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Background: Traumatic fibrinolytic dysfunction is often categorized into 3 phenotypes based on the result of thromboelastography (TEG) lysis at 30 minutes (LY30): fibrinolysis shutdown, physiologic fibrinolysis, and hyperfibrinolysis. However, the molecular pathophysiology of fibrinolytic dysfunction and the association with clinical outcomes have not been fully evaluated. Objectives: To assess whether posttraumatic fibrinolysis phenotypes identified by TEG correlate with levels of key fibrinolysis-related serum markers and with risk of mortality and hospital complications. Methods: This is a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. Patients were stratified according to the degree of fibrinolysis upon arrival using TEG LY30 values: low LY30,

Abstract Background Optimizing resuscitation to reduce inflammation and organ dysfunction following human trauma-associated hemorrhagic shock is a major clinical hurdle. This is limited by the short duration of pre-clinical studies and the sparsity of early data in the clinical setting. Methods We sought to bridge this gap by linking preclinical data in a porcine model with clinical data from patients from the Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) study via a three-compartment ordinary differential equation model of inflammation and coagulation. Results The mathematical model accurately predicts physiologic, inflammatory, and laboratory measures in both the porcine model and patients, as well as the outcome and time of death in the PROMMTT cohort. Model simulation suggests that resuscitation with plasma and red blood cells outperformed resuscitation with crystalloid or plasma alone, and that earlier plasma resuscitation reduced injury severity and increased survival time. Conclusions This workflow may serve as a translational bridge from pre-clinical to clinical studies in trauma-associated hemorrhagic shock and other complex disease settings.

Introduction Whole blood (WB) transfusion represents a promising resuscitation strategy for trauma patients. However, a paucity of data surrounding the optimal incorporation of WB into resuscitation strategies persists. We hypothesized that traumatically injured patients who received a greater proportion of WB compared with blood product components during their resuscitative efforts would have improved early mortality outcomes and decreased transfusion requirements compared with those who received a greater proportion of blood product components.Methods Retrospective review from our Level 1 trauma center of trauma patients during their initial resuscitation (2019–2022) was performed. WB to packed red blood cell ratios (WB:RBC) were assigned to patients based on their respective blood product resuscitation at 1, 2, 3, and 24 hours from presentation. Multivariable regression models were constructed to assess the relationship of WB:RBC to 4 and 24-hour mortality, and 24-hour transfusion requirements.Results 390 patients were evaluated (79% male, median age of 33 years old, 48% penetrating injury rate, and a median Injury Severity Score of 27). Overall mortality at 4 hours was 9%, while 24-hour mortality was 12%. A significantly decreased 4-hour mortality was demonstrated in patients who displayed a WB:RBC≥1 at 1 hour (5.9% vs. 12.3%; OR 0.17, p=0.015), 2 hours (5.5% vs. 13%; OR 0.16, p=0.019), and 3 hours (5.5% vs. 13%, OR 0.18, p

ABSTRACTThe use of blood products to resuscitate injured and massively bleeding patients in the prehospital and early in-hospital phase of the resuscitation is increasing. Using group O red blood cells (RBC) and low titer group O whole blood (LTOWB) avoids an immediate hemolytic reaction from recipient’s naturally occurring anti-A and – B, but choosing the RhD type for these products is more nuanced and requires the balancing of product availability and survival benefit against the risk of D-alloimmunization, especially in females of childbearing potential (FCP) due to the possible future occurrence of hemolytic disease of the fetus and newborn (HDFN). Recent models have estimated the risk of fetal/neonatal death from HDFN resulting from D-alloimmunization of an FCP during her trauma resuscitation at between 0-6.5% depending on her age at the time of the transfusion and other societal factors including trauma mortality, her age when she becomes pregnant, frequency of different RHD genotypes in the population, and the probability that the woman will have children with different fathers; this is counterbalanced by an approximately 24% risk of death from hemorrhagic shock. This review will discuss the different models of HDFN outcomes following RhD-positive transfusion as well as the results of recent surveys where the public was asked about their preferences for urgent transfusion in light of the risks of fetal/neonatal adverse events.

