NEJM This Week — April 2, 2026

This week's episode of NEJM This Week explores groundbreaking advances and critical debates in modern medicine. Key studies highlight the efficacy of perioperative Enfortumab-Vidotin and Pembrolizumab in muscle-invasive bladder cancer, showing improved survival and pathological complete response rates—though with increased adverse events—potentially reshaping treatment paradigms. In contrast, left atrial appendage closure failed to outperform medical therapy in high-risk atrial fibrillation patients, underscoring the need for caution in adopting new interventional devices without robust evidence. Gene editing therapies using CRISPR-Cas12a and base editing show remarkable promise for sickle cell disease and beta-thalassemia, with sustained fetal hemoglobin expression and transfusion independence, though development of one leading candidate, RenniCell, has been discontinued, turning early success into a 'Pyrrhic victory.' The episode also examines the non-inferiority of stopping beta blockers after myocardial infarction in stable patients, the broad benefits and risks of GLP-1 receptor agonists, and a clinical case of OTC deficiency triggered by a high-protein meal. Perspectives challenge the overreliance on chronological age in clinical decision-making, critique the corporatization of medicine, and warn of the legal threat posed by Chiles v. Salazar to mental health standards of care. The episode concludes with two striking clinical images: hepatic arterial buffer response and minocycline-induced hyperpigmentation.