NEJM evidence最新文献

{"title":"Surgical versus Nonsurgical Treatment for Cervical Radiculopathy.","authors":"Mirad Taso, Jon Håvard Sommernes, Jarle Sundseth, Are Hugo Pripp, Siri Bjorland, Kaia B Engebretsen, Frode Kolstad, John Anker Zwart, Jens Ivar Brox","doi":"10.1056/EVIDoa2400404","DOIUrl":"https://doi.org/10.1056/EVIDoa2400404","url":null,"abstract":"<p><strong>Background: </strong>Cervical radiculopathy is typically caused by disc herniation or spondylosis. Few trials have compared the efficacy of surgical versus nonsurgical treatment for these conditions.</p><p><strong>Methods: </strong>We conducted two randomized clinical trials among 180 patients presenting to the Oslo University Hospital in Norway with disabling radicular arm pain and cervical disc herniation (trial 1; n=89) or spondylosis (trial 2; n=91) proven by magnetic resonance imaging or computerized tomography. Patients were randomly assigned in a 1:1 ratio to receive either surgical or nonsurgical treatment. Surgery involved anterior cervical discectomy and fusion. Nonsurgical treatment involved three sessions with physical medicine/rehabilitation physicians and three sessions with physiotherapists for functional and cognitive behavioral support. The primary outcome in both trials was the Neck Disability Index (NDI) score (range, 0 to 100; higher scores indicate greater disability; minimal important difference is 15) at 12 months, which was self-reported by the patients.</p><p><strong>Results: </strong>Among the 87 patients in the disc herniation trial with 12-month data (surgical group, n=45; nonsurgical group, n=42), the mean difference in NDI adjusted for baseline was 7.4 (95% confidence interval [CI], 1.6 to 13.3; P=0.01) in favor of surgical treatment. Among the 88 patients in the spondylosis trial with 12-month data (surgical, n=44; nonsurgical, n=44), the mean difference in NDI adjusted for baseline was 2.3 (95% CI, -4.9 to 9.6; P=0.52). In the disc herniation trial, two patients in the nonsurgical group crossed over to have surgery. In the spondylosis trial, 11 patients in the nonsurgical group crossed over to have surgery. There were no serious adverse events.</p><p><strong>Conclusions: </strong>In patients with cervical radiculopathy, we found a statistically significant difference for NDI at 12 months in favor of surgical versus nonsurgical treatment in the disc herniation trial, but no difference in the spondylosis trial. (Funded by the Southern and Eastern Norway Regional Health Authority; HSØ#2017057; ClinicalTrials.gov number, NCT03674619.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 4","pages":"EVIDoa2400404"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702363","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 68-Year-Old Man with Urinary Incontinence.","authors":"Connor Lough, Nicholas Lanzotti, Ahmer Farooq, Ahmad M El-Arabi","doi":"10.1056/EVIDmr2400408","DOIUrl":"https://doi.org/10.1056/EVIDmr2400408","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 68-year-old man with a history of end-stage renal disease who presented with urinary incontinence following a kidney transplant. Through a structured clinical approach, including targeted history-taking, physical examination, and diagnostic testing, an illness script is constructed, 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 4","pages":"EVIDmr2400408"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702260","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 Use of ZSCAN4 for Telomere Elongation in Hematopoietic Stem Cells.","authors":"Kasiani C Myers, Stella M Davies, Carolyn Lutzko, Robin Wahle, David D Grier, Geraldine Aubert, Kevin Norris, Duncan M Baird, Minako Koga, Akihiro C Ko, Tomokazu Amano, Misa Amano, Hong Yu, Minoru S H Ko","doi":"10.1056/EVIDoa2400252","DOIUrl":"https://doi.org/10.1056/EVIDoa2400252","url":null,"abstract":"<p><strong>Background: </strong>Extremely short telomeres in patients with dyskeratosis congenita and related telomere biology disorders (TBDs) lead to premature cellular senescence and bone marrow failure. Zinc finger and SCAN domain-containing 4 (ZSCAN4) elongates telomeres by recombination.</p><p><strong>Methods: </strong>We report a clinical study in which EXG34217, the term given for autologous CD34+ hematopoietic stem cells from patients with TBD exposed to a temperature-sensitive Sendai virus vector encoding human <i>ZSCAN4</i> at 33°C for 24 hours, was infused into patients without preconditioning.</p><p><strong>Results: </strong>Four patients were enrolled; two experienced successful CD34+ mobilization during the second mobilization attempt and underwent apheresis and EXG34217 infusion, with follow-up of 5 and 24 months (both ongoing). We observed telomere elongation (1.06- to 1.34-fold) in CD34+ cells ex vivo. In one patient, the treatment was associated with a change in the mean absolute neutrophil count (ANC) from 1.78×10³ to 3.18×10³ cells/μl; the lymphocyte subpopulation telomere length changed from 3.6 to 6.7 kb (50th percentile for age). In the other patient, the treatment was associated with a change in the lowest ANC from 0.6×10³/μl to 1.2×10³/μl; this has occurred in 5 months without the patient receiving prior intermittent low-dose granulocyte-colony-stimulating factor injections. During mobilization, all patients experienced mild to moderate bone pain or pain after line replacement, and one patient had a blood infection associated with fever and hypoxemia. After EXG34217 infusion, no acute safety issues were noted; in one patient mild to moderate long-term cardiac and pulmonary adverse events were noted; these were similar to symptoms of the patient's underlying conditions.