New England Journal of Medicine最新文献

{"title":"Abdominal Aortic Occlusion from Left Atrial Myxoma Embolism.","authors":"Chirag A Buch,Nilam J Soni","doi":"10.1056/nejmicm2414920","DOIUrl":"https://doi.org/10.1056/nejmicm2414920","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"8 1","pages":"1732"},"PeriodicalIF":158.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897357","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":"Mepolizumab in COPD - If at First You Don't Succeed.","authors":"Mark T Dransfield,Daiana Stolz","doi":"10.1056/nejme2503292","DOIUrl":"https://doi.org/10.1056/nejme2503292","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"36 1","pages":"1746-1748"},"PeriodicalIF":158.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897435","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":"Anticoagulation or Antiplatelet Therapy for Device-Detected Atrial Fibrillation.","authors":"Sarah Gorey,Jeff S Healey,Paulus Kirchhof","doi":"10.1056/nejmclde2411897","DOIUrl":"https://doi.org/10.1056/nejmclde2411897","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"114 1","pages":"1749-1751"},"PeriodicalIF":158.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897356","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":"Initial Intraosseous or Intravenous Access for Out-of-Hospital Cardiac Arrest.","authors":"Joshua R Lupton, Jonathan Jui, Mohamad R Daya","doi":"10.1056/NEJMc2502751","DOIUrl":"https://doi.org/10.1056/NEJMc2502751","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 17","pages":"1763"},"PeriodicalIF":96.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992462","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":"Lepodisiran - A Long-Duration Small Interfering RNA Targeting Lipoprotein(a).","authors":"Steven E Nissen, Wei Ni, Xi Shen, Qiuqing Wang, Ann Marie Navar, Stephen J Nicholls, Kathy Wolski, Laura Michael, Axel Haupt, John H Krege","doi":"10.1056/NEJMoa2415818","DOIUrl":"10.1056/NEJMoa2415818","url":null,"abstract":"<p><strong>Background: </strong>Elevated lipoprotein(a) concentrations are associated with atherosclerotic cardiovascular disease. The safety and efficacy of lepodisiran, an extended-duration, small interfering RNA targeting hepatic synthesis of lipoprotein(a), are unknown.</p><p><strong>Methods: </strong>We randomly assigned participants in a 1:2:2:2:2 ratio to receive lepodisiran at a dose of 16 mg, 96 mg, or 400 mg at baseline and again at day 180, lepodisiran at a dose of 400 mg at baseline and placebo at day 180, or placebo at baseline and at day 180, all administered by subcutaneous injection. Data from the two groups that received lepodisiran at a dose of 400 mg at baseline were pooled for the primary analysis. The primary end point was the time-averaged percent change from baseline in the serum lipoprotein(a) concentration (lepodisiran difference from placebo [i.e., placebo-adjusted]) during the period from day 60 to day 180.</p><p><strong>Results: </strong>A total of 320 participants underwent randomization; the median baseline lipoprotein(a) concentration was 253.9 nmol per liter. The placebo-adjusted time-averaged percent change from baseline in the serum lipoprotein(a) concentration from day 60 to day 180 was -40.8 percentage points (95% confidence interval [CI], -55.8 to -20.6) in the 16-mg lepodisiran group, -75.2 percentage points (95% CI, -80.4 to -68.5) in the 96-mg group, and -93.9 percentage points (95% CI, -95.1 to -92.5) in the pooled 400-mg groups. The corresponding change from day 30 to day 360 was -41.2 percentage points (95% CI, -55.4 to -22.4), -77.2 percentage points (95% CI, -81.8 to -71.5), -88.5 percentage points (95% CI, -90.8 to -85.6), and -94.8 percentage points (95% CI, -95.9 to -93.4) in the 16-mg, 96-mg, 400-mg-placebo, and 400-mg-400-mg dose groups, respectively. Serious adverse events, none of which were deemed by investigators to be related to lepodisiran or placebo, occurred in 35 participants. Dose-dependent, generally mild injection-site reactions occurred in up to 12% (8 of 69) of the participants in the highest lepodisiran dose group.</p><p><strong>Conclusions: </strong>Lepodisiran reduced mean serum concentrations of lipoprotein(a) from 60 to 180 days after administration. (Funded by Eli Lilly; ALPACA ClinicalTrials.gov number, NCT05565742.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"1673-1683"},"PeriodicalIF":96.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756153","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":"The Physiology of Hunger. Reply.","authors":"Alessio Fasano","doi":"10.1056/NEJMc2502445","DOIUrl":"https://doi.org/10.1056/NEJMc2502445","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 17","pages":"1768"},"PeriodicalIF":96.