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Background: Palpation of anatomic landmarks is difficult in patients with obesity, which could increase difficulty of achieving femoral access and resuscitative endovascular balloon occlusion of the aorta (REBOA) placement. The primary aim of this study was to examine the association between obesity and successful REBOA placement. We hypothesized that higher body mass index (BMI) would decrease first-attempt success and increase time to successful aortic occlusion (AO)., Methods: A review of the Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery (AORTA) registry was performed on patients who underwent REBOA placement with initiation systolic blood pressure >0 mm Hg from years 2013-2022. Patients were excluded if they received cardiopulmonary resuscitation on arrival, underwent open AO, or missing data entries for variables of interest. Body mass index categorization was as follows: non-obese (<30), class I (30-34.9), class II (35-39.9), and class III (40+) obesity. Patients were also stratified by access technique, including use of palpation or ultrasound guidance., Results: Inclusion criteria were met by 410 patients. On binary analysis, no primary outcomes of interest, including rate of success, time to placement, or mortality, were significantly impacted by BMI. Among BMI subgroups, there was no statistical difference in injury severity, admission systolic blood pressure (SBP), or augmented SBP. At initiation of aortic occlusion, patients with class II and class III obesity had higher median SBP compared with non- and class I obese patients (p = 0.03). Body mass index subgroup did not impact likelihood of first-attempt success or conversion to open procedure. When stratified by access technique, there was no difference in success rates, time to success or mortality between groups., Conclusion: Body habitus did not impact success of REBOA placement, time to successful AO, or mortality. Further, ultrasound guidance was not superior to landmark palpation for arterial access. Following traumatic injury without hemodynamic collapse, obesity should not deter providers from considering REBOA placement., Level of Evidence: Therapeutic/Care management, Observational, Cross-sectional; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Gun violence disproportionately affects metropolitan areas of the United States (US). There is limited information regarding the influence of social determinants of health, such as food insecurity (FI) on firearm homicide mortality (FHM) in major metropolitan cities in the US. We sought to examine the relationship between FI and FHM., Materials and Methods: This was a cross-sectional analysis examining the largest 51 US major metropolitan statistical areas (MSAs) using data from 2018. Demographic data, markers of social inequities, and firearm homicide data were obtained from the US Census Bureau, US Department of Education, and the Frey and Brookings Institute. Food insecurity prevalence was obtained from Feeding America. Spearman ρ and linear regression were performed., Results: Using Spearman rho analysis, higher FI (r = 0.55, P < 0.001) was associated with FHM. Other variables associated with FHM included percent Black/African American (AA) (r = 0.77, P < 0.001), poverty rate (r = 0.53, P < 0.001), and percent of children living in single parent households (r = 0.58, P < 0.001). In linear regression analyses, FI was associated with increased FHM, with 1.3 additional FHM events for each unit increase in FI (β = 1.33, 95% CI 0.27-2.39, P = 0.02). The percent of a population that is Black/AA was also associated with FHM, with more than 4 additional cases for each 1% increase in the population (β = 4.32, 95% CI 3.26-5.38, P < 0.001)., Conclusion: Food insecurity may influence FHM in major US metropolitan cities. Community- and hospital-based programs that target FI may help combat the gun violence epidemic and decrease gun violence., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Retrograde Endovascular Balloon Occlusion of the Aorta (REBOA) is an effective management for the transient responder, but the ischemic consequences of complete aortic occlusion currently limit its use. Multiple DoD-funded preclinical studies have clearly demonstrated that partial REBOA reduces distal ischemia to potentially extend safe occlusion times, while still providing effective temporization of noncompressible torso hemorrhage. Early versions of REBOA devices were designed to completely