David B Meya,Fiona V Cresswell,Biyue Dai,Nicole Engen,Kogieleum Naidoo,Ahmad Rizal Ganiem,Darma Imran,Mable Kabahubya,Richard J Lessells,Vycke Yunivita,Riwanti Estiasari,Lillian Tugume,Bongeka Hlabisa,Media Yuni Kurniawati,Noveline Sagita,Enock Kagimu,Kartika Maharani,Jane Gakuru,Maula N Gaharu,Timothy Mugabi,Sarah Kimuda,Suzan Namombwe,Lindsey Te Brake,Rob Aarnoutse,Elin M Svensson,Ananta S Bangdiwala,Sylvia Namanda,Nathan C Bahr,Abdu K Musubire,Mahomed Yunus Suleman Moosa,Raph L Hamers,Suzaan Marais,David R Boulware,Reinout van Crevel,Rovina Ruslami,
BACKGROUNDTuberculous meningitis is often lethal, and many survivors have disabilities despite antimicrobial treatment and adjunctive glucocorticoid therapy. Standard-dose rifampin has limited central nervous system penetration. Whether high-dose rifampin could improve survival outcomes is unknown.METHODSWe performed a double-blind, randomized, placebo-controlled clinical trial involving adults with tuberculous meningitis in Indonesia, South Africa, and Uganda. We assigned persons with and those without human immunodeficiency virus (HIV) coinfection to receive standard daily isoniazid, rifampin (at a dose of 10 mg per kilogram of body weight), ethambutol, and pyrazinamide plus either additional rifampin (for a cumulative dose of 35 mg per kilogram; high-dose group) or matched placebo (standard-dose group) for 8 weeks; participants in both groups received standard therapy for the remainder of the 9-to-12-month treatment course. The primary outcome was 6-month mortality.RESULTSA total of 499 participants were included in the intention-to-treat population (249 randomly assigned to the high-dose group and 250 to the standard-dose group), of whom 304 (60.9%) were persons living with HIV and 428 (85.8%) had definite or probable tuberculous meningitis. During 6 months of follow-up, 109 participants (Kaplan-Meier estimate, 44.6%) in the high-dose group and 100 participants (Kaplan-Meier estimate, 40.7%) in the standard-dose group died (hazard ratio, 1.17; 95% confidence interval, 0.89 to 1.54; P = 0.25). Among the participants who died within 6 months, the median time to death was 13 days (interquartile range, 4 to 39) in the high-dose group and 24 days (interquartile range, 6 to 56) in the standard-dose group. Drug-induced liver injury occurred in 8.0% of the participants in the high-dose group and in 4.4% of those in the standard-dose group, but no deaths from drug-induced liver injury occurred.CONCLUSIONSAmong persons with tuberculous meningitis, no evidence of beneficial effect from high-dose rifampin was observed, and the potential for a harmful effect cannot be ruled out. (Funded by the U.K. Medical Research Council and others; ISRCTN Registry number, ISRCTN15668391.).
{"title":"Trial of High-Dose Oral Rifampin in Adults with Tuberculous Meningitis.","authors":"David B Meya,Fiona V Cresswell,Biyue Dai,Nicole Engen,Kogieleum Naidoo,Ahmad Rizal Ganiem,Darma Imran,Mable Kabahubya,Richard J Lessells,Vycke Yunivita,Riwanti Estiasari,Lillian Tugume,Bongeka Hlabisa,Media Yuni Kurniawati,Noveline Sagita,Enock Kagimu,Kartika Maharani,Jane Gakuru,Maula N Gaharu,Timothy Mugabi,Sarah Kimuda,Suzan Namombwe,Lindsey Te Brake,Rob Aarnoutse,Elin M Svensson,Ananta S Bangdiwala,Sylvia Namanda,Nathan C Bahr,Abdu K Musubire,Mahomed Yunus Suleman Moosa,Raph L Hamers,Suzaan Marais,David R Boulware,Reinout van Crevel,Rovina Ruslami, ","doi":"10.1056/nejmoa2502866","DOIUrl":"https://doi.org/10.1056/nejmoa2502866","url":null,"abstract":"BACKGROUNDTuberculous meningitis is often lethal, and many survivors have disabilities despite antimicrobial treatment and adjunctive glucocorticoid therapy. Standard-dose rifampin has limited central nervous system penetration. Whether high-dose rifampin could improve survival outcomes is unknown.METHODSWe performed a double-blind, randomized, placebo-controlled clinical trial involving adults with tuberculous meningitis in Indonesia, South Africa, and Uganda. We assigned persons with and those without human immunodeficiency virus (HIV) coinfection to receive standard daily isoniazid, rifampin (at a dose of 10 mg per kilogram of body weight), ethambutol, and pyrazinamide plus either additional rifampin (for a cumulative dose of 35 mg per kilogram; high-dose group) or matched placebo (standard-dose group) for 8 weeks; participants in both groups received standard therapy for the remainder of the 9-to-12-month treatment course. The primary outcome was 6-month mortality.RESULTSA total of 499 participants were included in the intention-to-treat population (249 randomly assigned to the high-dose group and 250 to the standard-dose group), of whom 304 (60.9%) were persons living with HIV and 428 (85.8%) had definite or probable tuberculous meningitis. During 6 months of follow-up, 109 participants (Kaplan-Meier estimate, 44.6%) in the high-dose group and 