BACKGROUND Danon disease is a rare, X-linked, monogenic cardiomyopathy caused by mutations in the lysosomal-associated membrane 2 gene (LAMP2), which encodes the LAMP2 protein. In male patients, the predominant phenotype is progressive cardiac hypertrophy, cardiac dysfunction, and early death. There are no directed therapies for the disease. METHODS In this phase 1 study, we evaluated the safety and

BACKGROUND Achondroplasia is a genetic skeletal condition that results in disproportionately short stature and medical complications throughout life. Infigratinib is an orally bioavailable FGFR1-3 selective tyrosine kinase inhibitor in development for achondroplasia. METHODS In this phase 2 dose-finding study, we evaluated the safety and efficacy of oral infigratinib in children with achondroplasia

BACKGROUND Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain. METHODS In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous

BACKGROUND Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, often fatal disease. Nexiguran ziclumeran (nex-z) is an investigational therapy based on CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease) targeting the gene encoding transthyretin (TTR). METHODS In this phase 1, open-label trial, we administered a single intravenous

BACKGROUND Effective targets for systolic blood-pressure control in patients with type 2 diabetes are unclear. METHODS We enrolled patients 50 years of age or older with type 2 diabetes, elevated systolic blood pressure, and an increased risk of cardiovascular disease at 145 clinical sites across China. Patients were randomly assigned to receive intensive treatment that targeted a systolic blood pressure

BACKGROUND Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, causes considerable weight loss, but data are lacking with respect to its effects on cardiovascular outcomes. METHODS In this international, double-blind, randomized, placebo-controlled trial

BACKGROUND Oral anticoagulation is recommended after ablation for atrial fibrillation among patients at high risk for stroke. Left atrial appendage closure is a mechanical alternative to anticoagulation, but data regarding its use after atrial fibrillation ablation are lacking. METHODS We conducted an international randomized trial involving 1600 patients with atrial fibrillation who had an elevated

BACKGROUND Patients with ventricular tachycardia and ischemic cardiomyopathy are at high risk for adverse outcomes. Catheter ablation is commonly used when antiarrhythmic drugs do not suppress ventricular tachycardia. Whether catheter ablation is more effective than antiarrhythmic drugs as a first-line therapy in patients with ventricular tachycardia is uncertain. METHODS In an international trial

BACKGROUND IgG4-related disease is a multiorgan, relapsing, fibroinflammatory, immune-mediated disorder with no approved therapy. Inebilizumab targets and depletes CD19+ B cells and may be effective for treating patients with IgG4-related disease. METHODS In this phase 3, multicenter, double-blind, randomized, placebo-controlled trial, adults with active IgG4-related disease underwent randomization

BACKGROUND Obesity is chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying

A gallery of portraits of prominent alumnae of color at Harvard Medical School provides inspiration for diverse current students and makes past sexist practices visible to all.

In this crossover trial in older adults with or without coronary artery disease, cardiac strain was reduced with fan use, skin wetting, or both in hot and humid conditions but worsened with fan use in very hot and dry conditions.

BACKGROUND Medication abortion, with a combination of mifepristone and misoprostol, is highly effective and safe. However, there is insufficient evidence on efficacy and safety at very early gestations before a pregnancy can be visualized with ultrasonography. METHODS We conducted a multicenter, noninferiority, randomized, controlled trial involving women requesting medication abortion at up to 42

When an older patient hears that his physician is of Indian descent, the two find an immediate, resonant connection in a haunting song recalled from long ago and far away.

Kamala Harris’s proposal for expanding Medicare to cover long-term care at home is a hopeful sign for millions of Americans, though key questions remain about eligibility, coverage, payments, and f...

The past two decades have witnessed a renaissance in the evaluation and treatment of patients with valvular heart disease, catalyzed by advances in surgical innovation, transcatheter techniques, an...

In a woman who had Oropouche virus infection in the third trimester of pregnancy followed by stillbirth, phylogenomic results confirmed the link between this stillbirth and the ongoing OROV outbrea...

Severe tricuspid regurgitation is associated with disabling symptoms and an increased risk of death. Data regarding outcomes after percutaneous transcatheter tricuspid-valve replacement are needed....

This case vignette of a 13-month-old girl with fever and acute otitis media in one ear is accompanied by two essays, one recommending watchful waiting with close follow-up and the other supporting ...

A 69-year-old man with a history of MI and cardiomyopathy presented with 2 days of dyspnea. Regular tachycardia (124 beats per min), diaphoresis, and rales were present. A diagnosis was made.

A 44-year-old man with infliximab-treated Crohn’s disease presented with a 2-day history of rash on his face. Well-demarcated, warm, erythematous, confluent plaques were seen across the cheeks, nos...

The treatment approach for patients with estrogen receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer has changed dramatically over the past 20 year...

Osteoarthritis is one of the world’s leading causes of disability. Roughly 4.3% of adults have painful knee osteoarthritis, with knee pain on most days1; the prevalence of disease is much higher th...

A study documents the long-term durability of weight loss and remission of related conditions after bariatric surgery, as well as the greater health benefits in adolescents than would be expected i...

To the Editor: In their review of human immunodeficiency virus (HIV)–associated tuberculosis, Meintjes and Maartens (July 25 issue)1 highlight the excess mortality from tuberculosis among patients ...

To the Editor: The study by Israel et al. (Aug. 8 issue),1 as reported in the Correspondence section, showed glycated hemoglobin levels that markedly underestimated glucose levels in patients with ...

To the Editor: In the article by Xie et al. (Aug. 8 issue)1 regarding postacute sequelae of SARS-CoV-2 infection (PASC) in the pre-delta, delta, and omicron eras, the authors note that 71.89% of th...

To the Editor: The report by Quiroz et al. (June 20 issue)1 on the Colombian PSEN1E280A pedigree suggests a protective effect of apolipoprotein E3 Christchurch (APOE3Ch) variant heterozygosity. The...

Chronic lead poisoning, even at low levels, is a risk factor for cardiovascular disease in adults and cognitive deficits in children. The authors review the effects of chronic, low-level lead poisoning.

Inavolisib is a highly potent and selective inhibitor of the alpha isoform of the p110 catalytic subunit of the phosphatidylinositol 3-kinase complex (encoded by PIK3CA) that also promotes the degr...

Weight reduction has been shown to alleviate symptoms of osteoarthritis of the knee, including pain. The effect of glucagon-like peptide-1 receptor agonists on outcomes in knee osteoarthritis among...

BACKGROUND In patients with out-of-hospital cardiac arrest, the effectiveness of drugs such as epinephrine is highly time-dependent. An intraosseous route of drug administration may enable more rapid drug administration than an intravenous route; however, its effect on clinical outcomes is uncertain. METHODS We conducted a multicenter, open-label, randomized trial across 11 emergency medical systems

BACKGROUND Out-of-hospital cardiac arrest is a leading cause of death worldwide. Establishing vascular access is critical for administering guideline-recommended drugs during cardiopulmonary resuscitation. Both the intraosseous route and the intravenous route are used routinely, but their comparative effectiveness remains unclear. METHODS We conducted a randomized clinical trial to compare the effectiveness