{"title":"Pembrolizumab in Early-Stage Triple-Negative Breast Cancer.","authors":"Patrick Neven, Giuseppe Floris, Christine Desmedt","doi":"10.1056/NEJMc2416491","DOIUrl":"https://doi.org/10.1056/NEJMc2416491","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 11","pages":"1140-1141"},"PeriodicalIF":96.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617987","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}
Carol Devamani, Neal Alexander, Daniel Chandramohan, John Stenos, Mary Cameron, Kundavaram P P Abhilash, Punam Mangtani, Stuart Blacksell, Huong Thi Thu Vu, Winsley Rose, Wolf-Peter Schmidt
Background: Hospital studies suggest that scrub typhus is a leading cause of severe undifferentiated fever in regions across Asia where the disease is endemic, but the population-based incidence of infection and illness has been little studied.
Methods: We conducted a population-based cohort study to assess epidemiologic and clinical characteristics of scrub typhus in 37 villages in Tamil Nadu, India, where the disease is highly endemic. Study participants were visited every 6 to 8 weeks over a period of 2 years; a venous blood sample was obtained from those who had had fever since the last visit. A subcohort of participants underwent blood sampling to estimate the incidence of serologically confirmed Orientia tsutsugamushi infection.
Results: We systematically assessed 32,279 participants from 7619 households for acute febrile illness. During 54,588 person-years of follow-up, we observed 6175 episodes of fever. A blood sample was obtained in 4474 episodes (72.5%), of which 328 (7.3%) met the clinical case definition of scrub typhus (detection of IgM against O. tsutsugamushi on enzyme-linked immunosorbent assay [ELISA] or detection of O. tsutsugamushi on polymerase-chain-reaction assay). The incidence of clinical infection was 6.0 cases per 1000 person-years (95% confidence interval [CI], 4.8 to 7.5). A total of 71 clinical cases (21.6%) resulted in hospitalization (incidence, 1.3 events per 1000 person-years; 95% CI, 1.0 to 1.7). A total of 29 clinical cases (8.8%) were severe, as indicated by the presence of organ dysfunction or adverse pregnancy outcomes (incidence, 0.5 cases per 1000 person-years; 95% CI, 0.4 to 0.8). Among 2128 participants in the subcohort who provided samples at the beginning and end of a study year, the incidence of seroconversion independent of any symptoms was 81.2 events per 1000 person-years (95% CI, 70.8 to 91.6). The incidence of clinical infection was higher in older age groups than in younger age groups and higher among female participants than among male participants. By contrast, the age-adjusted rate of severe infection was similar among male and female participants. Among 5602 participants assessed at the start of the first year of the study, the seroprevalence of IgG as assessed with ELISA was 42.8% (95% CI, 35.8 to 50.2). IgG seropositivity at the beginning of years 1 or 2 did not protect against clinical illness during the subsequent year but was associated with less severe disease than IgG seronegativity.
Conclusions: We describe the burden of scrub typhus, including the incidence of asymptomatic infection, in a region of Asia where the disease is endemic. (Funded by the U.K. Medical Research Council; ClinicalTrials.gov number, NCT04506944.).
