Lipidomic signatures align with inflammatory patterns and outcomes in critical illness

Abstract

Alterations in lipid metabolism have the potential to be markers as well as drivers of pathobiology of acute critical illness. Here, we took advantage of the temporal precision offered by trauma as a common cause of critical illness to identify the dynamic patterns in the circulating lipidome in critically ill humans. The major findings include an early loss of all classes of circulating lipids followed by a delayed and selective lipogenesis in patients destined to remain critically ill. The previously reported survival benefit of early thawed plasma administration was associated with preserved lipid levels that related to favorable changes in coagulation and inflammation biomarkers in causal modelling. Phosphatidylethanolamines (PE) were elevated in patients with persistent critical illness and PE levels were prognostic for worse outcomes not only in trauma but also severe COVID-19 patients. Here we show selective rise in systemic PE as a common prognostic feature of critical illness.

Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: A secondary analysis of a prospective randomized trial

“…We did not find differences in circulating levels of syndecan-1 at subsequent time points (24 or 72 hours) or persistent changes in sTM or PECAM-1, which may reflect a temporal relationship between TXA and endothelial cell protection. Our results add further weight to the notion that it is important to not only assess clinical outcomes, but also to understand the mechanisms by which these interventions alter trauma biology at the cellular and molecular level 25–28 …”

“…Of the patients in this sampled cohort, patients who received the placebo were similar to those who received prehospital TXA in terms of patient demographics, injury characteristics, prehospital interventions, and outcomes, suggesting that similar to the original study these were well-randomized populations even after subsampling the population for biomarker analysis. Specifically, patients were similar ages (placebo 39 [26,56] vs. TXA 38 [26,51], p = 0.20), similarly injured (placebo ISS 11 [4,21] vs. TXA ISS 12 [56,21], p = 0.3). Patients who received TXA survived to 30 days at similar rates as those who received the placebo (94% vs. 91%, p = 0.4).…”

Lipidome and inflammation interplay: the role of diet in this relationship

“…In another study, phosphatidylethanolamines were associated with higher persistence and worse prognosis in acute illnesses as trauma and COVID-19 [17 ▪▪ ]. Similarly, higher circulating levels of phosphatidylethanolamines were associated with a higher risk of chronic diseases as are CVD or T2D in a Mediterranean older population at high CVD risk [12,13,18].…”

Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19

“…Not only metabolites but also lipids such as carnitines and phosphatidylcholine ( Caterino et al, 2021b ; D’alessandro et al, 2021 ; Wu et al, 2022 ) and an NMR-determined pro-atherogenic lipoprotein profile have been associated to COVID-19 severity ( Schmelter et al, 2021 ; Rendeiro et al, 2022 ). In addition, the metabolic changes associated with severity are also correlated with immune response markers: between plasma oxylipins ( Karu et al, 2022 ) or acetylcholine ( Pérez et al, 2022 ) with chemokines/neutrophiles or between lysophosphatidyl choline (LPC) with IL-6 ( Sindelar et al, 2021 ).…”