Objective:. Develop a novel machine learning (ML) model to rapidly identify trauma patients with severe hemorrhage at risk of early mortality. Background:. The critical administration threshold (CAT, 3 or more units of red blood cells in a 60-minute period) indicates severe hemorrhage and predicts mortality, whereas early identification of such patients improves survival. Methods:. Patients from the PRospective, Observational, Multicenter, Major Trauma Transfusion and Pragmatic, Randomized Optimal Platelet, and Plasma Ratio studies were identified as either CAT+ or CAT−. Candidate variables were separated into 4 tiers based on the anticipated time of availability during the patient’s assessment. ML models were created with the stepwise addition of variables and compared with the baseline performance of the assessment of blood consumption (ABC) score for CAT+ prediction using a cross-validated training set and a hold-out validation test set. Results:. Of 1245 PRospective, Observational, Multicenter, Major Trauma Transfusion and 680 Pragmatic, Randomized Optimal Platelet and Plasma Ratio study patients, 1312 were included in this analysis, including 862 CAT+ and 450 CAT−. A CatBoost gradient-boosted decision tree model performed best. Using only variables available prehospital or on initial assessment (Tier 1), the ML model performed superior to the ABC score in predicting CAT+ patients [area under the receiver-operator curve (AUC = 0.71 vs 0.62)]. Model discrimination increased with the addition of Tier 2 (AUC = 0.75), Tier 3 (AUC = 0.77), and Tier 4 (AUC = 0.81) variables. Conclusions:. A dynamic ML model reliably identified CAT+ trauma patients with data available within minutes of trauma center arrival, and the quality of the prediction improved as more patient-level data became available. Such an approach can optimize the accuracy and timeliness of massive transfusion protocol activation.

Background Trauma patients exhibit a multifactorial hypercoagulable state and have increased risk of venous thromboembolism (VTE). Despite early and aggressive chemoprophylaxis (CP) with various heparin compounds (“standard” CP; sCP), VTE rates remain high. In high-quality studies, aspirin has been shown to decrease VTE in postoperative elective surgical and orthopedic trauma patients. We hypothesized that inhibiting platelet function with aspirin as an adjunct to sCP would reduce the risk of VTE in trauma patients.Methods We performed a retrospective observational study of prospectively collected data from all adult patients admitted to an American College of Surgeons Level I Trauma center from January 2012 to June 2015 to evaluate the addition of aspirin (sCP+A) to sCP regimens for VTE mitigation. Cox proportional hazard models were used to assess the potential benefit of adjunctive aspirin for symptomatic VTE incidence.Results 10,532 patients, median age 44 (IQR 28 to 62), 68% male, 89% blunt mechanism of injury, with a median Injury Severity Score (ISS) of 12 (IQR 9 to 19), were included in the study. 8646 (82%) of patients received only sCP, whereas 1886 (18%) patients received sCP+A. The sCP+A cohort displayed a higher median ISS compared with sCP (13 vs 11; p

Introduction The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial failed to demonstrate a mortality difference for hemorrhaging patients receiving a balanced (1:1:1) vs a 1:1:2 resuscitation at 24 hours and 30 days. Recent guidelines recommend earlier mortality end points for hemorrhage-control trials, and the use of contemporary statistical methods. The aim of this post hoc analysis of the PROPPR trial was to evaluate the impact of a balanced resuscitation strategy at early resuscitation time points using a Bayesian analytical framework.Methods Bayesian hierarchical models were created to assess mortality differences at the 1, 3, 6, 12, 18, and 24 hours time points between study cohorts. Posterior probabilities and Bayes factors were calculated for each time point.Results A 1:1:1 resuscitation displayed a 96%, 99%, 94%, 92%, 96%, and 94% probability for mortality benefit at 1, 3, 6, 12, 18, and 24 hours, respectively, when compared with a 1:1:2 approach. Associated Bayes factors for each respective time period were 21.2, 142, 14.9, 11.4, 26.4, and 15.5, indicating ‘strong’ to ‘decisive’ supporting evidence in favor of balanced transfusions.Conclusion This analysis provides evidence in support that a 1:1:1 resuscitation has a high probability of mortality benefit when compared with a 1:1:2 strategy, especially at the newly defined more proximate time points during the resuscitative period. Researchers should consider using Bayesian approaches, along with more proximate end points when assessing hemorrhage-related mortality, for the analysis of future clinical trials.Level of evidence Level III/Therapeutic.

