New England Journal of Medicine最新文献

{"title":"Sustained Clinical Benefit of AAV Gene Therapy in Severe Hemophilia B.","authors":"Ulrike M Reiss, Andrew M Davidoff, Edward G D Tuddenham, Pratima Chowdary, Jenny McIntosh, Vincent Muczynski, Malo Journou, Giulia Simini, Lydia Ireland, Saira Mohamed, Anne Riddell, Arnulfo J Pie, Andrew Hall, Alberto Quaglia, Sarah Mangles, Johnny Mahlangu, Kristina Haley, Michael Recht, Yu-Min Shen, Kathleen G Halka, Gail Fortner, Christopher L Morton, Zhengming Gu, Randall T Hayden, Ellis J Neufeld, Victoria I Okhomina, Guolian Kang, Amit C Nathwani","doi":"10.1056/NEJMoa2414783","DOIUrl":"10.1056/NEJMoa2414783","url":null,"abstract":"<p><strong>Background: </strong>Adeno-associated virus (AAV)-mediated gene therapy has emerged as a promising treatment for hemophilia B. Data on safety and durability from 13 years of follow-up in a cohort of patients who had been successfully treated with scAAV2/8-LP1-hFIXco gene therapy are now available.</p><p><strong>Methods: </strong>Ten men with severe hemophilia B received a single intravenous infusion of the scAAV2/8-LP1-hFIXco vector in one of three dose groups (low-dose: 2×10¹¹ vector genomes [vg] per kilogram of body weight [in two participants]; intermediate-dose: 6×10¹¹ vg per kilogram [in two]; or high-dose: 2×10¹² vg per kilogram [in six]). Efficacy outcomes included factor IX activity, the annualized bleeding rate, and factor IX concentrate use. Safety assessments included clinical events, liver function, and imaging.</p><p><strong>Results: </strong>Participants were followed for a median of 13.0 years (range, 11.1 to 13.8). Factor IX activity remained stable across the dose cohorts, with mean factor IX levels of 1.7 IU per deciliter in the low-dose group, 2.3 IU per deciliter in the intermediate-dose group, and 4.8 IU per deciliter in the high-dose group. Seven of the 10 participants did not receive prophylaxis. The median annualized bleeding rate decreased from 14.0 episodes (interquartile range, 12.0 to 21.5) to 1.5 episodes (interquartile range, 0.7 to 2.2), which represented a reduction by a factor of 9.7. Use of factor IX concentrate decreased by a factor of 12.4 (interquartile range, 2.2 to 27.1). A total of 15 vector-related adverse events occurred, primarily transient elevations in aminotransferase levels. Factor IX inhibitor, thrombosis, or chronic liver injury did not develop in any participant. Two cancers were identified but were deemed by the investigators, together with an expert multidisciplinary team, as being unrelated to the vector. A liver biopsy that was conducted in 1 participant 10 years after the infusion revealed transcriptionally active transgene expression in hepatocytes without fibrosis or dysplasia. Levels of neutralizing antibodies to AAV8 remained high throughout follow-up, thus indicating potential barriers to readministration of the vector.</p><p><strong>Conclusions: </strong>A single administration of scAAV2/8-LP1-hFIXco gene therapy resulted in durable factor IX expression, sustained clinical benefit, and no late-onset safety concerns over a period of 13 years. These data support the long-term efficacy and safety of AAV gene therapy for severe hemophilia B. (Funded by the U.K. Medical Research Council and others; ClinicalTrials.gov number, NCT00979238; EudraCT number, 2005-005711-17.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 22","pages":"2226-2234"},"PeriodicalIF":96.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276764","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 Crossover Trial of Hospital-Wide Lactated Ringer's Solution versus Normal Saline.","authors":"Lauralyn McIntyre, Dean Fergusson, Tracy McArdle, Shane English, Deborah J Cook, Alison E Fox-Robichaud, Claudio Martin, John Marshall, Michael Pugliese, Kusum Menon, Kednapa Thavorn, Ian D Graham, Steven Hawken, Akshai Iyengar, Kwadwo Kyeremanteng, Raphael Saginur, Andrew J E Seely, Ian G Stiell, Daniel Bainbridge, Charles Weijer, Monica Taljaard","doi":"10.1056/NEJMoa2416761","DOIUrl":"https://doi.org/10.1056/NEJMoa2416761","url":null,"abstract":"<p><strong>Background: </strong>Whether lactated Ringer's solution is clinically superior to normal saline for routine intravenous administration of fluids is uncertain.</p><p><strong>Methods: </strong>In an open-label, two-period, two-sequence, cross-sectional, cluster-randomized, crossover trial, we assigned hospitals in Ontario, Canada, to use either lactated Ringer's solution or normal saline hospital-wide for a period of 12 weeks. After a washout period, hospitals switched to the other fluid for 12 weeks. The primary outcome was a composite of death or readmission to the hospital within 90 days after the index admission. Secondary outcomes were the individual components of the primary outcome, as well as the length of stay in the hospital, initiation of dialysis within 90 days after the index admission, a visit to the emergency department within 90 days, and discharge to a facility other than home. Data on outcomes were obtained from health administrative databases. The analyses were conducted at the hospital level, and the primary estimand was the effect of the use of lactated Ringer's solution as compared with normal saline averaged across all participating hospitals.