New England Journal of Medicine最新文献

{"title":"Efruxifermin in Compensated Liver Cirrhosis Caused by MASH.","authors":"Mazen Noureddin,Mary E Rinella,Naga P Chalasani,Guy W Neff,K Jean Lucas,Manuel E Rodriguez,Madhavi Rudraraju,Rashmee Patil,Cynthia Behling,Mark Burch,Doreen C Chan,Erik J Tillman,Arian Zari,Brittany de Temple,Reshma Shringarpure,Meena Jain,Timothy Rolph,Andrew Cheng,Kitty Yale","doi":"10.1056/nejmoa2502242","DOIUrl":"https://doi.org/10.1056/nejmoa2502242","url":null,"abstract":"BACKGROUNDIn phase 2 trials involving patients with stage 2 or 3 fibrosis caused by metabolic dysfunction-associated steatohepatitis (MASH), efruxifermin, a bivalent fibroblast growth factor 21 (FGF21) analogue, reduced fibrosis and resolved MASH. Data are needed on the efficacy and safety of efruxifermin in patients with compensated cirrhosis (stage 4 fibrosis) caused by MASH.METHODSIn this phase 2b, randomized, placebo-controlled, double-blind trial, we assigned patients with MASH who had biopsy-confirmed compensated cirrhosis (stage 4 fibrosis) to receive subcutaneous efruxifermin (at a dose of 28 mg or 50 mg once daily) or placebo. The primary outcome was a reduction of at least one stage of fibrosis without worsening of MASH at week 36. Secondary outcomes included the same criterion at week 96.RESULTSA total of 181 patients underwent randomization and received at least one dose of efruxifermin or placebo. Of these patients, liver biopsy was performed in 154 patients at 36 weeks and in 134 patients at 96 weeks. At 36 weeks, a reduction in fibrosis without worsening of MASH occurred in 8 of 61 patients (13%) in the placebo group, in 10 of 57 patients (18%) in the 28-mg efruxifermin group (difference from placebo after adjustment for stratification factors, 3 percentage points; 95% confidence interval [CI], -11 to 17; P = 0.62), and in 12 of 63 patients (19%) in the 50-mg efruxifermin group (difference from placebo, 4 percentage points; 95% CI, -10 to 18; P = 0.52). At week 96, a reduction in fibrosis without worsening of MASH occurred in 7 of 61 patients (11%) in the placebo group, in 12 of 57 patients (21%) in the 28-mg efruxifermin group (difference from placebo, 10 percentage points; 95% CI, -4 to 24), and in 18 of 63 patients (29%) in the 50-mg efruxifermin group (difference from placebo, 16 percentage points; 95% CI, 2 to 30). Gastrointestinal adverse events were more common with efruxifermin; most events were mild or moderate.CONCLUSIONSIn patients with compensated cirrhosis caused by MASH, efruxifermin did not significantly reduce fibrosis at 36 weeks. (Funded by Akero Therapeutics; SYMMETRY ClinicalTrials.gov number, NCT05039450.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"25 1","pages":""},"PeriodicalIF":158.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932447","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":"BCG Revaccination for the Prevention of Mycobacterium tuberculosis Infection.","authors":"Alexander C Schmidt,Lee Fairlie,Elizabeth Hellström,Angelique Luabeya Kany Kany,Keren Middelkoop,Kogieleum Naidoo,Gonasagrie Nair,Anele Gela,Elisa Nemes,Thomas J Scriba,Amy Cinar,Nicole Frahm,Robin Mogg,David Kaufman,Michael W Dunne,Mark Hatherill,","doi":"10.1056/nejmoa2412381","DOIUrl":"https://doi.org/10.1056/nejmoa2412381","url":null,"abstract":"BACKGROUNDIn a previous phase 2 trial, bacille Calmette-Guérin (BCG) revaccination was not shown to provide protection from primary Mycobacterium tuberculosis infection but prevented sustained M. tuberculosis infection, defined by an initial conversion on a QuantiFERON-TB (QFT) test (an interferon-γ release assay) from negative to positive, followed by two additional positive QFT tests at 3 and 6 months after the initial conversion (a secondary end point). A vaccine efficacy of 45% (95% confidence interval [CI], 6 to 68) was observed.METHODSWe performed a phase 2b, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of BCG revaccination, as compared with placebo, for the prevention of sustained QFT test conversion (primary end point) in QFT test-negative, human immunodeficiency virus (HIV)-negative adolescents. Adverse