100 participants (Kaplan-Meier estimate, 40.7%) in the standard-dose group died (hazard ratio, 1.17; 95% confidence interval, 0.89 to 1.54; P = 0.25). Among the participants who died within 6 months, the median time to death was 13 days (interquartile range, 4 to 39) in the high-dose group and 24 days (interquartile range, 6 to 56) in the standard-dose group. Drug-induced liver injury occurred in 8.0% of the participants in the high-dose group and in 4.4% of those in the standard-dose group, but no deaths from drug-induced liver injury occurred.CONCLUSIONSAmong persons with tuberculous meningitis, no evidence of beneficial effect from high-dose rifampin was observed, and the potential for a harmful effect cannot be ruled out. (Funded by the U.K. Medical Research Council and others; ISRCTN Registry number, ISRCTN15668391.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"1 1","pages":"2434-2446"},"PeriodicalIF":158.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771340","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}
Pub Date : 2025-12-18Epub Date: 2025-06-25DOI: 10.1056/NEJMra2504516
Lien Anh Ha Do, Kim Mulholland
{"title":"Measles 2025.","authors":"Lien Anh Ha Do, Kim Mulholland","doi":"10.1056/NEJMra2504516","DOIUrl":"10.1056/NEJMra2504516","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"2447-2458"},"PeriodicalIF":78.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144499350","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 36-2025: A 55-Year-Old Woman with Dyspnea, Fatigue, and Gastrointestinal Bleeding.","authors":"Irun Bhan,Robert G Rasmussen,Vincent Wu","doi":"10.1056/nejmcpc2513535","DOIUrl":"https://doi.org/10.1056/nejmcpc2513535","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"24 1","pages":"2460-2468"},"PeriodicalIF":158.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771341","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":"Allogeneic Beta Cells with No Immunosuppression.","authors":"Pawan Kumar,Deepesh B Kenwar,Ashish Sharma","doi":"10.1056/nejmc2516172","DOIUrl":"https://doi.org/10.1056/nejmc2516172","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"56 1","pages":"2486"},"PeriodicalIF":158.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771539","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}
Clarissa P Diniz,Japjot Bal,Hallie Nelson,Molly Findley
{"title":"A Case of Cervical Ectopic Pregnancy after the Dobbs Decision.","authors":"Clarissa P Diniz,Japjot Bal,Hallie Nelson,Molly Findley","doi":"10.1056/nejmc2508182","DOIUrl":"https://doi.org/10.1056/nejmc2508182","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"44 1","pages":"2483-2484"},"PeriodicalIF":158.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771542","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":"Merkel-Cell Carcinoma.","authors":"Zunaid Ahmed, Willem Visser","doi":"10.1056/NEJMicm2513302","DOIUrl":"https://doi.org/10.1056/NEJMicm2513302","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"393 24","pages":"2459"},"PeriodicalIF":78.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776746","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":"Supporting Clinical Best Practices after Dobbs.","authors":"Michelle Oberman,Lisa Soleymani Lehmann,Yvonne Lindgren","doi":"10.1056/nejmms2510113","DOIUrl":"https://doi.org/10.1056/nejmms2510113","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"29 1","pages":"2478-2482"},"PeriodicalIF":158.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771541","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}
Christopher Calkins, Anand Vaidya, Cameron Nutt, Raymond Kwong, Thomas Tadros
{"title":"Tick Tock.","authors":"Christopher Calkins, Anand Vaidya, Cameron Nutt, Raymond Kwong, Thomas Tadros","doi":"10.1056/NEJMimc2506281","DOIUrl":"https://doi.org/10.1056/NEJMimc2506281","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"393 24","pages":"e43"},"PeriodicalIF":78.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776754","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":"Spiderweb-like Vessels in Retinopathy of Prematurity.","authors":"Jie Peng, Peiquan Zhao","doi":"10.1056/NEJMc2513189","DOIUrl":"https://doi.org/10.1056/NEJMc2513189","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"393 24","pages":"2487"},"PeriodicalIF":78.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776667","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":"Spiderweb-like Vessels in Retinopathy of Prematurity. Reply.","authors":"Xinyu Zhao, Guoming Zhang","doi":"10.1056/NEJMc2513189","DOIUrl":"https://doi.org/10.1056/NEJMc2513189","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"393 24","pages":"2488"},"PeriodicalIF":78.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776744","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}
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