and their families. Over the past decade, the field has undergone substantial growth and change, including an expanded evidence base, new care-delivery models, innovative payment mechanisms, and increasing public and professional awareness.

An 89-year-old male nursing home resident with a 10-year history of Alzheimer’s disease presents with a temperature of 38.3°C, a productive cough, and a respiratory rate of 28 breaths per minute. Nurses report that for the past 6 months he has been coughing at breakfast and having trouble swallowing. He has profound memory deficits, no longer recognizes his daughter (who is his health care proxy), is bedbound, is able to mumble a couple of words, and is unable to perform any activities of daily living. The nurse asks whether he should be hospitalized. How should this patient be evaluated and treated?

A 47-year-old black woman has heavy menstrual bleeding and iron-deficiency anemia.She reports nocturia and urinary frequency. A colonoscopy is negative. Ultrasonography shows a modestly enlarged uterus with three uterine fibroids. She is not planning to become pregnant. How should this case be evaluated and managed?