Background The effects of aortic occlusion (AO) on brain injury are not well defined. We examined the impact of AO by resuscitative endovascular balloon occlusion of the aorta (REBOA) and resuscitative thoracotomy (RT) on outcomes in the setting of traumatic brain injury (TBI).Methods Patients sustaining TBI who underwent RT or REBOA in zone 1 (thoracic aorta) from September 2013 to December 2018 were identified. The indication for REBOA or RT was hemodynamic collapse due to hemorrhage below the diaphragm. Primary outcomes included mortality and systemic complications.Results 282 patients underwent REBOA or RT. Of these, 76 had mild TBI (40 REBOA, 36 RT) and 206 sustained severe TBI (107 REBOA, 99 RT). Overall, the mean (±SD) age was 42±17 years, with an Injury Severity Score (ISS) of 40±17 and mean systolic blood pressure (SBP) at the time of REBOA or RT of 81±34 mm Hg. REBOA patients had a mean SBP at the time of AO of 78.39±29.45 mm Hg, whereas RT patients had a mean SBP of 83.18±37.87 mm Hg at the time of AO (p=0.24). 55% had ongoing cardiopulmonary resuscitation (CPR) at the time of AO, and the in-hospital mortality was 86%. Binomial logistic regression controlling for TBI severity, age, ISS, SBP at the time of AO, crystalloid infusion, and CPR during AO demonstrated that the odds of mortality are 3.1 times higher for RT compared with REBOA. No significant differences were found in systemic complications between RT and REBOA.Discussion Patients with TBI who receive REBOA may have improved survival, but no difference in systemic complications, compared with patients who receive RT for the same indication. Although some patients are receiving RT prior to arrest for extrathoracic hemorrhagic shock, these results suggest that REBOA should be considered as an alternative to RT when RT is chosen for the sole purpose of resuscitation in the setting of TBI.Level of evidence 4.

Introduction Major haemorrhage after injury is the leading cause of preventable death for trauma patients. Recent advancements in trauma care suggest damage control resuscitation (DCR) should start in the prehospital phase following major trauma. In Italy, Helicopter Emergency Medical Services (HEMS) assist the most complex injuries and deliver the most advanced interventions including DCR. The effect size of DCR delivered prehospitally on survival remains however unclear.Methods and analysis This is an investigator-initiated, large, national, prospective, observational cohort study aiming to recruit >500 patients in haemorrhagic shock after major trauma. We aim at describing the current practice of hypotensive trauma management as well as propose the creation of a national registry of patients with haemorrhagic shock. Primary objective: the exploration of the effect size of the variation in clinical practice on the mortality of hypotensive trauma patients. The primary outcome measure will be 24 hours, 7-day and 30-day mortality. Secondary outcomes include: association of prehospital factors and survival from injury to hospital admission, hospital length of stay, prehospital and in-hospital complications, hospital outcomes; use of prehospital ultrasound; association of prehospital factors and volume of first 24-hours blood product administration and evaluation of the prevalence of use, appropriateness, haemodynamic, metabolic and effects on mortality of prehospital blood transfusions. Inclusion criteria: age >18 years, traumatic injury attended by a HEMS team including a physician, a systolic blood pressure

Abstract Background Patients with hemorrhagic shock from trauma often require balanced blood product transfusion with red blood cells, plasma, and platelets. Resuscitation with whole blood resuscitation is becoming a common practice. We performed a systematic review and meta‐analysis of studies comparing whole blood transfusion with balanced component therapy in patients suffering from traumatic hemorrhagic shock. Methods We searched MEDLINE Ovid, EMBASE, and the Cochrane Library for human studies comparing whole blood with component blood therapy published from January 2007 to June 2019. We included studies from both civilian and military settings and that reported 24‐hour, in‐hospital, or 30‐day mortality. We followed the Preferred Reporting Items in Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, assessing study quality, publication bias, and heterogeneity. We used meta‐analytic models to determine the associations (odds ratio [OR] with 95% confidence interval [CI]) between whole blood transfusion and (1) 24‐hour mortality, and (2) in‐hospital or 30‐day mortality. Results A total of 1759 identified studies, 12 (reporting on n = 8431 patients) met inclusion criteria. There was heterogeneity in the design, setting, interventions, and outcomes of the studies. On meta‐analysis, whole blood transfusion was not associated with 24‐hour mortality (OR = 0.83; 95% CI = 0.56–1.24) or in‐hospital/30‐day mortality (OR = 0.79; 95% CI = 0.48–1.31). Conclusion In this systematic review and meta‐analysis, compared with conventional component transfusion, whole blood was not associated with 24‐hour or in‐hospital mortality. However, there were important limitations with and heterogeneity among the primary studies. Additional study is needed to determine the effectiveness of whole blood.

