Identifying Age-Specific Risk Factors for Poor Outcomes After Trauma With Machine Learning.

INTRODUCTION: Risk stratification for poor outcomes is not currently age-specific. Risk stratification of older patients based on observational cohorts primarily composed of young patients may result in suboptimal clinical care and inaccurate quality benchmarking. We assessed two hypotheses. First, we hypothesized that risk factors for poor outcomes after trauma are age-dependent and, second, that the relative importance of various risk factors are also age-dependent. METHODS: A cohort study of severely injured adult trauma patients admitted to the intensive care unit 2014-2018 was performed using trauma registry data. Random forest algorithms predicting poor outcomes (death or complication) were built and validated using three cohorts: (1) patients of all ages, (2) younger patients, and (3) older patients. Older patients were defined as aged 55 y or more to maintain consistency with prior trauma literature. Complications assessed included acute renal failure, acute respiratory distress syndrome, cardiac arrest, unplanned intubation, unplanned intensive care unit admission, and unplanned return to the operating room, as defined by the trauma quality improvement program. Mean decrease in model accuracy (MDA), if each variable was removed and scaled to a Z-score, was calculated. MDA change ≥4 standard deviations between age cohorts was considered significant. RESULTS: Of 5489 patients, 25% were older. Poor outcomes occurred in 12% of younger and 33% of older patients. Head injury was the most important predictor of poor outcome in all cohorts. In the full cohort, age was the most important predictor of poor outcomes after head injury. Within age cohorts, the most important predictors of poor outcomes, after head injury, were surgery requirement in younger patients and arrival Glasgow Coma Scale in older patients. Compared to younger patients, head injury and arrival Glasgow Coma Scale had the greatest increase in importance for older patients, while systolic blood pressure had the greatest decrease in importance. CONCLUSIONS: Supervised machine learning identified differences in risk factors and their relative associations with poor outcomes based on age. Age-specific models may improve hospital benchmarking and identify quality improvement targets for older trauma patients.

Patient-Reported Outcomes Following Severe Abdominal Trauma: A Secondary Analysis of the Damage Control Laparotomy Trial.

INTRODUCTION: Little is known about patient-reported outcomes (PROs) following abdominal trauma. We hypothesized that patients undergoing definitive laparotomy (DEF) would have better PROs compared to those treated with damage control laparotomy (DCL). METHODS: The DCL Trial randomized DEF versus DCL in abdominal trauma. PROs were measured using the European Quality of Life-5 Dimensions-5 Levels (EQ-5D) questionnaire at discharge and six months postdischarge (1 = perfect health, 0 = death, and <0 = worse than death) and Posttraumatic Stress Disorder (PTSD) Checklist-Civilian. Unadjusted Bayesian analysis with a neutral prior was used to assess the posterior probability of achieving minimal clinically important difference. RESULTS: Of 39 randomized patients (21 DEF versus 18 DCL), 8 patients died (7 DEF versus 1 DCL). Of those who survived, 28 completed the EQ-5D at discharge (12 DEF versus 16 DCL) and 25 at 6 mo (12 DEF versus 13 DCL). Most patients were male (79%) with a median age of 30 (interquartile range (IQR) 21-42), suffered blunt injury (56%), and were severely injured (median injury severity score 33, IQR 21 - 42). Median EQ-5D value at discharge was 0.20 (IQR 0.06 - 0.52) DEF versus 0.31 (IQR -0.03 - 0.43) DCL, and at six months 0.51 (IQR 0.30 - 0.74) DEF versus 0.50 (IQR 0.28 - 0.84) DCL. The posterior probability of minimal clinically important difference DEF versus DCL at discharge and six months was 16% and 23%, respectively. CONCLUSIONS: Functional deficits for trauma patients persist beyond the acute setting regardless of laparotomy status. These deficits warrant longitudinal studies to better inform patients on recovery expectations.

Randomized Controlled Trial of Surgical Rib Fixation to Nonoperative Management in Severe Chest Wall Injury.

