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Biomarkers of endothelial activation/dysfunction distinguish sub-groups of Ugandan patients with sepsis and differing mortality risks.

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Clark, Danielle V, Banura, Patrick, Bandeen-Roche, Karen, Liles, W Conrad, Kain, Kevin C, Scheld, W Michael, Moss, William J and Jacob, Shevin T ORCID: https://orcid.org/0000-0003-2425-9394 (2019) 'Biomarkers of endothelial activation/dysfunction distinguish sub-groups of Ugandan patients with sepsis and differing mortality risks.'. JCI insight, Vol 4, Issue 10, e127623.

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Abstract

BACKGROUND
Sepsis is a complex clinical syndrome with substantial heterogeneity. We sought to identify patterns of serum biomarkers of endothelial activation and dysfunction in individuals with sepsis and evaluate subgroup-specific differences in mortality.
METHODS
Adult patients with sepsis (n=426) were consecutively recruited from two hospitals in Uganda. Clinical information was collected and serum concentrations of eleven biomarkers involved in the endothelial response to infection were measured in samples from 315 patients. Latent variable models were fit to evaluate whether the endothelial response to sepsis consists of one unified biological process or multiple processes and to identify subgroups of patients with distinct host-response profiles. Differences in survival at day 28 were evaluated using Kaplan-Meier survival curves.
RESULTS
We identified three patient subgroups characterized by unique host endothelial response profiles. Patients fitting Profile 2 had significantly worse survival (log-rank p<0.001). Four latent factors (Factor 1-4) were identified, each potentially representing distinct biological processes for the endothelial response to sepsis: Factor 1 (CHI3L1, sTREM1, sFLT1); Factor 2 (ANGPT1, PF4, VEGF); Factor 3 (CXCL10, VWF, sICAM1); and Factor 4 (ANGPT2, sTEK).
CONCLUSION
Patient profiles based on patterns of circulating biomarkers of endothelial responses may provide a clinically meaningful way to categorize patients into homogeneous subgroups and may identify patients with a high risk of mortality. Profile 2 may represent dysfunction of the endothelial response to infection.
FUNDING
Primary funding: Investigator-Initiated Award provided by Pfizer, Inc (WMS, STJ). Additional support: Canadian Institutes of Health Research (CIHR) Foundation grant (KCK; FDN-148439) and the Canada Research Chair program (KCK).

Item Type: Article
Subjects: QS Anatomy > Histology > QS 532.5 Specific types of tissue
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 240 Bacteremia. Sepsis. Toxemias
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1172/jci.insight.127623
Depositing User: Stacy Murtagh
Date Deposited: 02 May 2019 13:03
Last Modified: 06 Sep 2019 09:56
URI: https://archive.lstmed.ac.uk/id/eprint/10744

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