NEJM evidence最新文献

{"title":"How Platform Trials Work.","authors":"Christos Kotanidis, C Corey Hardin, Daniel Müller, Chris Twichell, Alison Burke, Adam Straus, Sharon-Lise Normand, Chana A Sacks","doi":"10.1056/EVIDstat2600082","DOIUrl":"https://doi.org/10.1056/EVIDstat2600082","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 5","pages":"EVIDstat2600082"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Decontamination of the Digestive Tract in Adult Mechanically Ventilated Patients - An Updated Systematic Review with Bayesian Meta-Analysis.","authors":"Naomi E Hammond, Anthony Devaux, Ruan Vlok, Derick Adigbli, Brian H Cuthbertson, Simon R Finfer, Tessa Garside, Qiang Li, Sajeev Mahendran, Sharon Micallef, Srinivas Murthy, John Myburgh, Louise Rose, Ian Seppelt, Balasubramanian Venkatesh, Anthony Delaney","doi":"10.1056/EVIDoa2500264","DOIUrl":"10.1056/EVIDoa2500264","url":null,"abstract":"<p><strong>Background: </strong>There is uncertainty whether the use of selective decontamination of the digestive tract (SDD) as a preventive antimicrobial strategy reduces mortality in adult patients receiving mechanical ventilation in the intensive care unit (ICU). Following the publication of new data from a contemporary randomized clinical trial, an updated systematic review and meta-analysis was conducted to determine whether the use of SDD reduced hospital mortality compared to standard care.</p><p><strong>Methods: </strong>An updated systematic review of a previously published meta-analysis was conducted including a search from September 12, 2022, to August 18, 2025, for randomized clinical trials (RCTs) of adults receiving mechanical ventilation in an ICU that compared SDD to standard care. Data were pooled using a Bayesian framework. The primary outcome was hospital mortality or closest approximation.</p><p><strong>Results: </strong>One additional trial was identified, giving a total of 32 RCTs (27,687 participants), with 30 of the 32 RCTs (27,332 participants) contributing data to the primary outcome. The pooled estimated relative risk of hospital mortality for SDD compared to usual care or placebo was 0.91; 95% credible interval, 0.82 to 0.99, <i>I</i>²=33.3%; with a 99.2% posterior probability that SDD was associated with lower hospital mortality compared to standard care.</p><p><strong>Conclusions: </strong>There is a high probability that in mechanically ventilated adults in the ICU, SDD, compared to standard care, is associated with a reduction in the risk of in-hospital death.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDoa2500264"},"PeriodicalIF":11.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal Dynamics of Hematopoiesis in Aplastic Anemia after Immunosuppression and Eltrombopag.","authors":"Deniz Ece Kaya, Riley Cook, Simona Iacobelli, Giorgio Napolitani, Sila Gerlevik, Nogayhan Seymen, Flore Sicre de Fontbrune, Morag Griffin, Camilla Frieri, Constantijn J M Halkes, Christian Recher, Fiorenza Barraco, Edouard Forcade, Jean-Baptiste Méar, Marica Laurino, Beatrice Drexler, Etienne Daguindau, Marleen van Os, Sofie Terwel, Carlo Dufour, Mohammad M Karimi, Austin G Kulasekararaj, Regis Peffault De Latour, Antonio M Risitano, Ghulam Mufti","doi":"10.1056/EVIDoa2500174","DOIUrl":"10.1056/EVIDoa2500174","url":null,"abstract":"<p><strong>Background: </strong>A Phase 3 randomized trial compared immunosuppressive therapy with or without eltrombopag in untreated patients with aplastic anemia (AA) and showed that addition of eltrombopag increased the rate, rapidity, and durability of hematological response, without increasing transformation to myeloid malignancies. We sought to systematically investigate clonal hematopoiesis (CH) dynamics from patient samples from this trial.