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009215","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":"Initial Intraosseous or Intravenous Access for Out-of-Hospital Cardiac Arrest. Reply.","authors":"Mikael F Vallentin, Asger Granfeldt, Lars W Andersen","doi":"10.1056/NEJMc2502751","DOIUrl":"https://doi.org/10.1056/NEJMc2502751","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 17","pages":"1764"},"PeriodicalIF":96.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042961","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":"Initial Intraosseous or Intravenous Access for Out-of-Hospital Cardiac Arrest.","authors":"Joshua R Lupton,Jonathan Jui,Mohamad R Daya","doi":"10.1056/nejmc2502751","DOIUrl":"https://doi.org/10.1056/nejmc2502751","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"2 1","pages":"1763"},"PeriodicalIF":158.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897434","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":"Cholelithiasis, Cholecystitis, and Choledocholithiasis.","authors":"Zhuo-Long Tu, Jin-Fu Tu","doi":"10.1056/NEJMicm2412996","DOIUrl":"https://doi.org/10.1056/NEJMicm2412996","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 17","pages":"e42"},"PeriodicalIF":96.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995704","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 for Severe Leukocyte Adhesion Deficiency Type 1.","authors":"Claire Booth,Julián Sevilla,Elena Almarza,Caroline Y Kuo,Josune Zubicaray,Dayna Terrazas,Gráinne O'Toole,Maria Chitty-Lopez,Grace Choi,Eileen Nicoletti,Janel Long-Boyle,Augustine Fernandes,Kritika Chetty,Satiro De Oliveira,Crystal Banuelos,Jinhua Xu-Bayford,Antonella Lucía Bastone,Philipp John-Neek,Connie Jackson,Theodore B Moore,Kimberly Gilmour,Axel Schambach,Michael Rothe,Sanchali Kasbekar,Gayatri R Rao,Kinnari Patel,Gaurav Shah,Adrian J Thrasher,Juan A Bueren,Jonathan D Schwartz,Donald B Kohn","doi":"10.1056/nejmoa2407376","DOIUrl":"https://doi.org/10.1056/nejmoa2407376","url":null,"abstract":"BACKGROUNDThe β2 common integrin subunit CD18 is essential for leukocyte-endothelial adhesion and extravasation to inflamed or infected tissue. Damaging variants in ITGB2, which encodes CD18, cause leukocyte adhesion deficiency type I (LAD-I), an inborn error of immunity that leads to frequent life-threatening infections and a high risk of death among affected children. Allogeneic hematopoietic stem-cell transplantation (HSCT) represents a curative treatment but is limited by donor availability, a high incidence of graft-versus-host disease, and graft failure.METHODSIn a phase 1-2, multinational, open-label study, we enrolled nine children who had severe LAD-I and treated them with marnetegragene-autotemcel (marne-cel), a gene therapy of autologous CD34+ hematopoietic stem cells transduced with a self-inactivating lentiviral vector containing human ITGB2, and followed them for 24 months. The primary efficacy end point of the phase 2 study was survival without allogeneic HSCT (HSCT-free survival) at least 1 year after marne-cel infusion and at 2 years of age among the patients who were younger than 1 year of age at enrollment, tested against a null hypothesis of survival of 39% of the patients. We also report interim data from six patients enrolled in the long-term follow-up study.RESULTSSerious adverse events related to myeloablative busulfan conditioning were observed. No adverse events attributed to gene therapy were reported. None of the patients had graft failure. HSCT-free survival was 100% (95% confidence interval [CI], 66 to 100) at 1 year after infusion (P<0.001). All the patients who were enrolled at younger than 1 year of age were alive beyond 2 years of age. Pretreatment neutrophilia and skin abnormalities related to LAD-I resolved. The annualized incidence of infection-related hospitalizations beyond 90 days after engraftment through 24 months after marne-cel infusion was 74.45% lower than the incidence before marne-cel infusion, the annualized incidence of prolonged infection-related hospitalizations was 81.95% lower, and the annualized incidence of prespecified serious infections was 84.90% lower.CONCLUSIONSIn this study, lentiviral vector-transduced autologous CD34+ HSCT was successful in treating severe LAD-I. (Funded by Rocket Pharmaceuticals and the California Institute for Regenerative Medicine; ClinicalTrials.gov numbers, NCT03812263 and NCT06282432.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"2 1","pages":"1698-1709"},"PeriodicalIF":158.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897352","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}