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Abnormal fibrinolysis early after injury has been associated with increased mortality in trauma patients, but no studies have addressed patients with burn injury. This prospective cohort study aimed to characterize fibrinolytic phenotypes in burn patients and to see if they were associated with mortality. Patients presenting to a regional burn centre within 4 h of thermal injury were included. Blood was collected for sequential viscoelastic measurements using thromboelastography (RapidTEG™) over 12 h. The percentage decrease in clot strength 30 min after the time of maximal clot strength (LY30) was used to categorize patients into hypofibrinolytic/fibrinolytic shutdown (SD), physiological (PHYS) and hyperfibrinolytic (HF) phenotypes. Injury characteristics, demographics and outcomes were compared. Of 115 included patients, just over two thirds were male. Overall median age was 40 (i.q.r. 28-57) years and median total body surface area (TBSA) burn was 13 (i.q.r. 6-30) per cent. Some 42 (36.5 per cent) patients had severe burns affecting over 20 per cent TBSA. Overall mortality was 18.3 per cent. At admission 60.0 per cent were PHYS, 30.4 per cent were SD and 9.6 per cent HF. HF was associated with increased risk of mortality on admission (odds ratio 12.61 (95 per cent c.i. 1.12 to 142.57); P = 0.041) but not later during the admission when its incidence also decreased. Admission SD was not associated with mortality, but incidence increased and by 4 h and beyond, SD was associated with increased mortality, compared with PHYS (odds ratio 8.27 (95 per cent c.i. 1.16 to 58.95); P = 0.034). Early abnormal fibrinolytic function is associated with mortality in burn patients.

Review papers commonly summarize the current knowledge on a selected topic. These types of papers are considered narrative reviews. Narrative reviews rarely detail the methods used to select the literature included, nor do the authors typically report the purpose of the review. Narrative reviews may be biased due to inadequate literature reviews or individual beliefs. A systematic review limits bias by disclosing the purpose of the paper, the assembly of the literature, and the appraisal of study quality. A meta-analysis, a specific style of systematic review, quantitatively pools data from individual studies for re-analysis. Pooling data increases the sample size and improves statistical power. The common representation of a meta-analysis is the forest plot. The forest plot demonstrates the odds ratio of individual studies, the weight each trial contributes to the analysis, and the 95% confidence intervals. Systematic reviews and meta-analyses are not without shortcomings, including issues related to study heterogeneity. Because of their transparency, systematic evaluations of the literature are superior to narrative reviews. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE) is a preventable medical condition which has substantial impact on patient morbidity, mortality, and disability. Unfortunately, adherence to the published best practices for VTE prevention, based on patient centered outcomes research (PCOR), is highly variable across U.S. hospitals, which represents a gap between current evidence and clinical practice leading to adverse patient outcomes. This gap is especially large in the case of traumatic brain injury (TBI), where reluctance to initiate VTE prevention due to concerns for potentially increasing the rates of intracranial bleeding drives poor rates of VTE prophylaxis. This is despite research which has shown early initiation of VTE prophylaxis to be safe in TBI without increased risk of delayed neurosurgical intervention or death. Clinical decision support (CDS) is an indispensable solution to close this practice gap; however, design and implementation barriers hinder CDS adoption and successful scaling across health systems. Clinical practice guidelines (CPGs) informed by PCOR evidence can be deployed using CDS systems to improve the evidence to practice gap. In the Scaling AcceptabLE cDs (SCALED) study, we will implement a VTE prevention CPG within an interoperable CDS system and evaluate both CPG effectiveness (improved clinical outcomes) and CDS implementation., Methods: The SCALED trial is a hybrid type 2 randomized stepped wedge effectiveness-implementation trial to scale the CDS across 4 heterogeneous healthcare systems. Trial outcomes will be assessed using the RE 2 -AIM planning and evaluation framework. Efforts will be made to ensure implementation consistency. Nonetheless, it is expected that CDS adoption will vary across each site. To assess these differences, we will evaluate implementation processes across trial sites using the Exploration, Preparation, Implementation, and Sustainment (EPIS) implementation framework (a determinant framework) using mixed-methods. Finally, it is critical that PCOR CPGs are maintained as evidence evolves. To date, an accepted process for evidence maintenance does not exist. We will pilot a "Living Guideline" process model for the VTE prevention CDS system., Discussion: The stepped wedge hybrid type 2 trial will provide evidence regarding the effectiveness of CDS based on the Berne-Norwood criteria for VTE prevention in patients with TBI. Additionally, it will provide evidence regarding a successful strategy to scale interoperable CDS systems across U.S. healthcare systems, advancing both the fields of implementation science and health informatics., Trial Registration: Clinicaltrials.gov - NCT05628207. Prospectively registered 11/28/2022, https://classic., Clinicaltrials: gov/ct2/show/NCT05628207 ., (© 2024. The Author(s).)

