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© 2015 Moore et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Im

Background: Children of different racial/ethnic backgrounds have varying risks of cancer. However, to the authors' knowledge, few studies to date have examined cancer occurrence in children of mixed ancestry.Methods: This population-based case-control study examined cancer among children aged <15 years using linked cancer and birth registry data from 5 US states from 1978 through 2004. Data were available for 13,249 cancer cases and 36,996 controls selected from birth records. Parental race/ethnicity was determined from birth records. Logistic regression analysis was used to examine the association of cancer with different racial/ethnic groups.Results: Compared with whites, blacks had a 28% decreased risk of cancer (odds ratio [OR], 0.72; 95% confidence interval [95% CI], 0.65-0.80), whereas both Asians and Hispanics had an approximate 15% decrease. Children of mixed white/black ancestry also were found to be at decreased risk (OR, 0.71; 95% CI, 0.56-0.90), but estimates for mixed white/Asian and white/Hispanic children did not differ from those of whites. Compared with whites: 1) black and mixed white/black children had decreased ORs for acute lymphoblastic leukemia (OR, 0.39 [95% CI, 0.31-0.49] and OR, 0.58 [95% CI, 0.37-0.91], respectively); 2) Asian and mixed white/Asian children had decreased ORs for brain tumors (OR, 0.51 [95% CI, 0.39-0.68] and OR, 0.79 [95% CI, 0.54-1.16], respectively); and 3) Hispanic and mixed white/Hispanic children had decreased ORs for neuroblastoma (OR, 0.51 [95% CI, 0.42-0.61] and OR, 0.67 [95% CI, 0.50-0.90], respectively).Conclusions: Children of mixed ancestry tend to have disease risks that are more similar to those of racial/ethnic minority children than the white majority group. This tendency may help formulate etiologic studies designed to study possible genetic and environmental differences more directly. [ABSTRACT FROM AUTHOR]

Sociability and irritability are commonly cited symptoms of premenstrual syndrome but there has been little investigation of these cycle related changes using clearly defined test instruments. We examined the two symptoms using symptom specific subscales from the Multiscore Depression Inventory (Berndt, 1983). Clear and consistent cycle related changes in irritability and sociability were seen in 20 women with prospectively validated symptomatic premenstrual change but not in a control group of 8 women without symptomatic premenstrual change. The study suggests that these variables can be measured using specific brief scales. [ABSTRACT FROM AUTHOR]

Textual analysis was used to examine responses to an open ended question about women's experiences of premenstrual change. The question was the final item of the Premenstrual Assessment Form (PAF), a retrospective PMS questionnaire. Of the 336 women who answered the PAF, 261 provided a written narrative summary. We found a logical hierarchy of distinctions covering the presence or absence of changes, their timing, and attributive aspects, and a final cumulative distinction in which women provided information about the consequences of their premenstrual change. Although attribute aspects mirrored the PAF, distinctions in timing and in the cumulative effect of changes differed. The analysis suggests that questionnaires could be designed which more precisely reflect premenstrual change. [ABSTRACT FROM AUTHOR]

Fluid intake was measured at 3 phases of the menstrual cycle in twenty women with prospectively validated premenstrual syndrome and 8 women with prospectively validated absence of cyclic symptoms. There was no cycle related change in fluid intake in either group but fluid intake was significantly lower in women with PMS than in controls at all phases of the menstrual cycle. All subjects but one denied voluntary fluid restriction. The mechanism, therefore, appears subconscious and may be related to perceived increase in fluid retention. [ABSTRACT FROM AUTHOR]

PURPOSE: The purpose of this study is to determine the incidence of cancer among employees at two petrochemical facilities in south Louisiana, and to compare their cancer rates to those of the general population of south Louisiana. METHODS: Records on 4639 active and former employees and retirees from the two plants were linked to the Louisiana Tumor Registry (LTR) database by LTR staff to ascertain incident cases of cancer. Standardized incidence ratios (SIRs) were then calculated using the south Louisiana population as the comparison and adjusted for age, race, and time period. RESULTS: There was a significant 16% deficit of overall cancer cases for males in this cohort (SIR=0.84; 95% CI, 0.74-0.95). The only significantly elevated SIR in males was for cancer of the bone and joint (SIR=6.89; 95% CI, 1.42-20.1). This result was based on three non-fatal cases of bone cancer with different histologies, occurring in different parts of the body. These cases worked in different units of one plant. Significant deficits were seen for lung cancer, non-Hodgkin's lymphoma, and cancer of the oral cavity and pharynx. Cancer incidence among 719 female employees was non-significantly increased (SIR=1.24; 95% CI, 0.81-1.82). Breast cancer accounts for the excess (SIR=1.46; 95% CI, 0.73-2.61). Seventy percent of the breast cancer cases worked in an office setting. CONCLUSIONS: This study found little evidence of any association between cancer incidence and employment at these two petrochemical facilities. The increased incidence of bone cancer is unlikely to be due to occupational exposures. The non-significant excess of breast cancer may be due to early detection or other important unmeasured confounders, such as certain reproductive factors. [ABSTRACT FROM AUTHOR]

Background: The relationship between inflammatory biomarkers (IB) and organ space surgical site infections (OS-SSIs) after emergency laparotomy (EL) is poorly understood., Methods: Retrospective, single-center analysis of patients in the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial who underwent EL and survived 48 ​h after admission was performed. IB levels of IL-6, IL-8, G-CSF, MCP-1, neutrophil to lymphocyte ratio, and platelet to lymphocyte ratio were analyzed. IB and OS-SSIs association was evaluated using the Wilcoxon rank sum test., Results: Of 74 eligible patients, 80 ​% were male, 69 ​% sustained blunt trauma, the injury severity score was 31 (24-41), and 22 ​% developed OS-SSIs. Levels of IL-6 (12, 24 ​h), IL-8 (2, 12, 24, 72 ​h), and MCP-1 (24 ​h) were higher in OS-SSI patients (P ​< ​0.05)., Conclusions: IL-6, IL-8, and MCP-1 levels were associated with OS-SSIs in PROPPR patients who underwent EL. The IB may help to predict high-risk patients for OS-SSIs., Competing Interests: Declaration of interest statement This work was supported by the National Institutes of Health (T32GM008792 and UL1TR003167). The sponsor had no role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the article for publication. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in trauma patients, despite chemoprophylaxis. Statins have been shown capable of acting upon the endothelium. We hypothesized that statin therapy in the pre- or in-hospital settings leads to a decreased incidence of VTE., Methods: We conducted a retrospective cohort study of injured patients who received statin therapy pre- or in-hospital. Adult, highest-level trauma activation patients admitted from January 2018 to June 2022 were included. Patients on prehospital anticoagulants, had history of inherited bleeding disorder, and who died within the first 24 hours were excluded. Statin users were matched to nonusers by statin use indications including age, current heart and cardiovascular conditions and history, hyperlipidemia, injury severity, and body mass index. Time to in-hospital statin initiation and occurrence of VTE and other complications within 60 days were collected. Differences between groups were determined by univariate, multivariable logistic regression, and Cox proportional hazard analyses., Results: Of 3,062 eligible patients, 79 were statin users, who were matched to 79 nonusers. There were no differences in admission demographics, vital signs, injury pattern, transfusion volumes, lengths of stay, or mortality between groups. The overall VTE incidence was 10.8% (17 of 158). Incidence of VTE in statin users was significantly lower (3%) than nonusers (19%; p = 0.003). Differences between statin users and nonusers were observed for rates of deep vein thrombosis (0% vs. 9%), pulmonary embolism (3% vs. 15%), and sepsis (0% vs. 5%). Exposure to statins was associated with an 82% decreased risk of developing VTE (hazard ratio, 0.18; 95% confidence interval, 0.04-0.86; p = 0.033)., Conclusion: Statin exposure was associated with decline in VTE and lower individual rates of deep vein thrombosis, pulmonary embolism, and sepsis. Our findings indicate that statins should be evaluated further as a possible adjunctive therapy for VTE chemoprophylaxis after traumatic injury., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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, <0.8%; normal LY30, 0.81% to 0.9%; and high LY30, ≥3%. Serial values of molecular markers (0-72 hours after admission) and clinical outcomes were compared between fibrinolysis groups., Results: A total of 547 patients were included (low LY30, 320; normal LY30, 108; high LY30, 119). The high LY30 group had higher tissue plasminogen activator and plasmin-antiplasmin values upon hospital arrival than the low LY30 or normal LY30 groups ( P  < .001, respectively). There was no significant difference in levels of tissue plasminogen activator, plasmin-antiplasmin, and plasminogen activator inhibitor 1 between the low LY30 and normal LY30 groups. The high LY30 group was associated with an increased risk of 24-hour and 30-day mortality, while there was no significant difference in mortality between the low LY30 and normal LY30 groups., Conclusion: Our results suggest that hyperfibrinolysis is the most common form of traumatic fibrinolytic dysfunction and is associated with worse outcome., (© 2024 The Authors.)