occlude the aorta and had little ability to provide partial occlusion. Recently, a new REBOA device (pREBOA-PRO) was designed specifically to allow for partial occlusion, with the hypothesis that this may reduce the complications of aortic occlusion and extend safe occlusion times while maintaining the benefits on cardiac and cerebrovascular circulation as well as reductions in resuscitation requirements., Materials and Methods: To ascertain the impact of a new purpose-built partial REBOA device on the extension of safe occlusion time, the Partial REBOA Outcomes Multicenter ProspecTive (PROMPT) trial compared available data from the pREBOA-PRO with existing data from 200 clinical uses of pREBOA-PRO and available data in the AAST AORTA Registry were reviewed to design primary endpoints and clinical evidence for a prospective multi-center trial, the PROMPT Study. Together with the endpoints identified in preclinical studies of partial REBOA, primary endpoints for the PROMPT study were identified and power analyses were conducted to determine the target patient enrollment goals., Results: Results from the clinical implementation of partial REBOA at a single trauma center were used to conduct the initial power analysis for the primary endpoint of Acute Kidney Injury (AKI) after prolonged occlusion. The rate of AKI after complete REBOA was 55% (12/20) compared to 33% (4/12) after partial REBOA (Madurska et al., 2021). With an alpha of 0.05 and power (β) of 0.8, the projected sample size for comparison on a dichotomous outcome is 85 patients for the assessment of AKI. Initial power and endpoint analyses have been confirmed and extended with the ongoing analysis of partial and complete REBOA reported in the AORTA database. These analyses confirm preclinical findings which show that compared to complete REBOA, partial REBOA is associated with extended occlusion time in zone 1 (complete: 31 min vs. partial: 45 min, P = 0.003), lower rates of AKI after zone 1 occlusion (complete: 33% vs. partial: 19%, P = 0.05) and reduced resuscitation requirements (e.g., 25% reduction in pRBC administration: complete: 18 units vs. partial: 13 units, P = 0.02)., Conclusions: The DoD-funded PROMPT study of partial REBOA will provide prospective observational clinical data on patients being treated with pREBOA-PRO. Outcomes will be stratified based on partial or complete occlusion to address whether partial REBOA has additional clinical benefits over complete REBOA, such as decreased distal ischemia, extension of safe occlusion time, improved hemodynamics during transition to and from occlusion, and reduced interoperative bleeding and blood product use. The results from this study are expected to confirm previous data demonstrating reduction of ischemic sequalae, improved transition to reperfusion, and reduced resuscitative requirements compared to complete REBOA., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: Anti-inflammatory effects of tranexamic acid (TXA) in reducing trauma endotheliopathy may protect from acute lung injury. Clinical data showing this benefit in trauma patients is lacking. We hypothesized that TXA administration mitigates pulmonary complications in penetrating trauma patients., Materials and Methods: This is a post-hoc analysis of a multicenter, prospective, observational study of adults (18+ years) with penetrating torso and/or proximal extremity injury presenting at 25 urban trauma centers. Tranexamic acid administration in the prehospital setting or within three hours of admission was examined. Participants were propensity matched to compare similarly injured patients. The primary outcome was development of pulmonary complication (ARDS and/or pneumonia)., Results: A total of 2382 patients were included, and 206 (8.6%) received TXA. Of the 206, 93 (45%) received TXA prehospital and 113 (55%) received it within three hours of hospital admission. Age, sex, and incidence of massive transfusion did not differ. The TXA group was more severely injured, more frequently presented in shock (SBP < 90 mmHg), developed more pulmonary complications, and had lower survival ( P < 0.01 for all). After propensity matching, 410 patients remained (205 in each cohort) with no difference in age, sex, or rate of shock. On logistic regression, increased emergency department heart rate was associated with pulmonary complications. Tranexamic acid was not associated with different rate of pulmonary complications or survival on logistic regression. Survival was not