</p><p><strong>Methods: </strong>Peripheral blood and bone marrow aspirates were collected at diagnosis (i.e., baseline) and at 6 and 24 months from patients with severe or very severe AA. Genetic testing for somatic mutations was performed using 31-gene \"core\" and 291-gene \"extended\" custom targeted panels and analyzed longitudinally.</p><p><strong>Results: </strong>Samples were collected from patients at baseline (n=170) and 6 (n=150) and 24 months (n=103); 85 patients' samples were tested at all three timepoints. Somatic mutations were present in 30% of patients at baseline, 55.3% at 6 months and 79.6% at 24 months, with a mean number of mutations per patient of 0.4, 1.2, and 2.5, at baseline and 6 and 24 months, respectively.</p><p><strong>Conclusions: </strong>CH was frequent in patients with AA and its prevalence appeared to be higher at posttherapy timepoints than at diagnosis. CH in AA may reflect the survival and expansion of selected residual hematopoietic stem/progenitor cells associated with immune-mediated damage. (Funded by Cancer Research UK, Bloodwise UK, and Novartis AG; ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 5","pages":"EVIDoa2500174"},"PeriodicalIF":11.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Exchange about \"Prehospital Aspirin Use in the CELEBRATE Trial\".","authors":"","doi":"10.1056/EVIDex2500343","DOIUrl":"https://doi.org/10.1056/EVIDex2500343","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 5","pages":"EVIDex2500343"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Imsidolimab for Generalized Pustular Psoriasis.","authors":"Sandra Smieszek, Bartlomiej Przychodzen, Christina Tyner, Caroline Johnson, Margaret Bushman, Jennifer Brzezynski, Adam Reich, Hervé Bachelez, Evelyn Wen Yee Yap, Murat Borlu, Suteeraporn Chaowattanapanit, Mohamed Denguezli, Johann E Gudjonsson, Paul Lizzul, Martin Dahl, Stephen Parmley, Bruce Randazzo, Anne Severtson, Priya Raina, Khalil Saikali, Changfu Xiao, Christos Polymeropoulos, Gunther Birznieks, Mihael Polymeropoulos","doi":"10.1056/EVIDoa2500272","DOIUrl":"10.1056/EVIDoa2500272","url":null,"abstract":"<p><strong>Background: </strong>Generalized pustular psoriasis (GPP) is a rare, life-threatening disease attributed to aberrant interleukin-36 (IL-36) activity, often due to variants in the IL-36 receptor antagonist gene. Imsidolimab is a novel, humanized, affinity-matured immunoglobulin G4 monoclonal antibody that binds the IL-36 receptor and antagonizes IL-36 signaling.</p><p><strong>Methods: </strong>Two phase 3 trials were conducted at 26 clinical sites within 11 countries investigating imsidolimab treatment for GPP. GEMINI-1 was a double-blind, placebo-controlled trial that randomly assigned 45 patients (18-80 years of age) with a GPP flare to receive either a single intravenous dose of 300 mg of imsidolimab, 750 mg of imsidolimab, or placebo. The primary endpoint was GPP Physician Global Assessment (GPPPGA) scores of clear (0) or almost clear (1) at week 4 (range: 0 [clear] to 4 [severe]; minimally clinically important difference, 1.4). GEMINI-2 was a follow-on relapse prevention trial with a primary objective of evaluating the safety of imsidolimab up to 104 weeks. Patients who improved with treatment in GEMINI-1 were randomly assigned to receive either 200 mg of subcutaneous imsidolimab or placebo monthly, whereas partial responders received open-label 200 mg of subcutaneous imsidolimab monthly.</p><p><strong>Results: </strong>In GEMINI-1, 53% of patients in the groups that received either 300 mg (n=8/15) or 750 mg (n=8/15) of imsidolimab had GPPPGA scores of 0 or 1 at week 4, compared to 13% in the placebo group (n=2/15) (P=0.023 for both the 300 mg vs. placebo comparison and 750 mg vs. placebo comparison). In GEMINI-2, no serious adverse events led to imsidolimab discontinuation.