OBJECTIVE: To compare the effectiveness of surgical stabilization of rib fractures (SSRFs) to nonoperative management in severe chest wall injury. BACKGROUND: SSRF has been shown to improve outcomes in patients with clinical flail chest and respiratory failure. However, the effect of SSRF outcomes in severe chest wall injuries without clinical flail chest is unknown. METHODS: Randomized controlled trial comparing SSRF to nonoperative management in severe chest wall injury, defined as: (1) a radiographic flail segment without clinical flail or (2) ≥5 consecutive rib fractures or (3) any rib fracture with bicortical displacement. Randomization was stratified by the unit of admission as a proxy for injury severity. Primary outcome was hospital length of stay (LOS). Secondary outcomes included intensive care unit (ICU) LOS, ventilator days, opioid exposure, mortality, and incidences of pneumonia and tracheostomy. Quality of life at 1, 3, and 6 months was measured using the EQ-5D-5L survey. RESULTS: Eighty-four patients were randomized in an intention-to-treat analysis (usual care = 42, SSRF = 42). Baseline characteristics were similar between groups. The numbers of total fractures, displaced fractures, and segmental fractures per patient were also similar, as were the incidences of displaced fractures and radiographic flail segments. Hospital LOS was greater in the SSRF group. ICU LOS and ventilator days were similar. After adjusting for the stratification variable, hospital LOS remained greater in the SSRF group (RR: 1.48, 95% CI: 1.17-1.88). ICU LOS (RR: 1.65, 95% CI: 0.94-2.92) and ventilator days (RR: 1.49, 95% CI: 0.61--3.69) remained similar. Subgroup analysis showed that patients with displaced fractures were more likely to have LOS outcomes similar to their usual care counterparts. At 1 month, SSRF patients had greater impairment in mobility [3 (2-3) vs 2 (1-2), P = 0.012] and self-care [2 (1-2) vs 2 (2-3), P = 0.034] dimensions of the EQ-5D-5L. CONCLUSIONS: In severe chest wall injury, even in the absence of clinical flail chest, the majority of patients still reported moderate to extreme pain and impairment of usual physical activity at one month. SSRF increased hospital LOS and did not provide any quality of life benefit for up to 6 months.

Antithrombin Activity Is Associated with Persistent Thromboinflammation and Mortality in Patients with Severe COVID-19 Illness.

INTRODUCTION: Severe COVID-19 illness can lead to thrombotic complications, organ failure, and death. Antithrombin (AT) regulates thromboinflammation and is a key component of chemical thromboprophylaxis. Our goal was to examine the link between AT activity and responsiveness to thromboprophylaxis, markers of hypercoagulability, and inflammation among severe COVID-19 patients. METHODS: This was a single-center, prospective observational study enrolling SARS-CoV-2-positive patients admitted to the intensive care unit on prophylactic enoxaparin. Blood was collected daily for 7 days to assess AT activity and anti-factor Xa levels. Patient demographics, outcomes, and hospital laboratory results were collected. Continuous variables were compared using Mann-Whitney tests, and categorical variables were compared using χ2 tests. Multivariable logistic regression was used to determine the association between AT activity and mortality. RESULTS: In 36 patients, 3 thromboembolic events occurred, and 18 (50%) patients died. Patients who died had higher fibrinogen, D-dimer, and C-reactive protein (CRP) levels and lower AT activity. Reduced AT activity was independently associated with mortality and correlated with both markers of hypercoagulability (D-dimer) and inflammation (CRP). CONCLUSION: Low AT activity is associated with mortality and persistent hypercoagulable and proinflammatory states in severe COVID-19 patients. The anti-thromboinflammatory properties of AT make it an appealing therapeutic target for future studies.

Association of Opioid Administration During General Anesthesia and Survival for Severely Injured Trauma Patients: A Preplanned Secondary Analysis of the PROPPR Study.