Background: Viscoelastic assays have widely been used for evaluating coagulopathies but lack the addition of shear stress important to in vivo clot formation. Stasys technology subjects whole blood to shear forces over factor-coated surfaces. Microclot formation is analyzed to determine clot area (CA) and platelet contractile forces (PCFs). We hypothesize the CA and PCF from this novel assay will provide information that correlates with trauma-induced coagulopathy and transfusion requirements., Methods: Blood samples were collected on adult trauma patients from a single-institution prospective cohort study of high-level activations. Patient and injury characteristics, transfusion data, and outcomes were collected. Thromboelastography, coagulation studies, and Stasys assays were run on paired samples collected at admission. Stasys CA and PCFs were quantified as area under the curve calculations and maximum values. Normal ranges for Stasys assays were determined using healthy donors. Data were compared using Kruskal-Wallis tests and simple linear regression., Results: From March 2021 to January 2023, 108 samples were obtained. Median age was 37.5 (IQR 27.5-52) years; patients were 77% male. 71% suffered blunt trauma, 26% had an Injury Severity Score of ≥25. An elevated international normalized ratio significantly correlated with decreased cumulative PCF (p=0.05), maximum PCF (p=0.05) and CA (p=0.02). Lower cumulative PCF significantly correlated with transfusion of any products at 6 and 24 hours (p=0.04 and p=0.05) as well as packed red blood cells (pRBCs) at 6 and 24 hours (p=0.04 and p=0.03). A decreased maximum PCF showed significant correlation with receiving any transfusion at 6 (p=0.04) and 24 hours (p=0.02) as well as transfusion of pRBCs, fresh frozen plasma, and platelets in the first 6 hours (p=0.03, p=0.03, p=0.03, respectively)., Conclusions: Assessing coagulopathy in real time remains challenging in trauma patients. In this pilot study, we demonstrated that microfluidic approaches incorporating shear stress could predict transfusion requirements at time of admission as well as requirements in the first 24 hours., Level of Evidence: Level II., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Troponin T levels are routinely checked in trauma patients after experiencing a ground-level fall to identify potential cardiac causes of syncope. An elevated initial troponin prompts serial testing until the level peaks. However, the high sensitivity of the test may lead to repeat testing that is of little clinical value. Here, we examine the role of serial troponins in predicting the need for further cardiac workup in trauma patients after sustaining a fall., Methods: Retrospective review of all adult trauma activations for ground-level fall from January 1, 2021 to December 31, 2021 in patients who were hemodynamically and neurologically normal at presentation. Outcomes evaluated included need for cardiology consult, admission to cardiology service, outpatient cardiology follow-up, cardiology intervention and in-hospital mortality., Results: There were 1555 trauma activations for ground-level fall in the study period. The cohort included 560 patients evaluated for a possible syncopal fall, hemodynamically stable, Glasgow Coma Scale score of 15, and with a troponin drawn at presentation. The initial median troponin was 20 ng/L (13-37). Second troponin values were drawn on 58% (median 33 ng/L (22-52)), with 42% of patients having an increase from first to second test. 29% of patients had a third troponin drawn (median 42 ng/L (26-67)). The initial troponin value was significantly associated with undergoing a subsequent echo (p=0.01), cardiology consult (p<0.01), admission for cardiac evaluation (p<0.01), cardiology follow-up (p<0.01), and in-hospital mortality (p=0.01); the initial troponin was not associated with cardiac intervention (p=0.91). An increase from the first to second troponin was not associated with any of outcomes of interest. Analysis was done with cut-off values of 30 ng/L, 50 ng/L, 70 ng/L, and 90 ng/L; a troponin T threshold of 19 ng/L was significant for cardiology consult (p=0.01) and cardiology follow-up (p=0.04). When the threshold was increased to 50 ng/L, it was also significant for admission for cardiac issue (p<0.01). When the threshold was increased to 90 ng/L, it was significant for the same three outcomes and in-hospital mortality (p=0.04)., Conclusion: The initial serum troponin has clinical value in identifying underlying cardiac disease in patients who present after ground-level fall; however, that serial testing is likely of little value. Further, using a cut-off of >50 ng/L as a threshold for further clinical evaluation would improve the utility of the test and likely reduce unnecessary hospital stays and costs for otherwise healthy patients., Level of Evidence: Level III., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Cell-free hemoglobin (CFH) is a potent mediator of endothelial dysfunction, organ injury, coagulopathy, and immunomodulation in hemolysis. These mechanisms have been demonstrated in patients with sepsis, hemoglobinopathies, and those receiving transfusions. However, less is known about the role of CFH in the pathophysiology of trauma, despite the release of equivalent levels of free hemoglobin., Data Sources: Ovid MEDLINE, Embase, Web of Science Core Collection, and BIOSIS Previews were searched up to January 21, 2023, using key terms related to free hemoglobin and trauma., Data Extraction: Two independent reviewers selected studies focused on hemolysis in trauma patients, hemoglobin breakdown products, hemoglobin-mediated injury in trauma, transfusion, sepsis, or therapeutics., Data Synthesis: Data from the selected studies and their references were synthesized into a narrative review., Conclusions: Free hemoglobin likely plays a role in endothelial dysfunction, organ injury, coagulopathy, and immune dysfunction in polytrauma. This is a compelling area of investigation as multiple existing therapeutics effectively block these pathways., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objective: We aimed to examine biomarkers for screening unhealthy alcohol use in the trauma setting., Summary and Background Data: Self-report tools are the practice standard for screening unhealthy alcohol use; however, their collection suffers from recall bias and incomplete collection by staff., Methods: We performed a multi-center prospective clinical study of 251 adult patients who arrived within 24 hours of injury with external validation in another 60 patients. The Alcohol Use Disorders Identification Test served as the reference standard. The following biomarkers were measured: (1) PEth; (2) ethyl glucuronide; (3) ethyl sulfate; (4) gamma-glutamyl-transpeptidase; (5) carbohydrate deficient transferrin; and (6) blood alcohol concentration (BAC). Candidate single biomarkers and multivariable models were compared by considering discrimination (AUROC). The optimal cutpoint for the final model was identified using a criterion for setting the minimum value for specificity at 80% and maximizing sensitivity. Decision curve analysis was applied to compare to existing screening with BAC., Results: PEth alone had an AUROC of 0.93 [95% confidence interval (CI): 0.92-0.93] in internal validation with an optimal cutpoint of 25 ng/mL. A 4- variable biomarker model and the addition of any single biomarker to PEth did not improve AUROC over PEth alone ( P > 0.05). Decision curve analysis showed better performance of PEth over BAC across most predicted probability thresholds. In external validation, sensitivity and specificity were 76.0% (95% CI: 53.0%-92.0%) and 73.0% (95% CI: 56.0%-86.0%), respectively.Conclusion and Relevance: PEth alone proved to be the single best biomarker for screening of unhealthy alcohol use and performed better than existing screening systems with BAC. PEth may overcome existing screening barriers., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Posttraumatic venous thromboembolism (VTE) remains prevalent in severely injured patients despite chemoprophylaxis. Importantly, although platelets are central to thrombosis, they are not routinely targeted in prevention of posttraumatic VTE. Furthermore, platelets from injured patients show ex vivo evidence of increased activation yet impaired aggregation, consistent with functional exhaustion. However, the relationship of this platelet functional phenotype with development of posttraumatic VTE is unknown. We hypothesized that, following injury, impaired ex vivo platelet aggregation (PA) is associated with the development of posttraumatic VTE., Methods: We performed a secondary analysis of 133 severely injured patients from a prospective observational study investigating coagulation and inflammation (2011-2019). Platelet aggregation in response to stimulation with adenosine diphosphate (ADP), collagen, and thrombin was measured at presentation (preresuscitation) and 24 hours (postresuscitation). Viscoelastic clot strength and lysis were measured in parallel by thromboelastography. Multivariable regression examined relationships between PA at presentation, 24 hours, and the change (δ) in PA between presentation and 24 hours with development of VTE., Results: The 133 patients were severely injured (median Injury Severity Score, 25), and 14% developed VTE (all >48 hours after admission). At presentation, platelet count and PA were not significantly different between those with and without incident VTE. However, at 24 hours, those who subsequently developed VTE had significantly lower platelet counts (126 × 10 9 /L vs. 164 × 10 9 /L, p = 0.01) and lower PA in response to ADP ( p < 0.05), collagen ( p < 0.05), and thrombin ( p = 0.06). Importantly, the magnitude of decrease in PA (δ) from presentation to 24 hours was independently associated with development of VTE (adjusted odds ratios per 10 aggregation unit decrease: δ-ADP, 1.31 [ p = 0.03]; δ-collagen, 1.36 [ p = 0.01]; δ-thrombin, 1.41 [ p < 0.01])., Conclusion: Severely injured patients with decreasing ex vivo measures of PA despite resuscitation have an increased risk of developing VTE. This may have implications for predicting development of VTE and for studying platelet targeted chemoprophylaxis regimens., Level of Evidence: Prognostic/Epidemiological; Level III., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The Eastern Association for the Surgery of Trauma mission includes fostering research and providing career development opportunities. Eastern Association for the Surgery of Trauma has awarded for 20 years a research scholarship to a promising young investigator. The research mentorship efforts were expanded 5 years ago with the INVEST-C Hack-a-thon. INVEST-C provides an intensive, short-term engagement to propel junior faculty toward establishing research independence. This study investigates the impact of these programs on academic productivity., Methods: Pubmed records, National Institutes of Health (NIH) Reporter data, and SCOPUS h-index were acquired for all scholarship (SCH) awardees from 2002 to 2021 (n = 20) and all INVEST-C (INV) participants (2017-2020, n = 19). Current type of practice, total number of funding awards, and timing of first award were ascertained. INVEST-C participants were also surveyed on an annual basis to track their progress. Medians (interquartile range [IQR]) are reported and compared (analysis of variance)., Results: Median publications (PUBs) of SCH awardees were 56 (IQR, 33-88), h-index was 16 (IQR, 12-21), and 25% of awardees have ≥1 NIH grant since their SCH. Among the last 10 awardees with a minimum of 2 years from SCH, 40% have received an NIH award compared with a mean NIH funding rate of 18.5% over the same period. For those remaining in academics (90% SCH), PUBs were higher for those >5 years (66 [IQR, 51-115]) versus <5 years from their SCH (33 [22-59]; p = 0.05), but there was no difference in h-index (16 [IQR, 14-25] vs. 15 [9-19], p = NS). Comparing the most recent 5 years of SCH to INV group, there was no difference in academic productivity as measured by total PUBs (SCH, 33 [IQR, 22-59] vs. INV, 34 [IQR, 18-44]; p = 0.7) or h-index (INV, 9 [IQR, 5-14]; p = 0.1). However, no attendee held research funding before INV, but 31.6% (6 of 19 attendees) have subsequently acquired ≥1 funding award (11 non-NIH, 1 NIH) in the short interval since participation., Conclusion: Investments in research activities have translated to significant extramural funding. Those in the last 5 years have been particularly fruitful with INV participants already achieving equal median academic productivity to SCH recipients., Level of Evidence: Prognostic and Epidemiologic; Level III., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Impaired ex vivo platelet aggregation is common in trauma patients. The mechanisms driving these impairments remain incompletely understood, but functional platelet exhaustion due to excessive in vivo activation is implicated. Given platelet adrenoreceptors and known catecholamine surges after injury, impaired ex vivo platelet aggregation in trauma patients may be linked to catecholamine-induced functional platelet exhaustion., Objective: To determine the relationship of catecholamines with platelet-dependent hemostasis after injury and to model catecholamine-induced functional platelet exhaustion in healthy donor platelets., Patients/methods: Whole blood was collected from 67 trauma patients as part of a prospective cohort study. Platelet aggregometry and rotational thromboelastometry were performed, and plasma epinephrine (EPI) and norepinephrine (NE) concentrations were measured. The effect of catecholamines on healthy donor platelets was examined in a microfluidic model, with platelet aggregometry, and by flow cytometry examining surface markers of platelet activation., Results: In trauma patients, EPI and NE were associated with impaired platelet aggregation (both p < 0.05), and EPI was additionally associated with decreased viscoelastic clot strength, increased fibrinolysis, and mortality (all p < 0.05). In healthy donors, short duration incubation with EPI enhanced platelet aggregation, platelet adhesion under flow, and increased glycoprotein IIb/IIIa activation, while weaker effects were observed with NE. Compared with short incubation, longer incubation with EPI resulted in decreased platelet adhesion, platelet aggregation, and surface expression of glycoprotein IIb/IIIa., Conclusions: These findings suggest sympathoadrenal activation in trauma patients contributes to impaired ex vivo platelet aggregation, which mechanistically may be explained by a functionally exhausted platelet phenotype under prolonged exposure to high plasma catecholamine levels., (© 2022 International Society on Thrombosis and Haemostasis.)

Objective: Pediatric focused assessment with sonography for trauma (FAST) is a sequence of ultrasound views rapidly performed by clinicians to diagnose hemorrhage. A technical limitation of FAST is the lack of expertise to consistently acquire all required views. We sought to develop an accurate deep learning view classifier using a large heterogeneous dataset of clinician-performed pediatric FAST., Methods: We developed and conducted a retrospective cohort analysis of a deep learning view classifier on real-world FAST studies performed on injured children less than 18 years old in two pediatric emergency departments by 30 different clinicians. FAST was randomly distributed to training, validation, and test datasets, 70:20:10; each child was represented in only one dataset. The primary outcome was view classifier accuracy for video clips and still frames., Results: There were 699 FAST studies, representing 4925 video clips and 1,062,612 still frames, performed by 30 different clinicians. The overall classification accuracy was 97.8% (95% confidence interval [CI]: 96.0-99.0) for video clips and 93.4% (95% CI: 93.3-93.6) for still frames. Per view still frames were classified with an accuracy: 96.0% (95% CI: 95.9-96.1) cardiac, 99.8% (95% CI: 99.8-99.8) pleural, 95.2% (95% CI: 95.0-95.3) abdominal upper quadrants, and 95.9% (95% CI: 95.8-96.0) suprapubic., Conclusion: A deep learning classifier can accurately predict pediatric FAST views. Accurate view classification is important for quality assurance and feasibility of a multi-stage deep learning FAST model to enhance the evaluation of injured children., (© 2021 American Institute of Ultrasound in Medicine.)