{"title":"Incidence of Scrub Typhus in Rural South India.","authors":"Carol Devamani, Neal Alexander, Daniel Chandramohan, John Stenos, Mary Cameron, Kundavaram P P Abhilash, Punam Mangtani, Stuart Blacksell, Huong Thi Thu Vu, Winsley Rose, Wolf-Peter Schmidt","doi":"10.1056/NEJMoa2408645","DOIUrl":"10.1056/NEJMoa2408645","url":null,"abstract":"<p><strong>Background: </strong>Hospital studies suggest that scrub typhus is a leading cause of severe undifferentiated fever in regions across Asia where the disease is endemic, but the population-based incidence of infection and illness has been little studied.</p><p><strong>Methods: </strong>We conducted a population-based cohort study to assess epidemiologic and clinical characteristics of scrub typhus in 37 villages in Tamil Nadu, India, where the disease is highly endemic. Study participants were visited every 6 to 8 weeks over a period of 2 years; a venous blood sample was obtained from those who had had fever since the last visit. A subcohort of participants underwent blood sampling to estimate the incidence of serologically confirmed <i>Orientia tsutsugamushi</i> infection.</p><p><strong>Results: </strong>We systematically assessed 32,279 participants from 7619 households for acute febrile illness. During 54,588 person-years of follow-up, we observed 6175 episodes of fever. A blood sample was obtained in 4474 episodes (72.5%), of which 328 (7.3%) met the clinical case definition of scrub typhus (detection of IgM against <i>O. tsutsugamushi</i> on enzyme-linked immunosorbent assay [ELISA] or detection of <i>O. tsutsugamushi</i> on polymerase-chain-reaction assay). The incidence of clinical infection was 6.0 cases per 1000 person-years (95% confidence interval [CI], 4.8 to 7.5). A total of 71 clinical cases (21.6%) resulted in hospitalization (incidence, 1.3 events per 1000 person-years; 95% CI, 1.0 to 1.7). A total of 29 clinical cases (8.8%) were severe, as indicated by the presence of organ dysfunction or adverse pregnancy outcomes (incidence, 0.5 cases per 1000 person-years; 95% CI, 0.4 to 0.8). Among 2128 participants in the subcohort who provided samples at the beginning and end of a study year, the incidence of seroconversion independent of any symptoms was 81.2 events per 1000 person-years (95% CI, 70.8 to 91.6). The incidence of clinical infection was higher in older age groups than in younger age groups and higher among female participants than among male participants. By contrast, the age-adjusted rate of severe infection was similar among male and female participants. Among 5602 participants assessed at the start of the first year of the study, the seroprevalence of IgG as assessed with ELISA was 42.8% (95% CI, 35.8 to 50.2). IgG seropositivity at the beginning of years 1 or 2 did not protect against clinical illness during the subsequent year but was associated with less severe disease than IgG seronegativity.</p><p><strong>Conclusions: </strong>We describe the burden of scrub typhus, including the incidence of asymptomatic infection, in a region of Asia where the disease is endemic. (Funded by the U.K. Medical Research Council; ClinicalTrials.gov number, NCT04506944.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 11","pages":"1089-1099"},"PeriodicalIF":96.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617925","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}
Ole-Petter Riksfjord Hamnvik, Anand Vaidya, Jenny Siegel, Michael S Irwig
{"title":"A Smooth Transition.","authors":"Ole-Petter Riksfjord Hamnvik, Anand Vaidya, Jenny Siegel, Michael S Irwig","doi":"10.1056/NEJMimc2404250","DOIUrl":"https://doi.org/10.1056/NEJMimc2404250","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 11","pages":"e30"},"PeriodicalIF":96.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617867","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":"Middle Meningeal Artery Embolization for Subdural Hematoma. Reply.","authors":"David Fiorella, Adam Arthur","doi":"10.1056/NEJMc2416123","DOIUrl":"https://doi.org/10.1056/NEJMc2416123","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 11","pages":"1144"},"PeriodicalIF":96.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617982","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":"Pembrolizumab in Early-Stage Triple-Negative Breast Cancer. Reply.","authors":"Peter Schmid, Xuan Zhou, Rebecca Dent","doi":"10.1056/NEJMc2416491","DOIUrl":"https://doi.org/10.1056/NEJMc2416491","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 11","pages":"1142"},"PeriodicalIF":96.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617992","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}
