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

被引：49

作者：

Wu, Junru ^{[1
,2
,3
,4
,5
]}

Vodovotz, Yoram ^{[1
,2
]}

Abdelhamid, Sultan ^{[1
,2
]}

Guyette, Francis X. ^{[6
]}

Yaffe, Michael B. ^{[7
,8
]}

Gruen, Danielle S. ^{[1
,2
]}

Cyr, Anthony ^{[1
,2
]}

Okonkwo, David O. ^{[9
]}

Kar, Upendra K. ^{[1
,2
]}

Krishnamoorthi, Neha ^{[1
]}

Voinchet, Robert G. ^{[1
]}

Billiar, Isabel M. ^{[1
]}

Yazer, Mark H. ^{[10
]}

Namas, Rami A. ^{[1
,2
]}

Daley, Brian J. ^{[11
]}

Miller, Richard S. ^{[12
]}

Harbrecht, Brian G. ^{[13
]}

Claridge, Jeffrey A. ^{[14
]}

Phelan, Herbert A. ^{[15
]}

Zuckerbraun, Brian S. ^{[1
,2
]}

Johansson, Par, I ^{[16
]}

Stensballe, Jakob ^{[16
,17
,18
,19
]}

Morrissey, James H. ^{[20
]}

Tracy, Russell P. ^{[21
,22
]}

Wisniewski, Stephen R. ^{[23
]}

Neal, Matthew D. ^{[1
,2
]}

Sperry, Jason L. ^{[1
,2
]}

Billiar, Timothy R. ^{[1
,2
]}

机构：

[1] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15260 USA

[2] Univ Pittsburgh, Pittsburgh Trauma Res Ctr, Pittsburgh, PA 15260 USA

[3] Cent South Univ, Xiangya Hosp 3, Dept Cardiol, Changsha, Peoples R China

[4] Cent South Univ, Xiangya Hosp 3, Ctr Pharmacol, Changsha, Peoples R China

[5] Cent South Univ, Xiangya Sch Med, Eight Year Program Med, Changsha, Peoples R China

[6] Univ Pittsburgh, Dept Emergency Med, Med, Pittsburgh, PA USA

[7] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[8] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02115 USA

[9] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA

[10] Inst Transfus Med, Pittsburgh, PA USA

[11] Univ Tennessee, Hlth Sci Ctr, Dept Surg, Knoxville, TN USA

[12] JPS Hlth Network, Dept Surg, Ft Worth, TX USA

[13] Univ Louisville, Dept Surg, Louisville, KY 40292 USA

[14] Case Western Reserve Univ, Metro Hlth Med Ctr, Cleveland, OH 44106 USA

[15] Univ Texas Southwestern, Dept Surg, Dallas, TX USA

[16] Copenhagen Univ Hosp, Rigshosp, Sect Transfus Med, Capital Reg Blood Bank, Copenhagen, Denmark

[17] Copenhagen Univ Hosp, Rigshosp, Ctr Head & Orthopaed, Dept Anesthesia, Copenhagen, Denmark

[18] Copenhagen Univ Hosp, Rigshosp, Ctr Head & Orthopaed, Trauma Ctr, Copenhagen, Denmark

[19] Capital Reg Denmark, Emergency Med Serv, Hillerod, Denmark

[20] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA

[21] Univ Vermont, Lamer Coll Med, Dept Pathol, Colchester, VT USA

[22] Univ Vermont, Lamer Coll Med, Lab Med & Biochem, Colchester, VT USA

[23] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA

来源：

CELL REPORTS MEDICINE | 2021年 / 2卷 / 12期

基金：

美国国家卫生研究院;

关键词：

TRAUMA-INDUCED COAGULOPATHY; MOLECULAR-PATTERNS; COMPLEMENT; MORTALITY; PLASMA; RISK; INFLAMMATION; COAGULATION; MEDIATORS; IMMUNITY;

D O I：

10.1016/j.xcrm.2021.100478

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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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页数：23

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