BACKGROUND: There is a lack of reported clinical outcomes after opioid use in acute trauma patients undergoing anesthesia. Data from the Pragmatic, Randomized, Optimal Platelet and Plasma Ratios (PROPPR) study were analyzed to examine opioid dose and mortality. We hypothesized that higher dose opioids during anesthesia were associated with lower mortality in severely injured patients. METHODS: PROPPR examined blood component ratios in 680 bleeding trauma patients at 12 level 1 trauma centers in North America. Subjects undergoing anesthesia for an emergency procedure were identified, and opioid dose was calculated (morphine milligram equivalents [MMEs])/h. After separation of those who received no opioid (group 1), remaining subjects were divided into 4 groups of equal size with low to high opioid dose ranges. A generalized linear mixed model was used to assess impact of opioid dose on mortality (primary outcome, at 6 hours, 24 hours, and 30 days) and secondary morbidity outcomes, controlling for injury type, severity, and shock index as fixed effect factors and site as a random effect factor. RESULTS: Of 680 subjects, 579 had an emergent procedure requiring anesthesia, and 526 had complete anesthesia data. Patients who received any opioid had lower mortality at 6 hours (odds ratios [ORs], 0.02-0.04; [confidence intervals {CIs}, 0.003-0.1]), 24 hours (ORs, 0.01-0.03; [CIs, 0.003-0.09]), and 30 days (ORs, 0.04-0.08; [CIs, 0.01-0.18]) compared to those who received none (all P < .001) after adjusting for fixed effect factors. The lower mortality at 30 days in any opioid dose group persisted after analysis of those patients who survived >24 hours (P < .001). Adjusted analyses demonstrated an association with higher ventilator-associated pneumonia (VAP) incidence in the lowest opioid dose group compared to no opioid (P = .02), and lung complications were lower in the third opioid dose group compared to no opioid in those surviving 24 hours (P = .03). There were no other consistent associations of opioid dose with other morbidity outcomes. CONCLUSIONS: These results suggest that opioid administration during general anesthesia for severely injured patients is associated with improved survival, although the no-opioid group was more severely injured and hemodynamically unstable. Since this was a preplanned post hoc analysis and opioid dose not randomized, prospective studies are required. These findings from a large, multi-institutional study may be relevant to clinical practice.

Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury: The CRYOSTAT-2 Randomized Clinical Trial.

Importance: Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage. Objective: To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol. Design, Setting, and Participants: CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US major trauma centers from August 2017 to November 2021. Eligible patients were injured adults requiring activation of the hospital's major hemorrhage protocol with evidence of active hemorrhage, systolic blood pressure less than 90 mm Hg at any time, and receiving at least 1 U of a blood component transfusion. Intervention: Patients were randomly assigned (in a 1:1 ratio) to receive standard care, which was the local major hemorrhage protocol (reviewed for guideline adherence), or cryoprecipitate, in which 3 pools of cryoprecipitate (6-g fibrinogen equivalent) were to be administered in addition to standard care within 90 minutes of randomization and 3 hours of injury. Main Outcomes and Measures: The primary outcome was all-cause mortality at 28 days in the intention-to-treat population. Results: Among 1604 eligible patients, 799 were randomized to the cryoprecipitate group and 805 to the standard care group. Missing primary outcome data occurred in 73 patients (principally due to withdrawal of consent) and 1531 (95%) were included in the primary analysis population. The median (IQR) age of participants was 39 (26-55) years, 1251 (79%) were men, median (IQR) Injury Severity Score was 29 (18-43), 36% had penetrating injury, and 33% had systolic blood pressure less than 90 mm Hg at hospital arrival. All-cause 28-day mortality in the intention-to-treat population was 26.1% in the standard care group vs 25.3% in the cryoprecipitate group (odds ratio, 0.96 [95% CI, 0.75-1.23]; P = .74). There was no difference in safety outcomes or incidence of thrombotic events in the standard care vs cryoprecipitate group (12.9% vs 12.7%). Conclusions and Relevance: Among patients with trauma and bleeding who required activation of a major hemorrhage protocol, the addition of early and empirical high-dose cryoprecipitate to standard care did not improve all cause 28-day mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT04704869; ISRCTN Identifier: ISRCTN14998314.

Endothelial Cell Phenotypes Demonstrate Different Metabolic Patterns and Predict Mortality in Trauma Patients.

