EARLY DIFFERENTIATION BETWEEN SEPSIS AND STERILE INFLAMMATION VIA URINARY GENE SIGNATURES OF METABOLIC DYSREGULATION.
Journal
Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564
Informations de publication
Date de publication:
01 07 2022
01 07 2022
Historique:
pubmed:
30
7
2022
medline:
24
8
2022
entrez:
29
7
2022
Statut:
ppublish
Résumé
Objective: The aim of this study was to characterize early urinary gene expression differences between patients with sepsis and patients with sterile inflammation and summarize in terms of a reproducible sepsis probability score. Design: This was a prospective observational cohort study. Setting: The study was conducted in a quaternary care academic hospital. Patients: One hundred eighty-six sepsis patients and 78 systemic inflammatory response syndrome (SIRS) patients enrolled between January 2015 and February 2018. Interventions: Whole-genome transcriptomic analysis of RNA was extracted from urine obtained from sepsis patients within 12 hours of sepsis onset and from patients with surgery-acquired SIRS within 4 hours after major inpatient surgery. Measurements and Main Results: We identified 422 of 23,956 genes (1.7%) that were differentially expressed between sepsis and SIRS patients. Differentially expressed probes were provided to a collection of machine learning feature selection models to identify focused probe sets that differentiate between sepsis and SIRS. These probe sets were combined to find an optimal probe set (UrSepsisModel) and calculate a urinary sepsis score (UrSepsisScore), which is the geometric mean of downregulated genes subtracted from the geometric mean of upregulated genes. This approach summarizes the expression values of all decisive genes as a single sepsis score. The UrSepsisModel and UrSepsisScore achieved area under the receiver operating characteristic curves 0.91 (95% confidence interval, 0.86-0.96) and 0.80 (95% confidence interval, 0.70-0.88) on the validation cohort, respectively. Functional analyses of probes associated with sepsis demonstrated metabolic dysregulation manifest as reduced oxidative phosphorylation, decreased amino acid metabolism, and decreased oxidation of lipids and fatty acids. Conclusions: Whole-genome transcriptomic profiling of urinary cells revealed focused probe panels that can function as an early diagnostic tool for differentiating sepsis from sterile SIRS. Functional analysis of differentially expressed genes demonstrated a distinct metabolic dysregulation signature in sepsis.
Identifiants
pubmed: 35904146
doi: 10.1097/SHK.0000000000001952
pii: 00024382-202207000-00003
pmc: PMC9391290
mid: NIHMS1821010
doi:
Types de publication
Journal Article
Observational Study
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
20-27Subventions
Organisme : NIBIB NIH HHS
ID : R21 EB027344
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS120924
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK121730
Pays : United States
Organisme : NIGMS NIH HHS
ID : K23 GM140268
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM111152
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM110240
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB029699
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK120784
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001427
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: A.B. and T.O.-B. were supported by R01 GM110240 from the National Institute of General Medical Sciences. A.B. T.O.-B., M.-C.L., H.V.B., and M.S.S. were supported by Sepsis and Critical Illness Research Center Award P50 GM-111152 from the National Institute of General Medical Sciences. A.B. and P.R. were supported by R01 GM110240 from the National Institute of General Medical Sciences (NIH/NIGMS), by 1R01EB029699 and 1R21EB027344 from the National Institute of Biomedical Imaging and Bioengineering (NIH/NIBIB), and 1R01NS120924 from the National Institute of Neurological Disorders and Stroke (NIH/NINDS). P.R. was supported by the National Science Foundation CAREER award 1750192. A.B. was supported by UF Research AWD09458. T.O.-B. was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health grant K01 DK120784 and by UF Research AWD09459 and the Gatorade Trust, University of Florida. T.J.L. was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award K23 GM140268. The research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under University of Florida Clinical and Translational Science Awards UL1TR000064 and UL1TR001427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors report no conflicts of interest.
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