High Dimensional Multiomics Reveals Unique Characteristics of Early Plasma Administration in Polytrauma Patients With TBI.

Autor:	Wu J; Department of Cardiology, The 3rd Xiangya Hospital, Central South University, Changsha, China.; Department of Surgery, University of Pittsburgh, Pittsburgh, PA.; Pittsburgh Trauma Research Center, Division of Trauma and Acute Care Surgery, Pittsburgh, PA., Moheimani H; Department of Surgery, University of Pittsburgh, Pittsburgh, PA.; Pittsburgh Trauma Research Center, Division of Trauma and Acute Care Surgery, Pittsburgh, PA., Li S; Department of Surgery, University of Pittsburgh, Pittsburgh, PA.; Pittsburgh Trauma Research Center, Division of Trauma and Acute Care Surgery, Pittsburgh, PA., Kar UK; Department of Surgery, University of Pittsburgh, Pittsburgh, PA.; Pittsburgh Trauma Research Center, Division of Trauma and Acute Care Surgery, Pittsburgh, PA., Bonaroti J; Department of Surgery, University of Pittsburgh, Pittsburgh, PA.; Pittsburgh Trauma Research Center, Division of Trauma and Acute Care Surgery, Pittsburgh, PA., Miller RS; Department of Surgery, JPS Health Network in Fort Worth, TX., Daley BJ; Department of Surgery, University of Tennessee Health Science Center, Knoxville, TN., Harbrecht BG; Department of Surgery, University of Louisville, Louisville, KY., Claridge JA; Metro Health Medical Center, Case Western Reserve University, Cleveland, OH., Gruen DS; Department of Surgery, University of Pittsburgh, Pittsburgh, PA.; Pittsburgh Trauma Research Center, Division of Trauma and Acute Care Surgery, Pittsburgh, PA., Phelan HA; Department of Surgery, University Medical Center-New Orleans Burn Program, New Orleans, LA., Guyette FX; Department of Emergency Medicine, Medicine, University of Pittsburgh, Pittsburgh, PA., Neal MD; Department of Surgery, University of Pittsburgh, Pittsburgh, PA.; Pittsburgh Trauma Research Center, Division of Trauma and Acute Care Surgery, Pittsburgh, PA., Das J; Center for Systems Immunology, Departments of Immunology and Computational & Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA., Sperry JL; Department of Surgery, University of Pittsburgh, Pittsburgh, PA.; Pittsburgh Trauma Research Center, Division of Trauma and Acute Care Surgery, Pittsburgh, PA., Billiar TR; Department of Surgery, University of Pittsburgh, Pittsburgh, PA.; Pittsburgh Trauma Research Center, Division of Trauma and Acute Care Surgery, Pittsburgh, PA.
Jazyk:	angličtina
Zdroj:	Annals of surgery [Ann Surg] 2022 Oct 01; Vol. 276 (4), pp. 673-683. Date of Electronic Publication: 2022 Jul 19.
DOI:	10.1097/SLA.0000000000005610
Abstrakt:	Objectives: The authors sought to identify causal factors that explain the selective benefit of prehospital administration of thawed plasma (TP) in traumatic brain injury (TBI) patients using mediation analysis of a multiomic database. Background: The Prehospital Air Medical Plasma (PAMPer) Trial showed that patients with TBI and a pronounced systemic response to injury [defined as endotype 2 (E2)], have a survival benefit from prehospital administration of TP. An interrogation of high dimensional proteomics, lipidomics and metabolomics previously demonstrated unique patterns in circulating biomarkers in patients receiving prehospital TP, suggesting that a deeper analysis could reveal causal features specific to TBI patients. Methods: A novel proteomic database (SomaLogic Inc., aptamer-based assay, 7K platform) was generated using admission blood samples from a subset of patients (n=149) from the PAMPer Trial. This proteomic dataset was combined with previously reported metabolomic and lipidomic datasets from these same patients. A 2-step analysis was performed to identify factors that promote survival in E2-TBI patients who had received early TP. First, features were selected using both linear and multivariate-latent-factor regression analyses. Then, the selected features were entered into the causal mediation analysis. Results: Causal mediation analysis of observable features identified 16 proteins and 41 lipids with a high proportion of mediated effect (>50%) to explain the survival benefit of early TP in E2-TBI patients. The multivariate latent-factor regression analyses also uncovered 5 latent clusters of features with a proportion effect >30%, many in common with the observable features. Among the observable and latent features were protease inhibitors known to inhibit activated protein C and block fibrinolysis (SERPINA5 and CPB2), a clotting factor (factor XI), as well as proteins involved in lipid transport and metabolism (APOE3 and sPLA(2)-XIIA). Conclusions: These findings suggest that severely injured patients with TBI process exogenous plasma differently than those without TBI. The beneficial effects of early TP in E2-TBI patients may be the result of improved blood clotting and the effect of brain protective factors independent of coagulation. Competing Interests: T.R.B. is a stakeholder in Immunetrics Inc. M.D.N holds an equity stake in Haima Therapeutics. He has received research support and/or honoraria from Haemonetics, Instrumentation Laboratories, and Janssen Pharmaceuticals. The remaining authors report no conflicts of interest.
Databáze:	MEDLINE
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