New England Journal of Medicine最新文献

{"title":"Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors.","authors":"Jennifer A Chan, Susan Geyer, Tyler Zemla, Michael V Knopp, Spencer Behr, Sydney Pulsipher, Fang-Shu Ou, Amylou C Dueck, Jared Acoba, Ardaman Shergill, Edward M Wolin, Thorvardur R Halfdanarson, Bhavana Konda, Nikolaos A Trikalinos, Bernard Tawfik, Nitya Raj, Shagufta Shaheen, Namrata Vijayvergia, Arvind Dasari, Jonathan R Strosberg, Elise C Kohn, Matthew H Kulke, Eileen M O'Reilly, Jeffrey A Meyerhardt","doi":"10.1056/NEJMoa2403991","DOIUrl":"10.1056/NEJMoa2403991","url":null,"abstract":"<p><strong>Background: </strong>Treatment options for patients with advanced neuroendocrine tumors are limited. The efficacy of cabozantinib in the treatment of previously treated, progressive extrapancreatic or pancreatic neuroendocrine tumors is unclear.</p><p><strong>Methods: </strong>We enrolled two independent cohorts of patients - those with extrapancreatic neuroendocrine tumors and those with pancreatic neuroendocrine tumors - who had received peptide receptor radionuclide therapy or targeted therapy or both. Patients were randomly assigned in a 2:1 ratio to receive cabozantinib at a dose of 60 mg daily or placebo. The primary end point was progression-free survival as assessed by blinded independent central review. Key secondary end points included objective response, overall survival, and safety.</p><p><strong>Results: </strong>In the cohort of 203 patients with extrapancreatic neuroendocrine tumors, the median progression-free survival with cabozantinib was 8.4 months, as compared with 3.9 months with placebo (stratified hazard ratio for progression or death, 0.38; 95% confidence interval [CI], 0.25 to 0.59; P<0.001). In the cohort of 95 patients with pancreatic neuroendocrine tumors, the median progression-free survival with cabozantinib was 13.8 months, as compared with 4.4 months with placebo (stratified hazard ratio, 0.23; 95% CI, 0.12 to 0.42; P<0.001). The incidence of confirmed objective response with cabozantinib was 5% and 19% among patients with extrapancreatic and pancreatic neuroendocrine tumors, respectively, as compared with 0% with placebo. Grade 3 or higher adverse events were noted in 62 to 65% of the patients treated with cabozantinib, as compared with 23 to 27% of the patients who received placebo. Common treatment-related adverse events of grade 3 or higher included hypertension, fatigue, diarrhea, and thromboembolic events.</p><p><strong>Conclusions: </strong>Cabozantinib, as compared with placebo, significantly improved progression-free survival in patients with previously treated, progressive advanced extrapancreatic or pancreatic neuroendocrine tumors. Adverse events were consistent with the known safety profile of cabozantinib. (Funded by the National Cancer Institute and others; CABINET ClinicalTrials.gov number, NCT03375320.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"653-665"},"PeriodicalIF":96.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142301193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colchicine in Acute Myocardial Infarction.","authors":"Sanjit S Jolly, Marc-André d'Entremont, Shun Fu Lee, Rajibul Mian, Jessica Tyrwhitt, Sasko Kedev, Gilles Montalescot, Jan H Cornel, Goran Stanković, Raul Moreno, Robert F Storey, Timothy D Henry, Shamir R Mehta, Matthias Bossard, Petr Kala, Jamie Layland, Biljana Zafirovska, P J Devereaux, John Eikelboom, John A Cairns, Binita Shah, Tej Sheth, Sanjib K Sharma, Wadea Tarhuni, David Conen, Sarah Tawadros, Shahar Lavi, Salim Yusuf","doi":"10.1056/NEJMoa2405922","DOIUrl":"10.1056/NEJMoa2405922","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is associated with adverse cardiovascular events. Data from recent trials suggest that colchicine reduces the risk of cardiovascular events.</p><p><strong>Methods: </strong>In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients who had myocardial infarction to receive either colchicine or placebo and either spironolactone or placebo. The results of the colchicine trial are reported here. The primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization, evaluated in a time-to-event analysis. C-reactive protein was measured at 3 months in a subgroup of patients, and safety was also assessed.</p><p><strong>Results: </strong>A total of 7062 patients at 104 centers in 14 countries underwent randomization; at the time of analysis, the vital status was unknown for 45 patients (0.6%), and this information was most likely missing at random. A primary-outcome event occurred in 322 of 3528 patients (9.1%) in the colchicine group and 327 of 3534 patients (9.3%) in the placebo group over a median follow-up period of 3 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.16; P = 0.93). The incidence of individual components of the primary outcome appeared to be similar in the two groups. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at 3 months, adjusted according to the baseline values, was -1.28 mg per liter (95% CI, -1.81 to -0.75). Diarrhea occurred in a higher percentage of patients with colchicine than with placebo (10.2% vs. 6.6%; P<0.001), but the incidence of serious infections did not differ between groups.</p><p><strong>Conclusions: </strong>Among patients who had myocardial infarction, treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization). (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"633-642"},"PeriodicalIF":96.