In trauma patients, shock-induced endotheliopathy (SHINE) is associated with a poor prognosis. We have previously identified four metabolic phenotypes in a small cohort of trauma patients (N = 20) and displayed the intracellular metabolic profile of the endothelial cell by integrating quantified plasma metabolomic profiles into a genome-scale metabolic model (iEC-GEM). A retrospective observational study of 99 trauma patients admitted to a Level 1 Trauma Center. Mass spectrometry was conducted on admission samples of plasma metabolites. Quantified metabolites were analyzed by computational network analysis of the iEC-GEM. Four plasma metabolic phenotypes (A-D) were identified, of which phenotype D was associated with an increased injury severity score (p < 0.001); 90% (91.6%) of the patients who died within 72 h possessed this phenotype. The inferred EC metabolic patterns were found to be different between phenotype A and D. Phenotype D was unable to maintain adequate redox homeostasis. We confirm that trauma patients presented four metabolic phenotypes at admission. Phenotype D was associated with increased mortality. Different EC metabolic patterns were identified between phenotypes A and D, and the inability to maintain adequate redox balance may be linked to the high mortality.

Validation of the Adapted Clavien-Dindo in Trauma (ACDiT) Classifications in Medical and Surgical Management of Acute Diverticulitis.

OBJECTIVES: To validate the adapted Clavien-Dindo in trauma (ACDiT) tool as a novel outcome measure for patients with acute diverticulitis managed both operatively and nonoperatively. BACKGROUND: Complications following diverticulitis are difficult to classify because no traditional tools address patients managed both operatively and nonoperatively. The ACDiT grading system-graded from 0 to 5b-is applied in this manner but has not yet been validated for this patient group. METHODS: We performed a 5-year observational study of patients with acute diverticulitis at a safety-net hospital. Baseline demographics and hospitalization data were collected. ACDiT scores were assigned, and validation was undertaken by comparing scores with hospital-free days, and verifying that higher scores were associated with known risk factors for poor outcomes. Inverse probability weighted propensity scores were assigned for surgical management, and inverse probability weighted regression analysis was used to determine factors associated with ACDiT ≥ grade 2. RESULTS: Of 260 patients, 188 (72%) were managed nonoperatively. Eighty (31%) developed a complication; 73 (91%) were grades 1 to 3b. Higher grades correlated inversely with hospital-free days (rs = -0.67, P < 0.0001) for all patients and for nonoperative (rs = -0.63, P < 0.0001) and operative (rs = -0.62, P < 0.0001) patients. Hinchey 2 to 3 and initial operative management had higher odds of having a complication of ACDiT ≥ grade 2. CONCLUSION: The ACDiT tool was successfully applied to acute diverticulitis patients managed operatively and nonoperatively, is associated with known risk factors for adverse outcomes. ACDiT may be considered a meaningful outcome measure for comparing strategies for acute diverticulitis.

Prospective Observational Evaluation of the ER-REBOA Catheter at 6 U.S. Trauma Centers.

OBJECTIVE: To describe the current use of the ER-REBOA catheter and associated outcomes and complications. INTRODUCTION: Noncompressible truncal hemorrhage is the leading cause of potentially preventable death in trauma patients. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a novel strategy to obtain earlier temporary hemorrhage control, supporting cardiac, and cerebral perfusion before definitive hemostasis. METHODS: Prospective, observational study conducted at 6 Level 1 Trauma Centers over 12-months. Inclusion criteria were age >15 years of age with evidence of truncal hemorrhage below the diaphragm and decision for emergent hemorrhage control intervention within 60 minutes of arrival. REBOA details, demographics, mechanism of injury, complications, and outcomes were collected. RESULTS: A total of 8166 patients were screened for enrollment. In 75, REBOA was utilized for temporary hemorrhage control. Blunt injury occurred in 80% with a median injury severity score (ISS) 34 (21, 43). Forty-seven REBOAs were placed in Zone 1 and 28 in Zone 3. REBOA inflation increased systolic blood pressure from 67 (40, 83) mm Hg to 108 (90, 128) mm Hg 5 minutes after inflation (P = 0.02). Cardiopulmonary resuscitation was ongoing during REBOA insertion in 17 patients (26.6%) and 10 patients (58.8%) had return of spontaneous circulation after REBOA inflation. The procedural complication rate was 6.6%. Overall mortality was 52%. CONCLUSION: REBOA can be used in blunt and penetrating trauma patients, including those in arrest. Balloon inflation uniformly improved hemodynamics and was associated with a 59% rate of return of spontaneous circulation for patients in arrest. Use of the ER-REBOA catheter is technically safe with a low procedural complication rate.

