New England Journal of Medicine最新文献

{"title":"The Physiology of Hunger.","authors":"Sergio Loss, Joel Stefani, Luciana Viana","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":"1767"},"PeriodicalIF":96.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046354","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":"A Good Innings - A Tale of Hope, Heartbreak, and Healing.","authors":"Nihanthy D Sreenath","doi":"10.1056/NEJMp2415146","DOIUrl":"https://doi.org/10.1056/NEJMp2415146","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 17","pages":"1670-1671"},"PeriodicalIF":96.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042959","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":"Kaili Zhang","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":"1765-1766"},"PeriodicalIF":96.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040674","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. Reply.","authors":"Alok Srivastava, Trent Spencer","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":"1766"},"PeriodicalIF":96.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058431","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":"Keith Couper, Rachael T Fothergill, Gavin D Perkins","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":"1763-1764"},"PeriodicalIF":96.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058424","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":"Identification of Hepatic-like EPO as a Cause of Polycythemia.","authors":"Laurent Martin,Darko Maric,Salam Idriss,Marine Delamare,Amandine Le Roy,Nada Maaziz,Amandine Caillaud,Karim Si-Tayeb,Florence Robriquet,Marion Lenglet,Lucie Erceau,Christine Bellanné-Chantelot,Isabelle Plo,Bernard Aral,Céline Garrec,Fabrice Airaud,Clara Gianfermi,Vincent Antunes,Anna Keppner,Sarah Mathilda Vincent,Alexis Desfontaine,Nina Modé,Fabien Laporte,Anne Gaignerie,Caroline Chariau,Isabelle Leray,Coline Rogue,Laurent David,Richard Redon,Stéphane Bézieau,Lamisse Mansour-Hendili,Frédéric Galactéros,Thibault Maillet,Marlène Pasquet,Pierre Cougoul,Anne-Marie Nloga,Claude Gardin,Corinne Guitton,Viviane Dubruille,Vannina Giacobbi-Milet,Thierry Leblanc,Zuhre Kaya,Denis Semama,Chloé James,Serge Carillo,Marlène Ochmann,Anders Waage,Erwan Mortier,Mike Maillasson,Agnès Quéméner,Holger Cario,Radek C Skoda,Yaël Zermati,David Hoogewijs,Alexandre Marchand,François Girodon,Betty Gardie","doi":"10.1056/nejmoa2414954","DOIUrl":"https://doi.org/10.1056/nejmoa2414954","url":null,"abstract":"BACKGROUNDSecondary erythrocytosis often results from conditions that cause tissue hypoxia or an improper increase in erythropoietin (EPO) production. EPO, the major regulator of erythropoiesis, has a complex and tightly regulated expression during development, with a liver-to-kidney switch shortly after birth.METHODSWe identified six families with erythrocytosis that was associated with circulating EPO levels within the normal range and characterized as a novel molecular and functional entity. We investigated the effect of the identified pathogenic variants using EPO promoter-driven luciferase reporter genes. Induced pluripotent stem cells (iPSCs) were generated from patient cells and differentiated into hepatocyte-like EPO-producing cells. Samples of circulating EPO from patients with hereditary erythrocytosis and from healthy newborns were analyzed by means of isoelectric focusing, and EPO activity was assessed.RESULTSThree novel variants were identified in the noncoding regions of EPO. Experiments with reporter assays and iPSC-derived hepatocyte-like cells showed that the variants targeted previously uncharacterized regulatory elements of the gene, which, when the variants were present, showed high responsiveness to hypoxia. EPO samples from all the patients showed a modified isoelectric-focusing profile, identical to hepatic EPO that is expressed in premature neonates and in patients with acquired erythrocytosis associated with liver diseases. EPO that was purified from patient plasma and umbilical-cord blood samples showed enhanced EPO receptor signaling activity in vitro, which suggests a potential gain of function linked to the liver-type glycosylation of EPO.CONCLUSIONSWe found that secondary erythrocytosis can be related to variants in EPO that lead to the production of hepatic-like EPO with an atypical glycosylation pattern and increased activity. (Funded by Région des Pays de la Loire and others; ClinicalTrials.gov number, NCT03957863.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"10 1","pages":"1684-1697"},"PeriodicalIF":158.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897343","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":"Glofitamab with Polatuzumab Vedotin in Refractory Burkitt's Lymphoma.","authors":"Anca Prica,Mark Roschewski,Peter Beale,Stefania Pittaluga,Jan Delabie,Claudia Ortega,Robert Kridel","doi":"10.1056/nejmc2501018","DOIUrl":"https://doi.org/10.1056/nejmc2501018","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"13 1","pages":"1760-1762"},"PeriodicalIF":158.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897433","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":"Health Care in an Evolving Immigration Landscape - Providing Care while Upholding the Law.","authors":"Holland Kaplan,Anna Cabot,Peter Ubel","doi":"10.1056/nejmp2502570","DOIUrl":"https://doi.org/10.1056/nejmp2502570","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"36 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897362","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":"Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis.","authors":"Arun J Sanyal,Philip N Newsome,Iris Kliers,Laura Harms Østergaard,Michelle T Long,Mette Skalshøi Kjær,Anna M G Cali,Elisabetta Bugianesi,Mary E Rinella,Michael Roden,Vlad Ratziu,","doi":"10.1056/nejmoa2413258","DOIUrl":"https://doi.org/10.1056/nejmoa2413258","url":null,"abstract":"BACKGROUNDSemaglutide, a glucagon-like peptide-1 receptor agonist, is a candidate for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).METHODSIn this ongoing phase 3, multicenter, randomized, double-blind, placebo-controlled trial, we assigned 1197 patients with biopsy-defined MASH and fibrosis stage 2 or 3 in a 2:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. The results of a planned interim analysis conducted at week 72 involving the first 800 patients are reported here (part 1). The primary end points for part 1 were the resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.RESULTSResolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% confidence interval [CI], 21.1 to 36.2; P<0.001). A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of the patients in the semaglutide group and in 22.4% of those in the placebo group (estimated difference, 14.4 percentage points; 95% CI, 7.5 to 21.3; P<0.001). Results for the three secondary outcomes that were included in the plan to adjust for multiple testing were as follows: combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% of the patients in the semaglutide group and in 16.1% of those in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2 to 22.8; P<0.001). The mean change in body weight was -10.5% with semaglutide and -2.0% with placebo (estimated difference, -8.5 percentage points; 95% CI, -9.6 to -7.4; P<0.001). Mean changes in bodily pain scores did not differ significantly between the two groups. Gastrointestinal adverse events were more common in the semaglutide group.CONCLUSIONSIn patients with MASH and moderate or advanced liver fibrosis, once-weekly semaglutide at a dose of 2.4 mg improved liver histologic results. (Funded by Novo Nordisk; ClinicalTrials.gov number, NCT04822181.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"114 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897345","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 Power of Physicians in Dangerous Times.","authors":"Alice T Chen,Vivek H Murthy","doi":"10.1056/nejmp2502493","DOIUrl":"https://doi.org/10.1056/nejmp2502493","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"13 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897346","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}