The use of digital technology is increasing rapidly across surgical specialities, yet there is no consensus for the term 'digital surgery'. This is critical as digital health technologies present technical, governance, and legal challenges which are unique to the surgeon and surgical patient. We aim to define the term digital surgery and the ethical issues surrounding its clinical application, and to identify barriers and research goals for future practice. 38 international experts, across the fields of surgery, AI, industry, law, ethics and policy, participated in a four-round Delphi exercise. Issues were generated by an expert panel and public panel through a scoping questionnaire around key themes identified from the literature and voted upon in two subsequent questionnaire rounds. Consensus was defined if >70% of the panel deemed the statement important and <30% unimportant. A final online meeting was held to discuss consensus statements. The definition of digital surgery as the use of technology for the enhancement of preoperative planning, surgical performance, therapeutic support, or training, to improve outcomes and reduce harm achieved 100% consensus agreement. We highlight key ethical issues concerning data, privacy, confidentiality and public trust, consent, law, litigation and liability, and commercial partnerships within digital surgery and identify barriers and research goals for future practice. Developers and users of digital surgery must not only have an awareness of the ethical issues surrounding digital applications in healthcare, but also the ethical considerations unique to digital surgery. Future research into these issues must involve all digital surgery stakeholders including patients., (© 2022. The Author(s).)

The novel coronavirus COVID-19 has been implicated in a number of extra-pulmonary manifestations including rhabdomyolysis. It is hypothesized to be secondary to direct muscle damage from the virus. The usual treatment of rhabdomyolysis is resuscitation with aggressive fluid management to prevent acute renal failure. However, the combination of blunt thoracic trauma and COVID pneumonia has posed additional challenges for critical care management. A 68-year-old male presented to our institution after being found down for an unknown duration of time. He was diagnosed symptomatic COVID pneumonia. His traumatic injuries included 4 rib fractures, a rectus sheath hematoma, and rhabdomyolysis with a creatinine kinase (CK) level of 16,716 U/L. He was initially treated with steroids, prone positioning, and aggressive fluid administration. Despite treatment his CK level peaked at 146,328 U/L. Here we present the case of trauma and COVID-induced rhabdomyolysis with an extremely elevated CK level.

Objective: This study aimed to characterize changes in firearm injuries at 5 level 1 trauma centers in Northern California in the 12 months following the start of the COVID-19 pandemic compared with the preceding 4 years, accounting for regional variations and seasonal trends., Summary and Background Data: Increased firearm injuries have been reported during the early peaks of the COVID-19 pandemic despite shelter-in-place restrictions. However, these data are overwhelmingly from singlecenter studies, during the initial phase of the pandemic prior to lifting of shelter-in-place restrictions, or do not account for seasonal trends., Methods: An interrupted time-series analysis (ITSA) of all firearm injuries presenting to 5 adult level 1 trauma centers in Northern California was performed (January 2016to February 2021). ITSA modeled the association of the onset of the COVID-19 pandemic (March 2020) with monthly firearm injuries using the ordinary least-squares method, included month indicators to adjust for seasonality, and specified lags of up to 12 months to account for autocorrelation., Results: Prior to the start of COVID-19, firearm injuries averaged (±SD) of 86 (±16) and were decreasing by 0.5/month (P < 0.01). The start of COVID- 19 (March 2020) was associated with an alarming increase of 39 firearm injuries/month (P < 0.01) followed by an ongoing rise of 3.5/mo (P < 0.01). This resulted in an average of 130 (±26) firearm injuries/month during the COVID-19 period and included 8 of the 10 highest monthly firearm injury rates in the past 5 years., Conclusions: These data highlight an alarming escalation in firearm injuries in the 12 months following the onset of the COVID-19 pandemic in Northern California. Additional studies and resources are needed to better understand and address this parallel public health crisis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Multicenter data from 2 decades ago demonstrated that critically ill and injured patients spending more than 6 hours in the emergency department (ED) before transfer to the intensive care unit (ICU) had higher mortality rates. A contemporary analysis of ED length of stay in critically injured patients at American College of Surgeons' Trauma Quality Improvement Program (ACS-TQIP) centers was performed to test whether prolonged ED length of stay is still associated with mortality., Methods: This was an observational cohort study of critically injured patients admitted directly to ICU from the ED in ACS-TQIP centers from 2010-2015. Spending more than 6 hours in the ED was defined as prolonged ED length of stay. Patients with prolonged ED length of stay were matched to those with non-prolonged ED length of stay and mortality was compared., Main Results: A total of 113,097 patients were directly admitted from the ED to the ICU following injury. The median ED length of stay was 167 minutes. Prolonged ED length of stay occurred in 15,279 (13.5%) of patients. Women accounted for 29.4% of patients with prolonged ED length of stay but only 25.8% of patients with non-prolonged ED length of stay, P < 0.0001. Mortality rates were similar after matching-4.5% among patients with prolonged ED length of stay versus 4.2% among matched controls. Multivariable logistic regression of the matched cohorts demonstrated prolonged ED length of stay was not associated with mortality. However, women had higher adjusted mortality compared to men Odds Ratio = 1.41, 95% Confidence Interval 1.28 -1.61, P < 0.0001., Conclusion: Prolonged ED length of stay is no longer associated with mortality among critically injured patients. Women are more likely to have prolonged ED length of stay and mortality.

Background: The earliest measurable changes to postinjury platelet biology may be in the platelet transcriptome, as platelets are known to carry messenger ribonucleic acids (RNAs), and there is evidence in other inflammatory and infectious disease states of differential and alternative platelet RNA splicing in response to changing physiology. Thus, the aim of this exploratory pilot study was to examine the platelet transcriptome and platelet RNA splicing signatures in trauma patients compared with healthy donors., Methods: Preresuscitation platelets purified from trauma patients (n = 9) and healthy donors (n = 5) were assayed using deep RNA sequencing. Differential gene expression analysis, weighted gene coexpression network analysis, and differential alternative splicing analyses were performed. In parallel samples, platelet function was measured with platelet aggregometry, and clot formation was measured with thromboelastography., Results: Differential gene expression analysis identified 49 platelet RNAs to have differing abundance between trauma patients and healthy donors. Weighted gene coexpression network analysis identified coexpressed platelet RNAs that correlated with platelet aggregation. Differential alternative splicing analyses revealed 1,188 splicing events across 462 platelet RNAs that were highly statistically significant (false discovery rate <0.001) in trauma patients compared with healthy donors. Unsupervised principal component analysis of these platelet RNA splicing signatures segregated trauma patients in two main clusters separate from healthy controls., Conclusion: Our findings provide evidence of finetuning of the platelet transcriptome through differential alternative splicing of platelet RNA in trauma patients and that this finetuning may have relevance to downstream platelet signaling. Additional investigations of the trauma platelet transcriptome should be pursued to improve our understanding of the platelet functional responses to trauma on a molecular level., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Surgery of Trauma.)