Learning from suicide deaths in Harris County, Texas.

This study examined individual and community demographic characteristics surrounding suicides in one of the most populous counties in the United States. We paired medical examiner records with U.S. Census data and analyzed them using geospatial software. The majority of decedents were non-Hispanic, white males who died primarily of gunshot wounds. Salient age characteristics included interpersonal violence and depression among ages younger than 40. Despite lower incomes and education levels, areas with higher population density and racial/ethnic minorities had fewer suicides. Additional research should address depression among males and the elderly, interpersonal violence, firearm access, and culture.

Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma.

BACKGROUND: The endotheliopathy of trauma (EoT) is associated with increased mortality following injury. Herein, we describe the plasma proteome related to EoT in order to provide insight into the role of the endothelium within the systemic response to trauma. METHODS: 99 subjects requiring the highest level of trauma activation were included in the study. Enzyme-linked immunosorbent assays of endothelial and catecholamine biomarkers were performed on admission plasma samples, as well as untargeted proteome quantification utilizing high-performance liquid chromatography and tandem mass spectrometry. RESULTS: Plasma endothelial and catecholamine biomarker abundance was elevated in EoT. Patients with EoT (n = 62) had an increased incidence of death within 24 h at 21% compared to 3% for non-EoT (n = 37). Proteomic analysis revealed that 52 out of 290 proteins were differentially expressed between the EoT and non-EoT groups. These proteins are involved in endothelial activation, coagulation, inflammation, and oxidative stress, and include known damage-associated molecular patterns (DAMPs) and intracellular proteins specific to several organs. CONCLUSIONS: We report a proteomic profile of EoT suggestive of a surge of DAMPs and inflammation driving nonspecific activation of the endothelial, coagulation, and complement systems with subsequent end-organ damage and poor clinical outcome. These findings support the utility of EoT as an index of cellular injury and delineate protein candidates for therapeutic intervention.

Metabolic Response in Endothelial Cells to Catecholamine Stimulation Associated with Increased Vascular Permeability.

Disruption to endothelial cell homeostasis results in an extensive variety of human pathologies that are particularly relevant to major trauma. Circulating catecholamines, such as adrenaline and noradrenaline, activate endothelial adrenergic receptors triggering a potent response in endothelial function. The regulation of the endothelial cell metabolism is distinct and profoundly important to endothelium homeostasis. However, a precise catalogue of the metabolic alterations caused by sustained high catecholamine levels that results in endothelial dysfunction is still underexplored. Here, we uncover a set of up to 46 metabolites that exhibit a dose-response relationship to adrenaline-noradrenaline equimolar treatment. The identified metabolites align with the glutathione-ascorbate cycle and the nitric oxide biosynthesis pathway. Certain key metabolites, such as arginine and reduced glutathione, displayed a differential response to treatment in early (4 h) compared to late (24 h) stages of sustained stimulation, indicative of homeostatic metabolic feedback loops. Furthermore, we quantified an increase in the glucose consumption and aerobic respiration in endothelial cells upon catecholamine stimulation. Our results indicate that oxidative stress and nitric oxide metabolic pathways are downstream consequences of endothelial cell stimulation with sustained high levels of catecholamines. A precise understanding of the metabolic response in endothelial cells to pathological levels of catecholamines will facilitate the identification of more efficient clinical interventions in trauma patients.

Age-related Opioid Exposure in Trauma: A Secondary Analysis of the Multimodal Analgesia Strategies for Trauma (MAST) Randomized Trial.