Objectives:. Determine associations between biomarkers of endotheliopathy, 24-hour fibrinolysis phenotypes and clinical outcomes after trauma. Background:. The vascular endothelium is a critical regulator of hemostasis and organ function. The relationship between markers of endotheliopathy and fibrinolysis following trauma has not been evaluated. Methods:. We performed a secondary analysis of prospectively collected biomarker data in the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized controlled trial. We stratified subjects by 24-hour thromboelastography (TEG) percent clot lysis (LY30) and plasma d-dimer (DD) levels and evaluated differences in endotheliopathy biomarkers and clinical outcomes between subjects with one of four 24-hour fibrinolysis phenotypes: LY30 0.9% to 2.9% (LY30norm), LY30 > 2.9% (LY30high), LY30 < 0.9% and low DD (LY30low+DDlow), and LY30 < 0.9% and high DD (LY30low+DDhigh). Results:. The analysis included 168 subjects with LY30norm, 32 with LY30high, 147 with LY30low+DDlow, and 124 with LY30low+DDhigh. LY30low+DDhigh subjects had greater injury severity and a higher incidence of severe head injury, multiorgan failure (MOF), and mortality than the other phenotypes. All endotheliopathy biomarkers were significantly higher in the LY30low+DDhigh phenotype. Adjusting for injury severity, mechanism, and head trauma, 24-hour angiopoietin-2 and soluble thrombomodulin were independently associated with the LY30low+DDhigh phenotype. Both endothelial biomarkers were discriminating for MOF. Subjects with thrombomodulin level >9.5 ng/mL and angiopoietin-2 level >3.6 ng/mL accounted for 64% of subjects who developed MOF. Conclusions:. In a multicenter trauma cohort, subjects with a fibrinolysis phenotype characterized by low TEG lysis and elevated DD 24 hours after injury have significantly worse endotheliopathy and clinical outcomes. Our findings support mechanistic evaluations of the role of the endothelium in fibrinolysis dysregulation that may drive late-stage organ injury.

Background Although widely used in treating severe abdominal trauma, damage control laparotomy (DCL) has not been assessed in any randomized controlled trial. We conducted a pilot trial among patients for whom our surgeons had equipoise and hypothesized that definitive laparotomy (DEF) would reduce major abdominal complications (MAC) or death within 30 days compared with DCL.Methods Eligible patients undergoing emergency laparotomy were randomized during surgery to DCL or DEF from July 2016 to May 2019. The primary outcome was MAC or death within 30 days. Prespecified frequentist and Bayesian analyses were performed.Results Of 489 eligible patients, 39 patients were randomized (DCL 18, DEF 21) and included. Groups were similar in demographics and mechanism of injury. The DEF group had a higher Injury Severity Score (DEF median 34 (IQR 20, 43) vs DCL 29 (IQR 22, 41)) and received more prerandomization blood products (DEF median red blood cells 8 units (IQR 6, 11) vs DCL 6 units (IQR 2, 11)). In unadjusted analyses, the DEF group had more MAC or death within 30 days (1.71, 95% CI 0.81 to 3.63, p=0.159) due to more deaths within 30 days (DEF 33% vs DCL 0%, p=0.010). Adjustment for Injury Severity Score and prerandomization blood products reduced the risk ratio for MAC or death within 30 days to 1.54 (95% CI 0.71 to 3.32, p=0.274). The Bayesian probability that DEF increased MAC or death within 30 days was 85% in unadjusted analyses and 66% in adjusted analyses.Conclusion The findings of our single center pilot trial were inconclusive. Outcomes were not worse with DCL and, in fact, may have been better. A randomized clinical trial of DCL is feasible and a larger, multicenter trial is needed to compare DCL and DEF for patients with severe abdominal trauma.Level of evidence Level II.

Background ‘Community consultation’ (CC) is a key step when conducting Exception From Informed Consent research. Social-media-based CC has been shown to reach more people than traditional methods, but it is unclear whether those reached are representative of the community as a whole.Methods This is a retrospective analysis of the CC performed in preparation for the PHOXSTAT trial. Social media advertisement campaigns were conducted in the catchment areas of the three participating trauma centers and evaluated by examining Facebook user statistics. We compared these data to georeferenced population data obtained from the U.S. Census Bureau. We examined variations in the proportion of each age group reached, by gender.Results Our social media advertisements reached a total of 332 081 individuals in Los Angeles, Birmingham, and Nashville. Although there were differences in the proportion of individuals reached within each age group and gender groups, compared with the population in each area, these were small (within 5%). In Birmingham, participants 55 to 64 years old, 25 to 34 years old, and females 18 to 24 years old were slightly over-represented (a larger proportion of individuals in this age group were reached by the social media campaign, compared with the population resident in this area). In contrast, in Nashville, female participants 45 to 64 years old, and males 25 to 64 years old were over-represented. In Los Angeles, females 45 to 64 years old, and males 25 to 64 years and over were over-represented.Discussion In conclusion, this study demonstrates that social media CC campaigns can be used to reach a sample of the community broadly representative of the population as a whole, in terms of age and gender. This finding is helpful to IRBs and investigators, as it lends further support to the use of social media to conduct CC. Further work is needed to analyze how representative community samples are in terms of other characteristics, such as race, ethnicity, and socioeconomic status.Level III evidence Economic & Value-based Evaluations.