events were assessed in a secondary analysis, and immunogenicity was assessed in an exploratory analysis. Vaccine efficacy was evaluated in the modified intention-to-treat population, which included all the participants who had undergone randomization, received the BCG vaccine or placebo, and had a negative QFT test 10 weeks after receipt of BCG vaccine or placebo; the last criterion was added to exclude participants with M. tuberculosis infection around the time that the vaccine or placebo was administered. Hazard ratios and 95% confidence intervals were estimated from a stratified Cox proportional-hazards model.RESULTSA total of 1836 participants underwent randomization; 918 received the BCG vaccine, and 917 received placebo. After a median 30 months of follow-up, a sustained QFT test conversion was observed in 62 of 871 participants in the BCG-vaccine group and 59 of 849 participants in the placebo group. The hazard ratio for a sustained QFT test conversion (BCG vaccine vs. placebo) was 1.04 (95% CI, 0.73 to 1.48), for a vaccine efficacy point estimate of -3.8% (95% CI, -48.3 to 27.4). Adverse events occurred more frequently in the BCG-vaccine group than in the placebo group, and most were due to injection-site reactions (pain, redness, swelling, and ulceration). BCG revaccination induced cytokine-positive type 1 helper CD4 T cells.CONCLUSIONSBCG revaccination in QFT-test negative, HIV-negative adolescents did not provide protection from sustained M. tuberculosis infection. (Funded by the Gates Foundation; ClinicalTrials.gov number NCT04152161.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"3 1","pages":"1789-1800"},"PeriodicalIF":158.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921123","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":"Automated Insulin Pump in Type 2 Diabetes.","authors":"Betul Hatipoglu","doi":"10.1056/nejme2504046","DOIUrl":"https://doi.org/10.1056/nejme2504046","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"23 1","pages":"1862-1863"},"PeriodicalIF":158.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921126","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 Randomized Trial of Automated Insulin Delivery in Type 2 Diabetes.","authors":"Yogish C Kudva, Dan Raghinaru, John W Lum, Timothy E Graham, David Liljenquist, Elias K Spanakis, Francisco J Pasquel, Andrew Ahmann, David T Ahn, Grazia Aleppo, Thomas Blevins, Davida Kruger, Sue A Brown, Carol J Levy, Ruth S Weinstock, Devin W Steenkamp, Tamara Spaic, Irl B Hirsch, Frances Broyles, Michael R Rickels, Michael A Tsoukas, Philip Raskin, Betul Hatipoglu, Donna Desjardins, Adrienne N Terry, Lakshmi G Singh, Georgia M Davis, Caleb Schmid, Jelena Kravarusic, Kasey Coyne, Luis Casaubon, Valerie Espinosa, Jaye K Jones, Kathleen Estrada, Samina Afreen, Camilla Levister, Grenye O'Malley, Selina L Liu, Sheryl Marks, Amy J Peleckis, Melissa-Rosina Pasqua, Vanessa Tardio, Corey Kurek, Ryan D Luker, Jade Churchill, Farbod Z Tajrishi, Ariel Dean, Brittany Dennis, Evelyn Fronczyk, Jennifer Perez, Shereen Mukhashen, Jasmeen Dhillon, Aslihan Ipek, Suzan Bzdick, Astrid Atakov Castillo, Marsha Driscoll, Xenia Averkiou, Cornelia V Dalton-Bakes, Adelyn Moore, Lin F Jordan, Amanda Lesniak, Jordan E Pinsker, Ravid Sasson-Katchalski, Tiffany Campos, Charles Spanbauer, Lauren Kanapka, Craig Kollman, Roy W Beck","doi":"10.1056/NEJMoa2415948","DOIUrl":"10.1056/NEJMoa2415948","url":null,"abstract":"<p><strong>Background: </strong>Automated insulin delivery (AID) systems have been shown to be beneficial for patients with type 1 diabetes, but data are needed from randomized, controlled trials regarding their role in the management of insulin-treated type 2 diabetes.</p><p><strong>Methods: </strong>In this 13-week, multicenter trial, adults with insulin-treated type 2 diabetes were randomly assigned in a 2:1 ratio to receive AID or to continue their pretrial insulin-delivery method (control group); both groups received continuous glucose monitoring (CGM). The primary outcome was the glycated hemoglobin level at 13 weeks.