David B. Antcliffe, Estelle Peronnet, Frédéric Pène, Kristoffer Strålin, David Brealey, Sophie Blein, Richard Cleaver, Maria Cronhjort, Jean-Luc Diehl, Guillaume Voiriot, Aurore Fleurie, Claudia Lannsjö, Anne-Claire Lukaszewicz, Johan Mårtensson, Tài Pham, Nicolas De Prost, Jean-Damien Ricard, Mervyn Singer, Gabriel Terraz, Jean-François Timsit, Christian Unge, Antoine Vieillard-Baron, Rebecka Rubenson Wahlin, Jean-François Llitjos, Anthony C. Gordon
{"title":"An international observational study validating gene-expression sepsis immune subgroups","authors":"David B. Antcliffe, Estelle Peronnet, Frédéric Pène, Kristoffer Strålin, David Brealey, Sophie Blein, Richard Cleaver, Maria Cronhjort, Jean-Luc Diehl, Guillaume Voiriot, Aurore Fleurie, Claudia Lannsjö, Anne-Claire Lukaszewicz, Johan Mårtensson, Tài Pham, Nicolas De Prost, Jean-Damien Ricard, Mervyn Singer, Gabriel Terraz, Jean-François Timsit, Christian Unge, Antoine Vieillard-Baron, Rebecka Rubenson Wahlin, Jean-François Llitjos, Anthony C. Gordon","doi":"10.1186/s13054-025-05319-5","DOIUrl":null,"url":null,"abstract":"Sepsis gene-expression sub-phenotypes with prognostic and theranostic potential have been discovered. These have been identified retrospectively and have not been translated to methods that could be deployed at the bedside. We aimed to identify subgroups of septic patients at high-risk of poor outcome, using a rapid, multiplex RNA-based test. Adults with sepsis, in the intensive care unit (ICU) were recruited from 17 sites in the United Kingdom, Sweden and France. Blood was collected at days 2–5 (S1), 6–8 (S2) and 13–15 (S3) after ICU admission and analyzed centrally. Patients were assigned into ‘high’ and ‘low’ risk groups using two models previously developed for the Immune-Profiling Panel prototype on the bioMérieux FilmArray® system. 357 patients were recruited (March 2021–November 2022). 69% were male with a median age of 67 years, APACHE II score of 21 and a 30% 90-day mortality rate. The proportions of high-risk patients decreased over the three sampling times (model 1: 53%, 40%, 15% and model 2: 81%, 74%, 37%). In model 1, 90-day mortality was higher in a high-risk group at each time (S1: 35% vs 24%, p = 0.04; S2: 43% vs 20%, p < 0.001; S3: 52% vs 24%, p = 0.007). In model 2, mortality was only significantly different at the second sampling time (S1: 30% vs 27%, p = 0.77; S2: 34% vs 14%, p = 0.002; S3: 35% vs 23%, p = 0.13). Gene-expression diagnostics can identify patients with sepsis at high-risk of poor outcomes and could be used to identify patients for precision medicine trials. ISRCTN11364482 Registered 24th September 2020.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"26 1","pages":""},"PeriodicalIF":8.8000,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Care","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13054-025-05319-5","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
Sepsis gene-expression sub-phenotypes with prognostic and theranostic potential have been discovered. These have been identified retrospectively and have not been translated to methods that could be deployed at the bedside. We aimed to identify subgroups of septic patients at high-risk of poor outcome, using a rapid, multiplex RNA-based test. Adults with sepsis, in the intensive care unit (ICU) were recruited from 17 sites in the United Kingdom, Sweden and France. Blood was collected at days 2–5 (S1), 6–8 (S2) and 13–15 (S3) after ICU admission and analyzed centrally. Patients were assigned into ‘high’ and ‘low’ risk groups using two models previously developed for the Immune-Profiling Panel prototype on the bioMérieux FilmArray® system. 357 patients were recruited (March 2021–November 2022). 69% were male with a median age of 67 years, APACHE II score of 21 and a 30% 90-day mortality rate. The proportions of high-risk patients decreased over the three sampling times (model 1: 53%, 40%, 15% and model 2: 81%, 74%, 37%). In model 1, 90-day mortality was higher in a high-risk group at each time (S1: 35% vs 24%, p = 0.04; S2: 43% vs 20%, p < 0.001; S3: 52% vs 24%, p = 0.007). In model 2, mortality was only significantly different at the second sampling time (S1: 30% vs 27%, p = 0.77; S2: 34% vs 14%, p = 0.002; S3: 35% vs 23%, p = 0.13). Gene-expression diagnostics can identify patients with sepsis at high-risk of poor outcomes and could be used to identify patients for precision medicine trials. ISRCTN11364482 Registered 24th September 2020.
期刊介绍:
Critical Care is an esteemed international medical journal that undergoes a rigorous peer-review process to maintain its high quality standards. Its primary objective is to enhance the healthcare services offered to critically ill patients. To achieve this, the journal focuses on gathering, exchanging, disseminating, and endorsing evidence-based information that is highly relevant to intensivists. By doing so, Critical Care seeks to provide a thorough and inclusive examination of the intensive care field.