ObjectivesThis study encompassed fall-related deaths, including those who died prior to medical care, that were admitted to multiple healthcare institutions, regardless of whether they died at home, in long-term care, or in hospice. The common element was that all deaths resulted directly or indirectly from injuries sustained during a fall, regardless of the temporal relationship. This comprehensive approach provides an unusual illustration of the clinical sequence of fall-related deaths. Understanding this pathway lays the groundwork for identification of gaps in healthcare needs.DesignThis is a retrospective study of 2014 fall-related deaths recorded by one medical examiner's office (n = 511) within a larger dataset of all trauma related deaths (n = 1848). Decedent demographic characteristics and fall-related variables associated with the deaths were coded and described.ResultsOf those falling, 483 (94.5%) were from heights less than 10 feet and 394 (77.1%) were aged 65+. The largest proportion of deaths (n = 267, 52.3%) occurred post-discharge from an acute care setting. Of those who had a documented prior fall, 216 (42.3%) had a history of one fall while 31 (6.1%) had ≥2 falls prior to their fatal incident. For the 267 post-acute care deaths, 440 healthcare admissions were involved in their care. Of 267 deaths occurring post-acute care, 129 (48.3%) were readmitted within 30 days. Preventability, defined as opportunities for improvement in care that may have influenced the outcome, was assessed. Of the 1848 trauma deaths, 511 (27.7%) were due to falls of which 361 (70.6%) were determined to be preventable or potentially preventable.ConclusionOur data show that readmissions and repeated falls are frequent events in the clinical sequence of fall fatalities. Efforts to prevent fall-related readmissions should be a top priority for improving fall outcomes and increasing the quality of life among those at risk of falling.

Abstract Introduction Head injury and exsanguination are the leading causes of death in trauma patients. Hemorrhagic shock triggers systemic endothelial glycocalyx breakdown, potentially leading to traumatic endotheliopathy (EoT). Levels of syndecan-1, a main glycocalyx component, have been used to assess the integrity of the glycocalyx. In TBI patients, it remains unclear whether syndecan-1 shedding occurs and its correlation with outcomes. We aimed to determine the frequency of EoT+, defined as a syndecan-1 level of 40 ng/ml or higher, after TBI in isolated and polytraumatic injury. We also investigated how the presence of EoT+ affected outcomes in TBI patients. Methods Severely injured trauma patients were enrolled. From blood samples collected upon patients’ arrival to the hospital, we measured syndecan-1 (main biomarker of EoT+), soluble thrombomodulin (sTM, endothelial activation) adrenaline and noradrenaline (sympathoadrenal activation), and assessed TBI patients’ coagulation capacity. Results Of the enrolled patients (n = 331), those with TBI and polytrauma (n = 68) had the highest rate of EoT+ compared to isolated TBI (n = 58) and Non-TBI patients (n = 205) (Polytrauma-TBI 55.9% vs. Isolated-TBI 20.0% vs. non-TBI polytrauma 40.0%; p = 0.001). TBI patients with EoT+ exhibited marked increases in sTM, adrenaline and noradrenaline levels, and physiological and coagulation derangements. In isolated TBI patients, increasing syndecan-1 levels (β for every 10 ng/ml increase: 0.14; 95% CI: 0.02, 0.26) and hypocoagulability were negatively associated with survival. Conclusions This study provides evidence of syndecan-1 shedding after TBI supporting the notion that breakdown of the glycocalyx contributes to the physiological derangements after TBI.

Abstract: Transfusing platelets during massive hemorrhage is debated because of a lack of high-quality evidence concerning outcomes in trauma patients. The objective of this study was to examine the effect of platelet transfusions on mortality in severely injured trauma patients. This work analyzed PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial patients who received only the first cooler of blood products, which either did or did not contain platelets. Primary outcomes were all-cause mortality at 24 hours and 30 days and hemostasis. Secondary outcomes included cause of death, complications, and hospital-, intensive care unit (ICU)–, and ventilator-free days. Continuous variables were compared using Wilcoxon rank sum tests. Categorical variables were compared using Fisher's exact tests. There were 261 PROPPR patients who achieved hemostasis or died before receiving a second cooler of blood products (137 received platelets and 124 did not). Patients who received platelets also received more total plasma (median, 3 vs 2 U; P < .05) by PROPPR intervention design. There were no differences in total red blood cell transfusions between groups. After controlling for plasma volume, patients who received platelets had significantly decreased 24-hour (5.8% vs 16.9%; P < .05) and 30-day mortality (9.5% vs 20.2%; P < .05). More patients in the platelet group achieved hemostasis (94.9% vs 73.4%; P < .01), and fewer died as a result of exsanguination (1.5% vs 12.9%; P < .01). Patients who received platelets had a shorter time on mechanical ventilation (P < .05); however, no differences in hospital- or ICU-free days were observed. In conclusion, early platelet administration is associated with improved hemostasis and reduced mortality in severely injured, bleeding patients. This trial was registered at www.clinicaltrials.gov as # NCT01545232.