Background: Prehospital identification of the injured patient likely to require emergent care remains a challenge. End-tidal carbon dioxide (ETCO2) has been used in the prehospital setting to monitor respiratory physiology and confirmation of endotracheal tube placement. Low levels of ETCO2 have been demonstrated to correlate with injury severity and mortality in a number of in-hospital studies. We hypothesized that prehospital ETCO2 values would be predictive of mortality and need for massive transfusion (MT) in intubated patients., Methods: This was a retrospective multicenter trial with 24 participating centers. Prehospital, emergency department, and hospital values were collected. Receiver operating characteristic curves were created and compared. Massive transfusion defined as >10 U of blood in 6 hours or death in 6 hours with at least 1 U of blood transfused., Results: A total of 1,324 patients were enrolled. ETCO2 (area under the receiver operating characteristic curve [AUROC], 0.67; confidence interval [CI], 0.63-0.71) was better in predicting mortality than shock index (SI) (AUROC, 0.55; CI, 0.50-0.60) and systolic blood pressure (SBP) (AUROC, 0.58; CI, 0.53-0.62) (p < 0.0005). Prehospital lowest ETCO2 (AUROC, 0.69; CI, 0.64-0.75), SBP (AUROC, 0.75; CI, 0.70-0.81), and SI (AUROC, 0.74; CI, 0.68-0.79) were all predictive of MT. Analysis of patients with normotension demonstrated lowest prehospital ETCO2 (AUROC, 0.66; CI, 0.61-0.71), which was more predictive of mortality than SBP (AUROC, 0.52; CI, 0.47-0.58) or SI (AUROC, 0.56; CI, 0.50-0.62) (p < 0.001). Lowest prehospital ETCO2 (AUROC, 0.75; CI, 0.65-0.84), SBP (AUROC, 0.63; CI, 0.54-0.74), and SI (AUROC, 0.64; CI, 0.54-0.75) were predictive of MT in normotensive patients. ETCO2 cutoff for MT was 26 mm Hg. The positive predictive value was 16.1%, and negative predictive value was high at 98.1%., Conclusion: Prehospital ETCO2 is predictive of mortality and MT. ETCO2 outperformed traditional measures such as SBP and SI in the prediction of mortality. ETCO2 may outperform traditional measures in predicting need for transfusion in occult shock., Level of Evidence: Diagnostic test, level III., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The Bowel Injury Prediction Score (BIPS) is a tool for identifying patients at risk for blunt bowel and mesenteric injury (BBMI) requiring surgery. BIPS is calculated by assigning one point for each of the following: (1) WBC ≥ 17,000, (2) abdominal tenderness, and (3) injury grade ≥ 4 (mesenteric contusion or hematoma with bowel wall thickening or adjacent interloop fluid collection) on CT scan. A total score ≥ 2 is associated with BBMI requiring surgery. We aimed to validate the BIPS as a predictor for patients with BBMIs requiring operative intervention in a multi-center prospective study., Materials and Methods: Patients were prospectively enrolled at 15 U.S. trauma centers following blunt trauma with suspicion of BBMI on CT scan between July 1, 2018 and July 31, 2019. The BIPS was calculated for each patient enrolled in the study., Results: Of 313 patients, 38% had BBMI requiring operative intervention. Patients were significantly more likely to require surgery in the presence of abdominal tenderness (OR, 3.6; 95% CI, 1.6-8.0) and CT grade ≥ 4 (OR, 11.7; 95% CI, 5.7-23.7). Patients with a BIPS ≥ 2 were more than ten times more likely to require laparotomy than those with a BIPS < 2 (OR, 10.1; 95% CI, 5.0-20.4). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a BIPS ≥ 2 for BBMI requiring surgery was 72% (CI 0.6-0.8), 78% (CI 0.7-0.8), 67% (CI 0.6-0.8), and 82% (CI 0.8-0.9), respectively. The AUROC curve for BIPS ≥ 2 was 0.75. The sensitivity, specificity, PPV, and NPV of a BIPS ≥ 2 for BBMI requiring surgery in patients with severe alteration in mental status (GCS 3-8) was 70% (CI 0.5-0.9), 92% (CI 0.8-1.0), 82% (CI 0.6-1.0), and 86% (CI 0.7-1.0), respectively., Conclusion: This prospective multi-center trial validates BIPS as a predictor of BBMI requiring surgery. Calculation of BIPS during the initial evaluation of trauma patients is a useful adjunct to help general surgeons taking trauma call determine operative versus non-operative management of patients with BBMI including those with severe alteration in mental status., Competing Interests: Declarations of Competing Interest None., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: The goal of predictive analytics monitoring is the early detection of patients at high risk of subacute potentially catastrophic illnesses. An excellent example of a targeted illness is respiratory failure leading to urgent unplanned intubation, where early detection might lead to interventions that improve patient outcomes. Previously, we identified signatures of this illness in the continuous cardiorespiratory monitoring data of intensive care unit (ICU) patients and devised algorithms to identify patients at rising risk. Here, we externally validated three logistic regression models to estimate the risk of emergency intubation developed in Medical and Surgical ICUs at the University of Virginia., Approach: We calculated the model outputs for more than 8000 patients in the University of California-San Francisco ICUs, 240 of whom underwent emergency intubation as determined by individual chart review., Main Results: We found that the AUC of the models exceeded 0.75 in this external population, and that the risk rose appreciably over the 12 h before the event., Significance: We conclude that there are generalizable physiological signatures of impending respiratory failure in the continuous cardiorespiratory monitoring data., (Creative Commons Attribution license.)

Background: Despite the widespread institution of modern massive transfusion protocols with balanced blood product ratios, survival for patients with traumatic hemorrhage receiving ultramassive transfusion (UMT) (defined as ≥20 U of packed red blood cells [RBCs]) in 24 hours) remains low and resource consumption remains high. Therefore, we aimed to identify factors associated with mortality in trauma patients receiving UMT in the modern resuscitation era., Methods: An Eastern Association for the Surgery of Trauma multicenter retrospective study of 461 trauma patients from 17 trauma centers who received ≥20 U of RBCs in 24 hours was performed (2014-2019). Multivariable logistic regression and Classification and Regression Tree analysis were used to identify clinical characteristics associated with mortality., Results: The 461 patients were young (median age, 35 years), male (82%), severely injured (median Injury Severity Score, 33), in shock (median shock index, 1.2; base excess, -9), and transfused a median of 29 U of RBCs, 22 U of fresh frozen plasma (FFP), and 24 U of platelets (PLT). Mortality was 46% at 24 hours and 65% at discharge. Transfusion of RBC/FFP ≥1.5:1 or RBC/PLT ≥1.5:1 was significantly associated with mortality, most pronounced for the 18% of patients who received both RBC/PLT and RBC/FFP ≥1.5:1 (odds ratios, 3.11 and 2.81 for mortality at 24 hours and discharge; both p < 0.01). Classification and Regression Tree identified that age older than 50 years, low initial Glasgow Coma Scale, thrombocytopenia, and resuscitative thoracotomy were associated with low likelihood of survival (14-26%), while absence of these factors was associated with the highest survival (71%)., Conclusion: Despite modern massive transfusion protocols, one half of trauma patients receiving UMT are transfused with either RBC/FFP or RBC/PLT in unbalanced ratios ≥1.5:1, with increased associated mortality. Maintaining focus on balanced ratios during UMT is critical, and consideration of advanced age, poor initial mental status, thrombocytopenia, and resuscitative thoracotomy can aid in prognostication., Level of Evidence: Prognostic, level III., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Altered postinjury platelet behavior is recognized in the pathophysiology of trauma-induced coagulopathy (TIC), but the mechanisms remain largely undefined. Studies suggest that soluble factors released by injury may inhibit signaling pathways and induce structural changes in circulating platelets. Given this, we sought to examine the impact of treating healthy platelets with plasma from injured patients. We hypothesized that healthy platelets treated ex-vivo with plasma from injured patients with shock would impair platelet aggregation, while treatment with plasma from injured patients with significant injury burden, but without shock, would enhance platelet aggregation., Methods: Plasma samples were isolated from injured patients (pretransfusion) and healthy donors at a Level I trauma center and stored at -80°C. Plasma samples from four separate patients in each of the following stratified clinical groups were used: mild injury/no shock (injury severity score [ISS] 2-15, base excess [BE]>-6), mild injury/with shock (ISS 2-15, BE≤-6), severe injury/no shock (ISS>25, BE>-6), severe injury/with shock (ISS>25, BE≤-6), minimal injury (ISS 0/1, BE>-6), and healthy. Platelets were isolated from three healthy adult males and were treated with plasma for 30 min. Aggregation was stimulated with a thrombin receptor agonist and measured via multiple-electrode platelet aggregometry. Data were normalized to HEPES Tyrode's (HT) buffer-only treated platelets. Associations of plasma treatment groups with platelet aggregation measures were tested with Mann-Whitney U tests., Results: Platelets treated with plasma from patients with shock (regardless of degree of injury) had significantly impaired thrombin-stimulated aggregation compared with platelets treated with plasma from patients without shock (P = 0.002). Conversely, platelets treated with plasma from patients with severe injury, but without shock, had amplified thrombin-stimulated aggregation (P = 0.030)., Conclusion: Shock-mediated soluble factors impair platelet aggregation, and tissue injury-mediated soluble factors amplify platelet aggregation. Future characterization of these soluble factors will support development of novel treatments of TIC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

