NEJM evidence最新文献

{"title":"Safety and Efficacy of Senolytic UBX1325 in Diabetic Macular Edema.","authors":"Sharon Klier, Jamie Dananberg, Lauren Masaki, Robert B Bhisitkul, Arshad M Khanani, Raj Maturi, Hani Salehi-Had, Craig H Mallinckrodt, Joshua M Rathmell, Anirvan Ghosh, Przemyslaw Sapieha","doi":"10.1056/EVIDoa2400009","DOIUrl":"https://doi.org/10.1056/EVIDoa2400009","url":null,"abstract":"<p><strong>Background: </strong>We tested the ability of a single intravitreal injection of foselutoclax (hereafter UBX1325), a novel senolytic small molecule inhibitor of antiapoptotic protein B-cell lymphoma-extra large, to mitigate the impact of diabetic macular edema.</p><p><strong>Methods: </strong>Patients with diabetic macular edema with prior suboptimal response to anti-vascular endothelial growth factor treatment were randomly assigned (1:1) to either a single intravitreal injection of 10 μg of UBX1325 or sham and were followed for up to 48 weeks. The primary trial objective was to evaluate the safety and side-effect profile of UBX1325 as assessed by ocular and systemic treatment-emergent adverse events (TEAEs). Our secondary objective was to probe efficacy, defined as mean changes from baseline for UBX1325 versus sham in best corrected visual acuity measured in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters (range, 0-100 letters, higher scores indicate better vision) and retinal structure.</p><p><strong>Results: </strong>Between June 2021 and April 2022, 65 participants (32.3% women) were randomly assigned to either UBX1325 (n=32) or sham (n=33). There were four TEAEs of Grade 3 or greater in the sham group, of which three were considered serious, while there were five in the UBX1325 group of Grade 3 or greater and considered serious. There were no apparent between-group differences with respect to vital signs, electrocardiograms, or routine blood chemistries. For the secondary outcome of efficacy, the difference between UBX1325 and sham in mean change to week 48 in best corrected visual acuity was 5.6 more ETDRS letters (95% confidence interval, -1.5 to 12.7).</p><p><strong>Conclusions: </strong>In this sham-controlled trial there were no TEAEs that led to discontinuation of treatment with UBX1325 compared with sham. There were trends suggestive of potential efficacy; larger trials are needed to further evaluate these findings. (Funded by UNITY Biotechnology; ClinicalTrials.gov number, NCT04857996.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 5","pages":"EVIDoa2400009"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060513","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":"Induction versus Concurrent Chemotherapy for Advanced Nasopharyngeal Carcinoma.","authors":"Pei-Yu Huang, Xu-Yin Chen, Xi Ding, Ling Guo, Hao-Yuan Mo, Xiong Zou, Chong-Yang Duan, Li Ling, Rui You, Xin Yang, You-Ping Liu, Yu-Long Xie, Yi-Nuan Zhang, Jing-Yu Cao, Si-Han Liu, Zi-Meng Wang, Qi Yang, Chao Lin, Si-Yuan Chen, Yan-Feng Ouyang, Yong-Long Liu, Kai Wen, Xiao-Tong Duan, Rou Jiang, Rong-Zeng Liu, Tao Yu, Fang Qiu, Yi-Jun Hua, Ka-Jia Cao, Dong-Hua Luo, Ming-Yuan Chen","doi":"10.1056/EVIDoa2400214","DOIUrl":"https://doi.org/10.1056/EVIDoa2400214","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin-based concurrent chemoradiotherapy (CCRT) is the mainstay treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC), which usually leads to intolerable toxicities. We investigated whether or not induction chemotherapy (IC) plus intensity-modulated radiation therapy (IMRT) could replace CCRT.</p><p><strong>Methods: </strong>This is an open-label, phase 3, noninferiority trial. Patients with stage T1-4N2-3 or T3-4N0-1 LA-NPC were randomly assigned (1:1) to receive gemcitabine (1000 mg/m²) and cisplatin (80 mg/m²) for two cycles followed by IMRT, or IMRT plus concomitant weekly cisplatin (40 mg/m²) for up to seven cycles. Two-year failure-free survival (FFS) was the primary end point, and noninferiority was confirmed by an upper limit of the 95% confidence interval (CI) for a hazard ratio of less than 2.12 (absolute margin of -10 percentage points). Secondary end points include overall survival, locoregional recurrence-free survival, distant metastasis-free survival, toxicity profile, and quality of life (QoL).</p><p><strong>Results: </strong>We enrolled 124 patients in the IC group and 125 patients in the CCRT group. The median follow-up was 60 months. Two-year FFS was 90.2% for IC versus 86.3% for CCRT, with a hazard ratio of 0.636 (95% CI, 0.267 to 1.514) and an absolute difference of 3.9 percentage points (95% CI, -5.2 to 13.0). Compared with the CCRT group, fewer grade ≥3 adverse events occurred in the IC group (47.5% vs. 61.5%; P=0.029), including leukopenia, anemia, mucositis, nausea, and dysphagia. IC was associated with better QoL, including global health status, social and cognitive functioning, fatigue, nausea and vomiting, pain, appetite loss, and constipation.