Bioenergetic Crisis in ICU-Acquired Weakness Gene Signatures Was Associated With Sepsis-Related Mortality: A Brief Report.

• Type of Material: Article
• Authors: Craig Coopersmith, Emory University; Jocelyn Grunwell, Emory University; Rishikesan Kamaleswaran, Emory University; S Kobara, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA.; MG Rad, Department of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA.
• Language: English
• Date: 2022-12
• Publisher: Emory University Libraries
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/CCE.0000000000000818
• Title of Journal or Parent Work: Crit Care Explor
• Volume: 4
• Issue: 12
• Start Page: e0818
• End Page: e0818
• Keywords: immunosuppression, and catabolism syndrome; sepsis; persistent inflammation; intensive care unit-acquired weakness; mortality; post-intensive care syndrome
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Epidemiology

Abstract

UNLABELLED: To investigate the relationship between ICU-acquired weakness (ICUAW) signatures and sepsis-related mortality using gene expression from the blood within 24 hours of sepsis onset. DESIGN: Observational study using differential gene expression analysis. SETTING: Publicly available gene expression profile GSE54514, single-center medical and surgical ICU. PATIENTS: Patients with primary bacteremia- and respiratory-triggered sepsis including 8 nonsurvivors and 13 survivors who were 18 years old and older and admitted to ICU. MEASUREMENTS AND MAIN RESULTS: Among validated 526 ICUAW gene signatures, differential gene expression analysis controlling for age identified 38 significantly expressed genes between nonsurvivors and survivors. Functional enrichment analysis of differentially expressed ICUAW genes identified impaired cadherin binding, sarcomere formation, and energy metabolism among nonsurvivors. CONCLUSIONS: Our findings demonstrated a biological association between sepsis-related mortality and ICUAW signatures in the early phase of sepsis. Defects in energy metabolism and muscle fiber formation were associated with sepsis-related mortality.