Biomarkers of endothelial activation/dysfunction distinguish subgroups of Ugandan patients with sepsis and differing mortality risks

Danielle V. Clark, Patrick Banura, Karen J Bandeen Roche, W. Conrad Liles, Kevin C. Kain, W. Michael Scheld, William J Moss, Shevin T. Jacob

Research output: Contribution to journalArticle

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-specifc di?erences in mortality. METHODS. Adult patients with sepsis (n = 426) were consecutively recruited from 2 hospitals in Uganda. Clinical information was collected, and serum concentrations of 11 biomarkers involved in the endothelial response to infection were measured in samples from 315 patients. Latent variable models were ft to evaluate whether the endothelial response to sepsis consists of one unifed biologic process or multiple processes and to identify subgroups of patients with distinct host-response profles. Di?erences in survival at day 28 were evaluated using Kaplan-Meier survival curves. RESULTS. We identifed 3 patient subgroups characterized by unique host endothelial response profles. Patients ftting profle 2 had signifcantly worse survival (log-rank P 0.001). Four latent factors (factors 1-4) were identifed, each potentially representing distinct biologic 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 profles 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. Profle 2 may represent dysfunction of the endothelial response to infection. FUNDING. Primary funding: Investigator-Initiated Award provided by Pfzer Inc. Additional support: Canadian Institutes of Health Research Foundation grant (FDN-148439) and the Canada Research Chair program.

Original languageEnglish (US)
Article numbere127623
JournalJCI Insight
Volume4
Issue number10
DOIs
StatePublished - Jan 1 2019

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Sepsis
Biomarkers
Mortality
Uganda
Survival
Organized Financing
Kaplan-Meier Estimate
Infection
Serum
Vascular Endothelial Growth Factor A
Canada
Research Personnel
Health
Research

ASJC Scopus subject areas

  • Medicine(all)

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Biomarkers of endothelial activation/dysfunction distinguish subgroups of Ugandan patients with sepsis and differing mortality risks. / Clark, Danielle V.; Banura, Patrick; Bandeen Roche, Karen J; Conrad Liles, W.; Kain, Kevin C.; Michael Scheld, W.; Moss, William J; Jacob, Shevin T.

In: JCI Insight, Vol. 4, No. 10, e127623, 01.01.2019.

Research output: Contribution to journalArticle

Clark, Danielle V. ; Banura, Patrick ; Bandeen Roche, Karen J ; Conrad Liles, W. ; Kain, Kevin C. ; Michael Scheld, W. ; Moss, William J ; Jacob, Shevin T. / Biomarkers of endothelial activation/dysfunction distinguish subgroups of Ugandan patients with sepsis and differing mortality risks. In: JCI Insight. 2019 ; Vol. 4, No. 10.
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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-specifc di?erences in mortality. METHODS. Adult patients with sepsis (n = 426) were consecutively recruited from 2 hospitals in Uganda. Clinical information was collected, and serum concentrations of 11 biomarkers involved in the endothelial response to infection were measured in samples from 315 patients. Latent variable models were ft to evaluate whether the endothelial response to sepsis consists of one unifed biologic process or multiple processes and to identify subgroups of patients with distinct host-response profles. Di?erences in survival at day 28 were evaluated using Kaplan-Meier survival curves. RESULTS. We identifed 3 patient subgroups characterized by unique host endothelial response profles. Patients ftting profle 2 had signifcantly worse survival (log-rank P 0.001). Four latent factors (factors 1-4) were identifed, each potentially representing distinct biologic 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 profles 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. Profle 2 may represent dysfunction of the endothelial response to infection. FUNDING. Primary funding: Investigator-Initiated Award provided by Pfzer Inc. Additional support: Canadian Institutes of Health Research Foundation grant (FDN-148439) and the Canada Research Chair program.",
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AU - Conrad Liles, W.

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N2 - 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-specifc di?erences in mortality. METHODS. Adult patients with sepsis (n = 426) were consecutively recruited from 2 hospitals in Uganda. Clinical information was collected, and serum concentrations of 11 biomarkers involved in the endothelial response to infection were measured in samples from 315 patients. Latent variable models were ft to evaluate whether the endothelial response to sepsis consists of one unifed biologic process or multiple processes and to identify subgroups of patients with distinct host-response profles. Di?erences in survival at day 28 were evaluated using Kaplan-Meier survival curves. RESULTS. We identifed 3 patient subgroups characterized by unique host endothelial response profles. Patients ftting profle 2 had signifcantly worse survival (log-rank P 0.001). Four latent factors (factors 1-4) were identifed, each potentially representing distinct biologic 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 profles 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. Profle 2 may represent dysfunction of the endothelial response to infection. FUNDING. Primary funding: Investigator-Initiated Award provided by Pfzer Inc. Additional support: Canadian Institutes of Health Research Foundation grant (FDN-148439) and the Canada Research Chair program.

AB - 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-specifc di?erences in mortality. METHODS. Adult patients with sepsis (n = 426) were consecutively recruited from 2 hospitals in Uganda. Clinical information was collected, and serum concentrations of 11 biomarkers involved in the endothelial response to infection were measured in samples from 315 patients. Latent variable models were ft to evaluate whether the endothelial response to sepsis consists of one unifed biologic process or multiple processes and to identify subgroups of patients with distinct host-response profles. Di?erences in survival at day 28 were evaluated using Kaplan-Meier survival curves. RESULTS. We identifed 3 patient subgroups characterized by unique host endothelial response profles. Patients ftting profle 2 had signifcantly worse survival (log-rank P 0.001). Four latent factors (factors 1-4) were identifed, each potentially representing distinct biologic 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 profles 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. Profle 2 may represent dysfunction of the endothelial response to infection. FUNDING. Primary funding: Investigator-Initiated Award provided by Pfzer Inc. Additional support: Canadian Institutes of Health Research Foundation grant (FDN-148439) and the Canada Research Chair program.

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