</p><p><strong>Conclusions: </strong>Although definitive conclusions cannot be drawn from the two EXG34217-treated patients, these results warrant further investigation of CD34+ cells exposed to ZSCAN4 for treating TBDs. (Funded by Elixirgen Therapeutics; ClinicalTrials.gov number, NCT04211714.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDoa2400252"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495026","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":"Peanut Oral Immunotherapy in Children with High-Threshold Peanut Allergy.","authors":"Scott H Sicherer, Supinda Bunyavanich, M Cecilia Berin, Tracy Lo, Marion Groetch, Allison Schaible, Susan A Perry, Lisa M Wheatley, Patricia C Fulkerson, Helena L Chang, Mayte Suárez-Fariñas, Hugh A Sampson, Julie Wang","doi":"10.1056/EVIDoa2400306","DOIUrl":"10.1056/EVIDoa2400306","url":null,"abstract":"<p><strong>Background: </strong>Approved therapeutics for peanut allergy are not designed for the many patients with allergic reactions to more than one peanut.</p><p><strong>Methods: </strong>We randomly assigned (1:1) participants 4 to 14 years of age reacting to a challenge of between 443 mg and 5043 mg of peanut protein to peanut oral immunotherapy (P-OIT) using home-measured peanut butter versus peanut avoidance. The primary end point was the difference between groups in the proportion tolerating a two-dose-level increase or 9043 mg of peanut protein. For ingestion participants tolerating 9043 mg, sustained unresponsiveness (tolerance off treatment) was tested after 16 weeks of ad lib ingestion followed by 8 weeks of abstinence.</p><p><strong>Results: </strong>Of 73 participants, 38 were randomly assigned to P-OIT and 35 to avoidance. Thirty-two of 38 participants in the ingestion group (84.2%) and 30 of 35 in the avoidance group (85.7%) underwent the primary outcome food challenge. The primary analysis with prespecified multiple imputation for missing values showed 100% success for ingestion versus 21.0% for avoidance (between-group difference, 79.0 percentage points; 95% confidence interval [CI], 64.6 to 93.5; P<0.001). All 32 treated and 3 out of 30 avoiders (10%) tolerated 9043 mg. In the intention-to-treat analysis, sustained unresponsiveness occurred in 68.4% (26/38) on P-OIT versus 8.6% (3/35) tolerating 9043 mg among those avoiding (between-group difference, 59.9 percentage points; 95% CI, 42.4 to 77.3). No dosing reactions were greater than grade 1 severity, and no serious adverse events were reported.</p><p><strong>Conclusions: </strong>In this trial of P-OIT using store-bought, home-measured peanut versus peanut avoidance in high-threshold peanut allergy, those treated achieved significantly higher rates of desensitization with a durable response off treatment. (Funded by the National Center for Advancing Translational Sciences [UL1TR004419] and the National Institute of Allergy and Infectious [U19AI136053]; ClinicalTrials.gov number, NCT03907397.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDoa2400306"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383530","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":"To Eat or Not to Eat - Oral Immunotherapy for High-Threshold Peanut Allergy.","authors":"Corinne A Keet, A Wesley Burks","doi":"10.1056/EVIDe2400448","DOIUrl":"https://doi.org/10.1056/EVIDe2400448","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDe2400448"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495047","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":"Intact Fish Skin Graft to Treat Deep Diabetic Foot Ulcers.","authors":"","doi":"10.1056/EVIDx2500032","DOIUrl":"10.1056/EVIDx2500032","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDx2500032"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416505","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":"Haploidentical Bone Marrow Transplantation for Sickle Cell Disease.","authors":"Adetola A Kassim, Mark C Walters, Mary Eapen, Madoc Smith, Brent R Logan, Melhem Solh, Christopher McKinney, Michael Nieder, Maureen Ross, Michael Kent, Ghada A Abusin, Kanwaldeep Mallhi, Jorge Galvez Silva, Paul Shaughnessy, Julie Kanter, Hilary Haines, Rafic Farah, Yasser A Khaled, Nicole Ritzau, Adam Mendizabal, Allistair Abraham, Catherine Bollard, Kenneth Cooke, Josu de la Fuente, Rabi Hanna, Mary M Horowitz, Lori C Jordan, Nitya Bakshi, Lakshmanan Krishnamurti, Eric Leifer, Kris Michael Mahadeo, Shalini Shenoy, Richard J Jones, Michael R DeBaun, Robert A Brodsky","doi":"10.1056/EVIDoa2400192","DOIUrl":"10.1056/EVIDoa2400192","url":null,"abstract":"<p><strong>Background: </strong>Related human leukocyte antigen (HLA)-haploidentical bone marrow transplantation (BMT) with posttransplant cyclophosphamide may be curative for sickle cell disease. However, graft failure, severe graft-versus-host disease (GVHD), infections, and mortality remain a concern. We evaluated a novel conditioning regimen followed by related HLA-haploidentical BMT in adults with sickle cell disease.