different between the groups on logistic regression or propensity score-matched analysis., Conclusions: Tranexamic acid administration is not protective against pulmonary complications in penetrating trauma patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The endothelial glycocalyx on the luminal surface of endothelial cells contributes to the permeability barrier of the pulmonary vasculature. Dimethyl sulfoxide (DMSO) has a disordering effect on plasma membranes, which prevents the formation of ordered membrane domains important in the shedding of the endothelial glycocalyx. We hypothesized that DMSO would protect against protein leak by preserving the endothelial glycocalyx in a murine model of acute respiratory distress syndrome (ARDS)., Methods: C57BL/6 mice were given ARDS via intratracheally administered lipopolysaccharide (LPS). Dimethyl sulfoxide (220 mg/kg) was administered intravenously for 4 days. Animals were sacrificed postinjury day 4 after bronchoalveolar lavage (BAL). Bronchoalveolar lavage cell counts and protein content were quantified. Lung sections were stained with fluorescein isothiocyanate-labeled wheat germ agglutinin to quantify the endothelial glycocalyx. Human umbilical vein endothelial cells (HUVECs) were exposed to LPS. Endothelial glycocalyx was measured using fluorescein isothiocyanate-labeled wheat germ agglutinin, and co-immunoprecipitation was performed to measure interaction between sheddases and syndecan-1., Results: Dimethyl sulfoxide treatment resulted in greater endothelial glycocalyx staining intensity in the lung when compared with sham (9,641 vs. 36,659 arbitrary units, p < 0.001). Total BAL cell counts were less for animals receiving DMSO (6.93 × 10 6 vs. 2.49 × 10 6 cells, p = 0.04). The treated group had less BAL macrophages (189.2 vs. 76.9 cells, p = 0.02) and lymphocytes (527.7 vs. 200.0 cells, p = 0.02). Interleukin-6 levels were lower in DMSO treated. Animals that received DMSO had less protein leak in BAL (1.48 vs. 1.08 μg/μL, p = 0.02). Dimethyl sulfoxide prevented LPS-induced endothelial glycocalyx loss in HUVECs and reduced the interaction between matrix metalloproteinase 16 and syndecan-1., Conclusion: Systemically administered DMSO protects the endothelial glycocalyx in the pulmonary vasculature, mitigating pulmonary capillary leak after acute lung injury. Dimethyl sulfoxide also results in decreased inflammatory response. Dimethyl sulfoxide reduced the interaction between matrix metalloproteinase 16 and syndecan-1 and prevented LPS-induced glycocalyx damage in HUVECs. Dimethyl sulfoxide may be a novel therapeutic for ARDS., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chest pain is among the most common reasons for presentation to the emergency department (ED) worldwide. Additional studies on most cost-effective ways of differentiating serious vs. benign causes of chest pain are needed., Objectives: Our study aimed to evaluate the effectiveness of a novel risk stratification pathway utilizing 5 th generation high-sensitivity cardiac troponin T assay (Hs-cTnT) and HEART score (History, Electrocardiogram, Age, Risk factors, Troponin) in assessing nontraumatic chest pain patients in reducing ED resource utilization., Methods: A retrospective chart review was performed 6 months prior to and after the implementation of a novel risk stratification pathway that combined hs-cTnT with HEART score to guide evaluation of adult patients presenting with nontraumatic chest pain at a large academic quaternary care ED. Primary outcome was ED length of stay (LOS); secondary outcomes included cardiology consult rates, admission rates, number of ED boarders, and number of eloped patients., Results: A total of 1707 patients and 1529 patients were included pre- and postimplementation, respectively. Median overall ED LOS decreased from 317 to 286 min, an absolute reduction of 31 min (95% confidence interval 22-41 min), after pathway implementation (p < 0.001). Furthermore, cardiology consult rate decreased from 26.9% to 16.0% (p < 0.0001), rate of admission decreased from 30.1% to 22.7% (p < 0.0001), and number of ED boarders as a proportion of all nontraumatic chest pain patients decreased from 25.13% preimplementation to 18.63% postimplementation (p < 0.0001)., Conclusions: Implementation of our novel chest pain pathway improved numerous ED throughput metrics in the evaluation of nontraumatic chest pain patients., Competing Interests: Declaration of competing interest None., (Published by Elsevier Inc.)

