The Lancet最新文献

{"title":"Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial","authors":"Thierry André, Elena Elez, Heinz-Josef Lenz, Lars Henrik Jensen, Yann Touchefeu, Eric Van Cutsem, Rocio Garcia-Carbonero, David Tougeron, Guillermo Ariel Mendez, Michael Schenker, Christelle de la Fouchardiere, Maria Luisa Limon, Takayuki Yoshino, Jin Li, Jose Luis Manzano Mozo, Laetitia Dahan, Giampaolo Tortora, Myriam Chalabi, Eray Goekkurt, Maria Ignez Braghiroli, Sara Lonardi","doi":"10.1016/s0140-6736(24)02848-4","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02848-4","url":null,"abstract":"<h3>Background</h3>CheckMate 8HW prespecified dual primary endpoints, assessed in patients with centrally confirmed microsatellite instability-high or mismatch repair-deficient status: progression-free survival with nivolumab plus ipilimumab compared with chemotherapy as first-line therapy and progression-free survival with nivolumab plus ipilimumab compared with nivolumab alone, regardless of previous systemic treatment for metastatic disease. In our previous report, nivolumab plus ipilimumab showed superior progression-free survival versus chemotherapy in first-line microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer in the CheckMate 8HW trial. Here, we report results from the prespecified interim analysis for the other primary endpoint of progression-free survival for nivolumab plus ipilimumab versus nivolumab across all treatment lines.<h3>Methods</h3>CheckMate 8HW is a randomised, open-label, international, phase 3 trial at 128 hospitals and cancer centres across 23 countries. Immunotherapy-naive adults with unresectable or metastatic colorectal cancer across different lines of therapy and microsatellite instability-high or mismatch repair-deficient status per local testing were randomly assigned (2:2:1) to nivolumab plus ipilimumab (nivolumab 240 mg, ipilimumab 1 mg/kg, every 3 weeks for four doses; then nivolumab 480 mg every 4 weeks; all intravenously), nivolumab (240 mg every 2 weeks for six doses, then 480 mg every 4 weeks; all intravenously), or chemotherapy with or without targeted therapies. The dual independent primary endpoints were progression-free survival by blinded independent central review with nivolumab plus ipilimumab versus chemotherapy (first line) and progression-free survival by blinded independent central review with nivolumab plus ipilimumab versus nivolumab (all lines) in patients with centrally confirmed microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT04008030</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>).<h3>Findings</h3>Between Aug 16, 2019, and April 10, 2023, 707 patients were randomly assigned to nivolumab plus ipilimumab (n=354) or nivolumab alone (n=353). 296 (84%) of 354 patients in the nivolumab plus ipilimumab group and 286 (81%) of 353 patients in the nivolumab group were centrally confirmed to have microsatellite instability-high or mismatch repair-deficient status. At the data cutoff on Aug 28, 2024, median follow-up (from randomisation to data cutoff) was 47·0 months (IQR 38·","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034974","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":"Wildfires and health: building resilience in Los Angeles’ climate crisis","authors":"Ying-Ying Goh, Y Tony Yang","doi":"10.1016/s0140-6736(25)00129-1","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00129-1","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030806","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":"The R21/Matrix-M malaria vaccine: questions remain","authors":"Yue Li, Guangsen Liu","doi":"10.1016/s0140-6736(24)02777-6","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02777-6","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026326","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":"Trump's anticipated UNFPA defunding will harm millions","authors":"Udani Samarasekera","doi":"10.1016/s0140-6736(25)00134-5","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00134-5","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026692","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":"Taking the temperature of humankind | David N Livingstone, The Empire of Climate: A History of An Idea, Princeton University Press (2024), p. 552, US$38·00, £32·00, ISBN: 9780691236704","authors":"Philip Ball","doi":"10.1016/s0140-6736(25)00102-3","DOIUrl":"https://doi.org/10.1016/s0140-6736(25)00102-3","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026696","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":"Coronary CT angiography-guided management of patients with stable chest pain: 10-year outcomes from the SCOT-HEART randomised controlled trial in Scotland","authors":"Michelle C Williams, Ryan Wereski, Christopher Tuck, Philip D Adamson, Anoop S V Shah, Edwin J R van Beek, Giles Roditi, Colin Berry, Nicholas Boon, Marcus Flather, Steff Lewis, John Norrie, Adam D Timmis, Nicholas L Mills, Marc R Dweck, David E Newby","doi":"10.1016/s0140-6736(24)02679-5","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02679-5","url":null,"abstract":"<h3>Background</h3>The Scottish Computed Tomography of the Heart (SCOT-HEART) trial demonstrated that management guided by coronary CT angiography (CCTA) improved the diagnosis, management, and outcome of patients with stable chest pain. We aimed to assess whether CCTA-guided care results in sustained long-term improvements in management and outcomes.<h3>Methods</h3>SCOT-HEART was an open-label, multicentre, parallel group trial for which patients were recruited from 12 outpatient cardiology chest pain clinics across Scotland. Eligible patients were aged 18–75 years with symptoms of suspected stable angina due to coronary heart disease. Patients were randomly assigned (1:1) to standard of care plus CCTA or standard of care alone. In this prespecified 10-year analysis, prescribing data, coronary procedural interventions, and clinical outcomes were obtained through record linkage from national registries. The primary outcome was coronary heart disease death or non-fatal myocardial infarction on an intention-to-treat basis. This trial is registered at <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT01149590</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>) and is complete.