NEJM evidence最新文献

{"title":"Mepolizumab for COPD with Eosinophilic Phenotype following Hospitalization.","authors":"Cara A Flynn, Hamish J C McAuley, Omer Elneima, Hnin W W Aung, Wadah Ibrahim, Thomas J C Ward, Michelle Bourne, Tracey D Thornton, Vijay Mistry, Hannah R Gilbert, Ghazala Waheed, Adam K A Wright, Rachel A Evans, Michael C Steiner, Cassandra L Brookes, Christopher E Brightling, Neil J Greening","doi":"10.1056/EVIDoa2500012","DOIUrl":"10.1056/EVIDoa2500012","url":null,"abstract":"<p><strong>Background: </strong>Admission to hospital with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with a high risk of morbidity and mortality. Biologic treatment reduces COPD exacerbations in patients with eosinophilic inflammation. Mepolizumab, a monoclonal antibody to interleukin 5, reduces eosinophilic inflammation, but its effects on future hospitalization and mortality are uncertain.</p><p><strong>Methods: </strong>In this phase 2b, double-blind, placebo-controlled trial, we randomly assigned patients hospitalized with an AECOPD and a blood eosinophil count greater than or equal to 300 cells/μl any time in the preceding 12 months to receive either mepolizumab 100 mg or placebo every 4 weeks for 48 weeks, with treatment initiated at hospital discharge. The primary end point was the time to readmission or death from any cause. Key secondary end points included the number of hospital readmissions, exacerbations, and health-related quality of life.</p><p><strong>Results: </strong>A total of 238 patients were randomly assigned. The median time to hospitalization or death due to any cause was 25.4 weeks and 26.1 weeks in the mepolizumab and placebo groups, respectively, with Kaplan-Meier estimates of 33.9% and 31.0%, respectively (hazard ratio, 0.96; 95% confidence interval [CI], 0.70 to 1.32; P=0.811). The adjusted mean number of hospital readmissions was 1.65 (95% CI, 1.25 to 2.05) with mepolizumab and 1.85 (95% CI, 1.42 to 2.29) with placebo (risk ratio, 0.89; 95% CI, 0.64 to 1.25). The adjusted mean number of moderate or severe exacerbations was 2.80 (95% CI, 2.36 to 3.23) with mepolizumab and 3.45 (95% CI, 2.94 to 3.95) with placebo (risk ratio 0.81; 95% CI, 0.66 to 1.00). The numbers of adverse events and serious adverse events were similar between groups. No serious adverse event was attributed to the intervention.</p><p><strong>Conclusions: </strong>Patients hospitalized with an AECOPD and eosinophilic inflammation of greater than 300 cells/μl of blood within the prior 12 months, had no benefit in risk of time to readmission or death following treatment with mepolizumab for 48 weeks. The observed change in moderate or severe exacerbations, which included the null in the upper bound of the 95% confidence interval, was in the direction observed in previous trials. (Funded by GSK plc; ClinicalTrials.gov number, NCT04075331.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDoa2500012"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030436","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 47-Year-Old Woman with Left Shoulder Pain.","authors":"Justin Matthew Cheung, Daniel J Ikeda, Clement D Lee","doi":"10.1056/EVIDmr2500031","DOIUrl":"https://doi.org/10.1056/EVIDmr2500031","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 47-year-old woman who presented with pain in the left shoulder, fevers, and fatigue. Through a structured clinical approach, including targeted history, physical examination, and diagnostic testing, an illness script for the presentation emerges, and the differential diagnosis is refined. As the clinical course progresses, additional investigations provide key insights, leading to the final diagnosis.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 6","pages":"EVIDmr2500031"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152964","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":"Mepolizumab in COPD - If at First You Don't Succeed.","authors":"Mark T Dransfield, Daiana Stolz","doi":"10.1056/EVIDe2500080","DOIUrl":"10.1056/EVIDe2500080","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDe2500080"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000113","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":"Resiniferatoxin and the Future of Cancer Pain Management - A Step Forward?","authors":"Krishna B Shah, Bilal Dar","doi":"10.1056/EVIDe2500094","DOIUrl":"https://doi.org/10.1056/EVIDe2500094","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 6","pages":"EVIDe2500094"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152982","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":"Clinical Safety and Preliminary Efficacy of Regulatory T Cells for ALS.","authors":"Neil A Shneider, Alex V Nesta, Olivia M Rifai, Julia Yasek, Wassim Elyaman, Sonya Aziz-Zaman, Mi-Ae Lyu, Samuel H S Levy, Benjamin N Hoover, George Vlad, Meixian Huang, Ke Zeng, Tara Sadeghi, Anupama Reddy, Christopher R Flowers, Simrit Parmar","doi":"10.1056/EVIDoa2400249","DOIUrl":"https://doi.org/10.1056/EVIDoa2400249","url":null,"abstract":"<p><strong>Background: </strong>Peripheral and neuroinflammation have been previously associated with progression in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease involving progressive loss of motor neurons. We hypothesize that regulatory T cell (Treg) therapy can resolve inflammation and preserve function in those patients with ALS.