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33 reviewsBrendon P Scicluna, Lonneke A van Vught, Aeilko H Zwinderman, Maryse A Wiewel, Emma E Davenport, Katie L Burnham, Peter Nürnberg, Marcus J Schultz, Janneke Horn, Olaf L Cremer, Marc J Bonten, Charles J Hinds, Hector R Wong, Julian C Knight, Tom van der Poll, on behalf of the MARS consortium*Lancet Respir Med 2017; SummaryBackground Host responses during sepsis are highly heterogeneous, which hampers the identification of patients at 5: 816–26high risk of mortality and their selection for targeted therapies. In this study, we aimed to identify biologically relevant Published Onlinemolecular endotypes in patients with sepsis.August 29, 2017 This was a prospective observational cohort study that included consecutive patients admitted for sepsis to two S2213-2600(17)30294-1intensive care units (ICUs) in the Netherlands between Jan 1, 2011, and July 20, 2012 (discovery and first validation cohorts) See Comment page 767and patients admitted with sepsis due to community-acquired pneumonia to 29 ICUs in the UK (second validation *Members listed in the appendixcohort). We generated genome-wide blood gene expression profiles from admission samples and analysed them by Center for Experimental unsupervised consensus clustering and machine learning. The primary objective of this study was to establish endotypes Molecular Medicine for patients with sepsis, and assess the association of these endotypes with clinical traits and survival outcomes. We also (B P Scicluna PhD, L A van Vught MD, established candidate biomarkers for the endotypes to allow identification of patient endotypes in clinical practice.M A Wiewel MD, Prof T van der Poll MD), Findings The discovery cohort had 306 patients, the first validation cohort had 216, and the second validation Department of Clinical cohort had 265 patients. Four molecular endotypes for sepsis, designated Mars1–4, were identified in the discovery Epidemiology, Bio