Background: Maintaining balanced blood product ratios during damage control resuscitation (DCR) is independently associated with improved survival. We hypothesized that real-time performance improvement (RT-PI) would increase adherence to DCR best practice., Study Design and Methods: From December 2020-August 2021, we prospectively used a bedside RT-PI tool to guide DCR in severely injured patients surviving at least 30 min. RT-PI study patients were compared to contemporary control patients at our institution and historic PROMMTT study patients. A subset of patients transfused ≥6 U red blood cells (RBC) in 6 h (MT+) was also identified. The primary endpoint was percentage time in a high ratio range (≥3:4) of plasma (PLAS):RBC and platelet (PLT):RBC over 6 h. Secondary endpoints included time to massive transfusion protocol activation, time to calcium and tranexamic acid (TXA) dosing, and cumulative 6-h ratios., Results: Included patients (n = 772) were 35 (24-51) years old with an Injury Severity Score of 27 (17-38) and 42% had penetrating injuries. RT-PI (n = 10) patients spent 96% of the 6-h resuscitation in a high PLAS:RBC range, no different versus CONTROL (n = 87) (96%) but more than PROMMTT (n = 675) (25%, p < .001). In the MT+ subgroup, optimal PLAS:RBC and PLT:RBC were maintained for the entire 6 h in RT-PI (n = 4) versus PROMMTT (n = 391) patients for both PLAS (p < .001) and PLT ratios (p < .001). Time to TXA also improved significantly in RT-PI versus CONTROL patients (27 min [22-31] vs. 51 min [29-98], p = .035)., Conclusion: In this prospective study, RT-PI was associated with optimized DCR. Multicenter validation of this novel approach to optimizing DCR implementation is warranted., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Objective: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock., Background: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury., Methods: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality., Results: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared with 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P =0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups., Conclusions and Relevance: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences., Trial Registration: ClinicalTrials.gov identifier: NCT04667468., Competing Interests: J.L.S. reports grants from the DoD; F.X.G. reports grants from the DoD; S.R.W. reports grants from the DoD; L.Z.K. reports grants and consulting fees from University of Maryland/BARDA, personal fees from Gamma Diagnostics, Coagulant Therapeutics, Haemonetics, other from Cerus, outside the submitted work; A.E.K. reports being founder of CaptureDx; J.C. reports participates on the steering committee for Faraday Pharmaceuticals; M.D.N. has received grants from National Institutes of Health, Department of Defense, DARPA, Haemonetics, Alexion and Instrumentation Laboratories, honoraria for lectures from Haemonetics and Takeda, support for attending meetings and/or travel from Takeda; participates on a Data Safety Monitoring Board or Advisory Board from NHLBI CONNECTS Steering Committee; is the Chief Medical Officer, Haima Therapeutics, and has Patents planned, issued or pending (US Patent 11,408.844; US Patent 9.072,760), outside the submitted work; P.C.S. reports personal fees from Hemanext, Cerus, participates in advisory board for Octapharma,and Haima, and is the Co-Founder and Chief Medical Officer of Kalocyte, outside the submitted work. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., (© 2024. The Author(s).)

Objective: Traumatic brain injury (TBI) and hemorrhage are responsible for the largest proportion of all trauma-related deaths. In polytrauma patients at risk of hemorrhage and TBI, the diagnosis, prognosis, and management of TBI remain poorly characterized. The authors sought to characterize the predictive capabilities of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) measurements in patients with hemorrhagic shock with and without concomitant TBI., Methods: The authors performed a secondary analysis on serial blood samples derived from a prospective observational cohort study that focused on comparing early whole-blood and component resuscitation. A convenience sample of patients was used in which samples were collected at three time points and the presence of TBI or no TBI via CT imaging was documented. GFAP and UCH-L1 measurements were performed on plasma samples using the i-STAT Alinity point-of-care platform. Using classification tree recursive partitioning, the authors determined the measurement cut points for each biomarker to maximize the abilities for predicting the diagnosis of TBI, Rotterdam CT imaging scores, and 6-month Glasgow Outcome Scale-Extended (GOSE) scores., Results: Biomarker comparisons demonstrated that GFAP and UCH-L1 measurements were associated with the presence of TBI at all time points. Classification tree analyses demonstrated that a GFAP level > 286 pg/ml for the sample taken upon the patient's arrival had an area under the receiver operating characteristic curve of 0.77 for predicting the presence of TBI. The classification tree results demonstrated that a cut point of 3094 pg/ml for the arrival GFAP measurement was the most predictive for an elevated Rotterdam score on the initial and second CT scans and for TBI progression between scans. No significant associations between any of the most predictive cut points for UCH-L1 and Rotterdam CT scores or TBI progression were found. The predictive capabilities of UCH-L1 were limited by the range allowed by the point-of-care platform. Arrival GFAP cut points remained strong independent predictors after controlling for all potential polytrauma confounders, including injury characteristics, shock severity, and resuscitation., Conclusions: Early measurements of GFAP and UCH-L1 on a point-of-care device are significantly associated with CT-diagnosed TBI in patients with polytrauma and shock. Early elevated GFAP measurements are associated with worse head CT scan Rotterdam scores, TBI progression, and worse GOSE scores, and these associations are independent of other injury attributes, shock severity, and early resuscitation characteristics.

Objective: Treating traumatic hemorrhage is time sensitive. Prehospital care and transport modes (eg, helicopter and ground) may influence in-hospital events. We hypothesized that prehospital time (on-scene time [OST] and total prehospital time [TPT]) and transport mode are associated with same-day transfusion and mortality. Furthermore, we sought to identify regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types., Methods: We obtained prehospital, in-hospital, and trauma registry data from an 8-center cohort of adult nonburn trauma patients from 2017 to 2022 directly transported from the scene to the hospital and having an Injury Severity Score (ISS) > 9 for the Task Order 1 project of the Linking Investigators in Trauma and Emergency Services research network. We excluded patients missing prehospital times, patients < 18 years of age, patients from interfacility transfers, and recipients of prehospital blood. Our same-day outcomes were in-hospital transfusions within 4 hours and 24-hour mortality. Each outcome was adjusted using multivariable logistic regression for covariates of prehospital phases (OST and TPT), mode of transport (helicopter and ground), age, sex, ISS, Glasgow Coma Scale motor subscale score < 6, and field hypotension (systolic blood pressure < 90 mm Hg). We evaluated the association of prehospital time on outcomes for scene missions by transport mode across severe injury patterns defined by Abbreviated Injury Scale > 2 body regions., Results: Of 78,198 subjects, 34,504 were eligible for the study with a mean age of 47.6 ± 20.3 years, ISS of 18 ± 11, OST of 15.9 ± 9.5 minutes, and TPT of 48.7 ± 20.3 minutes. Adjusted for injury severity and demographic factors, transport type significantly modified the relationship between prehospital time and outcomes. The association of OST and TPT with the odds of 4-hour transfusion was absent for the ground emergency medical services (GEMS) cohort and present for the helicopter emergency medical services (HEMS) ambulance cohort, whereas these times were associated with decreased 24-hour mortality for both transport types. When stratifying by injury to most anatomic regions, OST and TPT were associated with a decreased need for 4-hour transfusions in the GEMS cohort. However, OST was associated with increased early transfusion only among patients with severe injuries of the thorax, and this association persisted after adjusting additionally for injury type (odds ratio [OR] = 1.03; 95% confidence interval [CI], 1.00-1.05; P = .02). The presence of polytrauma supported an association between prehospital time and decreased 24-hour mortality for the GEMS cohort (OST: OR = 0.97; 95% CI, 0.95-0.99; P < .01; TPT: OR = 0.99; 95% CI, 0.98-0.99; P = .02), whereas no injuries showed significant association of helicopter prehospital time on mortality after adjustment., Conclusion: We determined that transport type affects the relationship between prehospital time and hospital outcomes (4-hour transfusion: positive relationship for HEMS and negative for GEMS, 24-hour mortality: negative for both transport types). Furthermore, we identified regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. Of these regions, most notable were severe isolated injuries to the thorax that supported a positive relationship between HEMS OST and 4-hour transfusions and polytrauma that showed a negative relationship between GEMS OST or TPT and 24-hour mortality after adjustment., Competing Interests: Declaration of Competing Interest The author(s) have no relevant disclosures. There was no grant funding or financial support for this manuscript., (Copyright © 2023 Air Medical Journal Associates. All rights reserved.)

