High Dimensional Multiomics Reveals Unique Characteristics of Early Plasma Administration in Polytrauma Patients With TBI.
Journal
Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354
Informations de publication
Date de publication:
01 10 2022
01 10 2022
Historique:
pubmed:
22
7
2022
medline:
14
9
2022
entrez:
21
7
2022
Statut:
ppublish
Résumé
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. 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. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 35861072
doi: 10.1097/SLA.0000000000005610
pii: 00000658-202210000-00011
pmc: PMC9463104
mid: NIHMS1821322
doi:
Banques de données
ClinicalTrials.gov
['NCT01818427']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
673-683Subventions
Organisme : NHLBI NIH HHS
ID : T32 HL098036
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM127027
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141080
Pays : United States
Organisme : NHLBI NIH HHS
ID : R38 HL150207
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008516
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM119526
Pays : United States
Organisme : NIAID NIH HHS
ID : DP2 AI164325
Pays : United States
Déclaration de conflit d'intérêts
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.
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