Background The ability of focused assessment with sonography for trauma (FAST) to detect clinically significant hemorrhage in hypotensive injured patients remains unclear. We sought to describe the sensitivity and specificity of FAST using findings at laparotomy as the confirmatory test.Methods Patients from the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study that had a systolic blood pressure < 90mm Hg and underwent FAST were analysed. Results were compared with findings at laparotomy. A therapeutic laparotomy (T-LAP) was defined as an abdominal operation within 6 hours in which a definitive procedure was performed. The sensitivity and specificity of FAST were calculated.Results The cohort included 317 patients that underwent FAST (108 positive, 209 negative). T-LAP was performed in 69% (n=75) of FAST(+) patients and 22% (n=48) of FAST(−) patients. FAST had a sensitivity of 62% and specificity of 83%.Conclusions In our multicenter cohort, 22% of FAST(−) patients underwent T-LAP within 6 hours of admission. In hypotensive patients with a negative FAST, clinicians should still maintain a high index of suspicion for significant abdominal hemorrhage.Level of evidence Level IV.

Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a less-invasive technique for aortic occlusion (AO). Commonly performed in the emergency department (ED), the role of intraoperative placement is less defined. We hypothesized that operating room (OR) placement is associated with increased in-hospital mortality.Methods The American Association for the Surgery of Trauma AORTA registry was used to identify patients undergoing REBOA. Injury characteristics and outcomes data were compared between OR and ED groups. The primary outcome was in-hospital mortality; secondary outcomes included total AO time, transfusion requirements, and acute kidney injury.Results Location and timing of catheter insertion were available for 305 of 321 (95%) subjects. 58 patients underwent REBOA in the OR (19%). There were no differences with respect to sex, admission lactate, and Injury Severity Score. The OR group was younger (33 years vs. 41 years, p=0.01) and with more penetrating injuries (36% vs. 15%, p

Background: The introduction of low-profile devices designed for resuscitative endovascular balloon occlusion of the aorta (REBOA) after trauma has the potential to change practice, outcomes, and complication profiles. Methods: The AAST Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery (AORTA) registry was used to identify REBOA patients from 16 centers. Presentation, intervention, and outcome variables were compared via traditional 11–12 French access platforms and trauma-specific devices requiring only 7 French access. Results: From November 2013 to December 2017, 242 patients with complete data were identified, constituting 124 7 French and 118 11–12 French uses. Demographics of presentation were not diff erent between the two groups, except that patients using the 7 French had a higher mean Injury Severity Score (39.2 vs. 34.1, p = 0.028). The 7 French was associated with a lower cut-down requirement for access (22.6% vs. 37.3%, p = 0.049) and increased ultrasound guidance utilization (29.0% vs. 23.7%, p = 0.049). The 7 French afforded earlier aortic occlusion in the course of resuscitation (median 25.0 mins vs. 30 mins, p = 0.010) and a lower median requirement of packed red blood cells (10.0 vs. 15.5 units, p = 0.006) and fresh frozen plasma (7.5 vs. 14.0 units, p = 0.005). The 7 French patients were more likely to survive 24 h (58.1% vs. 42.4%, p = 0.015) and less likely to suff er in-hospital mortality (57.3% vs. 75.4%, p = 0.003). Finally, the 7 French device was associated with a four times lower rate of distal extremity embolism (20.0% vs. 5.6%, p = 0.014; OR 95% CI 4.25 [1.25–14.45]) compared to the 11–12 French. Conclusions: The introduction of trauma-specific 7 French REBOA devices appears to have infl uenced REBOA practices, with earlier use in severely injured hypotensive patients via less invasive means that are associated with lower transfusion requirements, fewer thrombotic complications, and improved survival. Additional study is required to determine optimal REBOA use.

