Source-specific host response and outcomes in critically ill patients with sepsis: a prospective cohort study.

Content Provider	Europe PMC
Author	Peters-Sengers, Hessel Butler, Joe M. Uhel, Fabrice Schultz, Marcus J. Bonten, Marc J. Cremer, Olaf L. Scicluna, Brendon P. van Vught, Lonneke A. van der Poll, Tom
Abstract	PurposeThere is limited knowledge on how the source of infection impacts the host response to sepsis. We aimed to compare the host response in sepsis patients with a single, known source at admission (< 24 h) to the intensive care unit.MethodsFrom the molecular diagnosis and risk stratification of sepsis (MARS) prospective cohort, we measured 16 plasma host response biomarkers reflective of key host response pathways in 621 sepsis patients. In a subgroup (n = 335), blood leukocyte transcriptomes were compared between the sources. Differences in clinical patient profiles and survival were compared in the whole sepsis cohort (n = 2019).ResultsThe plasma biomarker cohort was categorized into sepsis originating from the respiratory tract (n = 334, 53.8%), abdomen (n = 159, 25.6%), urinary tract (n = 44, 7.1%), cardiovascular (n = 41, 6.6%), central nervous system (CNS) (n = 18, 2.9%), or skin (n = 25, 4%). This analysis revealed stronger inflammatory and cytokine responses, loss of vascular integrity and coagulation activation in abdominal sepsis relative to respiratory. Endothelial cell activation was prominent in urinary, cardiovascular and skin infections, while CNS infection was associated with the least host response aberrations. The leukocyte transcriptional response showed the largest overlap between abdominal and pulmonary infections (76% in common); notable differences between the sources were detected regarding hemostasis, cytokine signaling, innate and adaptive immune, and metabolic transcriptional pathways. After adjustment for confounders, the source of infection remained an independent contributor to 30-day mortality (unadjusted p = 0.001, adjusted p = 0.028).ConclusionSepsis heterogeneity is partly explained by source-specific host response dysregulations and should be considered when selecting patients for trials testing immune modulatory drugs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00134-021-06574-0.
ISSN	03424642
Journal	Intensive Care Medicine
Volume Number	48
PubMed Central reference number	PMC8667541
Issue Number	1
PubMed reference number	34902047
e-ISSN	14321238
DOI	10.1007/s00134-021-06574-0
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2021-12-13
Publisher Place	Berlin/Heidelberg
Access Restriction	Open
Rights License	Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/. © The Author(s) 2021
Subject Keyword	Sepsis Source of infection Site of infection Host response Intensive care unit
Content Type	Text
Resource Type	Article
Subject	Critical Care and Intensive Care Medicine