Background: Partial occlusion of the aorta is a resuscitation technique designed to maximize proximal perfusion while allowing a graduated amount of distal flow to reduce the ischemic sequelae associated with complete aortic occlusion. The pREBOA catheter affords the ability to titrate perfusion as hemodynamics allows, however, the impact of this new technology for REBOA on blood use and other resuscitative requirements is currently unknown. We hypothesize pREBOA's ability to provide partial occlusion, when appropriate, decreases overall resuscitative requirements when compared to ER-REBOA., Methods: The entire AAST AORTA Registry was used to compare resuscitation requirements between all ER-REBOA and pREBOA. Unpaired t-tests were used to compare resuscitation strategies including packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, cryoprecipitate, crystalloids, and need for pressors., Results: When comparing ER-REBOA (n=800) use to pREBOA (n=155), initial patient presentations were similar except for age (44 vs 40 p=0.026) and rates of blunt injury (78.4% vs 78.7% p<0.010). Zone-1 occlusion was used less often in ER-REBOA (65.8 vs 71.7 p=0.046). Partial occlusion was performed in 85% of pREBOA compared to 11% in ER-REBOA (p<0.050). Vitals at the time of REBOA were worse in ER-REBOA, and received significantly more units of PRBCs, FFP, platelets, and liters of crystalloids than pREBOA (p<0.05). Rates of ARDS and septic shock were lower in pREBOA (p<0.05)., Conclusion: When comparing pREBOA to ER-REBOA, there has been a rise in Zone-1 and partial occlusion. In our pilot analysis of the AORTA Registry, there was a reduction in administration of pRBC, FFP, platelets, and crystalloids. Though further prospective studies are required, this is the first to demonstrate an association between pREBOA, partial occlusion, and reduced blood use and resuscitative requirements., Competing Interests: Conflicts of Interest: J Nguyen receives honoraria from Prytime Medical, Zimmer Biomet, and Teleflex for educational lectures. EE Moore receives grants from Haemonetics, Werfen, and Hemosonics for research support. BM Dennis serves on the Board of Directors for the Eastern Association for the Surgery of Trauma (EAST). WM Vassey recieved support from Prytime Medical for attendance at two educational symposia sponsored by Prytime Medical. C Spalding received travel support from Prytime Medical as part of their speaking bureau, lunch from Teleflex and Haemonetics for resident journal clubs. The trauma centers participating in the pREBOA-PRO Centers of Excellence are part of the limited market release of the FDA-approved pREBOA-PRO catheter. Additionally, EE Moore, U Pandya, BM Dennis, J Nguyen, and several institutions represented in this work participate in the DoD Grant funded study (W81xwh-22-90015) for Partial REBOA Outcomes Multi-Center Prospective (PROMPT) trial. The catheter is used as standard of care at the discretion of the physicians, without monetary or other incentives for use. All authors agree to be accountable for all aspects of work in ensuring the questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The authors have no additional conflicts of interest to report. All JTACS Disclosure forms have been supplied and are provided as supplemental digital content (http://links.lww.com/TA/D842)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Military experience has demonstrated mortality improvement when advanced resuscitative care (ARC) is provided for trauma patients with severe hemorrhage. The benefits of ARC for trauma in civilian emergency medical services (EMS) systems with short transport intervals are still unknown. We hypothesized that ARC implementation in an urban EMS system would reduce in-hospital mortality., Methods: This was a prospective analysis of ARC bundle administration between 2021 and 2023 in an urban EMS system with 70,000 annual responses. The ARC bundle consisted of calcium, tranexamic acid, and packed red blood cells via a rapid infuser. Advanced resuscitative care patients were compared with trauma registry controls from 2016 to 2019. Included were patients with a penetrating injury and systolic blood pressure ≤90 mm Hg. Excluded were isolated head trauma or prehospital cardiac arrest. In-hospital mortality was the primary outcome of interest., Results: A total of 210 patients (ARC, 61; controls, 149) met the criteria. The median age was 32 years, with no difference in demographics, initial systolic blood pressure or heart rate recorded by EMS, or New Injury Severity Score between groups. At hospital arrival, ARC patients had lower median heart rate and shock index than controls ( p ≤ 0.03). Fewer patients in the ARC group required prehospital advanced airway placement ( p < 0.001). Twenty-four-hour and total in-hospital mortality were lower in the ARC group ( p ≤ 0.04). Multivariable regression revealed an independent reduction in in-hospital mortality with ARC (odds ratio, 0.19; 95% confidence interval, 0.05-0.68; p = 0.01)., Conclusion: Early ARC in a fast-paced urban EMS system is achievable and may improve physiologic derangements while decreasing patient mortality. Advanced resuscitative care closer to the point of injury warrants consideration., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2024 American Association for the Surgery of Trauma.)

