Succinate Activation of SUCNR1 Predisposes Severely Injured Patients to Neutrophil-mediated ARDS.

Objectives: Identify the metabolites that are increased in the plasma of severely injured patients that developed ARDS versus severely injured patients that did not, and assay if these increased metabolites prime pulmonary sequestration of neutrophils (PMNs) and induce pulmonary sequestration in an animal model of ARDS. We hypothesize that metabolic derangement due to advanced shock in critically injured patients leads to the PMNs, which serves as the first event in the ARDS. Summary of Background Data: Intracellular metabolites accumulate in the plasma of severely injured patients.

Evaluation of a water-soluble contrast protocol for small bowel obstruction: A southwestern surgical congress multicenter trial.

Differentiation between SBO that will resolve with supportive measures and those requiring surgery remains challenging. WSC administration may be diagnostic and therapeutic. The purpose of this study was to evaluate use of a SBO protocol using WSC challenge.

The Extremity/Mechanism/Shock Index/GCS (EMS-G) score: A novel pre-hospital scoring system for early and appropriate MTP activation.

Background: Numerous in-hospital scoring systems to activate massive transfusion protocols (MTP) have been proposed; however, to date, pre-hospital scoring systems have not been robustly validated. Many trauma centers do not have blood or pre-thawed plasma available in the trauma bay, leading to delays in balanced transfusion. This study aims to assess pre-hospital injury and physiologic parameters to develop a pre-hospital scoring system predictive of need for massive transfusion (MT) prior to patient arrival.

Female platelets have distinct functional activity compared with male platelets: Implications in transfusion practice and treatment of trauma-induced coagulopathy.

Background: Females are hypercoagulable and have survival benefit in trauma-induced coagulopathy (TIC). The mechanism for this sex-specific hypercoagulability is unknown. Platelets and platelet function are central in providing hemostatic potential and are the largest contributor to clot strength.

Preventable death and interpersonal violence in the United States: Who can be saved?

Background: Public health initiatives to reduce mortality from penetrating trauma have largely developed from patterns of injury observed in military casualties, with a focus on hemorrhage control and use of tourniquets. Recent efforts show that injury patterns differ between civilian mass casualty events and combat settings, and no studies characterize wounding patterns in all types of civilian homicide. We hypothesize that many homicide deaths are due to nonsurvivable injuries, and that an effective strategy to reduce mortality must focus on both primary prevention as well as improvement in trauma prehospital care.

Obstruction reduction: Use of water-soluble contrast challenge to differentiate between partial and complete small bowel obstruction.

Differentiating SBO that will resolve conservatively from those requiring surgery remains challenging. Water-soluble contrast administration may be diagnostic and therapeutic. Our study evaluated use of a WSC challenge protocol.

Trauma Resuscitation Consideration: Sex Matters.

Background: Sex dimorphisms in coagulation have been recognized, but whole blood assessment of these dimorphisms and their relationship to outcomes in trauma have not been investigated. This study characterizes the viscoelastic hemostatic profile of severely injured patients by sex, and examines how sex-specific coagulation differences affect clinical outcomes, specifically, massive transfusion (MT) and death. We hypothesized that severely injured females are more hypercoagulable and therefore, have lower rates of MT and mortality.

The why and how our trauma patients die: A prospective Multicenter Western Trauma Association study.

Background: Historically, hemorrhage has been attributed as the leading cause (40%) of early death. However, a rigorous, real-time classification of the cause of death (COD) has not been performed. This study sought to prospectively adjudicate and classify COD to determine the epidemiology of trauma mortality.

Effect of Pre-Hospital Use of the Assessment of Blood Consumption Score and Pre-Thawed Fresh Frozen Plasma on Resuscitation and Trauma Mortality.

Background: Early blood product resuscitation reduces trauma patient mortality from hemorrhage. This mortality benefit depends on a system that can rapidly identify actively bleeding patients, initiate massive transfusion protocol (MTP), and mobilize resources to the bedside. We hypothesized that process improvement efforts that identify patients early and mobilize appropriate blood products to the bedside for immediate use would improve mortality.

Red blood cells in hemorrhagic shock: a critical role for glutaminolysis in fueling alanine transamination in rats.