Objective: The aim of this study was to evaluate the association of annual trauma patient volume on outcomes for emergency medical services (EMS) agencies., Background: Regionalization of trauma care saves lives. The underlying concept driving this is a volume-outcome relationship. EMS are the entry point to the trauma system, yet it is unknown if a volume-outcome relationship exists for EMS., Methods: A retrospective analysis of prospective cohort including 8 trauma centers and 20 EMS air medical and metropolitan ground transport agencies. Patients 18 to 90 years old with injury severity scores ≥9 transported from the scene were included. Patient and agency-level risk-adjusted regression determined the association between EMS agency trauma patient volume and early mortality., Results: A total of 33,511 were included with a median EMS agency volume of 374 patients annually (interquartile range: 90-580). Each 50-patient increase in EMS agency volume was associated with 5% decreased odds of 6-hour mortality (adjusted odds ratio=0.95; 95% CI: 0.92-0.99, P =0.03) and 3% decreased odds of 24-hour mortality (adjusted odds ratio=0.97; 95% CI: 0.95-0.99, P =0.04). Prespecified subgroup analysis showed EMS agency volume was associated with reduced odds of mortality for patients with prehospital shock, requiring prehospital airway placement, undergoing air medical transport, and those with traumatic brain injury. Agency-level analysis demonstrated that high-volume (>374 patients/year) EMS agencies had a significantly lower risk-standardized 6-hour mortality rate than low-volume (<374 patients/year) EMS agencies (1.9% vs 4.8%, P <0.01)., Conclusions: A higher volume of trauma patients transported at the EMS agency level is associated with improved early mortality. Further investigation of this volume-outcome relationship is necessary to leverage quality improvement, benchmarking, and educational initiatives., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive alternative to resuscitative thoracotomy (RT) for patients with hemorrhagic shock. However, the potential benefits of this approach remain subject of debate. The aim of this study was to compare the outcomes of REBOA and RT for traumatic cardiac arrest., Methods: A planned secondary analysis of the United States Department of Defense-funded Emergent Truncal Hemorrhage Control study was performed. Between 2017 and 2018, a prospective observational study of noncompressible torso hemorrhage was conducted at six Level I trauma centers. Patients were dichotomized by REBOA or RT, and baseline characteristics and outcomes were compared between groups., Results: A total of 454 patients were enrolled in the primary study, of which 72 patients were included in the secondary analysis (26 underwent REBOA and 46 underwent resuscitative thoracotomy). Resuscitative endovascular balloon occlusion of the aorta patients were older, had a greater body mass index, and were less likely to be the victims of penetrating trauma. Resuscitative endovascular balloon occlusion of the aorta patients also had less severe abdominal injuries and more severe extremity injuries, although the overall injury severity scores were similar. There was no difference in mortality between groups (88% vs. 93%, p = 0.767). However, time to aortic occlusion was longer in REBOA patients (7 vs. 4 minutes, p = 0.001) and they required more transfusions of red blood cells (4.5 vs. 2.5 units, p = 0.007) and plasma (3 vs. 1 unit, p = 0.032) in the emergency department. After adjusted analysis, mortality remained similar between groups (RR, 0.89; 95% confidence interval, 0.71-1.12, p = 0.304)., Conclusion: Resuscitative endovascular balloon occlusion of the aorta and RT were associated with similar survival after traumatic cardiac arrest, although time to successful aortic occlusion was longer in the REBOA group. Further research is needed to better define the role of REBOA in trauma., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This retrospective analysis of prospectively collected data from the PROPPR study describes volatile anesthetic use in severely injured trauma patients undergoing anesthesia., Methods: After exclusions, 402 subjects were reviewed of the original 680, and 292 had complete data available for analysis. Anesthesia was not protocolized, so analysis was of contemporary practice., Results: The small group who received no volatile anesthetic (n = 25) had greater injury burden (Glasgow Coma Scale P  = 0.05, Injury Severity Score P  = 0.001, Revised Trauma Score P  = 0.03), higher 6- and 24-hour mortality ( P  < 0.001), and higher incidence of systemic inflammatory response syndrome ( P  = 0.003) and ventilator-associated pneumonia ( P  = 0.02) than those receiving any volatile (n = 267). There were no differences in mortality between volatile agents at 6 hours ( P  = 0.51) or 24 hours ( P  = 0.35). The desflurane group was less severely injured than the isoflurane group. Mean minimum alveolar concentration was < 0.6 and lowest in the isoflurane group compared to the sevoflurane and desflurane groups (both P  < 0.01). The incidence of systemic inflammatory response syndrome was lower in the desflurane group than in the isoflurane group ( P  = 0.007)., Conclusion: In this acutely injured trauma population, choice of volatile anesthetic did not appear to influence short-term mortality and morbidity. Subjects who received no volatile were more severely injured with greater mortality, representing hemodynamic compromise where volatile agent was limited until stable. As anesthetic was not protocolized, these findings that choice of specific volatile was not associated with short-term survival require prospective, randomized evaluation., Competing Interests: No commercial funding was received for this work. DL and CL were recipients of a summer research scholarship from McGovern Medical School to initiate the project. SS is supported by the Biostatistics/Epidemiology/Research Design component of the Center for Clinical and Translational Sciences, currently funded through a National Center for Advancing Translational Sciences grant awarded to the University of Texas Health Science Center at Houston. This content does not represent the official views of the NCATS. EGP serves as a medical consultant for Lucid Lane, which offers virtual assistance to postsurgical patients with opioid management, and as a speaker for Haemonetics, Inc., neither of which have any relationship to the current study. None of the other authors have conflicts of interest to declare., (Copyright © 2023 Baylor University Medical Center.)