OBJECTIVE: Evaluate the effect of age on opioid consumption after traumatic injury. SUMMARY BACKGROUND DATA: Older trauma patients receive fewer opioids due to decreased metabolism and increased complications, but adequacy of pain control is unknown. We hypothesized that older trauma patients require fewer opioids to achieve adequate pain control. METHODS: A secondary analysis of the multimodal analgesia strategies for trauma Trial evaluating the effectiveness of 2 multimodal pain regimens in 1561 trauma patients aged 16 to 96 was performed. Older patients (≥55 years) were compared to younger patients. Median daily oral morphine milligram equivalents (MME) consumption, average numeric rating scale pain scores, complications, and death were assessed. Multivariable analyses were performed. RESULTS: Older patients (n = 562) had a median age of 68 years (interquartile range 61-78) compared to 33 (24-43) in younger patients. Older patients had lower injury severity scores (13 [9-20] vs 14 [9-22], P = 0.004), lower average pain scores (numeric rating scale 3 [1-4] vs 4 [2-5], P < 0.001), and consumed fewer MME/day (22 [10-45] vs 52 [28-78], P < 0.001). The multimodal analgesia strategies for trauma multi-modal pain regimen was effective at reducing opioid consumption at all ages. Additionally, on multivariable analysis including pain score adjustment, each decade age increase after 55 years was associated with a 23% reduction in MME/day consumed. CONCLUSIONS: Older trauma patients required fewer opioids than younger patients with similar characteristics and pain scores. Opioid dosing for post-traumatic pain should consider age. A 20 to 25% dose reduction per decade after age 55 may reduce opioid exposure without altering pain control.

Evaluation of Noninvasive Hemoglobin Measurements in Trauma Patients: A Repeat Study.

INTRODUCTION: Reliable, accurate, and non-invasive hemoglobin measurements would be useful in the trauma setting. The aim of this study was to re-examine the ability of the Masimo Radical 7 in this setting after recent hardware and software improvements. METHODS: Level 1 Trauma patients were prospectively enrolled in the study over a 9-mo period with the goal of obtaining 3 paired data points from 150 patients admitted to the ICU or IMU. Hospital laboratory hemoglobin values were compared with cyanomethemoglobin (HiCN) and Masimo device hemoglobin (SpHb) values using comparison plots and Bland-Altman analysis. RESULTS: A total of 380 patients were enrolled in the study with 150 of those being admitted to the ICU or IMU. Comparison of hospital lab hemoglobin and HiCN (n = 494) found a correlation of R2 = 0.92. Comparison of hospital lab hemoglobin and Masimo device hemoglobin (n = 218) found a correlation of R2 = 0.27. Bland-Altman analysis of the 218 of the comparable hospital hemoglobin and Masimo device hemoglobin values had a bias of 0.505 g/dL with 95% of values within the limits of agreement of 4.06 g/dL to -3.60 g/dL. CONCLUSIONS: The Masimo Radical 7 device has the potential to provide timely, useful clinical information, but it is not currently able to serve as an initial noninvasive diagnostic tool for trauma patients. There was poor correlation between clinical Hgb and SpHb, and because of that, SpHb should not be used to evaluate hemoglobin levels in trauma patients.

Predictors for Direct to Operating Room Admission in Severe Trauma.

BACKGROUND: Protocols for expediting critical trauma patients directly from the helipad to the operating room tend to vary by center, rely heavily on physician gestalt, and lack supporting evidence. We evaluated a population of severely injured trauma patients with the aim of determining objective factors associated with the need for immediate surgical intervention. METHODS: All highest-activation trauma patients transported by air ambulance between 1/1/16 and 12/31/17 were enrolled retrospectively. Transfer, pediatric, isolated burn, and isolated head trauma patients were excluded. Patients who underwent emergency general surgery within 30 min of arrival without the aid of cross-sectional imaging were compared to the remainder of the cohort. RESULTS: Of the 863 patients who were enrolled, 85 (10%) spent less than 30 min in the emergency department (ED) before undergoing an emergency operation. The remaining 778 patients (90%) formed the comparison group. The ED ≤ 30 min group had a higher percentage of penetrating injuries, lower blood pressure, and was more likely to have a positive FAST exam. The "Direct to Operating Room" (DTOR) score is a predictive scoring system devised to identify patients most likely to benefit from bypassing the ED. The odds ratio of emergency operation within 30 min of hospital arrival increased by 2.71 (95% confidence interval 2.23-3.29; P < 0.001) for every 1-point increase in DTOR score. CONCLUSIONS: Trauma patients with profound hypotension or acidosis and positive FAST were more likely to require surgery within 30 min of hospital presentation. Use of a scoring system may allow early identification of these patients in the prehospital setting by nonphysician providers.

Prehospital ABC Score Accurately Forecasts Patients Who Will Require Immediate Resource Utilization.