Background: Severe injury often results in substantial bleeding and mortality. Injury provokes cellular activation and release of extracellular vesicles. Circulating microvesicles (MVs) are predominantly platelet-derived and highly procoagulant. They support hemostasis and vascular function. The roles of MVs in survival after severe injury are largely unknown. We hypothesized that altered MV phenotypes would be associated with transfusion requirements and poor outcomes. Methods: This single-centre study was approved by the Institutional Review Board. The study cohort consisted of patients with major trauma requiring blood product transfusion and 26 healthy controls. Plasma samples for MVs were collected upon admission to the emergency department (n=169) and post-resuscitation (n=42), and analysed by flow cytometry for MV counts and cellular origin: platelet (PMV), erythrocyte (RMV), leukocyte (LMV), endothelial (EMV), tissue factor (TFMV), and annexin V (AVMV). Twenty-four hour mortality is the outcome measurement used to classify survivors versus non-survivors. Data were compared over time and analysed with demographic and clinical data. Results: The median age was 34 (IQR 23, 51), 72% were male, Injury Severity Score was 29 (IQR 19, 36), and 24 h mortality was 13%. MV levels and phenotypes differed between patients and controls. Elevated admission EMVs were found both in survivors (409/µL) and non-survivors (393/µL) compared to controls (23/µL, p

Background Damage control laparotomy (DCL) is an abbreviated operation intended to prevent the development of hypothermia, acidosis, and coagulopathy in seriously injured patients. The indications for DCL have since been broadened with no high-quality data to guide treatment. For patients with an indication for DCL, we aim to determine the effect of definitive laparotomy on patient morbidity.Method This is a pragmatic, parallel-group, randomized controlled pilot trial. Emergent laparotomy is defined as admission directly to the operating room from the emergency department within 90 min of arrival. DCL indications excluded from the study include packing of the liver or retroperitoneum, abdominal compartment syndrome prophylaxis, to expedite interventional radiology for hemorrhage control, and the need for ongoing transfusions and/or continuous vasopressor support. When a surgeon determines a DCL is indicated, the patient will be screened for inclusion and exclusion criteria. Patients with any indication for DCL that is not excluded are eligible for randomization. Patients will be randomized intraoperatively to DCL (control) or definitive fascial closure of the laparotomy (intervention). The primary outcome will be major abdominal complication or death within 30 days. Major abdominal complication is a composite outcome including fascial dehiscence, organ/space surgical site infection, enteric suture line failure, and unplanned reopening of the abdomen. Outcomes will be compared using both frequentist and Bayesian statistics.Discussion In patients with an indication for DCL, this trial will determine the effect of definitive laparotomy on major abdominal complications and death and will inform clinicians on the risks and benefits of this procedure. Regardless of the study outcome, the results will improve the quality of care provided to injured patients.Trial registration number NCT02706041.

This article describes a methodology to establish a trauma preventable death rate (PDR) in a densely populated county in the USA. Harris County has >4 million residents, encompasses a geographic area of 1777 square miles and includes the City of Houston, Texas. Although attempts have been made to address a national PDR, these studies had significant methodological flaws. There is no national consensus among varying groups of clinicians for defining preventability or documenting methods by which preventability is determined. Furthermore, although trauma centers routinely evaluate deaths within their hospital for preventability, few centers compare across regions, within the prehospital arena and even fewer have evaluated trauma deaths at non-trauma centers. Comprehensive population-based data on all trauma deaths within a defined region would provide a framework for effective prevention and intervention efforts at the regional and national levels. The authors adapted a military method recently used in Southwest Asia to determine the potential preventability of civilian trauma deaths occurring across a large and diverse population. The project design will allow a data-driven approach to improve services across the entire spectrum of trauma care, from prevention through rehabilitation.

John B Holcomb summarizes recent conceptual and practical advances in trauma care, in both military and civilian settings, and presents directions for future research.

Improving the treatment of trauma, a leading cause of death worldwide, is of great clinical and public health interest. This analysis introduces flexible statistical methods for estimating center-level effects on individual outcomes in the context of highly variable patient populations, such as those of the PRospective, Observational, Multi-center Major Trauma Transfusion study. Ten US level I trauma centers enrolled a total of 1,245 trauma patients who survived at least 30 minutes after admission and received at least one unit of red blood cells. Outcomes included death, multiple organ failure, substantial bleeding, and transfusion of blood products. The centers involved were classified as either large or small-volume based on the number of massive transfusion patients enrolled during the study period. We focused on estimation of parameters inspired by causal inference, specifically estimated impacts on patient outcomes related to the volume of the trauma hospital that treated them. We defined this association as the change in mean outcomes of interest that would be observed if, contrary to fact, subjects from large-volume sites were treated at small-volume sites (the effect of treatment among the treated). We estimated this parameter using three different methods, some of which use data-adaptive machine learning tools to derive the outcome models, minimizing residual confounding by reducing model misspecification. Differences between unadjusted and adjusted estimators sometimes differed dramatically, demonstrating the need to account for differences in patient characteristics in clinic comparisons. In addition, the estimators based on robust adjustment methods showed potential impacts of hospital volume. For instance, we estimated a survival benefit for patients who were treated at large-volume sites, which was not apparent in simpler, unadjusted comparisons. By removing arbitrary modeling decisions from the estimation process and concentrating on parameters that have more direct policy implications, these potentially automated approaches allow methodological standardization across similar comparativeness effectiveness studies.