Background: Acute traumatic coagulopathy (ATC) has many phenotypes and varying morbidity and mortality. The MA-R ratio, calculated from the admission thromboelastogram, serves as a biomarker to identify 1 phenotype of ATC and has previously been associated with significant derangements in the inflammatory response. This study evaluates outcomes related to abnormal MA-R ratios, including inflammatory responses, in a heterogeneous patient population., Study Design: Patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) dataset were included. The MA-R ratio was calculated from admission thromboelastography, with a CRITICAL ratio defined as 11 or less. Key inflammatory mediators were identified as a priori. Cytokine expression was assessed during 24 hours using multivariable logistic regression., Results: Significant elevations in the proinflammatory cytokines IL-1b, IL-6, and IL-8, as well as in the chemokines eotaxin, IFN-γ-induced protein 10, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1β, persisted during the first 24 hours. CRITICAL patients had significantly lower survival at 1, 3, 6, 12, and 18 hours and demonstrated significantly increased ARDS (odds ratio [OR] 1.817, 95% CI 1.082 to 3.051, p = 0.0239). CRITICAL patients had fewer ICU-free days (CRITICAL, 10 days, interquartile range [IQR] 0 to 25; vs NORMAL, 22 days, IQR 4 to 26, p < 0.0001) and fewer ventilator-free days (CRITICAL, 15 days, IQR 0 to 28; vs NORMAL, 26 days, IQR 9 to 28, p < 0.0001). CRITICAL patients were protected against systemic inflammatory response (OR 0.521, 95% CI 0.322 to 0.816, p = 0.0044)., Conclusions: The subtype of ATC identified by the low MA-R ratio is associated with significant elevations in multiple proinflammatory cytokines at admission. Early mortality remains elevated in the CRITICAL group, in part due to coagulopathy. The MA-R ratio at admission is associated with a particularly morbid type of coagulopathy, associated with significant alterations in the inflammatory response after severe injury in heterogeneous patient populations., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Importance: It is not clear which severely injured patients with hemorrhagic shock may benefit most from a 1:1:1 vs 1:1:2 (plasma:platelets:red blood cells) resuscitation strategy. Identification of trauma molecular endotypes may reveal subgroups of patients with differential treatment response to various resuscitation strategies., Objective: To derive trauma endotypes (TEs) from molecular data and determine whether these endotypes are associated with mortality and differential treatment response to 1:1:1 vs 1:1:2 resuscitation strategies., Design, Setting, and Participants: This was a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized clinical trial. The study cohort included individuals with severe injury from 12 North American trauma centers. The cohort was taken from the participants in the PROPPR trial who had complete plasma biomarker data available. Study data were analyzed on August 2, 2021, to October 25, 2022., Exposures: TEs identified by K-means clustering of plasma biomarkers collected at hospital arrival., Main Outcomes and Measures: An association between TEs and 30-day mortality was tested using multivariable relative risk (RR) regression adjusting for age, sex, trauma center, mechanism of injury, and injury severity score (ISS). Differential treatment response to transfusion strategy was assessed using an RR regression model for 30-day mortality by incorporating an interaction term for the product of endotype and treatment group adjusting for age, sex, trauma center, mechanism of injury, and ISS., Results: A total of 478 participants (median [IQR] age, 34.5 [25-51] years; 384 male [80%]) of the 680 participants in the PROPPR trial were included in this study analysis. A 2-class model that had optimal performance in K-means clustering was found. TE-1 (n = 270) was characterized by higher plasma concentrations of inflammatory biomarkers (eg, interleukin 8 and tumor necrosis factor α) and significantly higher 30-day mortality compared with TE-2 (n = 208). There was a significant interaction between treatment arm and TE for 30-day mortality. Mortality in TE-1 was 28.6% with 1:1:2 treatment vs 32.6% with 1:1:1 treatment, whereas mortality in TE-2 was 24.5% with 1:1:2 treatment vs 7.3% with 1:1:1 treatment (P for interaction = .001)., Conclusions and Relevance: Results of this secondary analysis suggest that endotypes derived from plasma biomarkers in trauma patients at hospital arrival were associated with a differential response to 1:1:1 vs 1:1:2 resuscitation strategies in trauma patients with severe injury. These findings support the concept of molecular heterogeneity in critically ill trauma populations and have implications for tailoring therapy for patients at high risk for adverse outcomes.

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., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2023 International Anesthesia Research Society.)

Abstract: Introduction: Although resuscitation guidelines for injured patients favor blood products, crystalloid resuscitation remains a mainstay in prehospital care. Our understanding of contemporary prehospital crystalloid (PHC) practices and their relationship with clinical outcomes is limited. Methods: The Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial data set was used for this investigation. We sought to identify factors associated with PHC volume variation and hypothesized that higher PHC volume is associated with worse coagulopathy and a higher risk of acute respiratory distress syndrome (ARDS) but a lower risk of acute kidney injury (AKI). Subjects were divided into groups that received <1,000 mL PHC (PHC<1,000) and ≥1,000 mL PHC (PHC≥1,000); initial laboratory values and outcomes (ARDS and AKI risk) were summarized with medians and interquartile ranges or percentages and compared using Wilcoxon rank-sum tests and chi-square tests. The primary outcome was ARDS risk. Multivariable regression was used to characterize the association of each 500 mL aliquot of PHC with initial laboratory values and clinical outcomes. Results: PHC volume among study subjects (n = 680) varied (median, 0.3 L; interquartile range, 0-0.9 L) with weak associations demonstrated among prehospital hemodynamics, intubation, Glasgow Coma Score, and Injury Severity Score (0.008 ≤ R2 ≤ 0.09); prehospital time and enrollment site explained more variation in PHC volume with R2 values of 0.2 and 0.54, respectively. Compared with PHC<1,000, PHC≥1,000 had higher INR, PT, PTT, and base deficit and lower hematocrit and platelets. The proportion of ARDS in the PHC≥1,000 group was higher than PHC<1,000 (21% vs. 12%, P < 0.01), whereas the rate of AKI was similar between groups (23% vs. 23%, P = 0.9). In regression analyses, each 500 mL of PHC was associated with increased INR and PTT, and decreased hematocrit and platelet count (P < 0.05). Each 500 mL of PHC was associated with increased ARDS risk and decreased AKI risk (P < 0.05). Conclusion: PHC administration correlates poorly with prehospital hemodynamics and injury characteristics. Increased PHC volume is associated with greater anemia, coagulopathy, and increased risk of ARDS, although it may be protective against AKI., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)

Importance: Venous thromboembolism (VTE) affects 2% to 20% of recovering trauma patients, despite aggressive prophylaxis with enoxaparin. Antithrombin is a primary circulating anticoagulant and crucial component of enoxaparin thromboprophylaxis. Approximately 20% of trauma patients present with antithrombin deficiency (antithrombin activity <80%)., Objective: To examine time-dependent changes in antithrombin activity, responsiveness to enoxaparin, as measured by anti-factor Xa (anti-FXa) levels, and incidence of VTE after severe trauma and to assess the association of ex vivo antithrombin supplementation with patients' sensitivity to enoxaparin prophylaxis., Design, Setting, and Participants: This single-center, prospective cohort study was performed at a level 1 trauma center between January 7, 2019, and February 28, 2020. Adult trauma patients admitted to the trauma service at high risk for VTE, based on injury pattern and severity, were screened and enrolled. Patients who were older than 70 years, were pregnant, had a known immunologic or coagulation disorder, or were receiving prehospital anticoagulants were excluded., Exposures: Blood samples were collected on emergency department arrival and daily for the first 8 days of hospitalization., Main Outcomes and Measures: Patients' antithrombin activity and anti-FXa levels were measured by a coagulation analyzer, and thrombin generation was measured by calibrated automated thrombography. Responsiveness to enoxaparin was assessed by measuring anti-FXa levels 4 to 6 hours after the first daily enoxaparin dose and compared between patients who developed VTE and who did not. In addition, the associations of ex vivo supplementation of antithrombin with plasma anti-FXa levels were assessed., Results: Among 150 patients enrolled (median [IQR] age, 35 [27-53] years; 37 [24.7%] female and 113 [75.3%] male; 5 [3.3%] Asian, 32 [21.3%] Black, and 113 [75.3%] White; and 51 [34.0%] of Hispanic ethnicity), 28 (18.7%) developed VTE. Patients with VTE had significantly lower antithrombin activity on admission compared with patients without VTE (median [IQR], 91% [79%-104%] vs 100% [88%-112%]; P = .04), as well as lower antithrombin activity on hospital days 5 (median (IQR), 90% [83%-99%] vs 114% [99%-130%]; P = .011), 6 (median [IQR], 97% [81%-109%] vs 123% [104%-134%]; P = .003), 7 (median [IQR], 82% [74%-89%] vs 123% [110%-140%]; P < .001), and 8 (median [IQR], 99% [85%-100%] vs 123% [109%-146%]; P = .011). Anti-FXa levels were significantly lower in patients with VTE vs those without VTE at hospital day 4 (median [IQR], 0.10 [0.05-0.14] IU/mL vs 0.18 [0.13-0.23] IU/mL; P = .006), day 6 (median [IQR], 0.12 [0.08-0.14] IU/mL vs 0.22 [0.13-0.28] IU/mL; P = .02), and day 7 (median [IQR], 0.11 [0.08-0.12] IU/mL vs 0.21 [0.13, 0.28] IU/mL; P = .002). Multivariable analyses found that for every 10% decrease in antithrombin activity during the first 3 days, the risk of VTE increased 1.5-fold., Conclusions and Relevance: The results of this cohort study suggest that after severe trauma, antithrombin deficiency is common and contributes to enoxaparin resistance and VTE. Interventional studies are necessary to determine the efficacy of antithrombin supplementation in the reduction of VTE incidence.

