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Multi-omic analysis in injured humans: Patterns align with outcomes and treatment responses.

Cell reports. Medicine (2022-01-15)
Junru Wu, Yoram Vodovotz, Sultan Abdelhamid, Francis X Guyette, Michael B Yaffe, Danielle S Gruen, Anthony Cyr, David O Okonkwo, Upendra K Kar, Neha Krishnamoorthi, Robert G Voinchet, Isabel M Billiar, Mark H Yazer, Rami A Namas, Brian J Daley, Richard S Miller, Brian G Harbrecht, Jeffrey A Claridge, Herbert A Phelan, Brian S Zuckerbraun, Pär I Johansson, Jakob Stensballe, James H Morrissey, Russell P Tracy, Stephen R Wisniewski, Matthew D Neal, Jason L Sperry, Timothy R Billiar
RESUMEN

Trauma is a leading cause of death and morbidity worldwide. Here, we present the analysis of a longitudinal multi-omic dataset comprising clinical, cytokine, endotheliopathy biomarker, lipidome, metabolome, and proteome data from severely injured humans. A "systemic storm" pattern with release of 1,061 markers, together with a pattern suggestive of the "massive consumption" of 892 constitutive circulating markers, is identified in the acute phase post-trauma. Data integration reveals two human injury response endotypes, which align with clinical trajectory. Prehospital thawed plasma rescues only endotype 2 patients with traumatic brain injury (30-day mortality: 30.3 versus 75.0%; p = 0.0015). Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) was identified as the most predictive circulating biomarker to identify endotype 2-traumatic brain injury (TBI) patients. These response patterns refine the paradigm for human injury, while the datasets provide a resource for the study of critical illness, trauma, and human stress responses.

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