</p><p><strong>Conclusions: </strong>For 2-year FFS for LA-NPC, gemcitabine and cisplatin IC plus IMRT alone was noninferior to CCRT. (Funded by Key-Area Research and Development of Guangdong Province and others.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 5","pages":"EVIDoa2400214"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044003","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":"Tension-Free Vaginal Tape versus Polyacrylamide Hydrogel Injection for Stress Urinary Incontinence - 5-Year Follow-Up.","authors":"Anna-Maija Itkonen Freitas, Camilla Isaksson, Päivi Rahkola-Soisalo, Maarit Mentula, Tomi S Mikkola","doi":"10.1056/EVIDoa2400216","DOIUrl":"https://doi.org/10.1056/EVIDoa2400216","url":null,"abstract":"<p><strong>Background: </strong>Tension-free vaginal tape has been the gold standard of treatment for female stress urinary incontinence, but concerns have risen about the safety of mesh. Transurethral injection of polyacrylamide hydrogel (PAHG) is a minimally invasive alternative. However, the long-term safety, efficacy, and patient satisfaction of PAHG is undefined.</p><p><strong>Methods: </strong>We conducted a randomized, controlled, noninferiority (margin 20%) trial at Helsinki University Hospital, Finland, comparing tension-free vaginal tape with PAHG treatment. The primary outcome was patient satisfaction. Secondary outcomes were effectiveness and complications. The results at 1 and 3 years have been previously reported. Herein, we report the 5-year follow-up.</p><p><strong>Results: </strong>Of the 223 women originally randomly assigned to a treatment group, 212 women underwent treatment as randomly assigned and, at 5 years, 195 (92.0%) women attended the follow-up. The median satisfaction score (visual analog scale: range, 0 to 100; higher scores indicated higher satisfaction) was 98 (interquartile range, 86 to 100) in the tension-free vaginal tape group, and 90 (interquartile range, 75 to 99) in the PAHG group, whereas a score of 80 or more was reached in 89 (92.7%) and 74 (74.7%) participants (difference, 18.0 percentage points; 95% confidence interval [CI], 7.7 to 28.0), respectively. Thus, PAHG did not meet the noninferiority criteria set in our trial. Within the 5-year follow-up, a peri- or postoperative complication before crossover between the groups was detected in 42 (43.8%) women in the tension-free vaginal tape group and 22 (22.2%) women in the PAHG group (difference, 21.5 percentage points; 95% CI, 8.4 to 33.8).</p><p><strong>Conclusions: </strong>In long-term follow-up, treatment of stress urinary incontinence with PAHG was not noninferior to treatment with tension-free vaginal tape with respect to patient satisfaction scores. Complications were twice as common in the tension-free vaginal tape group. (Funded by Helsinki University Hospital and Contura; ClinicalTrials.gov number, NCT02538991.).</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 5","pages":"EVIDoa2400216"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038078","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 7-Year-Old Boy with Prolonged Fever.","authors":"Zoe King, Brenda I Anosike, Rachel Offenbacher, Kaitlin Strumph","doi":"10.1056/EVIDmr2400330","DOIUrl":"https://doi.org/10.1056/EVIDmr2400330","url":null,"abstract":"<p><p>AbstractMorning Report is a time-honored tradition in which physicians-in-training present cases to their colleagues and clinical experts to collaboratively explore a patient's presentation. The Morning Report section continues this tradition by presenting a patient's chief concern and clinical course, inviting readers to develop a differential diagnosis and uncover the final diagnosis alongside the authors. This report details the story of a previously healthy 7-year-old boy who presented with 10 days of fever after travel to Bangladesh. Through targeted history, physical examination, and diagnostic testing, an illness script is developed. As the case progresses, the differential diagnosis is refined until a final diagnosis is established.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 5","pages":"EVIDmr2400330"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058728","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":"Margin Call - On the Selection of the Noninferiority Margin in Noninferiority Clinical Trials.","authors":"Juned Siddique, Shirlene D Wang","doi":"10.1056/EVIDe2500068","DOIUrl":"10.1056/EVIDe2500068","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 5","pages":"EVIDe2500068"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060151","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":"Natural Experiments to Inform Clinical Practice.","authors":"Atheendar S Venkataramani, Elizabeth F Bair","doi":"10.1056/EVIDra2400268","DOIUrl":"https://doi.org/10.1056/EVIDra2400268","url":null,"abstract":"<p><p>AbstractNatural experiments refer to events or practices that