Background: Severe injury initiates a complex physiologic response encompassing multiple systems and varies phenotypically between patients. Trauma-induced coagulopathy may be an early warning of a poorly coordinated response at the molecular level, including a deleterious immunologic response and worsening of shock states. The onset of trauma-induced coagulopathy (TIC) may be subtle however. In previous work, we identified an early warning sign of coagulopathy from the admission thromboelastogram, called the MAR ratio. We hypothesized that a low MAR ratio would be associated with specific derangements in the inflammatory response., Methods: In this prospective, observational study, 88 blunt trauma patients admitted to the intensive care unit (ICU) were identified. Concentrations of inflammatory mediators were recorded serially over the course of a week and the MAR ratio was calculated from the admission thromboelastogram. Correlation analysis was used to assess the relationship between MAR and inflammatory mediators. Dynamic network analysis was used to assess coordination of immunologic response., Results: Seventy-nine percent of patients were male and mean age was 37 years (SD 12). The mean ISS was 30.2 (SD 12) and mortality was 7.2%. CRITICAL patients (MAR ratio ≤14.2) had statistically higher shock volumes at three time points in the first day compared to NORMAL patients (MAR ratio >14.2). CRITICAL patients had significant differences in IL-6 (P=0.0065), IL-8 (P=0.0115), IL-10 (P=0.0316) and MCP-1 (P=0.0039) concentrations compared to NORMAL. Differences in degree of expression and discoordination of immune response continued in CRITICAL patients throughout the first day., Conclusions: The admission MAR ratio may be the earliest warning signal of a pathologic inflammatory response associated with hypoperfusion and TIC. A low MAR ratio is an early indication of complicated dysfunction of multiple molecular processes following trauma., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-3651). YV serves as an unpaid editorial board member of Annals of Translational Medicine from Mar 2019 to Feb 2021. Dr. YV reports grants from Indiana University internal funds, during the conduct of the study; other from Immunetrics, Inc., outside the submitted work. Dr. RAC reports grants from NIH, during the conduct of the study. Dr. TOM reports personal fees from Innomed, outside the submitted work. The other authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Background: Mobilization of intra and extracellular calcium is required for platelet activation, aggregation, and degranulation. However, the importance of alterations in the calcium-platelet axis after injury is unknown. We hypothesized that in injured patients, in vivo initial calcium concentrations (pretransfusion) predict ex vivo platelet activation and aggregation, viscoelastic clot strength, and transfusion of blood products. We additionally hypothesized that increasing calcium concentrations ex vivo increases the expression of platelet activation surface receptors and platelet aggregation responses to agonist stimulation in healthy donor blood., Methods: Blood samples were collected from 538 trauma patients on arrival to the emergency department. Standard assays (including calcium), platelet aggregometry (PA) and thromboelastometry (ROTEM) were performed. In PA, platelet activation (prestimulation impedance [Ω]) and aggregation responses to agonist stimulation (area under the aggregation curve [AUC]) with adenosine diphosphate (ADP), thrombin receptor-activating peptide, arachidonic acid (AA), and collagen (COL) were measured. Multivariable regression tested the associations of calcium with PA, ROTEM, and transfusions. To further examine the calcium-platelet axis, calcium was titrated in healthy blood. Platelet aggregometry and ROTEM were performed, and expression of platelet glycoprotein IIb/IIIa and P-selectin was measured by flow cytometry., Results: The patients were moderately injured with normal calcium and platelet counts. Higher calcium on arrival (pretransfusion) was independently associated with increased platelet activation (prestimulation, Ω; p < 0.001), aggregation (ADP-stimulated, AUC; p = 0.002; thrombin receptor-activating peptide-stimulated, AUC; p = 0.038), and clot strength (ROTEM max clot firmness; p < 0.001), and inversely associated with 24-hour transfusions of blood, plasma, and platelets (all p < 0.005). Up-titrating calcium in healthy blood increased platelet activation (prestimulation, Ω; p < 0.001), aggregation (ADP, AA, COL-stimulated AUCs; p < 0.050), and expression of P-selectin (p = 0.003)., Conclusion: Initial calcium concentrations (pretransfusion) are independently associated with platelet activation, aggregation, clot-strength, and transfusions after injury. These changes may be mediated by calcium driven expression of surface receptors necessary for platelet activation and aggregation. However, the therapeutic benefit of early, empiric calcium repletion in trauma patients remains undefined., Level of Evidence: Prognostic, level V.

Competing Interests: Disclosure: The authors declare that they have nothing to disclose.

Background: Platelet behavior in trauma-induced coagulopathy is poorly understood. Injured patients have impaired platelet aggregation (dysfunction) in ex vivo agonist-stimulated platelet aggregometry (PA). However, PA assumes that platelets are inactivated before ex vivo stimulated aggregation, which may be altered by injury. We hypothesized that following trauma, platelet aggregation (area under the curve) is decreased regardless of injury burden, but that (1) minor injury is associated with an increased baseline electrical impedance, characteristic of a functional platelet phenotype (platelets that activate in response to injury), and that (2) severe injury is not associated with an increased baseline electrical impedance, characteristic of a dysfunctional phenotype (platelets that do not activate well in response to injury) compared with healthy controls., Methods: Blood from 458 trauma patients and 30 healthy donors was collected for PA. Baseline electrical impedance (Ω); platelet aggregation stimulated by adenosine diphosphate, collagen, thrombin, and arachidonic acid; and rotational thromboelastometry were measured. Multivariate regression was performed to identify associations of PA measures with blood transfusion., Results: Compared with healthy controls, injured patients had impaired platelet aggregation in response to ex vivo stimulation, regardless of injury burden. However, minorly injured patients had increased endogenous platelet activation (baseline electrical impedance, Ω: with shock, p = 0.012; without shock, p = 0.084), but severely injured patients did not have significant increases in endogenous platelet activation (baseline electrical impedance, Ω: with shock, p = 0.86; without shock, p = 0.37). For every 10 Ω increase in baseline electrical impedance, there was an 8% decrease in units of blood transfused in the first 24 h (-0.08; confidence interval, -0.14 to -0.02; p = 0.015)., Conclusion: Injury and shock confer differential patterns of platelet aggregation in PA. Minor injury overestimates the presence of platelet dysfunction, while severe injury induces a truly dysfunctional phenotype-platelets that do not activate nor aggregate appropriately after injury. This is consequential in improving accurate phenotyping of postinjury platelet behavior for platelet-based therapeutics., Level of Evidence: Prognostic, level IV.

Background: The mechanisms of aberrant circulating platelet behavior following injury remain unclear. Platelets retain megakaryocyte immature ribonucleic acid (RNA) splicing and protein synthesis machinery to alter their functions based on physiologic signals. We sought to identify fluctuating platelet-specific RNA transcripts in cell-free plasma (CFP) from traumatic brain injury (TBI) patients as proof-of-concept for using RNA sequencing to improve our understanding of postinjury platelet behavior. We hypothesized that we could identify differential expression of activated platelet-specific spliced RNA transcripts from CFP of patients with isolated severe fatal TBI (fTBI) compared with minimally injured trauma controls (t-controls), filtered by healthy control (h-control) data sets., Methods: High-read depth RNA sequencing was applied to CFP from 10 patients with fTBI (Abbreviated Injury Scale [AIS] for head ≥3, AIS for all other categories <3, and expired) and five t-controls (Injury Severity Score ≤1, and survived). A publicly available CFP RNA sequencing data set from 23 h-controls was used to determine the relative steady state of splice-form RNA transcripts discoverable in CFP. Activated platelet-specific spliced RNA transcripts were derived from studies of ex vivo platelet activation and identified by splice junction presence greater than 1.5-fold or less than 0.67-fold ex vivo nonactivated platelet-specific RNA transcripts., Results: Forty-two differentially spliced activated platelet-specific RNA transcripts in 34 genes were altered in CFP from fTBI patients (both upregulated and downregulated)., Conclusion: We have discovered differentially expressed activated platelet-specific spliced RNA transcripts present in CFP from isolated severe fTBI patients that are upregulated or downregulated compared with minimally injured trauma controls. This proof-of-concept suggests that a pool of immature platelet RNAs undergo splicing events after injury for presumed modulation of platelet protein products involved in platelet function. This validates our exploration of injury-induced platelet RNA transcript modulation as an upstream "liquid biopsy" to identify novel postinjury platelet biology and treatment targets for aberrant platelet behavior., Level of Evidence: Diagnostic tests, level V.

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.)

Introduction: Women are under-represented in the surgical disciplines and gender bias is believed to play a factor. We aimed to understand the gender distribution of membership, leadership opportunities, and scientific contributions to annual trauma professional meetings as a case study of gender issues in trauma surgery., Methods: Retrospective collection of membership, leadership, presentation and publication data from 2016 to 2018 Trauma/Acute Care Surgery/Surgical Critical Care (TACSCC) Annual Meetings. Gender was assigned based on self-identification in demographic information, established relationships, or public sources., Results: Women remain under-represented with only 28.1% of those ascertaining American Board of Surgery certification in critical care self-identifying as female. The proportion of female members in Eastern Association for the Surgery of Trauma (EAST) was comparable (29.4%), slightly lower for Western Trauma Association (WTA) (19.0%), and lowest for American Association for the Surgery of Trauma (AAST) (12.8%, p<0.05). In contrast, AAST had the highest proportion of female participants in executive leadership (AAST 32.5%, WTA 19.0%, EAST 18.8%) and WTA the highest for committee chairs (WTA 33.3%, AAST 27.8%, EAST 20.5%). AAST had the most significant increase in executive leadership during the last 3 years (AAST 28.6% to 41.6%). Invited lectureships, masters, panelists and senior author scientific contributions demonstrated the largest gap of academic representation of female TACSCC surgeons., Conclusion: Fewer women than men pursue careers in the trauma field. Continuing to provide mentorship, leadership, and scientific recognition will increase gender diversity in TACSCC. We must continue to promote, sponsor, recognize, invite, and elect 'her'., Level of Evidence: III, Epidemiology., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Trauma-induced coagulopathy is a major driver of mortality following severe injury. Viscoelastic goal-directed resuscitation can reduce mortality after injury. The TEG 5000 system is widely used for viscoelastic testing. However, the TEG 6s system incorporates newer technology, with encouraging results in cardiovascular interventions. The purpose of this study was to validate the TEG 6s system for use in trauma patients., Methods: Multicenter noninvasive observational study for method comparison conducted at 12 US Levels I and II trauma centers. Agreement between the TEG 6s and TEG 5000 systems was examined using citrated kaolin reaction time (CK.R), citrated functional fibrinogen maximum amplitude (CFF.MA), citrated kaolin percent clot lysis at 30 minutes (CK.LY30), citrated RapidTEG maximum amplitude (CRT.MA), and citrated kaolin maximum amplitude (CK.MA) parameters in adults meeting full or limited trauma team criteria. Blood was drawn ≤1 hour after admission. Assays were repeated in duplicate. Reliability (TEG 5000 vs. TEG 6s analyzers) and repeatability (interdevice comparison) was quantified. Linear regression was used to define the relationship between TEG 6s and TEG 5000 devices., Results: A total of 475 patients were enrolled. The cohort was predominantly male (68.6%) with a median age of 49 years. Regression line slope estimates (ß) and linear correlation estimates (p) were as follows: CK.R (ß = 1.05, ρ = 0.9), CFF.MA (ß = 0.99, ρ = 0.95), CK.LY30 (ß = 1.01, ρ = 0.91), CRT.MA (TEG 6s) versus CK.MA (TEG 5000) (ß = 1.06, ρ = 0.86) as well as versus CRT.MA (TEG 5000) (ß = 0.93, ρ = 0.93), indicating strong reliability between the devices. Overall, within-device repeatability was better for TEG 6s versus TEG 5000, particularly for CFF.MA and CK.LY30., Conclusion: The TEG 6s device appears to be highly reliable for use in trauma patients, with close correlation to the TEG 5000 device and equivalent/improved within-device reliability. Given the potential advantages of using the TEG 6s device at the site of care, confirmation of agreement between the devices represents an important advance in diagnostic testing., Level of Evidence: Diagnostic test, level II.