Introduction: Trauma-induced coagulopathy is a continuum ranging from hypercoagulable to hypercoagulable phenotypes. In single-center studies, the maximum amplitude (MA) to r-time (R) (MA-R) ratio has identified a phenotype of injured patients with high mortality risk. The purpose of this study was to determine the relationship between MA-R and mortality using multicenter data and to investigate fibrinogen consumption in the development of this specific coagulopathy phenotype., Methods: Using the Pragmatic Randomized Optimal Platelet and Plasma Ratios data set, patients were divided into blunt and penetrating injury cohorts. MA was divided by R time from admission thromboelastogram to calculate MA-R. MA-R was used to assess odds of early and late mortality using multivariable models. Multivariable models were used to assess thrombogram values in both cohorts. Refinement of the MA-R cut point was performed with Youden index. Repeat multivariable analysis was performed with a binary CRITICAL and NORMAL MA-R., Results: In initial analysis, MA-R quartiles were not associated with mortality in the penetrating cohort. In the blunt cohort, there was an association between low MA-R and early and late mortality. A refined cut point of 11 was identified (CRITICAL: MA-R, ≤11; NORMAL: MA-R, >11). CRITICAL MA-R was associated with mortality in both penetrating and blunt subgroups. In further injury subgroup analysis, CRITICAL patients had significantly decreased fibrinogen levels in the blunt subgroup only. In both blunt and penetrating injury, there was no difference in time to initiation of thrombin burst (lagtime). However, both endogenous thrombin potential and peak thrombin levels were significantly lower in CRITICAL patients., Conclusions: MA-R identifies a trauma-induced coagulopathy phenotype characterized in blunt injury by impaired thrombin generation that is associated with early and late mortality. The endotheliopathy and tissue factor release likely plays a role in the cascade of impaired thrombin burst, possible early fibrinogen consumption and the weaker clot identified by MA-R., Level of Evidence: Therapeutic/care management, level II., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors declare no conflict of interests., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Damage-control resuscitation (DCR) improves survival in severely bleeding patients. However, deviating from balanced transfusion ratios during a resuscitation may limit this benefit. We hypothesized that maintaining a balanced resuscitation during DCR is independently associated with improved survival., Methods: This was a secondary analysis of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. Patients receiving >3 U of packed red blood cells (PRBCs) during any 1-hour period over the first 6 hours and surviving beyond 30 minutes were included. Linear regression assessed the effect of percent time in a high-ratio range on 24-hour survival. We identified an optimal ratio and percent of time above the target ratio threshold by Youden's index. We compared patients with a 6-hour ratio above the target and above the percent time threshold (on-target) with all others (off-target). Kaplan-Meier analysis assessed the combined effect of blood product ratio and percent time over the target ratio on 24-hour and 30-day survival. Multivariable logistic regression identified factors independently associated with 24-hour and 30-day survival., Results: Of 1,245 PROMMTT patients, 524 met the inclusion criteria. Optimal targets were plasma/PRBC and platelet/PRBC of 0.75 (3:4) and ≥40% time spent over this threshold. For plasma/PRBC, on-target (n = 213) versus off-target (n = 311) patients were younger (median, 31 years; interquartile range, [22-50] vs. 40 [25-54]; p = 0.002) with similar injury burdens and presenting physiology. Similar patterns were observed for platelet/PRBC on-target (n = 116) and off-target (n = 408) patients. After adjusting for differences, on-target plasma/PRBC patients had significantly improved 24-hour (odds ratio, 2.25; 95% confidence interval, 1.20-4.23) and 30-day (odds ratio, 1.97; 95% confidence interval, 1.14-3.41) survival, while on-target platelet/PRBC patients did not., Conclusion: Maintaining a high ratio of plasma/PRBC during DCR is independently associated with improved survival. Performance improvement efforts and prospective studies should capture time spent in a high-ratio range., Level of Evidence: Epidemiologic/prognostic study, level II; Therapeutic, level IV., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Surgery of Trauma.)

Background: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial showed that 15% of patients developed venous thromboembolism (VTE) following hemorrhage, but the mechanisms are unknown. Since inflammation is associated with hypercoagulability and thrombosis, our goal was to compare the temporal inflammatory profile following hemorrhagic shock in patients with and without VTE., Study Design: Secondary analysis was performed on data collected from PROPPR. Blood samples collected at 0 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours following admission were assayed on a 27-target cytokine panel, and compared between VTE (n = 83) and non-VTE (n = 475) patients. p < 0.05 indicated significance., Results: Over time, both groups exhibited elevations in proinflammatory mediators interleukin (IL)-6, IL-8, IL-10, granulocyte colony-stimulating factor 57, monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β, and anti-inflammatory mediators IL-1ra and IL-10 (p < 0.05 vs. admission). Venous thromboembolism patients showed amplified responses for IL-6 (6-72 hours) and IL-8 (6-24 hours), which peaked at later time points, and granulocyte colony-stimulating factor 57 (12-24 hours), monocyte chemoattractant protein 1 (6-72 hours), and macrophage inflammatory protein-1 β (2-12 hours) (p < 0.05 vs. non-VTE per time point) that peaked at similar time points to non-VTE patients. The anti-inflammatory responses were similar between groups, but the interleukin-mediated proinflammatory responses continued to rise after the peak anti-inflammatory response in the VTE group. The occurrence rate of adverse events was higher in VTE (97%) versus non-VTE (87%, p = 0.009) and was associated with higher inflammation., Conclusion: Patients with VTE following hemorrhagic shock exhibited a prolonged and amplified proinflammatory responses mediated by select interleukin, chemotactic, and glycoprotein cytokines that are not antagonized by anti-inflammatory mediators. This response is not related to randomization group, injury severity or degree of shock, but may be linked to adverse events., Level of Evidence: Prognostic, level III., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Non-compressible truncal hemorrhage (NCTH) is the leading cause of preventable death after trauma. Resuscitative endovascular balloon occlusion of the aorta (REBOA) achieves temporary hemorrhage control, supporting cardiac and cerebral perfusion prior to definitive hemostasis. Aortic zone selection algorithms vary among institutions. We evaluated the efficacy of an algorithm for REBOA use., Methods: A multicenter prospective, observational study conducted at six level 1 trauma centers over 12 months. Inclusion criteria were age >15 years with evidence of infradiaphragmatic NCTH needing emergent hemorrhage control within 60 min of ED arrival. An algorithm characterized by the results of focused assessment with sonography in trauma and pelvic X-ray was assessed post hoc for efficacy in a cohort of patients receiving REBOA., Results: Of the 8166 patients screened, 78 patients had a REBOA placed. 21 patients were excluded, leaving 57 patients for analysis. The algorithm ensures REBOA deployment proximal to hemorrhage source to control bleeding in 98.2% of cases and accurately predicts the optimal REBOA zone in 78.9% of cases. If the algorithm was violated, bleeding was optimally controlled in only 43.8% (p=0.01). Three (75.0%) of the patients that received an inappropriate zone 1 REBOA died, two from multiple organ failure (MOF). All three patients that died with an inappropriate zone 3 REBOA died from exsanguination., Discussion: This algorithm ensures proximal hemorrhage control and accurately predicts the primary source of hemorrhage. We propose a new algorithm that will be more inclusive. A zone 3 REBOA should not be performed when a zone 1 is indicated by the algorithm as 100% of these patients exsanguinated. MOF, perhaps from visceral ischemia in patients with an inappropriate zone 1 REBOA, may have been prevented with zone 3 placement or limited zone 1 occlusion time., Level of Evidence: Level III., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Both groups A and AB plasma have been approved for emergency-release transfusion in acutely bleeding trauma patients before blood grouping being performed. The safety profile associated with this practice has not been well characterized, particularly in patients requiring massive transfusion., Methods: This secondary analysis of the Pragmatic, Randomized, Optimal Platelet and Plasma Ratios trial examined whether exposure to group A emergency-release plasma (ERP) was noninferior to group AB ERP. We also examined patients whose blood groups were compatible with group A ERP versus patients whose blood groups were incompatible with group A ERP. Outcomes included 30-day mortality and complication rates including systemic inflammatory response syndrome, infection, renal injury, pulmonary dysfunction, and thromboembolism., Results: Of the 680 patients predicted to receive a massive transfusion, 584 (85.9%) received at least 1 U of ERP. Of the 584 patients analyzed, 462 (79.1%) received group AB and 122 (20.9%) received group A ERP. Using a hazard ratio (HR) of 1.35 as the noninferiority margin, transfusion with group A versus group AB ERP was not associated with increased thromboembolic rates (HR, 0.52; 95% confidence interval [CI], 0.31-0.90). Mortality (HR, 1.15; 95% CI, 0.91-1.45) and nonfatal complication rates (HR, 1.24; 95% CI, 0.87-1.77) were inconclusive. In the subgroup analysis, transfusion with incompatible ERP (group B or AB patients receiving group A ERP) was not associated with increased nonfatal complications (HR, 1.02; 95% CI, 0.80-1.30). There were no reported hemolytic transfusion reactions., Conclusion: The use of ERP is common in patients requiring massive transfusion and facilitates the rapid balanced resuscitation of patients who have sustained blood loss. Group A ERP is an acceptable option for patients requiring massive transfusion, especially if group AB ERP is not readily available., Level of Evidence: Therapeutic/Care Management, level IV; Prognostic, level III.