<h3>Findings</h3>Between Nov 18, 2010, and Sept 24, 2014, 4146 patients were recruited (mean age 57 years [SD 10], 2325 [56·1%] male, 1821 [43·9%] female), with 2073 randomly assigned to standard care and CCTA and 2073 to standard care alone. After a median of 10·0 years (IQR 9·3–11·0), coronary heart disease death or non-fatal myocardial infarction was less frequent in the CCTA group compared with the standard care group (137 [6·6%] <em>vs</em> 171 [8·2%]; hazard ratio [HR] 0·79 [95% CI 0·63–0·99], p=0·044). Rates of all-cause, cardiovascular, and coronary heart disease death, and non-fatal stroke, were similar between the groups (p>0·05 for all), but non-fatal myocardial infarctions (90 [4·3%] <em>vs</em> 124 [6·0%]; HR 0·72 [0·55–0·94], p=0·017) and major adverse cardiovascular events (172 [8·3%] <em>vs</em> 214 [10·3%]; HR 0·80 [0·65–0·97], p=0·026) were less frequent in the CCTA group. Rates of coronary revascularisation procedures were similar (315 [15·2%] <em>vs</em> 318 [15·3%]; HR 1·00 [0·86–1·17], p=0·99) but preventive therapy prescribing remained more frequent in the CCTA group (831 [55·9%] of 1486 <em>vs</em> 728 [49·0%] of 1485 patients with available data; odds ratio 1·17 [95% CI 1·01–1·36], p=0·034).<h3>Interpretation</h3>After 10 years, CCTA-guided management of patients with stable chest pain was associated with a sustained reduction in coronary heart disease death or non-fatal myocardial infar","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026754","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":"Polio in Sudan and other conflict zones: a call for urgent support","authors":"Yousif Ali, Emmanuel Edwar Siddig, Ayman Ahmed","doi":"10.1016/s0140-6736(24)02793-4","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02793-4","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"96 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026322","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":"The R21/Matrix-M malaria vaccine: questions remain","authors":"Peter Aaby, Anders Björkman, Allan Schapira, Christine Stabell Benn","doi":"10.1016/s0140-6736(24)02779-x","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02779-x","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026328","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":"Undervaccination and severe COVID-19 outcomes – Authors' reply","authors":"Steven Kerr, Chris Robertson, Aziz Sheikh","doi":"10.1016/s0140-6736(24)02866-6","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02866-6","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026339","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":"Impact of SARS-CoV-2 spike antibody positivity on infection and hospitalisation rates in immunosuppressed populations during the omicron period: the MELODY study","authors":"Lisa Mumford, Rachel Hogg, Adam Taylor, Peter Lanyon, Mary Bythell, Sean McPhail, Joseph Chilcot, Gillian Powter, Graham S Cooke, Helen Ward, Helen Thomas, Stephen P McAdoo, Liz Lightstone, Sean H Lim, Gavin J Pettigrew, Fiona A Pearce, Michelle Willicombe","doi":"10.1016/s0140-6736(24)02560-1","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02560-1","url":null,"abstract":"<h3>Background</h3>In the UK, booster COVID-19 vaccinations have been recommended biannually to people considered immune vulnerable. We investigated, at a population level, whether the absence of detectable anti-SARS-CoV-2 spike protein IgG antibody (anti-S Ab) following three or more vaccinations in immunosuppressed individuals was associated with greater risks of infection and severity of infection.<h3>Methods</h3>In this prospective cohort study using UK national disease registers, we recruited participants with solid organ transplants (SOTs), rare autoimmune rheumatic diseases (RAIRDs), and lymphoid malignancies. All participants were tested for anti-S Ab using a lateral flow immunoassay, completed a questionnaire on sociodemographic and clinical characteristics, and were followed up for 6 months using linked data from the National Health Service in England. SARS-CoV-2 infection was primarily defined using UK Health Security Agency data and supplemented with hospitalisation and therapeutics data, and hospitalisation due to SARS-CoV-2 was defined as an admission within 14 days of a positive test.<h3>Findings</h3>Between Dec 7, 2021, and June 26, 2022, we recruited 21 575 participants. Anti-S Ab was detected in 6519 (77·0%) of 8466 participants with SOTs, 5594 (85·9%) of 6516 with RAIRDs, and 5227 (79·3%) of 6593 with lymphoid malignancies. COVID-19 infection was recorded in 3907 (18·5%) participants, with 556 requiring a COVID-19-related hospital admission and 17 dying within 28 days of infection. Rates of infection varied by sociodemographic and clinical characteristics but, in adjusted analysis, having detectable anti-S Ab was independently associated with a reduced incidence of infection, with incident rate ratios (IRRs) of 0·69 (95% CI 0·65–0·73) in the SOT cohort, 0·57 (0·49–0·67) in the RAIRD cohort, and 0·62 (0·54–0·71) in the lymphoid malignancy cohort. In adjusted analysis, having detectable anti-S Ab was also associated with a reduced incidence of hospitalisation, with IRRs of 0·40 (0·35–0·46) in the SOT cohort, 0·32 (0·22–0·46) in the RAIRD cohort, and 0·41 (0·29–0·58) in the lymphoid malignancy cohort.<h3>Interpretation</h3>All people with immunosuppression require ongoing access to COVID-19 protection strategies. Assessment of anti-S Ab responses, which can be performed at scale, can identify people with immunosuppression who remain most at risk, providing a mechanism to further individualise protection approaches.<h3>Funding</h3>UK Research and Innovation, Kidney Research UK, Blood Cancer UK, Vasculitis UK, and Cystic Fibrosis Trust.","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026749","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}