Background: Impaired postinjury platelet aggregation is common, but the effect of transfusion on this remains unclear. Data suggest that following injury platelet transfusion may not correct impaired platelet aggregation, and impaired platelet aggregation may not predict the need for platelet transfusion. We sought to further investigate platelet aggregation responses to transfusions, using regression statistics to isolate the independent effects of transfusions given in discrete time intervals from injury on both immediate and longitudinal platelet aggregation. We hypothesized that platelet aggregation response to platelet transfusion increases over time from injury., Methods: Serial (0-96 hours) blood samples were collected from 248 trauma patients. Platelet aggregation was assessed in vitro with impedance aggregometry stimulated by adenosine diphosphate, collagen, and thrombin receptor-activating peptide-6. Using regression, transfusion exposure was modeled against platelet aggregation at each subsequent timepoint and adjusted for confounders (Injury Severity Score, international normalized ratio (INR), base deficit, platelet count, and interval transfusions). The expected change in platelet aggregation at each timepoint under the intervention of transfusion exposure was calculated and compared with the observed platelet aggregation., Results: The 248 patients analyzed were severely injured (Injury Severity Score, 21 ± 19), with normal platelet counts (mean, 268 × 10/L ± 90), and 62% were transfused in 24 hours. The independent effect of transfusions on subsequent platelet aggregation over time was modeled with observed platelet aggregation under hypothetical treatment of one unit transfusion of blood, plasma, or platelets. Platelet transfusions had increasing expected effects on subsequent platelet aggregation over time, with the maximal expected effect occurring late (4-5 days from injury)., Conclusion: Controversy exists on whether transfusions improve impaired postinjury platelet aggregation. Using regression modeling, we identified that expected transfusion effects on subsequent platelet aggregation are maximal with platelet transfusion given late after injury. This is critical for tailored resuscitation, identifying a potential early period of resistance to platelet transfusion that resolves by 96 hours., Level of Evidence: Therapeutic, level V.

Objectives: Examine the effect of different types of firearms on readmission due to acute stress disorder (ASD) and/or post-traumatic stress disorder (PTSD) in firearm-injury victims., Background: Survivors of firearm-related injuries suffer long-term sequelae such as disability, work loss, and deterioration in the quality of life. There is a paucity of data describing the long-term mental health outcomes in these patients., Methods: We performed a 5-year (2011-2015) analysis of the Nationwide Readmission Database. All adult patients with firearm injuries were stratified into 3 groups by firearm type: handgun, shotgun, and semiautomatic rifle. Outcome measures were the incidence and predictors of ASD/PTSD., Results: A total of 100,704 victims of firearm-related injuries were identified, of which 13.3% (n = 13,393) were readmitted within 6 months of index hospitalization, 6.7% (n = 8970) of these due to ASD/PTSD. Mean age was 34 ± 14 years, 88% were men. Of those readmitted due to ASD/PTSD, 24% (n = 2153) sustained a handgun-related injury on index hospitalization, 12% (n = 1076) shotgun, and 64% (n = 5741) semiautomatic gun (P = 0.039). On regression analysis, semiautomatic gun and shotgun victims had higher odds of developing ASD/PTSD upon readmission [odds ratio (OR): 2.05 (1.10-4.12) and OR: 1.41 (1.08-2.11)] compared to handgun. Female sex [OR: 1.79 (1.05-3.05)] and younger age representing those younger than 25 years [OR: 4.66 (1.12-6.74)] were also independently associated with higher odds of ASD/PTSD., Conclusions: Apart from the lives lost, survivors of semiautomatic rifle- and shotgun-related injuries suffer long-term mental health sequalae. These secondary and debilitating mental health outcomes are important considerations for capturing the overall burden of the disease.

Background: Granular data on gun sales has been historically difficult to obtain. In 2016, California (CA) made monthly data from 1996 to 2015 publically available. Control charts are a method to analyze how a process changes over time in response to nonroutine events. We utilized this technique to study the impact of US mass shootings on CA gun sales., Methods: Monthly gun sales were provided by the CA Department of Justice and monthly fatalities from the CDC Wonder Death Certificate Registry. Mass shooting events were obtained from after-action reports, news media, and court proceedings. Time-ordered data were analyzed with control charts with 95% confidence intervals (upper control limit, lower control limit) using QiMacros., Results: Individual gun sales of 9,917,811 occurred in CA with a median monthly rate of 41,324 (range, 20,057-132,903). A median of 263 people lost their lives monthly from firearms (124 homicides, 128 suicides), totaling 53,975 fatalities from 1999 to 2015. Fifteen of 21 current deadliest mass shootings occurred during this study period with 40% from 2012 to 2015. Also, 36 school shootings occurred during the study (mean, 5 deaths; range, 0-33; 6 injuries; range, 0-23) with 31% in 2012 to 2015 at rate of 3 events/year versus 1.4 events/year in the 17 prior years (p < 0.05). Sales were generally consistent from 1996 to 2011 (except post-Columbine, Col). Starting in 2011, sales exceeded the 95% predicted upper control limit every single month. Before October 2011, there was no statistically significant sustained effect of mass shootings on sales (except Col); however, since a statistically significant proportional spike in sales occurred in the months immediately following every single deadliest mass shooting event. Every year since 2012, CA has strengthened gun laws in response to mass shootings yet sales have risen immediately preceding enactment of these laws each January., Conclusion: Gun sales are more frequent since 2012, with an additional increase following both mass shootings and legislative changes enacted in response to these shootings., Level of Evidence: Epidemiology, level III.

Background: Acute respiratory distress syndrome (ARDS) following trauma is historically associated with crystalloid and blood product exposure. Advances in resuscitation have occurred over the last decade, but their impact on ARDS is unknown. We sought to investigate predictors of postinjury ARDS in the era of hemostatic resuscitation., Methods: Data were prospectively collected from arrival to 28 days for 914 highest-level trauma activations who required intubation and survived more than 6 hours from 2005 to 2016 at a Level I trauma center. Patients with ratio of partial pressure of oxygen to fraction of inspired oxygen of 300 mmHg or less during the first 8 days were identified. Two blinded expert clinicians adjudicated all chest radiographs for bilateral infiltrates in the first 8 days. Those with left-sided heart failure detected were excluded. Multivariate logistic regression was used to define predictors of ARDS., Results: Of the 914 intubated patients, 63% had a ratio of partial pressure of oxygen to fraction of inspired oxygen of 300 or less, and 22% developed ARDS; among the ARDS cases, 57% were diagnosed early (in the first 24 hours), and 43% later. Patients with ARDS diagnosed later were more severely injured (ISS 32 vs. 20, p = 0.001), with higher rates of blunt injury (84% vs. 72%, p = 0.008), chest injury (58% vs. 36%, p < 0.001), and traumatic brain injury (72% vs. 48%, p < 0.001) compared with the no ARDS group. In multivariate analysis, head/chest Abbreviated Injury Score scores, crystalloid from 0 to 6 hours, and platelet transfusion from 0 to 6 hours and 7 to 24 hours were independent predictors of ARDS developing after 24 hours., Conclusions: Blood and plasma transfusion were not independently associated with ARDS. However, platelet transfusion was a significant independent risk factor. The role of platelets warrants further investigation but may be mechanistically explained by lung injury models of pulmonary platelet sequestration with peripheral thrombocytopenia., Level of Evidence: Prognostic study, level IV.

Background: Trauma has long been considered unpredictable. Artificial neural networks (ANN) have recently shown the ability to predict admission volume, acuity, and operative needs at a single trauma center with very high reliability. This model has not been tested in a multicenter model with differing climate and geography. We hypothesize that an ANN can accurately predict trauma admission volume, penetrating trauma admissions, and mean Injury Severity Score (ISS) with a high degree of reliability across multiple trauma centers., Methods: Three years of admission data were collected from five geographically distinct US Level I trauma centers. Patients with incomplete data, pediatric patients, and primary thermal injuries were excluded. Daily number of traumas, number of penetrating cases, and mean ISS were tabulated from each center along with National Oceanic and Atmospheric Administration data from local airports. We trained a single two-layer feed-forward ANN on a random majority (70%) partitioning of data from all centers using Bayesian Regularization and minimizing mean squared error. Pearson's product-moment correlation coefficient was calculated for each partition, each trauma center, and for high- and low-volume days (>1 standard deviation above or below mean total number of traumas)., Results: There were 5,410 days included. There were 43,380 traumas, including 4,982 penetrating traumas. The mean ISS was 11.78 (SD = 6.12). On the training partition, we achieved R = 0.8733. On the testing partition (new data to the model), we achieved R = 0.8732, with a combined R = 0.8732. For high- and low-volume days, we achieved R = 0.8934 and R = 0.7963, respectively., Conclusion: An ANN successfully predicted trauma volumes and acuity across multiple trauma centers with very high levels of reliability. The correlation was highest during periods of peak volume. This can potentially provide a framework for determining resource allocation at both the trauma system level and the individual hospital level., Level of Evidence: Care Management, level IV.

