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

被引:54
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
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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