OBJECTIVE: To determine the incidence and effect on mortality of early acute kidney injury in severely injured trauma patients using the Acute Kidney Injury Network creatinine criteria. DESIGN: A retrospective cohort study of severely injured trauma patients admitted to the shock trauma intensive care unit. SETTING: Texas Trauma Institute, a state designated level I trauma unit certified by the American College of Surgeons Committee on Trauma. PATIENTS: 901 severely injured trauma patients admitted over a 15 month period to the shock trauma intensive care unit. INTERVENTIONS: Retrospective analysis of prospectively collected data abstracted from an electronic trauma database. MEASUREMENTS AND MAIN RESULTS: Of 901 eligible patients admitted to the shock trauma intensive care unit after traumatic injury, 54 patients (6%) developed acute kidney injury, of whom 10 (19%) required renal replacement therapy. The 30-day mortality rate for the entire cohort was 83/901 (9.2%). Patients with early acute kidney injury had a mortality rate of 16/54 (29.6%). When corrected for multiple covariates including injury severity scores, the development of early acute kidney injury was associated with a significantly higher risk of death at 30 days with an OR of 3.4 (95% CI 1.6-7.4). CONCLUSIONS: Applying the Acute Kidney Injury Network creatinine criteria in severely injured trauma patients, the incidence of early acute kidney injury was 6%. After correction for injury severity, development of early acute kidney injury was independently associated with significantly higher 30-day mortality.

The early use of fresh frozen plasma as a resuscitative agent after hemorrhagic shock has been associated with improved survival, but the mechanism of protection is unknown. Hemorrhagic shock causes endothelial cell dysfunction and we hypothesized that fresh frozen plasma would restore endothelial integrity and reduce syndecan-1 shedding after hemorrhagic shock. A prospective, observational study in severely injured patients in hemorrhagic shock demonstrated significantly elevated levels of syndecan-1 (554±93 ng/ml) after injury, which decreased with resuscitation (187±36 ng/ml) but was elevated compared to normal donors (27±1 ng/ml). Three pro-inflammatory cytokines, interferon-γ, fractalkine, and interleukin-1β, negatively correlated while one anti-inflammatory cytokine, IL-10, positively correlated with shed syndecan-1. These cytokines all play an important role in maintaining endothelial integrity. An in vitro model of endothelial injury then specifically examined endothelial permeability after treatment with fresh frozen plasma orlactated Ringers. Shock or endothelial injury disrupted junctional integrity and increased permeability, which was improved with fresh frozen plasma, but not lactated Ringers. Changes in endothelial cell permeability correlated with syndecan-1 shedding. These data suggest that plasma based resuscitation preserved endothelial syndecan-1 and maintained endothelial integrity, and may help to explain the protective effects of fresh frozen plasma after hemorrhagic shock.

Hemorrhagic shock (HS) and trauma is currently the leading cause of death in young adults worldwide. Morbidity and mortality after HS and trauma is often the result of multi-organ failure such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), conditions with few therapeutic options. Bone marrow derived mesenchymal stem cells (MSCs) are a multipotent stem cell population that has shown therapeutic promise in numerous pre-clinical and clinical models of disease. In this paper, in vitro studies with pulmonary endothelial cells (PECs) reveal that conditioned media (CM) from MSCs and MSC-PEC co-cultures inhibits PEC permeability by preserving adherens junctions (VE-cadherin and β-catenin). Leukocyte adhesion and adhesion molecule expression (VCAM-1 and ICAM-1) are inhibited in PECs treated with CM from MSC-PEC co-cultures. Further support for the modulatory effects of MSCs on pulmonary endothelial function and inflammation is demonstrated in our in vivo studies on HS in the rat. In a rat "fixed volume" model of mild HS, we show that MSCs administered IV potently inhibit systemic levels of inflammatory cytokines and chemokines in the serum of treated animals. In vivo MSCs also inhibit pulmonary endothelial permeability and lung edema with concurrent preservation of the vascular endothelial barrier proteins: VE-cadherin, Claudin-1, and Occludin-1. Leukocyte infiltrates (CD68 and MPO positive cells) are also decreased in lungs with MSC treatment. Taken together, these data suggest that MSCs, acting directly and through soluble factors, are potent stabilizers of the vascular endothelium and inflammation. These data are the first to demonstrate the therapeutic potential of MSCs in HS and have implications for the potential use of MSCs as a cellular therapy in HS-induced lung injury.