</p><p><strong>Conclusions: </strong>Compared with placebo, a significantly higher proportion of patients with GPP randomly assigned to receive a single intravenous dose of imsidolimab were clear or almost clear of the disease after 4 weeks based on the GPPPGA. There were no serious adverse events that led to treatment discontinuation with imsidolimab up to 104 weeks of treatment. (Funded by AnaptysBio; ClinicalTrials.gov number, NCT05352893 for GEMINI-1 and NCT05366855 for GEMINI-2.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 5","pages":"EVIDoa2500272"},"PeriodicalIF":11.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpreting Evidence with Bayesian Meta-Analysis.","authors":"Sharon-Lise T Normand","doi":"10.1056/EVIDe2600097","DOIUrl":"10.1056/EVIDe2600097","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDe2600097"},"PeriodicalIF":11.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal Selection and Evolution after Treatment of Severe Aplastic Anemia.","authors":"Fernanda Gutierrez-Rodrigues, Emma M Groarke, Rui Miao, Ruba Shalhoub, Lemlem Alemu, Hiroki Mizumaki, Olga Rios, Joshua Glass, Jibran Durrani, Luiz Fernando Bazzo Catto, Luca Arcuri, Sachiko Kajigaya, Shouguo Gao, Subrata Paul, Justin Lack, Masanori Yoshida, Diego Quinones Raffo, Jennifer Lotter, Colin O Wu, Cynthia E Dunbar, Marcin Wlodarski, Neal S Young, Bhavisha A Patel","doi":"10.1056/EVIDoa2500171","DOIUrl":"10.1056/EVIDoa2500171","url":null,"abstract":"<p><strong>Background: </strong>Clonal hematopoiesis (CH) is a feature of severe aplastic anemia (SAA), but its clinical significance is debated.</p><p><strong>Methods: </strong>We integrated longitudinal clinical and CH data from patients with SAA treated with immunosuppression plus eltrombopag (IST-EPAG) in a phase 2 trial to characterize clonal dynamics during recovery and progression to myeloid cancer or paroxysmal nocturnal hemoglobinuria (PNH); CH was defined as the presence of somatic mutations at a variant allele frequency of 0.1% or greater.</p><p><strong>Results: </strong>In total, 204 SAA patients treated with IST-EPAG were evaluated from disease onset to median follow-up of 5.5 years. CH was observed in 128 of 204 (63%) patients before treatment and in 131 of 180 (73%) after therapy who were evaluated at the 6-month timepoint and were not off-study. Patients mostly had CH in <i>PIGA</i> (N=53, 26%), DNMT3A (N=42, 21%), BCOR (N=35, 17%), and <i>ASXL1</i> (N=25, 12%). There appeared to be two distinct patterns of malignant clonal evolution. Early evolutions, within 1 year from treatment, were primarily chromosome 7 aberrations and occurred in 11 (5%) patients. In another eight (4%) patients, late evolutions, 4-5 years after therapy, were initiated by early selection of <i>ASXL1-</i>mutated or <i>U2AF1</i>-mutated clones. Evolution to PNH, observed in 10 of 204 patients (5%), was associated with expansion of <i>PIGA</i> clones usually present before treatment.</p><p><strong>Conclusions: </strong>Among patients with SAA treated with IST-EPAG, early and late patterns of clonal evolution to myeloid cancer were observed: Chromosome 7 abnormalities occurred within 1 year, whereas later events (4-5 years) involved stepwise mutation acquisition in preexisting <i>ASXL1-</i> or <i>U2AF1-</i>mutated clones.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 5","pages":"EVIDoa2500171"},"PeriodicalIF":11.