Background: Trauma-induced coagulopathy can present as abnormalities in a conventional or viscoelastic coagulation assay or both. We hypothesized that patients with discordant coagulopathies reflect different clinical phenotypes., Methods: Blood samples were collected prospectively from critically injured patients upon arrival at two urban Level I trauma centers. International normalized ratio (INR), partial thromboplastin time (PTT), thromboelastography (TEG), and coagulation factors were assayed., Results: 278 patients (median ISS 17, mortality 26%) were coagulopathic: 20% with isolated abnormal INR and/or PTT (CONVENTIONAL), 49% with isolated abnormal TEG (VISCOELASTIC), and 31% with abnormal INR/PTT and TEG (BOTH). Compared with VISCOELASTIC, CONVENTIONAL and BOTH had higher ISS, lower GCS, larger base deficit, and decreased factor activities (all p < 0.017). They received more blood products and had more ICU/ventilation days (all p < 0.017). Mortality was higher in CONVENTIONAL (40%) and BOTH (49%) than VISCOELASTIC (6%, p < 0.017)., Conclusions: Although TEG-guided resuscitation improves survival after injury, INR and PTT identify coagulopathic patients with highest mortality regardless of TEG and likely represent distinct mechanisms independent of biochemical clot strength., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Historically, hemorrhage has been attributed as the leading cause (40%) of early death. However, a rigorous, real-time classification of the cause of death (COD) has not been performed. This study sought to prospectively adjudicate and classify COD to determine the epidemiology of trauma mortality., Methods: Eighteen trauma centers prospectively enrolled all adult trauma patients at the time of death during December 2015 to August 2017. Immediately following death, attending providers adjudicated the primary and contributing secondary COD using standardized definitions. Data were confirmed by autopsies, if performed., Results: One thousand five hundred thirty-six patients were enrolled with a median age of 55 years (interquartile range, 32-75 years), 74.5% were male. Penetrating mechanism (n = 412) patients were younger (32 vs. 64, p < 0.0001) and more likely to be male (86.7% vs. 69.9%, p < 0.0001). Falls were the most common mechanism of injury (26.6%), with gunshot wounds second (24.3%). The most common overall primary COD was traumatic brain injury (TBI) (45%), followed by exsanguination (23%). Traumatic brain injury was nonsurvivable in 82.2% of cases. Blunt patients were more likely to have TBI (47.8% vs. 37.4%, p < 0.0001) and penetrating patients exsanguination (51.7% vs. 12.5%, p < 0.0001) as the primary COD. Exsanguination was the predominant prehospital (44.7%) and early COD (39.1%) with TBI as the most common later. Penetrating mechanism patients died earlier with 80.1% on day 0 (vs. 38.5%, p < 0.0001). Most deaths were deemed disease-related (69.3%), rather than by limitation of further aggressive care (30.7%). Hemorrhage was a contributing cause to 38.8% of deaths that occurred due to withdrawal of care., Conclusion: Exsanguination remains the predominant early primary COD with TBI accounting for most deaths at later time points. Timing and primary COD vary significantly by mechanism. Contemporaneous adjudication of COD is essential to elucidate the true understanding of patient outcome, center performance, and future research., Level of Evidence: Epidemiologic, level II.

Objective: Machine learning techniques have demonstrated superior discrimination compared to conventional statistical approaches in predicting trauma death. The objective of this study is to evaluate whether machine learning algorithms can be used to assess risk and dynamically identify patient-specific modifiable factors critical to patient trajectory for multiple key outcomes after severe injury., Methods: SuperLearner, an ensemble machine-learning algorithm, was applied to prospective observational cohort data from 1494 critically-injured patients. Over 1000 agnostic predictors were used to generate prediction models from multiple candidate learners for outcomes of interest at serial time points post-injury. Model accuracy was estimated using cross-validation and area under the curve was compared to select among predictors. Clinical variables responsible for driving outcomes were estimated at each time point., Results: SuperLearner fits demonstrated excellent cross-validated prediction of death (overall AUC 0.94-0.97), multi-organ failure (overall AUC 0.84-0.90), and transfusion (overall AUC 0.87-0.9) across multiple post-injury time points, and good prediction of Acute Respiratory Distress Syndrome (overall AUC 0.84-0.89) and venous thromboembolism (overall AUC 0.73-0.83). Outcomes with inferior data quality included coagulopathic trajectory (AUC 0.48-0.88). Key clinical predictors evolved over the post-injury timecourse and included both anticipated and unexpected variables. Non-random missingness of data was identified as a predictor of multiple outcomes over time., Conclusions: Machine learning algorithms can be used to generate dynamic prediction after injury while avoiding the risk of over- and under-fitting inherent in ad hoc statistical approaches. SuperLearner prediction after injury demonstrates promise as an adaptable means of helping clinicians integrate voluminous, evolving data on severely-injured patients into real-time, dynamic decision-making support., Competing Interests: The authors have declared that no competing interests exist.

Background: Payers have approached select complications as never events, yet there is rationale that achieving a zero incidence of these events is impractical. Prior 2005 National Trauma Data Bank (NTDB) analysis showed high rates (37%) of centers reporting no complications data making national estimates for determining standardized complication rates difficult to ascertain., Methods: The 2008-2012 NTDB National Sample Program nationally weighted files were used to calculate yearly national estimates. Rates were compared in all centers and those reporting complications data. Hospital characteristics were compared using Student t test. In 2011, an other complication category was introduced; overall rates were calculated with and without this category. Yearly estimates were reported for patients receiving care within centers reporting complications data., Results: From 2008-2012 NTDB, there were raw data on 3,657,884 patients. A total of 594,894 patients (16.3%) experienced one or more complications (82.7% one complication; 17.3% two or more complications). Excluding the other complication category, the overall weighted rate was 8.4% to 9.2%. Pneumonia was the most common complication (2.7-3.0%), occurring at twice the 2005 rate. The number of centers reporting no complications data dropped to 8.1% in 2011 (2008, 14.5%; 2009, 18.2%; 2010, 15.9%; 2012, 8.9%). By 2012, nearly all level I centers reported complications, whereas 46.4% of level IVs reported none (I 0.5%, II 2.7%, III 8.5%, p = 0.04). Data were reported the least frequently in nonteaching hospitals (15.8%, p = 0.007), those in the South (19.6%, p = 0.007), and those with less than 200 beds (23.6%, p = 0.005)., Conclusion: Overall rates of complications from 2008 to 2012 were nearly twofold higher than 2005 data. Reporting has increased, and NTDB may provide a valuable platform for establishing rational and achievable measures for specific complications., Level of Evidence: Prognostic and epidemiological, level IV.

Background: Increased knowledge of the temporal patterns in the distribution of trauma admissions could be beneficial to staffing and resource allocation efforts. However, little work has been done to understand how this distribution varies based on patient acuity, trauma mechanism or need for intervention. We hypothesize that temporal patterns exist in the distribution of trauma admissions, and that deep patterns exist when traumas are analyzed by their type and severity., Study Design: We conducted a cross-sectional observational study of adult patient flow at a level one trauma center over three years, 7/1/2013-6/30/2016. Primary thermal injuries were excluded. Frequency analysis was performed for patients grouped by ED disposition and mechanism against timing of admission; in subgroup analysis additional exclusion criteria were imposed., Results: 10,684 trauma contacts were analyzed. Trauma contacts were more frequent on Saturdays and Sundays than on weekdays (p<0.001). Peak arrival time was centered around evening shift change (6-7pm), but differed based on ED disposition: OR and ICU or Step-Down admissions (p = 0.0007), OR and floor admissions (p<0.0001), and ICU or Step-Down and floor admissions (p<0.0001). Step-Down and ICU arrival times (p = 0.42) were not different. Penetrating injuries peaked later than blunt (p<0.0001). Trauma varies throughout the year; we establish a high incidence trauma season (April to late October). Different mechanisms have varying dependence upon season; Motorcycle crashes (MCCs) have the greatest dependence., Conclusion: We identify new patterns in the temporal and seasonal variation of trauma and of specific mechanisms of injury, including the novel findings that 1) penetrating trauma tends to present at later times than blunt, and 2) critically ill patients requiring an OR tend to present later than those who are less acute and require an ICU or Step-Down unit. These patients present later than those who are admitted to the floor. Penetrating trauma patients arriving later than blunt may be the underlying reason why operative patients arrive later than other patients., Competing Interests: The authors have declared that no competing interests exist.