Red blood cells (RBCs) are the most abundant host cell in the human body and play a critical role in oxygen transport and systemic metabolic homeostasis. Hypoxic metabolic reprogramming of RBCs in response to high-altitude hypoxia or anaerobic storage in the blood bank has been extensively described. However, little is known about the RBC metabolism following hemorrhagic shock (HS), the most common preventable cause of death in trauma, the global leading cause of total life-years lost.

The Metabolopathy of Tissue Injury, Hemorrhagic Shock, and Resuscitation in a Rat Model.

Introduction: The metabolic consequences of trauma induce significant clinical pathology. In this study, we evaluate the independent, metabolic contributions of tissue injury (TI) and combined tissue injury and hemorrhagic shock (TI/HS) using mass spectrometry (MS) metabolomics in a controlled animal model of critical injury.

Methods: Sprague-Dawley rats (n = 14) underwent TI alone or TI/HS, followed by resuscitation with normal saline and shed blood.

Glutamine metabolism drives succinate accumulation in plasma and the lung during hemorrhagic shock.

Background: Metabolomic investigations have consistently reported succinate accumulation in plasma after critical injury. Succinate receptors have been identified on numerous tissues, and succinate has been directly implicated in postischemic inflammation, organ dysfunction, platelet activation, and the generation of reactive oxygen species, which may potentiate morbidity and mortality risk to patients. Metabolic flux (heavy-isotope labeling) studies demonstrate that glycolysis is not the primary source of increased plasma succinate during protracted shock.

Trauma/hemorrhagic shock instigates aberrant metabolic flux through glycolytic pathways, as revealed by preliminary (13)C-glucose labeling metabolomics.

Background: Metabolic derangement is a key hallmark of major traumatic injury. The recent introduction of mass spectrometry-based metabolomics technologies in the field of trauma shed new light on metabolic aberrations in plasma that are triggered by trauma and hemorrhagic shock. Alteration in metabolites associated with catabolism, acidosis and hyperglycemia have been identified.

Pathologic metabolism: an exploratory study of the plasma metabolome of critical injury.

Background: Severe trauma is associated with massive alterations in metabolism. Thus far, investigations have relied on traditional bioanalytic approaches including calorimetry or nuclear magnetic resonance. However, recent strides in mass spectrometry (MS)-based metabolomics present enhanced analytic opportunities to characterize a wide range of metabolites in the critical care setting.

Dynamic changes in rat mesenteric lymph proteins following trauma using label-free mass spectrometry.

Early events triggered by posttrauma/hemorrhagic shock currently represent a leading cause of morbidity and mortality in these patients. The causative agents of these events have been associated with increased neutrophil priming secondary to shock-dependent alterations of mesenteric lymph. Previous studies have suggested that unknown soluble components of the postshock mesenteric lymph are main drivers of these events.

Early tracheostomy improves outcomes in severely injured children and adolescents.

Background: Early tracheostomy has been advocated for adult trauma patients to improve outcomes and resource utilization. We hypothesized that timing of tracheostomy for severely injured children would similarly impact outcomes.

Methods: Injured children undergoing tracheostomy over a 10-year period (2002-2012) were reviewed.

Proteomic profiling of the mesenteric lymph after hemorrhagic shock: Differential gel electrophoresis and mass spectrometry analysis.

Experiments show that upon traumatic injury the composition of mesenteric lymph changes such that it initiates an immune response that can ultimately result in multiple organ dysfunction syndrome (MODS). To identify candidate protein mediators of this process we carried out a quantitative proteomic study on mesenteric lymph from a well characterized rat shock model. We analyzed three animals using analytical 2D differential gel electrophoresis.

Proteome and system ontology of hemorrhagic shock: exploring early constitutive changes in postshock mesenteric lymph.

Background: Postshock mesenteric lymph (PSML) is the mechanistic link between splanchnic ischemia reperfusion (IR) and remote organ injury. We hypothesize that an unbiased inspection of the proteome of PSML will reveal previously unrecognized aberrations in systems biology provoked by hemorrhage-induced mesenteric IR injury in vivo.

Methods: Shock was induced in male Sprague-Dawley rats by controlled hemorrhage, and the mesenteric duct was cannulated for lymph collection.

HMGB1 is markedly elevated within 6 hours of mechanical trauma in humans.

High-mobility group box 1 (HMGB1) is a late mediator of the systemic inflammation associated with sepsis. Recently, HMGB1 has been shown in animals to be a mediator of hemorrhage-induced organ dysfunction. However, the time course of plasma HMGB1 elevations after trauma in humans remains to be elucidated.