OBJECTIVES: Scoring systems, such as the Assessment of Blood Consumption (ABC) Score, are used to identify patients at risk for massive transfusion (MT, ≥10 U red blood cells in 24 hours). Our aeromedical transport helicopter uses ultrasound to perform the Focused Assessment with Sonography for Trauma (FAST) examination. Our objective was to evaluate the ability of the Prehospital ABC (PhABC) Score to predict blood transfusions and the need for emergent laparotomy. METHODS: Post hoc analysis of a prospective observational study of trauma patients who underwent an in-flight FAST during aeromedical transport during a 7-month period. PhABC Score was positive if ≥2 of the following were present in flight: penetrating trauma, heart rate >120 bpm, systolic blood pressure <90 mm Hg, or a positive abdominal FAST. The PhABC Score was evaluated by area under the receiver operating characteristic (AUROC) curves and logistic regression. RESULTS: A total of 291 trauma patients met inclusion criteria, 23 underwent emergent laparotomy, and 12 received an MT. A positive PhABC Score predicted emergent laparotomy, with a positive predictive value of 48% and a negative predictive value of 95% (sensitivity 46%, specificity 96%, AUROC curve 0.83). A positive PhABC Score also predicted receipt of an MT with a positive predictive value of 28% and a negative predictive value of 94% (sensitivity 33%, specificity 93%, AUROC curve 0.77). Multiple logistic regression identified FAST as the most powerful contributor of the PhABC Score to the prediction of both emergent laparotomy (odds ratio 8.5, P < 0.001) and MT (odds ratio 5.9, P < 0.001). CONCLUSIONS: The PhABC Score effectively predicts in-hospital resource utilization. It provides an outstanding undertriage rate from the prehospital setting, and it is helpful to improve trauma team activation, mobilize blood products, and prepare the operating room.

Microelectromechanical System Measurement of Platelet Contraction: Direct Interrogation of Myosin Light Chain Phosphorylation.

Myosin Light Chain (MLC) regulates platelet contraction through its phosphorylation by Myosin Light Chain Kinase (MLCK) or dephosphorylation by Myosin Light Chain Phosphatase (MLCP). The correlation between platelet contraction force and levels of MLC phosphorylation is unknown. We investigate the relationship between platelet contraction force and MLC phosphorylation using a novel microelectromechanical (MEMS) based clot contraction sensor (CCS). The MLCK and MLCP pair were interrogated by inhibitors and activators of platelet function. The CCS was fabricated from silicon using photolithography techniques and force was validated over a range of deflection for different chip spring constants. The force of platelet contraction measured by the clot contraction sensor (CCS) was compared to the degree of MLC phosphorylation by Western Blotting (WB) and ELISA. Stimulators of MLC phosphorylation produced higher contraction force, higher phosphorylated MLC signal in ELISA and higher intensity bands in WB. Inhibitors of MLC phosphorylation produced the opposite. Contraction force is linearly related to levels of phosphorylated MLC. Direct measurements of clot contractile force are possible using a MEMS sensor platform and correlate linearly with the degree of MLC phosphorylation during coagulation. Measured force represents the mechanical output of the actin/myosin motor in platelets regulated by myosin light chain phosphorylation.

Metabolic Systems Analysis of Shock-Induced Endotheliopathy (SHINE) in Trauma: A New Research Paradigm.

OBJECTIVE: Investigate the endothelial cell phenotype (s) that causes Shock-Induced Endotheliopathy in trauma. BACKGROUND: We have studied more than 2750 trauma patients and identified that patients with high circulating syndecan-1 (endothelial glycocalyx damage marker) in plasma have an increased mortality rate compared with patients with lower levels. Notably, we found that patients suffering from the same trauma severity could develop significantly different degrees of endothelial dysfunction as measured by syndecan-1. METHODS: Prospective observational study of 20 trauma patients admitted to a Level 1 Trauma Centre and 20 healthy controls. Admission plasma syndecan-1 level and mass spectrometry were measured and analyzed by computational network analysis of our genome-scale metabolic model of the microvascular endothelial cell function. RESULTS: Trauma patients had a significantly different endothelial metabolic profile compared with controls. Among the patients, 4 phenotypes were identified. Three phenotypes were independent of syndecan-1 levels. We developed genome-scale metabolic models representative of the observed phenotypes. Within these phenotypes, we observed differences in the cell fluxes from glucose and palmitate to produce Acetyl-CoA, and secretion of heparan sulfate proteoglycan (component of syndecan-1). CONCLUSIONS: We confirm that trauma patients have a significantly different metabolic profile compared with controls. A minimum of 4 shock-induced endotheliopathy phenotypes were identified, which were independent of syndecan-1level (except 1 phenotype) verifying that the endothelial response to trauma is heterogeneous and most likely driven by a genetic component. Moreover, we introduced a new research tool in trauma by using metabolic systems biology, laying the foundation for personalized medicine.

