TY - JOUR

T1 - LASSO regression shows histidine and sphingosine 1 phosphate are linked to both sepsis mortality and endothelial damage

AU - Johansson, Pär I.

AU - Henriksen, Hanne H.

AU - Karvelsson, Sigurður T.

AU - Rolfsson, Óttar

AU - Schønemann-Lund, Martin

AU - Bestle, Morten H.

AU - McGarrity, Sarah

N1 - Publisher Copyright: © 2024, The Author(s).

PY - 2024

Y1 - 2024

N2 - Sepsis is a major cause of death worldwide, with a mortality rate that has remained stubbornly high. The current gold standard of risk stratifying sepsis patients provides limited mechanistic insight for therapeutic targeting. An improved ability to predict sepsis mortality and to understand the risk factors would allow better treatment targeting. Sepsis causes metabolic dysregulation in patients; therefore, metabolomics offers a promising tool to study sepsis. It is also known that that in sepsis endothelial cells affecting their function regarding blood clotting and vascular permeability. We integrated metabolomics data from patients admitted to an intensive care unit for sepsis, with commonly collected clinical features of their cases and two measures of endothelial function relevant to blood vessel function, platelet endothelial cell adhesion molecule and soluble thrombomodulin concentrations in plasma. We used least absolute shrinkage and selection operator penalized regression, and pathway enrichment analysis to identify features most able to predict 30-day survival. The features important to sepsis survival include carnitines, and amino acids. Endothelial proteins in plasma also predict 30-day mortality and the levels of these proteins also correlate with a somewhat overlapping set of metabolites. Overall metabolic dysregulation, particularly in endothelial cells, may be a contributory factor to sepsis response. By exploring sepsis metabolomics data in conjunction with clinical features and endothelial proteins we have gained a better understanding of sepsis risk factors.

AB - Sepsis is a major cause of death worldwide, with a mortality rate that has remained stubbornly high. The current gold standard of risk stratifying sepsis patients provides limited mechanistic insight for therapeutic targeting. An improved ability to predict sepsis mortality and to understand the risk factors would allow better treatment targeting. Sepsis causes metabolic dysregulation in patients; therefore, metabolomics offers a promising tool to study sepsis. It is also known that that in sepsis endothelial cells affecting their function regarding blood clotting and vascular permeability. We integrated metabolomics data from patients admitted to an intensive care unit for sepsis, with commonly collected clinical features of their cases and two measures of endothelial function relevant to blood vessel function, platelet endothelial cell adhesion molecule and soluble thrombomodulin concentrations in plasma. We used least absolute shrinkage and selection operator penalized regression, and pathway enrichment analysis to identify features most able to predict 30-day survival. The features important to sepsis survival include carnitines, and amino acids. Endothelial proteins in plasma also predict 30-day mortality and the levels of these proteins also correlate with a somewhat overlapping set of metabolites. Overall metabolic dysregulation, particularly in endothelial cells, may be a contributory factor to sepsis response. By exploring sepsis metabolomics data in conjunction with clinical features and endothelial proteins we have gained a better understanding of sepsis risk factors.

U2 - 10.1186/s40001-023-01612-7

DO - 10.1186/s40001-023-01612-7

M3 - Journal article

C2 - 38245777

AN - SCOPUS:85182659871

VL - 29

JO - European Journal of Medical Research

JF - European Journal of Medical Research

SN - 0949-2321

IS - 1

M1 - 71

ER -