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Exchange about \"Oral Diuretic Intensification as a Worsening Heart Failure Event in the Primary Outcome of Clinical Trials\".","authors":"","doi":"10.1056/EVIDe2500363","DOIUrl":"https://doi.org/10.1056/EVIDe2500363","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 4","pages":"EVIDe2500363"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequencing of Pleural Fluid and Plasma for Tuberculous Pleuritis.","authors":"W K Jacky Lam, Ken K P Chan, Guangya Wang, Christopher K C Lai, Guannan Kang, Christopher Chan, Angela C Y Leung, Natalie H L Wong, Crystal S N Tso, K M Chow, Saravanan Ramakrishnan, K T Wong, Charlotte H Y Lau, Joyce K C Ng, Rachel L P Lo, W H Yip, Jenny C L Ngai, K W To, Irene O L Tse, S H Cheng, Huimin Shang, K W Chan, Angel Lai, Charles M L Chan, Vicky C T Lee, Yasine Malki, L Y Lois Choy, Mary-Jane L Ma, Qing Zhou, Stephanie C Y Yu, Peiyong Jiang, Fanny W S Ko, K C Allen Chan, David S C Hui, Y C Gary Lee, Y M Dennis Lo","doi":"10.1056/EVIDoa2500237","DOIUrl":"10.1056/EVIDoa2500237","url":null,"abstract":"<p><strong>Background: </strong>The laboratory diagnosis of tuberculous pleuritis (TBP) is hindered by the paucibacillary nature of <i>Mycobacterium tuberculosis</i> in the pleural space, resulting in low sensitivity of microbiological culture and polymerase chain reaction-based analyses on pleural fluid. The use of metagenomic next-generation sequencing for diagnosing TBP may be limited by the background noise of DNA from nontuberculous mycobacteria.</p><p><strong>Methods: </strong>We performed targeted sequencing to analyze <i>M. tuberculosis</i> DNA in paired pleural fluid and plasma from prospectively enrolled consecutive patients with new-onset pleural effusion. We used a bioinformatics alignment algorithm to the <i>M. tuberculosis</i> genome that was masked for regions with high sequence similarity to nontuberculous mycobacteria. Our primary outcome was a comparison of diagnostic sensitivity between <i>M. tuberculosis</i> sequencing as described above and culture using McNemar's test.</p><p><strong>Results: </strong>Among the included 329 patients with pleural effusion, 34 patients with TBP were identified. Targeted sequencing detected <i>M. tuberculosis</i> DNA fragments in the pleural fluid of all TBP cases (median, 267.6 reads per 10 million [RP10M]; interquartile range [IQR], 30.8-2644.3) but absent in 288 out of 295 (97.6%) non-TBP samples (median, 0 RP10M; IQR, 0-0). Targeted sequencing of pleural fluid achieved a sensitivity of 97.1% for TBP detection at a cutoff of 2 RP10M, in contrast to 47.1% by <i>M. tuberculosis</i> culture (P<0.001, McNemar's test). Sequencing yielded an area-under-the-curve value of 0.9996 (95% confidence interval, 0.9988-1.0000) for differentiating TBP and non-TBP. Plasma analysis by targeted sequencing with the same alignment algorithm reported an area-under-the-curve value of 0.9475 (95% confidence interval, 0.8929-1.0000).</p><p><strong>Conclusions: </strong>Targeted sequencing of pleural fluid with selectively masked <i>M. tuberculosis</i> genomic alignment accurately diagnosed TBP and outperformed conventional diagnostic tests. (Supported by InnoHK and the Hong Kong Tuberculosis, Chest and Heart Diseases Association; ClinicalTrials.gov number, NCT05397730.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 4","pages":"EVIDoa2500237"},"PeriodicalIF":11.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tobacco Product Use among U.S. Adults, 2023-2024.","authors":"Israel Agaku","doi":"10.1056/EVIDpha2500339","DOIUrl":"10.1056/EVIDpha2500339","url":null,"abstract":"<p><p>AbstractAnalysis of 2023-2024 National Health Interview Survey data suggest that prevalence of cigarette smoking among U.S. adults declined from 10.8% of the population in 2023 to 9.9% in 2024. Use of other tobacco products, including cigars and e-cigarettes, remained unchanged, and 18.8% of adults (47.7 million) used at least one tobacco product.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDpha2500339"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}