</p><p><strong>Methods: </strong>Participants with ALS received infusions of a fixed dose (100×10⁶ cells) of umbilical cord blood-derived, allogeneic, nonhuman leukocyte antigen-matched, cryopreserved Treg product (TREG), administered as four weekly infusions followed by six monthly infusions. No lymphodepletion, immunosuppression, or interleukin 2 was administered. The primary outcome was dose-limiting toxicity, including infusion reaction within 24 hours (as graded by National Cancer Institute - Common Terminology Criteria for Adverse Events, Version 4.0) and/or regimen-related death, or grade 3 or 4 cytokine release syndrome within 14 days postinfusion. We measured clinical response using the Revised ALS Functional Rating Scale (ALSFRS-R; range 0 to 48, with lower numbers indicating lower functional ability). Exploratory analyses measured serum and plasma neurofilament light (NfL) and inflammatory biomarkers.</p><p><strong>Results: </strong>Six participants with a median age of 48.5 years (range 27 to 66 years) and baseline ALSFRS-R score of 31.5 (range 23 to 43) were treated with a median of 11 (range 6 to 22) TREG infusions in an ambulatory setting. No dose-limiting toxicity was observed. In participants with sufficient data points (n=4), the mean ALSFRS-R slope of decline was -1.66±1.03 points/month before treatment, -0.41±0.45/month during treatment, and -0.60±0.59/month posttreatment. Biomarkers including NfL and inflammatory markers MIP-1δ (macrophage inflammatory protein-1 delta), CTACK (cutaneous T cell-attracting chemokine), and GROα (growth-regulated oncogene alpha) exhibited different relationships with ALSFRS-R score between participants.</p><p><strong>Conclusions: </strong>This study demonstrates the preliminary safety of \"off-the-shelf\", allogeneic Treg-cell therapy.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 5","pages":"EVIDoa2400249"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013961","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":"Larsucosterol for the Treatment of Alcohol-Associated Hepatitis.","authors":"","doi":"10.1056/EVIDx2500084","DOIUrl":"https://doi.org/10.1056/EVIDx2500084","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 5","pages":"EVIDx2500084"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058221","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 Randomized Trial of Shared Decision-Making in Code Status Discussions.","authors":"Christoph Becker, Sebastian Gross, Katharina Beck, Simon A Amacher, Alessia Vincent, Jonas Mueller, Nina Loretz, Rene Blatter, Chantal Bohren, Tabita Urben, Armon Arpagaus, Rainer Schaefert, Philipp Schuetz, Nina Kaegi-Braun, Lena Stalder, Jörg D Leuppi, Drahomir Aujesky, Christine Baumgartner, Balthasar Hug, Hannah Schmieg, Valentina Delfine, Thomas Peters, Arnoud J Templeton, Stefano Bassetti, Sabina Hunziker","doi":"10.1056/EVIDoa2400422","DOIUrl":"10.1056/EVIDoa2400422","url":null,"abstract":"<p><strong>Background: </strong>The effect of a shared decision-making approach on patients' code status decisions remains unknown. We compared an approach for shared decision-making with usual care to evaluate the effect on patients' code status preferences and quality of decision-making.</p><p><strong>Methods: </strong>In a pragmatic cluster-randomized controlled trial conducted in six teaching hospitals in Switzerland, we randomly assigned residents to conduct code status discussions based on either an approach incorporating didactic teaching, observation, and feedback and a shared decision-making checklist with a decision aid, or usual care. The primary end point was patients choosing a do-not-resuscitate (DNR) code status in the event of a cardiac arrest. The key secondary end point was patients' decisional uncertainty, measured by the Decisional Conflict Scale (range 0 to 100, with lower scores indicating lower decisional uncertainty).</p><p><strong>Results: </strong>A total of 206 residents caring for 2663 medical patients were included in the trial. Compared with patients in the usual care group, patients in the intervention group had a significantly higher frequency of choosing DNR as their code status (685/1370 (50.0%) vs. 481/1293 (37.2%); adjusted risk ratio, 1.37 (95% confidence interval, 1.25 to 1.50); P<0.001). The intervention was associated with lower decisional uncertainty (Decisional Conflict Scale score, 14.4±15.3 vs. 21.8±20.2 points; adjusted difference, -7.06 (95% confidence interval, -9.43 to -4.68).</p><p><strong>Conclusions: </strong>An approach for shared decision-making that included the discussion of expected outcomes had a significant influence on the code status of medical patients, with a higher preference for DNR code status, and was associated with less uncertainty around the decision. (Funded by the Swiss National Science Foundation and the Swiss Society of General Internal Medicine; ClinicalTrials.gov number, NCT03872154.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 5","pages":"EVIDoa2400422"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031817","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":"Regulatory T Cell-Based Therapies - A New Piece of the ALS Therapeutic Puzzle?","authors":"Elena Abati","doi":"10.1056/EVIDe2500078","DOIUrl":"https://doi.org/10.1056/EVIDe2500078","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 5","pages":"EVIDe2500078"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052737","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":"Instrumental Variables in Randomized Trials.","authors":"","doi":"10.1056/EVIDx2500085","DOIUrl":"10.1056/EVIDx2500085","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDcx2500085"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782037","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":"Goals-of-Care Conversations - What Is the Goal?","authors":"Chad R Beck, Bruno L Ferreyro","doi":"10.1056/EVIDe2500063","DOIUrl":"https://doi.org/10.1056/EVIDe2500063","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 5","pages":"EVIDe2500063"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030736","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}