</p><p><strong>Results: </strong>A total of 319 patients underwent randomization. Glycated hemoglobin levels decreased by 0.9 percentage points (from 8.2±1.4% at baseline to 7.3±0.9% at week 13) in the AID group and by 0.3 percentage points (from 8.1±1.2% to 7.7±1.1%) in the control group (mean adjusted difference, -0.6 percentage points; 95% confidence interval [CI], -0.8 to -0.4; P<0.001). The mean percentage of time that patients were in the target glucose range of 70 to 180 mg per deciliter increased from 48±24% to 64±16% in the AID group and from 51±21% to 52±21% in the control group (mean difference, 14 percentage points; 95% CI, 11 to 17; P<0.001). All other multiplicity-controlled CGM outcomes reflective of hyperglycemia that were measured were significantly better in the AID group than in the control group. The frequency of CGM-measured hypoglycemia was low in both groups. A severe hypoglycemia event occurred in one patient in the AID group.</p><p><strong>Conclusions: </strong>In this 13-week, randomized, controlled trial involving adults with insulin-treated type 2 diabetes, AID was associated with a greater reduction in glycated hemoglobin levels than CGM alone. (Funded by Tandem Diabetes Care; 2IQP ClinicalTrials.gov number, NCT05785832.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"1801-1812"},"PeriodicalIF":96.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659644","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":"Liraglutide for Children 6 to <12 Years of Age with Obesity.","authors":"Saul Malozowski","doi":"10.1056/NEJMc2503084","DOIUrl":"https://doi.org/10.1056/NEJMc2503084","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 18","pages":"1866-1867"},"PeriodicalIF":96.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043063","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 Last Dose.","authors":"David N Korones","doi":"10.1056/NEJMp2415430","DOIUrl":"https://doi.org/10.1056/NEJMp2415430","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 18","pages":"1774-1775"},"PeriodicalIF":96.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992464","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":"Liraglutide for Children 6 to <12 Years of Age with Obesity. Reply.","authors":"Claudia K Fox, Nina M Harder-Lauridsen, Silva Arslanian","doi":"10.1056/NEJMc2503084","DOIUrl":"https://doi.org/10.1056/NEJMc2503084","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 18","pages":"1868"},"PeriodicalIF":96.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058149","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":"More on Acquired Osteomalacia and Autoantibodies against PHEX. Reply.","authors":"Yoshitomo Hoshino, Kazuo Okamoto, Nobuaki Ito","doi":"10.1056/NEJMc2502747","DOIUrl":"https://doi.org/10.1056/NEJMc2502747","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 18","pages":"1871-1872"},"PeriodicalIF":96.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052962","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 13-2025: A 70-Year-Old Man with Weight Loss, Weakness, and Anorexia.","authors":"Matthew G Gartland,Samuel C D Cartmell,John S Albin,Daniel Restrepo,Anthony R Russo","doi":"10.1056/nejmcpc2412518","DOIUrl":"https://doi.org/10.1056/nejmcpc2412518","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"117 1","pages":"1847-1856"},"PeriodicalIF":158.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921128","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":"Pegivirus-Associated Encephalomyelitis in Immunosuppressed Patients.","authors":"Franziska Scheibe, Julia Melchert, Helena Radbruch, Eberhard Siebert, Till D Best, Siegfried Kohler, Mira Fitzek, Alexander Kowski, Volker Siffrin, Jenny Meinhardt, Raphael Raspe, Viktor Horst, Bianca Zukunft, Klemens Budde, Frank K H van Landeghem, Christopher Power, Kai-Uwe Eckardt, Matthias Endres, Christian Drosten, Victor M Corman, Klemens Ruprecht","doi":"10.1056/NEJMc2501512","DOIUrl":"https://doi.org/10.1056/NEJMc2501512","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 18","pages":"1864-1866"},"PeriodicalIF":96.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057901","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}