Background: Massive transfusion protocols to treat postinjury hemorrhage are based on predefined blood product transfusion ratios followed by goal-directed transfusion based on patient's clinical evolution. However, it remains unclear how these transfusion ratios impact patient outcomes over time from injury., Methods: The Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) is a phase 3, randomized controlled trial, across 12 Level I trauma centers in North America. From 2012 to 2013, 680 severely injured patients required massive transfusion. We used semiparametric machine learning techniques and causal inference methods to augment the intent-to-treat analysis of PROPPR, estimating the dynamic relationship between transfusion ratios and outcomes: mortality and hemostasis at different timepoints during the first 24 hours after admission., Results: In the intention-to-treat analysis, the 1:1:1 group tended to have decreased mortality, but with no statistical significance. For patients in whom hemostasis took longer than 2 hours, the 1:1:1 ratio was associated with a higher probability of hemostasis, statistically significant from the 4 hour on. In the per-protocol, actual-transfusion-ratios-received analysis, during four successive time intervals, no significant association was found between the actual ratios and mortality. When comparing patient groups who received both high plasma/PRBC and high platelet/PRBC ratios to the group of low ratios in both, the relative risk of achieving hemostasis was 2.49 (95% confidence interval, 1.19-5.22) during the third hour after admission, suggesting a significant beneficial impact of higher transfusion ratios of plasma and platelets on hemostasis., Conclusion: Our results suggest that the impact of transfusion ratios on hemostasis is dynamic. Overall, the transfusion ratios had no significant impact on mortality over time. However, receiving higher ratios of platelets and plasma relative to red blood cells hastens hemostasis in subjects who have yet to achieve hemostasis within 3 hours after hospital admission., Level of Evidence: Therapeutic IV.

Background: There have been no prior investigations of the cost effectiveness of transfusion strategies for trauma resuscitation. The Pragmatic, Randomized, Optimal Platelet and Plasma Ratios (PROPPR) study was a Phase III multisite, randomized trial in 680 subjects comparing the efficacy of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with the 1:1:2 ratio. We hypothesized that 1:1:1 transfusion results in an acceptable incremental cost-effectiveness ratio, when estimated using patients' age-specific life expectancy and cost of care during the 30-day PROPPR trial period., Study Design and Methods: International Classification of Diseases, Ninth Revision codes were prospectively collected, and subjects were matched 1:2 to subjects in the Healthcare Utilization Program State Inpatient Data to estimate cost weights. We used a decision tree analysis, combined with standard costs and estimated years of expected survival to determine the cost effectiveness of the two treatments., Results: The 1:1:1 group had higher overall costs for the blood products but were more likely to achieve hemostasis and decreased hemorrhagic death by 24 hours (p = 0.006). For every 100 patients treated in the 1:1:1 group, eight more achieved hemostasis than in the 1:1:2 group. At 30 days, the total hospital cost per 100 patients was $5.6 million in the 1:1:1 group compared with $5.0 million in the 1:1:2 group. For each 100 patients, the 1:1:1 group had 218.5 more years of life expectancy. This was at a cost of $2994 per year gained., Conclusion: The 1:1:1 transfusion ratio in severely injured hemorrhaging trauma patients is a very cost-effective strategy for increasing hemostasis and decreasing trauma deaths., (© 2020 AABB.)

Background: Most studies of trauma deaths include non-preventable deaths, potentially limiting successful intervention efforts. In this study we aimed to compare the potentially preventable trauma deaths between 2 time periods at our institution., Methods: Trauma patients who died in our hospital in 2005-2006 or 2012-2013 were included, non-preventable deaths were excluded from analysis. The Mann-Whitney and chi square test were used to compare variables between both time periods., Results: 80% of deaths were non-preventable. Between the study time periods there was a decrease in potentially preventable deaths, from 29% to 12%, p < 0.001. Head injury deaths significantly decreased (40.6%-24.6%, p = 0.03), while hemorrhage deaths were stable during both time periods (47.6%-43.1%, p = 0.55)., Conclusion: Potentially preventable trauma deaths decreased during the study period. Hemorrhage remains constant as the leading cause of potentially preventable deaths. Continued research to improve survival from hemorrhage is warranted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Backdrop: Clinicians intuitively recognize that faster time to hemostasis is important in bleeding trauma patients, but these times are rarely reported., Methods: Prospectively collected data from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial were analyzed. Hemostasis was predefined as no intraoperative bleeding requiring intervention in the surgical field or resolution of contrast blush on interventional radiology (IR). Patients who underwent an emergent (within 90 minutes) operating room (OR) or IR procedure were included. Mixed-effects Poisson regression with robust error variance (controlling for age, Injury Severity Score, treatment arm, injury mechanism, base excess on admission [missing values estimated by multiple imputation], and time to OR/IR as fixed effects and study site as a random effect) with modified Bonferroni corrections tested the hypothesis that decreased time to hemostasis was associated with decreased mortality and decreased incidence of acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), multiple-organ failure (MOF), sepsis, and venous thromboembolism., Results: Of 680 enrolled patients, 468 (69%) underwent an emergent procedure. Patients with decreased time to hemostasis were less severely injured, had less deranged base excess on admission, and lower incidence of blunt trauma (all p < 0.05). In 408 (87%) patients in whom hemostasis was achieved, every 15-minute decrease in time to hemostasis was associated with decreased 30-day mortality (RR, 0.97; 95% confidence interval [CI], 0.94-0.99), AKI (RR, 0.97; 95% CI, 0.96-0.98), ARDS (RR, 0.98; 95% CI, 0.97-0.99), MOF (RR, 0.94; 95% CI, 0.91-0.97), and sepsis (RR, 0.98; 95% CI, 0.96-0.99), but not venous thromboembolism (RR, 0.99; 95% CI, 0.96-1.03)., Conclusion: Earlier time to hemostasis was independently associated with decreased incidence of 30-day mortality, AKI, ARDS, MOF, and sepsis in bleeding trauma patients. Time to hemostasis should be considered as an endpoint in trauma studies and as a potential quality indicator., Level of Evidence: Therapeutic/care management, level III.