result in similar individuals receiving different services or interventions for arbitrary reasons. In the clinical context, researchers may wish to leverage natural experiments to estimate the causal impact of a particular treatment on a health outcome in situations where randomized clinical trial data are unavailable and other observational research designs are likely to yield biased results. This review provides an overview of natural experiments, discusses the potential for natural experiments to establish cause and effect, illustrates applications to specific clinical questions, and outlines situations and practices where natural experiments are most likely to answer the question at hand. Overall, while natural experiments have become popular in health policy, the widespread application of these approaches to specific clinical questions faces several challenges.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 5","pages":"EVIDra2400268"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030782","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":"Foselutoclax (UBX1325) for Diabetic Macular Edema - A Potential Novel Therapy?","authors":"Emily Y Chew","doi":"10.1056/EVIDe2500004","DOIUrl":"https://doi.org/10.1056/EVIDe2500004","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 5","pages":"EVIDe2500004"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999870","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/EVIDcx2500084","DOIUrl":"10.1056/EVIDcx2500084","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":" ","pages":"EVIDcx2500084"},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805058","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":"Cervical Radiculopathy and the Role of Surgery - \"First, Do No Harm\".","authors":"Jerome Paquet","doi":"10.1056/EVIDe2500008","DOIUrl":"https://doi.org/10.1056/EVIDe2500008","url":null,"abstract":"","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 4","pages":"EVIDe2500008"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702271","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":"Associations between Class I, II, or III Obesity and Health Outcomes.","authors":"Zhiqi Yao, Beverly G Tchang, Michael Albert, Roger S Blumenthal, Khurram Nasir, Michael J Blaha","doi":"10.1056/EVIDoa2400229","DOIUrl":"10.1056/EVIDoa2400229","url":null,"abstract":"<p><strong>Background: </strong>The burden of obesity-related health conditions remains incompletely explored. Previous studies have been underpowered to study severe obesity, focused on a limited set of health outcomes, and lacked diversity in study populations.</p><p><strong>Methods: </strong>We studied 270,657 participants from the All of Us research program with linked electronic health records and body mass index (the weight in kilograms divided by the square of the height in meters) greater than or equal to 18.5. We investigated the prevalence and incidence of 16 a priori-identified outcomes covering cardiovascular-kidney-metabolic syndrome and others: hypertension, type 2 diabetes mellitus, hyperlipidemia/dyslipidemia, heart failure, atrial fibrillation, atherosclerotic cardiovascular disease, chronic kidney disease, pulmonary embolism, deep vein thrombosis, gout, metabolic dysfunction-associated steatotic liver disease, biliary calculus, obstructive sleep apnea, asthma, gastroesophageal reflux disease, and osteoarthritis. Adjusted hazard ratios were calculated for each BMI category and compared with normal weight. The population-attributable fraction was calculated for different obesity classifications.</p><p><strong>Results: </strong>The included population was 62.0% women and 22.0% Black. Class I, II, and III obesity was observed in 21.2%, 11.3%, and 9.8% of participants, respectively. Obesity was strongly associated with all incident outcomes, with graded associations across higher classes of obesity. Class III obesity was most strongly associated with obstructive sleep apnea, type 2 diabetes mellitus, and metabolic dysfunction-associated steatotic liver disease (hazard ratio [95% confidence interval {CI}], 10.94 [9.97 to 12.00], 7.74 [7.03 to 8.53], and 6.72 [6.01 to 7.50], respectively), with weaker associations for asthma, osteoarthritis, and atherosclerotic cardiovascular disease (hazard ratio [95% CI], 2.14 [1.95 to 2.35], 2.06 [1.94 to 2.19], and 1.96 [1.70 to 2.25], respectively). Associations were consistent across sex and race. The obesity-related population-attributed fraction ranged from 14.0% (osteoarthritis) to 51.5% (obstructive sleep apnea) in this population.</p><p><strong>Conclusions: </strong>Obesity, particularly severe obesity, was strongly associated with the incidence of 16 common health outcomes.</p>","PeriodicalId":74256,"journal":{"name":"NEJM evidence","volume":"4 4","pages":"EVIDoa2400229"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702287","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}