New England Journal of Medicine最新文献

{"title":"Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy.","authors":"Mohamad Zaidan","doi":"10.1056/NEJMc2501792","DOIUrl":"https://doi.org/10.1056/NEJMc2501792","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 18","pages":"1870"},"PeriodicalIF":96.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cabozantinib in Advanced Neuroendocrine Tumors. Reply.","authors":"Jennifer A Chan, Susan Geyer, Jeffrey A Meyerhardt","doi":"10.1056/NEJMc2503524","DOIUrl":"https://doi.org/10.1056/NEJMc2503524","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 18","pages":"1869-1870"},"PeriodicalIF":96.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Death by a Thousand Cuts - The Crushing Weight of Nonclinical Demands in Primary Care.","authors":"Bruce E Landon, Sara B Fazio, Jennifer L Cluett, Eileen E Reynolds, Jennifer Potter","doi":"10.1056/NEJMp2415431","DOIUrl":"https://doi.org/10.1056/NEJMp2415431","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 18","pages":"1771-1773"},"PeriodicalIF":96.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical Complexity of Food and Implications for Therapeutics.","authors":"Giulia Menichetti,Albert-László Barabási,Joseph Loscalzo","doi":"10.1056/nejmra2413243","DOIUrl":"https://doi.org/10.1056/nejmra2413243","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"68 1","pages":"1836-1845"},"PeriodicalIF":158.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced CAR T-Cell Therapy for Lymphoma after Previous Failure.","authors":"Jakub Svoboda,Daniel J Landsburg,James Gerson,Sunita D Nasta,Stefan K Barta,Elise A Chong,Michael Cook,Noelle V Frey,Joanne Shea,Amanda Cervini,Amy Marshall,Megan Four,Megan M Davis,Julie K Jadlowsky,Anne Chew,Edward Pequignot,Vanessa Gonzalez,Julia Han Noll,Luca Paruzzo,Juliana Rojas-Levine,Gabriela Plesa,John Scholler,Donald L Siegel,Bruce L Levine,David L Porter,Saba Ghassemi,Marco Ruella,Andrew Rech,Rachel M Leskowitz,Joseph A Fraietta,Wei-Ting Hwang,Elizabeth Hexner,Stephen J Schuster,Carl H June","doi":"10.1056/nejmoa2408771","DOIUrl":"https://doi.org/10.1056/nejmoa2408771","url":null,"abstract":"BACKGROUNDChimeric 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.METHODSIn this study, we assessed the safety, feasibility, and preliminary efficacy of huCART19-IL18 in patients with relapsed or refractory lymphoma after previous anti-CD19 CAR T-cell therapy. Using a 3-day manufacturing process, we administered huCART19-IL18-positive cells in doses ranging from 3×106 to 3×108.RESULTSA total of 21 patients received huCART19-IL18. Cytokine release syndrome occurred in 62% of the patients (47% with grade 1 or 2), and immune effector-cell-associated neurotoxicity syndrome occurred in 14% (all grade 1 or 2). No unexpected adverse events were observed. Robust CAR T-cell expansion was detected across all dose levels. At 3 months after infusion, a complete or partial response was seen in 81% of the patients (90% confidence interval [CI], 62 to 93) and a complete response in 52% (90% CI, 33 to 71). With a median follow-up of 17.5 months (range, 3 to 34), the median duration of response was 9.6 months (90% CI, 5.5 to not reached).CONCLUSIONSIn this small study, huCART19-IL18 had a safety profile consistent with other CAR T-cell treatments and showed promising efficacy at low cell doses in patients with lymphoma after the failure of previous anti-CD19 CAR T-cell therapy. (ClinicalTrials.gov number, NCT04684563.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"19 1","pages":"1824-1835"},"PeriodicalIF":158.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk.","authors":"Stephen J Nicholls,Adam J Nelson,Marc Ditmarsch,John J P Kastelein,Christie M Ballantyne,Kausik K Ray,Ann Marie Navar,Steven E Nissen,Mariko Harada-Shiba,Danielle L Curcio,Annie Neild,Douglas Kling,Andrew Hsieh,Julie Butters,Brian A Ference,Ulrich Laufs,Maciej Banach,Roxana Mehran,Alberico L Catapano,Yong Huo,Michael Szarek,Violeta Balinskaite,Michael H Davidson,","doi":"10.1056/nejmoa2415820","DOIUrl":"https://doi.org/10.1056/nejmoa2415820","url":null,"abstract":"BACKGROUNDObicetrapib 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.METHODSWe conducted a multinational, randomized, placebo-controlled trial involving patients with heterozygous familial hypercholesterolemia or a history of atherosclerotic cardiovascular disease who were receiving maximum tolerated doses of lipid-lowering therapy. Patients with an LDL cholesterol level of 100 mg per deciliter or higher or a non-high-density lipoprotein (HDL) cholesterol level of 130 mg per deciliter or higher, as well as those with an LDL cholesterol level of 55 to 100 mg per deciliter or a non-HDL cholesterol level of 85 to 130 mg per deciliter and at least one additional cardiovascular risk factor, were eligible for inclusion. The patients were randomly assigned in a 2:1 ratio to receive either 10 mg of obicetrapib once daily or matching placebo for 365 days. The primary end point was the percent change in the LDL cholesterol level from baseline to day 84.RESULTSA total of 2530 patients underwent randomization; 1686 patients were assigned to receive obicetrapib and 844 to receive placebo. The mean age of the patients was 65 years, 34% were women, and the mean baseline LDL cholesterol level was 98 mg per deciliter. The least-squares mean percent change from baseline to day 84 in the LDL cholesterol level was -29.9% (95% confidence interval [CI], -32.1 to -27.8) in the obicetrapib group, as compared with 2.7% (95% CI, -0.4 to 5.8) in the placebo group, for a between-group difference of -32.6 percentage points (95% CI, -35.8 to -29.5; P<0.001). The incidence of adverse events appeared to be similar in the two groups.CONCLUSIONSAmong patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who were receiving maximum tolerated doses of lipid-lowering therapy and were at high risk for cardiovascular events, obicetrapib reduced LDL cholesterol levels by 29.9%. (Funded by NewAmsterdam Pharma; BROADWAY ClinicalTrials.gov number, NCT05142722.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"125 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"U.S. Research Leadership at a Crossroads - The Impact of Reducing NIH Indirect-Cost Coverage.","authors":"Amar H Kelkar","doi":"10.1056/nejmp2502451","DOIUrl":"https://doi.org/10.1056/nejmp2502451","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"74 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Judicial Invalidation of the FDA's Laboratory-Developed Test Rule - Legal and Public Health Consequences.","authors":"Rachel E Sachs,Joshua M Sharfstein,Patricia J Zettler","doi":"10.1056/nejmp2504926","DOIUrl":"https://doi.org/10.1056/nejmp2504926","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"9 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Routine Surveillance for Cancer Metastases - Does It Help or Harm Patients?","authors":"H Gilbert Welch, Lesly A Dossett","doi":"10.1056/NEJMp2414159","DOIUrl":"https://doi.org/10.1056/NEJMp2414159","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 17","pages":"1667-1670"},"PeriodicalIF":96.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lentiviral Gene Therapy with CD34+ Hematopoietic Cells for Hemophilia A.","authors":"Madhusudana Girija Sanal, Ankur Jindal","doi":"10.1056/NEJMc2502741","DOIUrl":"https://doi.org/10.1056/NEJMc2502741","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 17","pages":"1765"},"PeriodicalIF":96.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}