Introduction: Prehospital resuscitation with blood products is gaining popularity for patients with traumatic hemorrhage. The MEDEVAC trial demonstrated a survival benefit exclusively among patients who received blood or plasma within 15 minutes of air medical evacuation. In fast-paced urban EMS systems with a high incidence of penetrating trauma, mortality data based on the timing to first blood administration is scarce. We hypothesize a survival benefit in patients with severe hemorrhage when blood is administered within the first 15 minutes of EMS patient contact., Methods: This was a retrospective analysis of a prospective database of prehospital blood (PHB) administration between 2021 and 2023 in an urban EMS system facing increasing rates of gun violence. PHB patients were compared to trauma registry controls from an era before prehospital blood utilization (2016-2019). Included were patients with penetrating injury and SBP ≤ 90 mmHg at initial EMS evaluation that received at least one unit of blood product after injury. Excluded were isolated head trauma or prehospital cardiac arrest. Time to initiation of blood administration before and after PHB implementation and in-hospital mortality were the primary variables of interest., Results: A total of 143 patients (PHB = 61, controls = 82) were included for analysis. Median age was 34 years with no difference in demographics. Median scene and transport intervals were longer in the PHB cohort, with a 5-minute increase in total prehospital time. Time to administration of first unit of blood was significantly lower in the PHB vs. control group (8 min vs 27 min; p < 0.01). In-hospital mortality was lower in the PHB vs. control group (7% vs 29%; p < 0.01). When controlling for patient age, NISS, tachycardia on EMS evaluation, and total prehospital time interval, multivariate regression revealed an independent increase in mortality by 11% with each minute delay to blood administration following injury (OR 1.11, 95%CI 1.04-1.19)., Conclusion: Compared to patients with penetrating trauma and hypotension who first received blood after hospital arrival, resuscitation with blood products was started 19 minutes earlier after initiation of a PHB program despite a 5-minute increase in prehospital time. A survival for early PHB use was demonstrated, with an 11% mortality increase for each minute delay to blood administration. Interventions such as PHB may improve patient outcomes by helping capture opportunities to improve trauma resuscitation closer to the point of injury., Level of Evidence: Prospective, Level IV., Competing Interests: Conflict of Interest: JTACS Conflict-of-Interest forms have been supplied (http://links.lww.com/TA/D747). Dr. Piehl is Founder and CMO, 410 Medical, Durham, NC. Dr. De Maio is Director of Clinical Science and Research, 410 Medical, Durham, NC., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Hemorrhage is a major cause of preventable trauma deaths, and the ABC approach is widely used during the primary survey. We hypothesize that prioritizing circulation over intubation (CAB) can improve outcomes in patients with exsanguinating injuries., Methods: A prospective observational study involving international trauma centers was conducted. Patients with systolic blood pressure below 90 who were intubated within 30 min of arrival were included. Prioritizing circulation (CAB) was defined as delaying intubation until blood products were started, and/or bleeding control was performed before securing the airway. Demographics, clinical data, and outcomes were recorded., Results: The study included 278 eligible patients, with 61.5% falling within the "CAB" cohort and 38.5% in the "ABC" cohort. Demographic and disease characteristics, including age, sex, ISS, use of blood products, and other relevant factors, exhibited comparable distributions between the two cohorts. The CAB group had a higher proportion of penetrating injuries and more patients receiving intubation in the operating room. Notably, patients in the CAB group demonstrated higher GCS scores, lower SBP values before intubation but higher after intubation, and a significantly lower incidence of cardiac arrest and post-intubation hypotension. Key outcomes revealed significantly lower 24-hour mortality in the CAB group (11.1% vs. 69.2%), a lower rate of renal failure, and a higher rate of ARDS. Multivariable logistic regression models showed a 91% reduction in the odds of mortality within 24 h and an 89% reduction at 30 days for the CAB cohort compared to the ABC cohort. These findings suggest that prioritizing circulation before intubation is associated with improved outcomes in patients with exsanguinating injuries., Conclusion: Post-intubation hypotension is observed to be correlated with worse outcomes. The consideration of prioritizing circulation over intubation in patients with exsanguinating injuries, allowing for resuscitation, or bleeding control, appears to be associated with potential improvements in survival. Emphasizing the importance of circulation and resuscitation is crucial, and this approach might offer benefits for various bleeding-related conditions., (© 2024. The Author(s).)