Pub Date : 2025-03-13Epub Date: 2025-03-08DOI: 10.1056/NEJMicm2414582
Jean Regina, Gérard Waeber
{"title":"Thin Skin in Cushing's Syndrome.","authors":"Jean Regina, Gérard Waeber","doi":"10.1056/NEJMicm2414582","DOIUrl":"10.1056/NEJMicm2414582","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"e28"},"PeriodicalIF":96.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588130","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":"Middle Meningeal Artery Embolization for Subdural Hematoma. Reply.","authors":"Ying Mao","doi":"10.1056/NEJMc2416123","DOIUrl":"10.1056/NEJMc2416123","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 11","pages":"1143-1144"},"PeriodicalIF":96.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617986","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":"Eight Days a Week - BALANCING Duration and Efficacy.","authors":"Vance G Fowler","doi":"10.1056/NEJMe2414037","DOIUrl":"https://doi.org/10.1056/NEJMe2414037","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 11","pages":"1136-1137"},"PeriodicalIF":96.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617915","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":"Pembrolizumab in Early-Stage Triple-Negative Breast Cancer.","authors":"Steven Sorscher","doi":"10.1056/NEJMc2416491","DOIUrl":"10.1056/NEJMc2416491","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 11","pages":"1141-1142"},"PeriodicalIF":96.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617990","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}
Pub Date : 2025-03-13Epub Date: 2024-12-09DOI: 10.1056/NEJMoa2410962
Shane W English, Anthony Delaney, Dean A Fergusson, Michaël Chassé, Alexis F Turgeon, François Lauzier, Angie Tuttle, Ofer Sadan, Donald E Griesdale, Gary Redekop, Martin Chapman, Mathew Hannouche, Andreas Kramer, Ian Seppelt, Andrew Udy, Demetrios J Kutsogiannis, Ryan Zarychanski, Frédérick D'Aragon, J Gordon Boyd, Gavin Salt, Judith Bellapart, Gordon Wood, Luis Cava, Gwynedd Pickett, Lauren Koffman, Irene Watpool, Frances Bass, Naomi Hammond, Tim Ramsay, Ranjeeta Mallick, Damon C Scales, Christopher R Andersen, Emily Fitzgerald, Phil Talbot, Dar Dowlatshahi, John Sinclair, Jason Acker, Shawn C Marshall, Lauralyn McIntyre
Background: The effect of a liberal red-cell transfusion strategy as compared with a restrictive strategy in patients during the critical care period after an aneurysmal subarachnoid hemorrhage is unclear.
Methods: We randomly assigned critically ill adults with acute aneurysmal subarachnoid hemorrhage and anemia to a liberal strategy (mandatory transfusion at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (optional transfusion at a hemoglobin level of ≤8 g per deciliter). The primary outcome was an unfavorable neurologic outcome, defined as a score of 4 or higher on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at 12 months. Secondary outcomes included 12-month functional independence as assessed with the Functional Independence Measure (FIM; scores range from 18 to 126) and quality of life as assessed with the EuroQol five-dimension, five-level (EQ-5D-5L) utility index (scores range from -0.1 to 0.95) and a visual analogue scale (VAS; scores range from 0 to 100); on each assessment, higher scores indicate better health status or quality of life.
Results: A total of 742 patients underwent randomization at 23 centers. The analysis of the primary outcome at 12 months included 725 patients (97.7%). An unfavorable neurologic outcome occurred in 122 of 364 patients (33.5%) in the liberal-strategy group and in 136 of 361 patients (37.7%) in the restrictive-strategy group (risk ratio, 0.88; 95% confidence interval [CI], 0.72 to 1.09; P = 0.22). The mean (±SD) FIM score was 82.8±54.6 in the liberal-strategy group and 79.8±54.5 in the restrictive-strategy group (mean difference, 3.01; 95% CI, -5.49 to 11.51). The mean EQ-5D-5L utility index score was 0.5±0.4 in both groups (mean difference, 0.02; 95% CI, -0.04 to 0.09). The mean VAS score was 52.1±37.5 in the liberal-strategy group and 50±37.1 in the restrictive-strategy group (mean difference, 2.08; 95% CI, -3.76 to 7.93). The incidence of adverse events was similar in the two groups.