Background: Focused assessment with sonography for trauma (FAST) performance metrics are unknown in patients with non-compressible torso hemorrhage (NCTH)., Methods: Retrospective review of a dedicated NCTH database from four level 1 trauma centers (2008-2012). NCTH was defined as (1) named axial torso vessel disruption; (2) AIS chest or abdomen >2 with shock (base deficit < -4) or truncal operation in ≤ 90 min; or (3) pelvic fracture with ring disruption. Patients were grouped by cavity of hemorrhage source and by shock (SBP ≤ 90)., Results: 274 patients had a FAST prior to diagnosis of NCTH. FAST was positive in 51% of patients with abdominal/pelvic hemorrhage for a false negative rate (FNR) of 49%. FNR was higher for pelvic (61%) versus abdominal (43%) sources (p = 0.02). There was no difference between FAST negative or positive patients for ISS, shock, length of stay, or mortality (all p = NS). FNR was not improved among the subgroup of NCTH patients with shock (p = NS)., Conclusion: FAST identified abdominal/pelvic hemorrhage in approximately half of NCTH patients, and this was not improved among patients presenting with shock., (Published by Elsevier Inc.)

Background: Hypothermia is associated with poor outcomes after injury. The relationship between hypothermia during contemporary large volume resuscitation and blood product consumption is unknown. We evaluated this association, and the predictive value of hypothermia on mortality., Methods: Patients predicted to receive massive transfusion at 12 level 1 trauma centers were randomized in the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial and were grouped into those who were hypothermic (<36°C) or normothermic (36-38.5°C) within the first 6 hours of emergency department arrival. The impact of hypothermia or normothermia on the volume of blood product required during the first 24 hours was determined via negative binomial regression, adjusting for treatment arm, injury severity score, mechanism, demographics, pre-emergency department fluid volume, blood administered before becoming hypothermic, pulse and systolic blood pressure on arrival, and the time exposed to hypothermic or normothermic temperatures., Results: Of 680 patients, 590 had a temperature measured during the first 6 hours in hospital, and 399 experienced hypothermia. The mean number of red blood cell (RBC) units given to all patients in the first 24 hours of admission was 8.8 (95% confidence interval [CI], 7.9-9.6). In multivariable analysis, every 1°C decrease in temperature below 36.0°C was associated with a 10% increase (incidence rate ratio, 0.90; 95% CI, 0.89-0.92; p < 0.00) in consumption of RBCs during the first 24 hours of admission. There was no association between RBC administration and a temperature above 36°C. Hypothermia on arrival was an independent predictor of mortality, with an adjusted odds ratio of 2.7 (95% CI, 1.7-4.5; p < 0.00) for 24-hour mortality and 1.8 (95% CI, 1.3-2.4; p < 0.00) for 30-day mortality., Conclusion: Hypothermia is associated with increase in blood product consumption and mortality. These findings support the maintenance of normothermia in trauma patients and suggest that further investigation on the impact of cooling or rewarming during massive transfusion is warranted., Level of Evidence: Prognostic, level III.

Background: Temporal changes in fibrinolytic activity after injury and their impact on outcomes remain poorly defined. We conducted a prospective, multicenter cohort study to determine the incidence of fibrinolytic phenotypes after injury and the trajectories and associated outcomes of these phenotypes over time., Methods: We included adults that arrived within 6 hours of injury to three American Level I trauma centers. Clot lysis at 30 minutes (LY-30) was measured at presentation and at 3 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, and 120 hours. LY-30 was used to categorize patients into the following fibrinolytic phenotypes: fibrinolysis shutdown (SD, LY-30 ≤0.8%), physiologic fibrinolysis (PHYS, LY-30 >0.8% to <3%), or hyperfibrinolysis (HF, LY-30 ≥3%). We used multivariable logistic regression to estimate adjusted odds ratios for mortality., Results: We included 795 adults (median age, 38 years; median Injury Severity Scale score, 21). In total, 44% presented with SD, 36% with PHYS, and 21% with HF. Mortality was highest among those who presented with HF (20%) followed by SD (10%) and PHYS (7%) (p = 0.001). While mortality within the first 24 hours was highest with admission HF (14% vs. 5% SD vs. 4% PHYS; p = 0.001), both admission HF (7%) and SD (6%) had higher mortality after 24 hours compared with PHYS (3%) (p = 0.04). All patients who presented with HF switched into another phenotype or died within 24 hours. The majority of patients that presented in SD remained in that phenotype, including 71% at 24 hours and 72% at 120 hours. Persistent SD at 24 hours was independently associated with increased mortality after 24 hours (odds ratio, 3.20; 95% confidence interval, 1.51-6.67)., Conclusion: Approximately 70% of major trauma patients who present with SD remain in this phenotype up to 120 hours postinjury. In contrast, patients presenting with HF transition into another phenotype or die within 24 hours. While early mortality is highest with the HF phenotype, persistent SD at 24 hours is associated with elevated late mortality., Level of Evidence: Prognostic and epidemiological study, level II.

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., Competing Interests: Competing interests: JBH reported serving on the board for Tenaxis, the Regional Advisory Council for Trauma and the National Trauma Institute; providing expert testimony for the Department of Justice; grants funded by the Haemonetics Corporation and KCI USA and consultant fees from the Winkenwerder Company. No other disclosures were reported.

Background: To address deficiencies associated with the classic definition of massive transfusion (MT), critical administration threshold (CAT) and resuscitation intensity (RI) were developed to better quantify the overall severity of illness and predict the need for transfusions and early mortality. We sought to evaluate these as more appropriate replacements for MT in defining mortality risk in patients undergoing major transfusions., Methods: Patients predicted to receive MT at 12 Level I trauma centers were randomized in the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial. MT of 10 U or greater red blood cell (RBC) in 24 hours; CAT+, 3 U or greater RBC in the first hour; and RI, total products in the first 30 minutes (1 U RBC, 1 U plasma, 1000 mL crystalloid, 500 mL colloid each valued at 1 U). Resuscitation intensity was evaluated as a continuous variable and dichotomized as RI4+, where RI is 4 U or greater. Each metric was evaluated for its ability to predict mortality at 3 hours, 6 hours, and 24 hours, and at 30 days., Results: Of the 680 patients, 301 patients met MT definition, 521 were CAT+, and 445 were RI4+. Of those that died, 23% never reached MT threshold, but all were captured by CAT+ and RI4+. The 3-hour (9% vs. 9%), 6-hour (14% vs. 14%), 24-hour (17% vs. 18%), and 30-day mortality rates (28% vs. 29%) were similar between CAT+ and RI4+ patients. When RI was evaluated as a continuous variable, each unit increase was associated with a 20% increase in hemorrhage-related mortality (odds ratio, 1.20; 95% confidence interval, 1.15-1.29; p < 0.05)., Conclusion: Both RI and CAT are valid surrogates for early mortality in patients undergoing major transfusion, capturing patients omitted by the MT definition. The CAT+ showed the best sensitivity; RI4+ demonstrated better specificity and good positive predictive values and negative predictive values. While CAT+ may be suited for patients receiving an RBC-dominant resuscitation, RI4+ is more comprehensive. RI can also be used as a continuous variable to provide quantitative as well as qualitative risk of death., Level of Evidence: Prognostic, level III.

