High Dimensional Proteomics Identifies Organ Injury Patterns Associated with Outcomes in Human Trauma

Shimena Li, Hamed Moheimani, Brachman Herzig, Michael Kail, Neha Krishnamoorthi, Junru Wu, Sultan Abdelhamid, Jacob Scioscia, Eunseo Sung, Anna Rosengart, Jillian Bonaroti, Par I Johansson, Jakob Stensballe, Matthew Neal, Jishnu Das, Upendra Kar, Jason Sperry, Timothy Billiar


INTRODUCTION: Severe traumatic injury with shock can lead to direct and indirect organ injury, however, tissue-specific biomarkers are limited in clinical panels. We utilized proteomic and metabolomic databases to identify organ injury patterns after severe injury in humans.

METHODS: Plasma samples (times 0-, 24-, and 72-hours [h] after arrival to trauma center) from injured patients enrolled in two randomized prehospital trials were subjected to multiplexed proteomics (SomaLogic Inc.). Patients were categorized by outcome: Non-resolvers (died >72 h or required ≥7 days of critical care), Resolvers (survived to 30-days and required <7 days of critical care), and low injury severity score (ISS) controls. Established tissue-specific biomarkers were identified through a literature review and cross-referenced with tissue-specificity from the Human Protein Atlas. Untargeted plasma metabolomics (Metabolon Inc.), inflammatory mediators, and endothelial damage markers were correlated with injury biomarkers. Kruskal-Wallis/Mann-Whitney-U tests with false discovery rate correction assessed differences in biomarker expression across outcome groups (significance; P-value <0.1).

RESULTS: Of 142 patients, 78 were Non-resolvers (median ISS = 30), 34 Resolvers (median ISS = 22), and 30 low ISS controls (median ISS = 1). A broad release of tissue-specific damage markers was observed at admission; this was greater in Non-resolvers. By 72 h, 9 cardiac, 3 liver, 8 neurologic, and 3 pulmonary proteins remained significantly elevated in Non-resolvers compared to Resolvers. Cardiac damage biomarkers showed the greatest elevations at 72 h in Non-resolvers and had significant positive correlations with pro-inflammatory mediators and endothelial damage markers. Non-resolvers had lower concentrations of fatty acid metabolites compared to Resolvers, particularly acyl carnitines and cholines.

CONCLUSIONS: We identified an immediate release of tissue-specific biomarkers with sustained elevation in the liver, pulmonary, neurologic, and especially cardiac injury biomarkers in patients with complex clinical courses after severe injury. The persistent myocardial injury in Non-resolvers may be due to a combination of factors including metabolic stress, inflammation, and endotheliopathy.

STUDY TYPE: Level III, Prognostic/Epidemiological.

TidsskriftThe journal of trauma and acute care surgery
StatusE-pub ahead of print - 13 feb. 2023


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