Trauma remains the leading cause of years of life lost in the United States and multiple organ failure (MOF) is the primary cause of late postinjury death. The Human Subjects Core (HSC) will coordinate the patient-oriented research of the """"""""Trauma Primes Cells"""""""" RCTBPI Grant. Given that a large portion of this proposal focuses on the study of injured and/or critically ill patients, the HSC is recommended as an effective manner to coordinate the development and implementation of standard protocols, recruitment and consent of subjects, as well as collection and appropriate storage/distribution of samples and clinical data. This proposal for the HSC has four major functions: 1) to continue to maximize two-way translational research from basic to clinical science and vice-versa within the Center as well as through collaborations with other investigators;2) to conduct timely studies to investigate significant clinical questions regarding resuscitation protocols and management of postinjury critical care patients;3) to refine, improve and update scoring systems for monitoring critical care patients, most especially the Denver MOF score, and 4) to conduct hypotheses generating studies to stimulate new sets of questions at the basic and clinical science level. To support these functions, two strategies are proposed: 1) MOF database: this detailed clinical registry of over 2000 critically injured patients at risk for MOF, initiated over a decade ago, and to our knowledge, the largest, sustained clinical database of its kind;and 2) Tissue Databank: initiated 5 years ago during our last cycle, this consists of discarded tissue and fluid samples of patients included in the MOF database (therefore with complete clinical and laboratorial data) appropriately stored and available for translational research. Analysis of these data provides pivotal insights on risk factors, outcome and possible mechanisms for the pathogenesis of postinjury MOF as well as landmark findings with direct implications to resuscitation protocols, especially in the area of blood products use, and management of critical care patients. It is important to emphasize that trauma patients provide a particularly appealing subpopulation, mostly young and free of comorbid disease, minimizing confounding and facilitating the interpretation of the results. Findings in this population often have implications for the management of other critical care populations, amplifying the scope and impact of our findings. In addition, we are improving standardization of care, while ensuring protection of human subjects, and maximizing translational science.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Specialized Center (P50)
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Special Emphasis Panel (ZGM1-PPBC-5)
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University of Colorado Denver
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Slaughter, Anne L; D'Alessandro, Angelo; Moore, Ernest E et al. (2016) Glutamine metabolism drives succinate accumulation in plasma and the lung during hemorrhagic shock. J Trauma Acute Care Surg 81:1012-1019
D'Alessandro, Angelo; Moore, Hunter B; Moore, Ernest E et al. (2016) Plasma First Resuscitation Reduces Lactate Acidosis, Enhances Redox Homeostasis, Amino Acid and Purine Catabolism in a Rat Model of Profound Hemorrhagic Shock. Shock 46:173-82
Kelher, Marguerite R; McLaughlin, Nathan J D; Banerjee, Anirban et al. (2016) LysoPCs induce Hck- and PKCδ-mediated activation of PKCγ causing p47phox phosphorylation and membrane translocation in neutrophils. J Leukoc Biol :
Moore, Hunter B; Moore, Ernest E; Burlew, Clay C et al. (2016) Establishing Benchmarks for Resuscitation of Traumatic Circulatory Arrest: Success-to-Rescue and Survival among 1,708 Patients. J Am Coll Surg 223:42-50
Moore, Hunter B; Moore, Ernest E; Liras, Ioannis N et al. (2016) Acute Fibrinolysis Shutdown after Injury Occurs Frequently and Increases Mortality: A Multicenter Evaluation of 2,540 Severely Injured Patients. J Am Coll Surg 222:347-55
Chapman, Michael P; Moore, Ernest E; Moore, Hunter B et al. (2016) Overwhelming tPA release, not PAI-1 degradation, is responsible for hyperfibrinolysis in severely injured trauma patients. J Trauma Acute Care Surg 80:16-23; discussion 23-5
D'alessandro, Angelo; Nemkov, Travis; Moore, Hunter B et al. (2016) Metabolomics of trauma-associated death: shared and fluid-specific features of human plasma vs lymph. Blood Transfus 14:185-94
Nemkov, Travis; D'Alessandro, Angelo; Hansen, Kirk C (2015) Three-minute method for amino acid analysis by UHPLC and high-resolution quadrupole orbitrap mass spectrometry. Amino Acids 47:2345-57
Chapman, Michael P; Moore, Ernest E; Chin, Theresa L et al. (2015) Combat: Initial Experience with a Randomized Clinical Trial of Plasma-Based Resuscitation in the Field for Traumatic Hemorrhagic Shock. Shock 44 Suppl 1:63-70
D'Alessandro, Angelo; Nemkov, Travis; Kelher, Marguerite et al. (2015) Routine storage of red blood cell (RBC) units in additive solution-3: a comprehensive investigation of the RBC metabolome. Transfusion 55:1155-68

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