BACKGROUND Evidence suggests that incretin-based dual agonist pharmacotherapy is helpful in persons with obesity. Mazdutide, a glucagon-like peptide-1 and glucagon receptor dual agonist, may have efficacy in persons with overweight or obesity. METHODS In a phase 3, double-blind, placebo-controlled trial in China, we randomly assigned, in a 1:1:1 ratio, adults 18 to 75 years of age who had a body-mass

BACKGROUND The safety and efficacy of treatment with intravenous tenecteplase before endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion remain uncertain. METHODS In this open-label trial conducted in China, we randomly assigned patients with acute ischemic stroke due to large-vessel occlusion who had presented within 4.5 hours after onset and were eligible

BACKGROUND Nerandomilast (BI 1015550) is an orally administered preferential inhibitor of phosphodiesterase 4B with antifibrotic and immunomodulatory properties. Nerandomilast has been shown to slow the progression of idiopathic pulmonary fibrosis, but an assessment of its effects in other types of progressive pulmonary fibrosis is needed. METHODS In a phase 3, double-blind trial, we randomly assigned

BACKGROUND Nerandomilast (BI 1015550) is an orally administered preferential inhibitor of phosphodiesterase 4B with antifibrotic and immunomodulatory effects. In a phase 2 trial involving patients with idiopathic pulmonary fibrosis, treatment with nerandomilast stabilized lung function over a period of 12 weeks. METHODS In this phase 3, double-blind trial, we randomly assigned patients with idiopathic

BACKGROUND Each year, millions of pulmonary nodules are identified incidentally or through lung cancer screening, and many involve biopsy to distinguish cancer from benign processes. Both navigational bronchoscopy and computed tomography-guided transthoracic needle biopsy are commonly used in patients undergoing biopsies of peripheral pulmonary nodules, but the relative diagnostic accuracy of these

BACKGROUND Prednisone is currently recommended as the first-line treatment for pulmonary sarcoidosis but is associated with many side effects. Methotrexate, which is recommended as a second-line treatment, appears to have fewer side effects than prednisone but a slower onset of action. Data are needed on the efficacy and side-effect profile of methotrexate as compared with prednisone as first-line

Base editors can correct disease-causing genetic variants. After a neonate had received a diagnosis of severe carbamoyl-phosphate synthetase 1 deficiency, a disease with an estimated 50% mortality in early infancy, we immediately began to develop a customized lipid nanoparticle-delivered base-editing therapy. After regulatory approval had been obtained for the therapy, the patient received two infusions

BACKGROUND Narcolepsy type 1 is a disorder of hypersomnolence caused by a loss of orexin neurons, which results in low orexin levels in the brain. METHODS In this phase 2, randomized, placebo-controlled trial, participants with narcolepsy type 1 received once- or twice-daily oveporexton (TAK-861), an oral orexin receptor 2-selective agonist, or placebo. The primary end point was the mean change from

BACKGROUND A total of 14 million Medicare beneficiaries receive the Low-Income Subsidy (LIS), which reduces cost sharing in Medicare Part D. Losing the LIS may impede medication access and affect mortality. METHODS Using 2015-2023 Medicare data, we identified dual-eligible Medicare-Medicaid beneficiaries, who automatically receive the LIS, and calculated annual rates of Medicaid and LIS loss. To examine

BACKGROUND Tirzepatide and semaglutide are highly effective medications for obesity management. The efficacy and safety of tirzepatide as compared with semaglutide in adults with obesity but without type 2 diabetes is unknown. METHODS In this phase 3b, open-label, controlled trial, adult participants with obesity but without type 2 diabetes were randomly assigned in a 1:1 ratio to receive the maximum

BACKGROUND In phase 2 trials involving patients with stage 2 or 3 fibrosis caused by metabolic dysfunction-associated steatohepatitis (MASH), efruxifermin, a bivalent fibroblast growth factor 21 (FGF21) analogue, reduced fibrosis and resolved MASH. Data are needed on the efficacy and safety of efruxifermin in patients with compensated cirrhosis (stage 4 fibrosis) caused by MASH. METHODS In this phase

BACKGROUND In a previous phase 2 trial, bacille Calmette-Guérin (BCG) revaccination was not shown to provide protection from primary Mycobacterium tuberculosis infection but prevented sustained M. tuberculosis infection, defined by an initial conversion on a QuantiFERON-TB (QFT) test (an interferon-γ release assay) from negative to positive, followed by two additional positive QFT tests at 3 and 6

BACKGROUND Chimeric antigen receptor (CAR) T cells targeting CD19 have transformed the treatment of B-cell cancers, but many patients do not have long-term remission. We designed an anti-CD19 enhanced (armored) CAR T-cell product (huCART19-IL18) that secretes interleukin-18 to enhance antitumor activity. METHODS In this study, we assessed the safety, feasibility, and preliminary efficacy of huCART19-IL18

BACKGROUND Obicetrapib is a highly selective cholesteryl ester transfer protein inhibitor that reduces low-density lipoprotein (LDL) cholesterol levels. The efficacy and safety of obicetrapib have not been fully characterized among patients at high risk for cardiovascular events. METHODS We conducted a multinational, randomized, placebo-controlled trial involving patients with heterozygous familial