Background: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) study evaluated the effects of plasma and platelets on hemostasis and mortality after hemorrhage. The pulmonary consequences of resuscitation strategies that mimic whole blood, remain unknown., Methods: A secondary analysis of the PROPPR study was performed. Injured patients predicted to receive a massive transfusion were randomized to 1:1:1 versus 1:1:2 plasma-platelet-red blood cell ratios at 12 Level I North American trauma centers. Patients with survival >24 h, an intensive care unit (ICU) stay, and a recorded PaO2/FiO2 (P/F) ratio were included. Acute respiratory distress syndrome (ARDS) was defined as a P/F ratio < 200, with bilateral pulmonary infiltrates, and adjudicated by investigators., Results: Four hundred fifty-four patients were reviewed (230 received 1:1:1, 224 1:1:2). Age, sex, injury mechanism, and regional abbreviated injury scale (AIS) scores did not differ between cohorts. Tidal volume, positive end-expiratory pressure, and lowest P/F ratio did not differ. No significant differences in ARDS rates (14.8% vs. 18.4%), ventilator-free (24 vs. 24) or ICU-free days (17.5 vs. 18), hospital length of stay (22 days vs. 18 days), or 30-day mortality were found (28% vs. 28%). ARDS was associated with blunt injury (OR 3.61 [1.53-8.81] P < 0.01) and increasing chest AIS (OR 1.40 [1.15-1.71] P < 0.01). Each 500 mL of crystalloid infused during hours 0 to 6 was associated with a 9% increase in the rate of ARDS (OR 1.09 [1.04-1.14] P < 0.01). Blood given at 0 to 6 or 7 to 24 h were not risk factors for lung injury., Conclusion: Acute crystalloid exposure, but not blood products, is a potentially modifiable risk factor for the prevention of ARDS following hemorrhage.

Background: While transfusion-related acute lung injury (TRALI) remains the primary cause of transfusion-related fatalities (37%), recent reports estimate the incidence of TRALI at 0.008% per unit of plasma transfused and 0.004% per all products transfused. Because blood banks have moved toward male-predominant plasma, TRALI appears, anecdotally, to have been reduced to an extremely rare event. The purpose of this study was to estimate the current incidence of TRALI at a large, urban center known for its early and aggressive use of plasma in the setting of trauma, hemorrhagic shock, and massive transfusion., Methods: The Blood Bank Registry of our hospital was queried for all transfused patients admitted from September 2002 through March 2013. The blood bank collected and investigated all cases of clinical acute lung injury meeting the consensus definition for TRALI, as well as potential cases for which the donor product was recalled for having a high reactivity level of human leukocyte antigen antibodies (ie, the antibodies that could cause TRALI). Clinical reactions were reviewed in conjunction with independent serological testing and classified by transfusion medicine physicians as being "probable TRALI" or of "unrelated etiology." The total number of units transfused at our facility during this time period was also obtained, allowing the incidence of TRALI to be estimated. Cases were analyzed based on demographics, outcome, blood types, observed symptoms and their duration, and type of product transfused., Results: Seven cases were identified at our center for the indicated time period, with only 3 of these occurring in trauma. A total of 714,757 units of blood products were transfused between September 2002 and March 2013. The incidence of TRALI was estimated to be 1 case per 100,000 units of product for the entire study period. A broad range of patients was affected. Consistent with previous descriptions, an acute duration of symptoms (average, 1.4 days) was observed and usually resolved with supportive care. Reactions were observed predominantly in plasma products, both type specific and nontype specific., Conclusions: This study demonstrates that while TRALI still occurs, clinically meaningful cases are rare. Moreover, TRALI rates remain low despite the increasingly aggressive use of plasma and platelets in the trauma setting.

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., (© 2018 by The American Society of Hematology.)

Background: Objective parameters predicting futility of care in severely injured pediatric patients are lacking. Although futility of care has been investigated in a limited number of studies in trauma patients, none of these studies achieves a 100% success rate in a large cohort of pediatric patients. The purpose of the current study was to identify extreme laboratory values that could be used to predict 100% mortality in severely injured children., Study Design: We evaluated a registry-based, historical cohort of all severely injured children (Level I trauma, younger than 16 years old) who were not dead on arrival between January 2010 and December 2016 from a single Level I trauma center. Extreme arrival laboratory data were evaluated both alone and in conjunction with traumatic brain injury., Results: There were 1,292 patients who met inclusion criteria, of which 1,169 (90.5%) survived and 123 (9.5%) died. Those who died were significantly younger, with higher head Abbreviated Injury Scale scores and overall Injury Severity Scores. Single extreme laboratory values were identified that predicted mortality perfectly (100% positive predictive value): international normalized ratio ≥3.0, pH ≤6.95, base excess ≤ -22, platelet count ≤30,000, hemoglobin ≤5.0 g/dL, rapid thromboelastography ≤30 mm, and rapid thromboelastography lysis at 30 minutes ≥50%. When 2 laboratory values or the presence of traumatic brain injury were added, lower thresholds for futility were noted., Conclusions: Extreme admission laboratory values are capable of predicting 100% mortality and futility of additional care in severely injured children with a high level of accuracy. Validation of these single-center findings is warranted and, if supported, should initiate a discussion within the pediatric trauma community about application and cessation of resuscitation efforts to optimize resource use., (Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Laboratory-based evidence of coagulopathy (LC) is observed in 25-35% of trauma patients, but clinically-evident coagulopathy (CC) is not well described., Methods: Prospective observational study of adult trauma patients transported by helicopter from the scene to nine Level 1 trauma centers in 2015. Patients meeting predefined highest-risk criteria were divided into CC+ (predefined as surgeon-confirmed bleeding from uninjured sites or injured sites not controllable by sutures) or CC-. We used a mixed-effects, Poisson regression with robust error variance to test the hypothesis that abnormalities on rapid thrombelastography (r-TEG) and international normalized ratio (INR) were independently associated with CC+., Results: Of 1,019 highest-risk patients, CC+ (n=41, 4%) were more severely injured (median ISS 32 vs 17), had evidence of LC on r-TEG and INR, received more transfused blood products at 4 hours (37 vs 0 units), and had greater 30-day mortality (59% vs 12%) than CC- (n=978, 96%). The overall incidence of LC was 39%. 30-day mortality was 22% vs 9% in those with and without LC. In two separate models, r-TEG K-time >2.5 min (RR 1.3, 95% CI 1.1-1.7), r-TEG mA <55 mm (RR 2.5, 95% CI 2.0-3.2), platelet count <150 x 10 9 /L (RR 1.2, 95% CI 1.1-1.3), and INR >1.5 (RR 5.4, 95% CI 1.8-16.3) were independently associated with CC+. A combined regression model was not generated because too few patients underwent both r-TEG and INR., Conclusion: CC was rare compared to LC. CC was associated with poor outcomes and impairment of both clotting factor and platelet-mediated coagulation components., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Recently, observational studies analyzing prehospital blood product transfusions (PHT) for trauma have become more widespread in both military and civilian communities. Due to these studies' non-random treatment assignment, propensity score (PS) methodologies are often used to determine an intervention's effectiveness. However, there are no guidelines on how to appropriately conduct PS analyses in prehospital studies. Such analyses are complicated when treatments are given in emergent settings as the ability to administer treatment early, often before hospital admission, can interfere with assumptions of PS modeling. This study conducts a systematic review of literature from military and civilian populations to assess current practice of PS methodology in PHT analyses. The decision-making process from the multicenter Prehospital Resuscitation on Helicopter Study (PROHS) is discussed and used as a motivating example. Results show that researchers often omit or incorrectly assess variable balance between treatment groups and include inappropriate variables in the propensity model. When used correctly, PS methodology is an effective statistical technique to show that aggressive en route resuscitation strategies, including PHT, can reduce mortality in individuals with severe trauma. This review provides guidelines for best practices in study design and analyses that will advance trauma care.