Establishing a Regional Trauma Preventable/Potentially Preventable Death Rate.

OBJECTIVE: To establish a trauma preventable/potentially preventable death rate (PPPDR) within a heavily populated county in Texas. SUMMARY: The National Academies of Sciences estimated the trauma preventable death rate in the United States to be 20%, issued a call for zero preventable deaths, while acknowledging that an accurate preventable death rate was lacking. In this absence, effective strategies to improve quality of care across trauma systems will remain difficult. METHODS: A retrospective review of death-related records that occurred during 2014 in Harris County, TX, a diverse population of 4.4 million. Patient demographics, mechanism of injury, cause, timing, and location of deaths were assessed. Deaths were categorized using uniform criteria and recorded as preventable, potentially preventable or nonpreventable. RESULTS: Of 1848 deaths, 85% had an autopsy and 99.7% were assigned a level of preventability, resulting in a trauma PPPDR of 36.2%. Sex, age, and race/ethnicity varied across preventability categories (P < 0.01). Of 847 prehospital deaths, 758 (89.5%) were nonpreventable. Among 89 prehospital preventable/potentially preventable (P/PP) deaths, hemorrhage accounted for 55.1%. Of the 657 initial acute care setting deaths, 292 (44.4%) were P/PP; of these, hemorrhage, sepsis, and traumatic brain injury accounted for 73.3%. Of 339 deaths occurring after initial hospitalization, 287 (84.7%) were P/PP, of these 117 resulted from sepsis and 31 from pulmonary thromboembolism, accounted for 51.6%. CONCLUSIONS: The trauma PPPDR was almost double that estimated by the National Academies of Sciences. Data regarding P/PP deaths offers opportunity to target research, prevention, intervention, and treatment corresponding to all phases of the trauma system.

A Novel Platelet Function Assay for Trauma.

BACKGROUND: Platelet function tests such as thrombelastography platelet mapping and impedance aggregometry have demonstrated universal platelet dysfunction in trauma patients. In this study, we introduce the measurement of platelet contraction force as a test of platelet function. We hypothesize that force will correlate with established coagulation tests such as thrombelastography, demonstrate significant differences between healthy subjects and trauma patients, and identify critically ill trauma patients. METHODS: Blood samples were prospectively collected from level 1 trauma patients at initial presentation, assayed for force of and time to contraction and compared with thrombelastography. Blood from healthy subjects was assayed to establish a reference range. Results from trauma patients were compared with healthy controls and trauma patients that died. RESULTS: The study includes one hundred trauma patients with mean age 45 y, 74% were male, and median injury severity score of 14 ± 12. Patients that survived (n = 90) demonstrated significantly elevated platelet contraction force compared with healthy controls (n = 12) (6390 ± 2340 versus 4790 ± 470 µN, P = 0.043) and trauma patients that died (n = 10) (6390 ± 2340 versus 2860 ± 1830 µN, P = 0.0001). Elapsed time to start of platelet contraction was faster in trauma patients that survived compared with healthy controls (660 ± 467 versus 1130 ± 140 s, P = 0.0022) and those that died (660 ± 470 versus 1460 ± 1340 s, P < 0.0001). CONCLUSIONS: In contrast with all existing platelet function tests reported in the literature, which report platelet dysfunction in trauma patients, contractile force demonstrates hyperfunction in surviving trauma patients and dysfunction in nonsurvivors. Platelet contraction reflects platelet metabolic reserve and thus may be a potential biomarker for survival after trauma. Contractile force warrants further investigation to predict mortality in severely injured trauma patients.