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving Epidemiology of Mpox in Africa in 2024.","authors":"Nicaise Ndembi, Morenike O Folayan, Allan Komakech, Kyeng Mercy, Sofonias Tessema, Placide Mbala-Kingebeni, Christian Ngandu, Ngashi Ngongo, Jean Kaseya, Salim S Abdool Karim","doi":"10.1056/NEJMoa2411368","DOIUrl":"10.1056/NEJMoa2411368","url":null,"abstract":"<p><strong>Background: </strong>For decades after the identification of mpox in humans in the Democratic Republic of Congo (DRC) in 1970, the disease was largely confined to the rural areas of Central and West Africa and thus did not garner broad attention. On August 13, 2024, mpox was declared a Public Health Emergency of Continental Security (PHECS) by the Africa Centers for Disease Control and Prevention (Africa CDC), a notice that was followed the next day by a declaration of a Public Health Emergency of International Concern (PHEIC) by the World Health Organization.</p><p><strong>Methods: </strong>In this study we analyzed all mpox cases and deaths, based on clinical or laboratory diagnosis, that were reported to the Africa CDC from January 1, 2022, to October 30, 2024, to identify temporal variations, geographic distributions, and epidemiologic trends.</p><p><strong>Results: </strong>From January 1, 2022, to August 18, 2024, a total of 45,652 mpox cases were clinically diagnosed and laboratory-confirmed in 12 African countries. These cases resulted in 1492 deaths (case fatality rate, 3.3%). From 2022 to 2024, weekly laboratory-confirmed mpox cases increased by a factor of 2.8 (from 176 to 489 cases), whereas all weekly reported cases (including those with a clinical diagnosis) increased by a factor of 4.3 (from 669 to 2900 cases). The DRC, which had reported approximately 88% of mpox cases in Africa in 2024, had 19,513 cases before the emergency declaration, with a case fatality rate of 3.1% - a weekly average of 591 cases as compared with 281 in 2023. In 2024, six African countries reported their first imported mpox infections, with Burundi also reporting local transmission.</p><p><strong>Conclusions: </strong>The high mpox disease burden in Africa, especially in the DRC - with a rising number of cases, high case fatality rate, and high degree of spread to other previously mpox-free African countries - is cause for increased international concern. Case detection, contact tracing, public health measures, and affordable vaccines are needed to implement interventions in the DRC to reduce the risk of global spread of the virus.</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"666-676"},"PeriodicalIF":96.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated <i>KRAS</i> G12C.","authors":"","doi":"10.1056/NEJMx240006","DOIUrl":"https://doi.org/10.1056/NEJMx240006","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 7","pages":"728"},"PeriodicalIF":96.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation.","authors":"Kazuo Komamura, Toyoaki Murohara, Mitsunori Iwase","doi":"10.1056/NEJMc2416116","DOIUrl":"https://doi.org/10.1056/NEJMc2416116","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 7","pages":"724"},"PeriodicalIF":96.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Consequences of Silencing the \"Voice of CDC\".","authors":"Sonja A Rasmussen, Mary Lou Lindegren, Lawrence K Altman, Michael F Iademarco","doi":"10.1056/NEJMp2501622","DOIUrl":"https://doi.org/10.1056/NEJMp2501622","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Answering the Call - Sustaining Equity Efforts in the Face of Regression.","authors":"Samantha X Y Wang, Kevin Chi","doi":"10.1056/NEJMp2501471","DOIUrl":"https://doi.org/10.1056/NEJMp2501471","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VITT-like Monoclonal Gammopathy of Thrombotic Significance.","authors":"Jing Jing Wang, Theodore E Warkentin, Linda Schönborn, Matthew B Wheeler, William H Geerts, Nathalie Costedoat-Chalumeau, Nicolas Gendron, Gabriela Ene, Miquel Lozano, Florian Langer, Edelgard Lindhoff-Last, Kathrin Budde, Tim Chataway, Alexander Troelnikov, Jo-Ann I Sheppard, Yi Zhang, Donald M Arnold, Tom P Gordon, Thomas Thiele, Andreas Greinacher, Ishac Nazy","doi":"10.1056/NEJMoa2415930","DOIUrl":"https://doi.org/10.1056/NEJMoa2415930","url":null,"abstract":"<p><p>Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is associated with antibodies that target platelet factor 4 (PF4) and are heparin-independent. VITT antibodies are implicated in acute, transient prothrombotic disorders that are triggered by adenoviral vector vaccines against coronavirus disease 2019 or by adenovirus infection. We describe chronic prothrombotic disorders featuring anticoagulant-refractory thromboses and intermittent thrombocytopenia that were associated with VITT-like antibodies in five patients (four patients with newly reported cases and the index patient). The patients had low levels of M proteins (median level, 0.14 g per deciliter); in each patient, we found that the M protein was the VITT-like antibody. The antibody clonotype profiles and binding epitopes on PF4 were different from those observed with the acute disorders occurring after vaccination or viral infection, features that reflect distinct immunopathogenesis. Treatment strategies besides anticoagulation alone are needed for the chronic disorders, referred to as VITT-like monoclonal gammopathy of thrombotic significance. (Funded by the Canadian Institutes of Health Research and others.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Transgender Health amid Rising Policy Threats.","authors":"David R A Coelho, Alexander L Chen, Alex S Keuroghlian","doi":"10.1056/NEJMp2416382","DOIUrl":"https://doi.org/10.1056/NEJMp2416382","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulse Oximetry and Skin Tone in Children.","authors":"Joseph R Starnes, Wendi Welch, Christopher C Henderson, Stephen Hudson, Scott Risney, George T Nicholson, Thomas P Doyle, Dana R Janssen, Bevan P Londergan, David A Parra, James C Slaughter, Muktar H Aliyu, John A Graves, Jonathan H Soslow","doi":"10.1056/NEJMc2414937","DOIUrl":"https://doi.org/10.1056/NEJMc2414937","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}