@article{7e0c3512ae6048f4bb95b4444990853b,
title = "Systemic inflammation and metabolic disturbances underlie inpatient mortality among ill children with severe malnutrition",
abstract = "Children admitted to hospital with an acute illness and concurrent severe malnutrition [complicated severe malnutrition (CSM)] have a high risk of dying. The biological processes underlying their mortality are poorly understood. In this case-control study nested within a multicenter randomized controlled trial among children with CSM in Kenya and Malawi, we found that blood metabolomic and proteomic profiles robustly differentiated children who died (n = 92) from those who survived (n = 92). Fatalities were characterized by increased energetic substrates (tricarboxylic acid cycle metabolites), microbial metabolites (e.g., propionate and isobutyrate), acute phase proteins (e.g., calprotectin and C-reactive protein), and inflammatory markers (e.g., interleukin-8 and tumor necrosis factor–α). These perturbations indicated disruptions in mitochondria-related bioenergetic pathways and sepsis-like responses. This study identified specific biomolecular disturbances associated with CSM mortality, revealing that systemic inflammation and bioenergetic deficits are targetable pathophysiological processes for improving survival of this vulnerable population.",
author = "Bijun Wen and Njunge, {James M.} and Celine Bourdon and Gonzales, {Gerard Bryan} and Gichuki, {Bonface M.} and Dorothy Lee and Wishart, {David S.} and Moses Ngari and Emmanuel Chimwezi and Johnstone Thitiri and Laura Mwalekwa and Wieger Voskuijl and Berkley, {James A.} and Bandsma, {Robert H. J.}",
note = "Funding Information: This work was supported, in whole or in part, by the Bill & Melinda Gates Foundation (Grant Number OPP1131320). Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author-Accepted Manuscript version that might arise from this submission. The parent clinical trial was funded by the Thrasher Research Fund to J.A.B. at the University of Oxford (9403). Support for J.M.N., C.B., W.V., J.T., M.N., B.M.G., and J.A.B. was provided by the Bill & Melinda Gates Foundation to J.A.B. (Grant Number OPP1131320). J.A.B. and L.M. were supported by the MRC/DfID/Wellcome Trust Global Health Trials Scheme (Grant Number MR/M007367/1). G.B.G. was supported by the Research Foundation Flanders, the Thrasher Foundation Early Career Award (15122), and VLIR-UOS-Ghent University Global Minds Fund. This work was in part supported by the Canadian Institutes of Health Research (156307). B.W. was supported by the Research Training Competition (RESTRACOMP) Graduate Scholarship at the Hospital for Sick Children and the Ontario Graduate Scholarship (OGS) at the University of Toronto. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: Copyright {\textcopyright} 2022 The Authors, some rights reserved.",
year = "2022",
month = feb,
day = "1",
doi = "https://doi.org/10.1126/sciadv.abj6779",
language = "English",
volume = "8",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "7",
}