Risk assessment with gene expression markers in sepsis development.

Infection is a commonplace, usually self-limiting, condition but can lead to sepsis, a severe life-threatening dysregulated host response. We investigate the individual phenotypic predisposition to developing uncomplicated infection or sepsis in a large cohort of non-infected patients undergoing major elective surgery. Whole-blood RNA sequencing analysis was performed on preoperative samples from 267 patients. These patients developed postoperative infection with (n = 77) or without (n = 49) sepsis, developed non-infectious systemic inflammatory response (n = 31), or had an uncomplicated postoperative course (n = 110). Machine learning classification models built on preoperative transcriptomic signatures predict postoperative outcomes including sepsis with an area under the curve of up to 0.910 (mean 0.855) and sensitivity/specificity up to 0.767/0.804 (mean 0.746/0.769). Our models, confirmed by quantitative reverse-transcription PCR (RT-qPCR), potentially offer a risk prediction tool for the development of postoperative sepsis with implications for patient management. They identify an individual predisposition to developing sepsis that warrants further exploration to better understand the underlying pathophysiology.

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Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests E.J.G.-B. has received honoraria from Abbott Products Operations AG, bioMérieux, Brahms GmbH, GSK, InflaRx GmbH, Sobi, and Xbiotech Inc; independent educational grants from Abbott Products Operations, bioMérieux, Inc, InflaRx GmbH, Johnson & Johnson, MSD, UCB, and Swedish Orphan Biovitrum AB; and funding from the Horizon 2020 European Grants ImmunoSep and RISCinCOVID and the Horizon Health grant EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis). M.S. received grants from NewB, Apollo Therapeutics, and UCL Technology Fund and others from Abbott, Amormed, bioMérieux, Biotest, Deltex Medical, Fresenius, Mindray, NewB, Pfizer, Radiometer, Roche Diagnostics, Safeguard Biosystems, Shionogi, and Spiden outside of this project. M.S. is an unpaid advisor to Presymptom Health Ltd, hemotune, deepUll, and Santersus, and R.L. is a part-time advisor to Presymptom Health Ltd.