</p><p><strong>Results: </strong>Seven hospitals completed both 12-week periods before the trial was interrupted owing to the coronavirus disease 2019 pandemic. Data on the primary outcome were available for 43,626 eligible patients. The mean (±SD) incidence of the composite of death or readmission to the hospital within 90 days after the index admission was 20.3±3.5% with lactated Ringer's solution and 21.4±3.3% with normal saline (adjusted difference, -0.53 percentage points; 95% confidence interval, -1.85 to 0.79; P = 0.35). Results for all secondary outcomes were consistent with those for the primary outcome. No serious adverse events were reported.</p><p><strong>Conclusions: </strong>A hospital-wide policy to administer lactated Ringer's solution rather than normal saline did not result in a significantly lower incidence of death or readmission to the hospital within 90 days after the index admission. (Funded by the Canadian Institutes of Health Research and the Ottawa Hospital Academic Medical Organization; FLUID ClinicalTrials.gov number, NCT04512950.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276724","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":"Long-Term Effects of Empagliflozin in Chronic Kidney Disease.","authors":"Jacob Ilany","doi":"10.1056/NEJMc2504181","DOIUrl":"https://doi.org/10.1056/NEJMc2504181","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 22","pages":"2284-2285"},"PeriodicalIF":96.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276733","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":"Cardiac Injury Detected by Smartwatch.","authors":"Thomas R Basala, Scott W Sharkey","doi":"10.1056/NEJMicm2500438","DOIUrl":"10.1056/NEJMicm2500438","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"2256"},"PeriodicalIF":96.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250932","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":"Acknowledging Racism, Building Trust - Conversations That Matter in Maternal Medicine.","authors":"Bronwen F Kahn","doi":"10.1056/NEJMp2416191","DOIUrl":"10.1056/NEJMp2416191","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"2189-2191"},"PeriodicalIF":96.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250930","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":"Addressing Antifungal Drug Resistance - A \"One Health-One World\" Challenge.","authors":"George R Thompson, Angel N Desai","doi":"10.1056/NEJMp2416548","DOIUrl":"10.1056/NEJMp2416548","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"2187-2189"},"PeriodicalIF":96.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250931","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":"Case 4-2025: A Man with Syncope, Ankle Swelling, and Abnormal Chest Imaging. Reply.","authors":"Daniel Restrepo, Jeffrey A Sparks","doi":"10.1056/NEJMc2503283","DOIUrl":"https://doi.org/10.1056/NEJMc2503283","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 22","pages":"2287-2288"},"PeriodicalIF":96.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276731","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":"John Collins Warren - <i>Journal</i> Founder, Institution Builder, and Racial Theorist.","authors":"Christopher D E Willoughby, Dominic Hall, Evelynn M Hammonds, Scott H Podolsky","doi":"10.1056/NEJMms2415759","DOIUrl":"https://doi.org/10.1056/NEJMms2415759","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 22","pages":"2277-2281"},"PeriodicalIF":96.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276732","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":"Malnutrition in Older Adults.","authors":"Alfonso J Cruz-Jentoft, Dorothee Volkert","doi":"10.1056/NEJMra2412275","DOIUrl":"https://doi.org/10.1056/NEJMra2412275","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 22","pages":"2244-2255"},"PeriodicalIF":96.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276762","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":"Ramsay Hunt Syndrome.","authors":"Jiangtao Guo, Wenbin Li","doi":"10.1056/NEJMicm2500293","DOIUrl":"https://doi.org/10.1056/NEJMicm2500293","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 22","pages":"e53"},"PeriodicalIF":96.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276763","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}