</p><p><strong>Methods: </strong>In a phase 2, open-label, single-arm, multicenter study, 54 eligible participants from 19 U.S. centers were enrolled. Of these, 42 (78%) received transplantation with conditioning including antithymocyte globulin, fludarabine, cyclophosphamide, thiotepa, and total body irradiation. GVHD prophylaxis included posttransplant cyclophosphamide, mycophenolate mofetil, and sirolimus. The primary outcome was event-free survival at 2 years, while secondary outcomes included overall survival and other transplant-related end points.</p><p><strong>Results: </strong>The median age at enrollment was 22.8 years (range, 15.5 to 43.2), and the median follow-up period was 37.2 months (range, 20.4 to 56.4). The 2-year event-free and overall survival rates were 88.0% (95% confidence interval [CI], 73.5 to 94.8%) and 95.0% (95% CI, 81.5 to 98.7%), respectively. Two participants experienced primary and another secondary graft failure. The incidence of grade-3-to-4 acute GVHD at day 100 was 4.8% (95% CI, 0.9 to 14.4%), while the 2-year chronic GVHD rate was 22.4% (95% CI, 10.9 to 36.4%). Two of the four reported deaths were due to early infectious complications.</p><p><strong>Conclusions: </strong>HLA-haploidentical BMT is an accessible and potentially curative therapy for adults with sickle cell disease. Adverse events were those anticipated from this procedure, including GVHD. (Funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; BMT CTN 1507; ClinicalTrials.gov number, NCT03263559).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDoa2400192"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nirsevimab for Respiratory Syncytial Virus Prophylaxis in Newborns and Infants.","authors":"Bernhard Resch","doi":"10.1056/EVIDe2400440","DOIUrl":"https://doi.org/10.1056/EVIDe2400440","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDe2400440"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495046","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":"Nirsevimab Effectiveness at Preventing RSV-Related Hospitalization in Infants.","authors":"Marie Joelle Jabagi, Jérémie Cohen, Marion Bertrand, Martin Chalumeau, Mahmoud Zureik","doi":"10.1056/EVIDoa2400275","DOIUrl":"https://doi.org/10.1056/EVIDoa2400275","url":null,"abstract":"<p><strong>Background: </strong>In pivotal trials, nirsevimab showed promising efficacy in reducing hospitalizations for respiratory syncytial virus-associated lower respiratory tract infections (RSV-LRTIs). Nirsevimab's real-world effectiveness needs to be assessed.</p><p><strong>Methods: </strong>This population-based study used the French National Health Data System. All infants born between February 6 and September 15, 2023 were eligible. Each day during the study period (September 15, 2023, to January 31, 2024), all infants newly passively immunized with nirsevimab were matched to unimmunized controls in a 1:1 ratio according to sex, birth month, gestational age, department of residence, and the French Social Deprivation Index (Fdep). Study outcomes included RSV-LRTI-related hospitalization, RSV-LRTI necessitating admission to a pediatric intensive care unit (PICU) or high dependency unit (HDU), and RSV-LRTI requiring ventilation support or oxygen therapy. We estimated nirsevimab effectiveness using propensity score-weighted conditional Cox models.</p><p><strong>Results: </strong>The study included 82,474 infants (41,237 in each group) with a median follow-up of 118 days (interquartile range, 76 to 125). The population included predominantly male infants (52.5%) born at term (94.6%), mostly between April and July 2023 (64.0%), and from more advantaged municipalities (FDep first quintile: 29.8%). In total, 342 infants (0.8%) in the nirsevimab group and 992 (2.4%) in the unimmunized group were hospitalized for RSV-LRTI. Nirsevimab's effectiveness was 65% (95% confidence interval [CI], 61 to 69) for RSV-LRTI hospitalizations; 74% (95% CI, 56 to 85) for RSV-LRTI PICU admissions; 64% (95% CI, 55 to 71) for RSV-LRTI HDU admissions; 66% (95% CI, 51 to 76) for RSV-LRTI hospitalization requiring ventilation support; and 67% (95% CI, 57 to 75) for RSV-LRTI hospitalization requiring oxygen therapy. Subgroup and sensitivity analyses yielded consistent effectiveness estimates.</p><p><strong>Conclusions: </strong>This study in a nationwide monoclonal antibody infusion setting suggests that a single injection of nirsevimab was associated with substantial protection of infants against hospitalization for RSV-LRTI.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDoa2400275"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495034","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":"Cures for Sickle Cell Abound - How about Access?","authors":"Sanghee Hong, Mitchell E Horwitz","doi":"10.1056/EVIDe2400428","DOIUrl":"https://doi.org/10.1056/EVIDe2400428","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 3","pages":"EVIDe2400428"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495028","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}