Background: At the 2023 ATLS symposium, the priority of circulation was emphasized through the "x-airway-breathing-circulation (ABC)" sequence, where "x" stands for exsanguinating hemorrhage control. With growing evidence from military and civilian studies supporting an x-ABC approach to trauma care, a prehospital advanced resuscitative care (ARC) bundle emphasizing early transfusion was developed in our emergency medical services (EMS) system. We hypothesized that prioritization of prehospital x-ABC through ARC would reduce in-hospital mortality., Study Design: This was a single-year prospective analysis of patients with severe hemorrhage. These patients were combined with our institution's historic controls before prehospital blood implementation. Included were patients with systolic blood pressure (SBP) less than 90 mmHg. Excluded were patients with penetrating head trauma or prehospital cardiac arrest. Two-to-one propensity matching for x-ABC to ABC groups was conducted, and the primary outcome, in-hospital mortality, was compared between groups., Results: A total of 93 patients (x-ABC = 62, ABC = 31) met the inclusion criteria. There was no difference in patient age, sex, initial SBP, initial Glasgow Coma Score, and initial shock index between groups. When compared with the ABC group, x-ABC patients had significant improvement in vitals at emergency department admission. Overall mortality was lower in the x-ABC group (13% vs 47%, p < 0.001). Multivariable regression revealed that prehospital circulation-first prioritization was independently associated with decreased in-hospital mortality (odds ratio 0.15, 95% CI 0.04 to 0.54, p = 0.004)., Conclusions: This is the first analysis to demonstrate a prehospital survival benefit of x-ABC in this subset of patient with severe injury and hemorrhagic shock. Standardization of prehospital x-ABC management in this patient population warrants special consideration., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Succinate is a proinflammatory citric acid cycle metabolite that accumulates in tissues during pathophysiological states. Oxidation of succinate after ischemia-reperfusion leads to reversal of the electron transport chain and generation of reactive oxygen species. Dimethyl malonate (DMM) is a competitive inhibitor of succinate dehydrogenase, which has been shown to reduce succinate accumulation. We hypothesized that DMM would protect against inflammation in a murine model of ARDS., Methods: C57BL/6 mice were given ARDS via 67.7 μg of intratracheally administered lipopolysaccharide. Dimethyl malonate (50 mg/kg) was administered via tail vein injection 30 minutes after injury, then daily for 3 days. The animals were sacrificed on day 4 after bronchoalveolar lavage (BAL). Bronchoalveolar lavage cell counts were performed to examine cellular influx. Supernatant protein was quantified via Bradford protein assay. Animals receiving DMM (n = 8) were compared with those receiving sham injection (n = 8). Cells were fixed and stained with FITC-labeled wheat germ agglutinin to quantify the endothelial glycocalyx (EGX)., Results: Total cell counts in BAL was less for animals receiving DMM (6.93 × 10 6 vs. 2.46 × 10 6 , p = 0.04). The DMM group had less BAL macrophages (168.6 vs. 85.1, p = 0.04) and lymphocytes (527.7 vs. 248.3; p = 0.04). Dimethyl malonate-treated animals had less protein leak in BAL than sham treated (1.48 vs. 1.15 μg/μl, p = 0.03). Treatment with DMM resulted in greater staining intensity of the EGX in the lung when compared with sham (12,016 vs. 15,186 arbitrary units, p = 0.03). Untreated animals had a greater degree of weight loss than treated animals (3.7% vs. 1.1%, p = 0.04). Dimethyl malonate prevented the upregulation of monocyte chemoattractant protein-1 (1.66 vs. 0.92 RE, p = 0.02) and ICAM-1 (1.40 vs. 1.01 RE, p = 0.05)., Conclusion: Dimethyl malonate reduces lung inflammation and capillary leak in ARDS. This may be mediated by protection of the EGX and inhibition of monocyte chemoattractant protein-1 and ICAM-1. Dimethyl malonate may be a novel therapeutic for ARDS., (Copyright © 2023 American Association for the Surgery of Trauma.)