Background: Severely injured patients often progress from early hypocoagulable to normal and eventually hypercoagulable states, developing increased risk for venous thromboembolism (VTE). Prophylactic anticoagulation can decrease this risk, but its initiation is frequently delayed for extended periods due to concerns for bleeding. To facilitate timely introduction of VTE chemoprophylaxis, we characterized the transition from hypo- to hypercoagulability and hypothesized that trauma-induced coagulopathy resolves within 24 hours after injury., Methods: Serial blood samples were collected prospectively from critically injured patients for 120 hours after arrival at an urban Level I trauma center. Extrinsic thromboelastometry maximum clot firmness was used to classify patients as hypocoagulable (HYPO, <49 mm), normocoagulable (NORM, 49-71 mm), or hypercoagulable (HYPER, >71 mm) at each time point. Changes in coagulability over hospital course, VTE occurrence, and timing of prophylaxis initiation were analyzed., Results: 898 patients (median Injury Severity Score, 13; mortality, 12%; VTE, 8%) were enrolled. Upon arrival, 3% were HYPO (90% NORM, 7% HYPER), which increased to 9% at 6 hours before down-trending. Ninety-seven percent were NORM by 24 hours, and 53% were HYPER at 120 hours. Median maximum clot firmness began in the NORM range, up-trended gradually, and entered the HYPER range at 120 hours. Patients with traumatic brain injury (TBI) followed a similar course and were not more HYPO at any time point than those without TBI. Failure to initiate prophylaxis by 72 hours was predicted by TBI and associated with VTE development (27% vs 16%, p < 0.05)., Conclusions: Regardless of injury pattern, trauma-induced coagulopathy largely resolves within 24 hours, after which hypercoagulability becomes increasingly more prevalent. Deferring initiation of chemoprophylaxis, which is often biased toward patients with intracranial injuries, is associated with VTE development., Level of Evidence: Prognostic study, level III; Therapeutic, level IV.

Background: Injury to the blood-brain barrier exposes endothelium rich in von Willebrand factor (vWF), which may play a role in altered platelet aggregation following traumatic brain injury (TBI). Ristocetin is an antimicrobial substance that induces vWF-mediated aggregation of platelets. We examined these mechanisms in injured patients by measuring the aggregation response of platelets to stimulating agonists (including ristocetin) via whole-blood multiple-electrode platelet aggregometry. We hypothesized that patients with TBI have an altered platelet aggregation response to ristocetin stimulation compared with patients without TBI., Methods: Blood was collected from 233 trauma patients without thrombocytopenia. Platelet aggregation was assessed using multiple-electrode platelet aggregometry (Multiplate). Platelet aggregation response to stimulating agonists collagen, thrombin receptor-activating peptide 6, adenosine diphosphate, arachidonic acid, and ristocetin was measured. Factor activity was measured., Results: Of the 233 patients, 23% had TBI. There were no differences in platelet aggregation responses to any agonists between TBI and non-TBI patients except ristocetin. Platelet aggregation response to ristocetin stimulation was significantly lower in TBI patients (p = 0.03). Patients with TBI also had higher factor VIII activity (215% vs. 156%, p = 0.01). In multivariate analysis, there was a significant independent association of impaired platelet aggregation response to ristocetin stimulation with TBI (odds ratio, 3.05; p = 0.04)., Conclusions: Given the importance of platelets in hemostasis, understanding the mechanisms of impaired platelet aggregation following injury is critical. The impaired platelet aggregation response to ristocetin stimulation and corresponding increase in factor VIII activity in TBI patients may be secondary to a TBI-induced effect on vWF quantity (due to injury-driven consumption of vWF) or vWF function with resultant increase in circulating factor VIII activity (due to impaired carrying capacity of vWF). Given there are multiple known therapies for vWF deficits including desmopressin, purified and recombinant vWF, and estrogens, these lines of investigation are particularly compelling in patients with TBI and hemorrhage., Level of Evidence: Prognostic study, level II.

Background: Mortality prediction aids clinical decision making and is necessary for quality improvement initiatives. Validated metrics rely on prespecified variables and often require advanced diagnostics, which are unfeasible in resource-constrained contexts. We hypothesize that machine learning will generate superior mortality prediction in both high-income and low- and middle-income country cohorts., Methods: SuperLearner, an ensemble machine-learning algorithm, was applied to data from three prospective trauma cohorts: a highest-activation cohort in the United States, a high-volume center cohort in South Africa (SA), and a multicenter registry in Cameroon. Cross-validation was used to assess model discrimination of discharge mortality by site using receiver operating characteristic curves. SuperLearner discrimination was compared with standard scoring methods. Clinical variables driving SuperLearner prediction at each site were evaluated., Results: Data from 28,212 injured patients were used to generate prediction. Discharge mortality was 17%, 1.3%, and 1.7% among US, SA, and Cameroonian cohorts. SuperLearner delivered superior prediction of discharge mortality in the United States (area under the curve [AUC], 94-97%) and vastly superior prediction in Cameroon (AUC, 90-94%) compared with conventional scoring algorithms. It provided similar prediction to standard scores in the SA cohort (AUC, 90-95%). Context-specific variables (partial thromboplastin time in the United States and hospital distance in Cameroon) were prime drivers of predicted mortality in their respective cohorts, whereas severe brain injury predicted mortality across sites., Conclusions: Machine learning provides excellent discrimination of injury mortality in diverse settings. Unlike traditional scores, data-adaptive methods are well suited to optimizing precise site-specific prediction regardless of diagnostic capabilities or data set inclusion allowing for individualized decision making and expanded access to quality improvement programming., Level of Evidence: Prognostic and therapeutic, level II and III.

Background: Since 1967, in California it has been illegal to openly carry a loaded firearm in public except when engaged in hunting or law enforcement. However, beginning January 1, 2012, public open carry of unloaded handguns also became illegal. Fatal and non-fatal (NF) firearm injuries were examined before and after adoption of the 2012 ban to quantify the effect of the new law on public health., Methods: State-level data were obtained directly from California and nine other US state inpatient and emergency department (ED) discharge databases, and the Centers for Disease Control Web-Based Injury Statistics Query and Reporting System. Case numbers of firearm fatalities, NF hospitalizations, NF ED visits, and state-level population estimates were extracted. Each incident was classified as unintentional, self-inflicted, or assault. Crude incidence rates were calculated. The strength of gun laws was quantified using the Brady grade. There were no changes to open carry in these nine states during the study. Using a difference-in-difference technique, the rate trends 3 years preban and postban were compared., Results: The 2012 open carry ban resulted in a significantly lower incident rate of both firearm-related fatalities and NF hospitalizations (p<0.001). The effect of the law remained significant when controlling for baseline state gun laws (p<0.001). Firearm incident rate drops in California were significant for male homicide (p=0.023), hospitalization for NF assault (p=0.021  male; p=0.025 female), and ED NF assault visits (p=0.04). No significant decreases were observed by sex for suicides or unintentional injury. Changing the law saved an estimated 337 lives (3.6% fewer deaths) and 1285 NF visits in California during the postban period., Discussion: Open carry ban decreases fatalities and healthcare utilization even in a state with baseline strict gun laws. The most significant impact is from decreasing firearm-related fatal and NF assaults., Level of Evidence: III, epidemiology., Competing Interests: Competing interests: None declared.

Introduction: Goal-directed hemostatic resuscitation based on thrombelastography (TEG) has a survival benefit compared with conventional coagulation assays such as international normalized ratio, activated partial thromboplastin time, fibrinogen level, and platelet count. While TEG-based transfusion thresholds for patients at risk for massive transfusion (MT) have been defined using rapid TEG, cutoffs have not been defined for TEG using other activators such as kaolin. The purpose of this study was to develop thresholds for blood product transfusion using citrated kaolin TEG (CK-TEG) in patients at risk for MT., Methods: CK-TEG was assessed in trauma activation patients at two Level 1 trauma centers admitted between 2010 and 2017. Receiver operating characteristic (ROC) curve analyses were performed to test the predictive performance of CK-TEG measurements in patients requiring MT, defined as >10 units of red blood cells or death within the first 6 hours. The Youden Index defined optimal thresholds for CK-TEG-based resuscitation., Results: Of the 825 trauma activations, 671 (81.3%) were men, 419 (50.8%) suffered a blunt injury, and 62 (7.5%) received a MT. Patients who had a MT were more severely injured, had signs of more pronounced shock, and more abnormal coagulation assays. CK-TEG R-time was longer (4.9 vs. 4.4 min, p = 0.0084), angle was lower (66.2 vs. 70.3 degrees, p < 0.0001), maximum amplitude was lower in MT (57 vs. 65.5 mm, p < 0.0001), and LY30 was greater (1.8% vs. 1.2%, p = 0.0012) in patients with MT compared with non-MT. To predict MT, R-time yielded an area under the ROC curve (AUROC) = 0.6002 and a cut point of >4.45 min. Angle had an AUROC = 0.6931 and a cut point of <67 degrees. CMA had an AUROC = 0.7425, and a cut point of <60 mm. LY30 had an AUROC = 0.623 with a cut point of >4.55%., Conclusion: We have identified CK-TEG thresholds that can guide MT in trauma. We propose plasma transfusion for R-time >4.45 min, fibrinogen products for an angle <67 degrees, platelet transfusion for MA <60 mm, and antifibrinolytics for LY30 >4.55%., Level of Evidence: Therapeutic study, level V.

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.