Conclusions: In patients with aneurysmal subarachnoid hemorrhage and anemia, a liberal transfusion strategy did not result in a lower risk of an unfavorable neurologic outcome at 12 months than a restrictive strategy. (Funded by the Canadian Institutes of Health Research and others; SAHARA ClinicalTrials.gov number, NCT03309579.).
{"title":"Liberal or Restrictive Transfusion Strategy in Aneurysmal Subarachnoid Hemorrhage.","authors":"Shane W English, Anthony Delaney, Dean A Fergusson, Michaël Chassé, Alexis F Turgeon, François Lauzier, Angie Tuttle, Ofer Sadan, Donald E Griesdale, Gary Redekop, Martin Chapman, Mathew Hannouche, Andreas Kramer, Ian Seppelt, Andrew Udy, Demetrios J Kutsogiannis, Ryan Zarychanski, Frédérick D'Aragon, J Gordon Boyd, Gavin Salt, Judith Bellapart, Gordon Wood, Luis Cava, Gwynedd Pickett, Lauren Koffman, Irene Watpool, Frances Bass, Naomi Hammond, Tim Ramsay, Ranjeeta Mallick, Damon C Scales, Christopher R Andersen, Emily Fitzgerald, Phil Talbot, Dar Dowlatshahi, John Sinclair, Jason Acker, Shawn C Marshall, Lauralyn McIntyre","doi":"10.1056/NEJMoa2410962","DOIUrl":"10.1056/NEJMoa2410962","url":null,"abstract":"<p><strong>Background: </strong>The effect of a liberal red-cell transfusion strategy as compared with a restrictive strategy in patients during the critical care period after an aneurysmal subarachnoid hemorrhage is unclear.</p><p><strong>Methods: </strong>We randomly assigned critically ill adults with acute aneurysmal subarachnoid hemorrhage and anemia to a liberal strategy (mandatory transfusion at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (optional transfusion at a hemoglobin level of ≤8 g per deciliter). The primary outcome was an unfavorable neurologic outcome, defined as a score of 4 or higher on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at 12 months. Secondary outcomes included 12-month functional independence as assessed with the Functional Independence Measure (FIM; scores range from 18 to 126) and quality of life as assessed with the EuroQol five-dimension, five-level (EQ-5D-5L) utility index (scores range from -0.1 to 0.95) and a visual analogue scale (VAS; scores range from 0 to 100); on each assessment, higher scores indicate better health status or quality of life.</p><p><strong>Results: </strong>A total of 742 patients underwent randomization at 23 centers. The analysis of the primary outcome at 12 months included 725 patients (97.7%). An unfavorable neurologic outcome occurred in 122 of 364 patients (33.5%) in the liberal-strategy group and in 136 of 361 patients (37.7%) in the restrictive-strategy group (risk ratio, 0.88; 95% confidence interval [CI], 0.72 to 1.09; P = 0.22). The mean (±SD) FIM score was 82.8±54.6 in the liberal-strategy group and 79.8±54.5 in the restrictive-strategy group (mean difference, 3.01; 95% CI, -5.49 to 11.51). The mean EQ-5D-5L utility index score was 0.5±0.4 in both groups (mean difference, 0.02; 95% CI, -0.04 to 0.09). The mean VAS score was 52.1±37.5 in the liberal-strategy group and 50±37.1 in the restrictive-strategy group (mean difference, 2.08; 95% CI, -3.76 to 7.93). The incidence of adverse events was similar in the two groups.</p><p><strong>Conclusions: </strong>In patients with aneurysmal subarachnoid hemorrhage and anemia, a liberal transfusion strategy did not result in a lower risk of an unfavorable neurologic outcome at 12 months than a restrictive strategy. (Funded by the Canadian Institutes of Health Research and others; SAHARA ClinicalTrials.gov number, NCT03309579.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"1079-1088"},"PeriodicalIF":96.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803544","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}