NEJM evidence最新文献

{"title":"Exertional Heat Illness in Active Populations.","authors":"Caroline E Murphy, David W DeGroot, Francis G O'Connor","doi":"10.1056/EVIDra2500270","DOIUrl":"https://doi.org/10.1056/EVIDra2500270","url":null,"abstract":"<p><p>AbstractExertional heat illness (EHI) is a leading yet preventable cause of morbidity and mortality in active populations. EHI develops when the body's integrated thermoregulatory responses, including cardiovascular adjustments and evaporative cooling, are unable to dissipate the combined burden of metabolic heat production, environmental heat stress, clothing or protective equipment, and other contributing factors. This review examines the physiological mechanisms that underlie EHI and the effects of heat stress on the exercising heart. We also summarize best practices for the prevention, recognition, and management of exertional heat illness.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 5","pages":"EVIDra2500270"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791479","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":"A 65-Year-Old Woman with Fatigue and Leg Pain.","authors":"Niloufar Ebrahimi, Amir Abdipour, Pravir Baxi","doi":"10.1056/EVIDmr2500335","DOIUrl":"https://doi.org/10.1056/EVIDmr2500335","url":null,"abstract":"<p><p>AbstractMorning Report is a time-honored tradition where physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient's chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case. This report examines the story of a 65-year-old woman who presented to the emergency department with fatigue and progressively worsening leg pain. Using questions, physical examination, and testing, an illness script for the presentation emerges. As the clinical course progresses, the differential is refined until a diagnosis is made.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 5","pages":"EVIDmr2500335"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791487","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 Hematopoiesis after Immune Suppression - Adaptive Remodeling without Evolution? Early Lessons from the RACE Trial.","authors":"Simona Pagliuca, Carmelo Gurnari","doi":"10.1056/EVIDe2500310","DOIUrl":"https://doi.org/10.1056/EVIDe2500310","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 5","pages":"EVIDe2500310"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791499","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 Hematopoiesis Diversity in Aplastic Anemia - When Does It Matter Clinically?","authors":"Rodrigo T Calado, Mayko J S Vasconcelos","doi":"10.1056/EVIDe2500304","DOIUrl":"https://doi.org/10.1056/EVIDe2500304","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"5 5","pages":"EVIDe2500304"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791508","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":"Emergence of Medetomidine in New York's Illicit Drug Supply.","authors":"John S Angles, Lucila M Zamboni, Jeffery Sauer, Matthew Fallico, Leonardo Dominguez-Gomez, Anne Delvecchio, Hannah Helmy, Sophia Reinicke, Izza Zaidi, Brittany Okon, Ellenie Tuazon, Gail Cooper, Rebecca Linn-Walton, David R Holtgrave","doi":"10.1056/EVIDpha2600045","DOIUrl":"10.1056/EVIDpha2600045","url":null,"abstract":"<p><p>AbstractNew York State and New York City health departments have closely monitored the emergence of medetomidine, a sedative that can cause prolonged sedation and a complex withdrawal syndrome, in the illicit drug supply. Drug checking and toxicology data first detected medetomidine in New York in mid-2024, and through 2025 it was identified in 25.1% of opioid samples analyzed. This Public Health Alerts report highlights state and local collaboration to detect emerging substances of concern in the illicit drug supply and to implement data-guided programmatic responses, including enhanced surveillance, public alerts, and medetomidine test strip distribution.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDpha2600045"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655503","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":"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":0.0,"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":"https://doi.org/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":0.0,"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":"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":"https://doi.org/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":0.0,"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":"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}