Abstract: Background: Patients receiving massive transfusion protocol (MTP) are at risk for posttransfusion hypocalcemia and hyperkalemia. Previous retrospective analysis has suggested the potassium/ionized calcium (K/iCa) ratio as a prognostic indicator of mortality. This prospective study sought to validate the value of the K/iCa ratio as a predictor for mortality in patients receiving MTP. Methods: This was a prospective analysis of adult trauma patients who underwent MTP activation from May 2019 to March 2021 at an urban level 1 trauma center. Serum potassium and iCa levels within 0 to 1 h of MTP initiation were used to obtain K/iCa. Receiver operator characteristic curve analysis assessed predictive capacity of K/iCa on mortality. Kaplan-Meier survival analysis and Cox regression examined the effect of K/iCa ratio on survival. Results: A total of 110 of 300 MTP activation patients met inclusion criteria. Overall mortality rate was 31.8%. No significant differences between the elevated K/iCa and lower K/iCa groups were found for prehospital or emergency department initial vitals, shock index, or injury severity. However, nonsurvivors had a significantly higher median K/iCa ratio compared with those who survived ( P < 0.01). Multivariable logistic regression revealed the total number of blood products to be significantly associated with elevated K/iCa (odds ratio, 1.02; 95% CI, 1.01-1.04; P = 0.01). The Kaplan Meier survival curve demonstrated a significantly increased rate of survival for those with an elevated K/iCa ratio ( P < 0.01). Multivariable Cox regression adjusted for confounders showed a significant association between K/iCa and mortality (Hazard Ratio, 4.12; 95% CI, 1.89-8.96; P < 0.001). Conclusion: This evidence further highlights the importance of the K/iCa ratio in predicting mortality among trauma patients receiving MTP. Furthermore, it demonstrates that posttransfusion K levels along with iCa levels should be carefully monitored in the MTP setting. Level of Evidence: Level II. Study Type: Prognostic/epidemiological., Competing Interests: Conflicts of Interest and Source of funding: All authors have nothing to disclose, and no funding was received for this manuscript., (Copyright © 2023 by the Shock Society.)

Importance: The root cause of mass shooting events (MSEs) and the populations most affected by them are poorly understood., Objective: To examine the association between structural racism and mass shootings in major metropolitan cities in the United States., Design, Setting, and Participants: This cross-sectional study of MSEs in the 51 largest metropolitan statistical areas (MSAs) in the United States analyzes population-based data from 2015 to 2019 and the Gun Violence Archive. The data analysis was performed from February 2021 to January 2022., Exposure: Shooting event where 4 or more people not including the shooter were injured or killed., Main Outcome and Measures: MSE incidence and markers of structural racism from demographic data, Gini income coefficient, Black-White segregation index, and violent crime rate., Results: There were 865 MSEs across all 51 MSAs from 2015 to 2019 with a total of 3968 injuries and 828 fatalities. Higher segregation index (ρ = 0.46, P = .003) was associated with MSE incidence (adjusted per 100 000 population) using Spearman ρ analysis. Percentage of the MSA population comprising Black individuals (ρ = 0.76, P < .001), children in a single-parent household (ρ = 0.44, P < .001), and violent crime rate (ρ = 0.34, P = .03) were other variables associated with MSEs. On linear regression, structural racism, as measured by percentage of the MSA population comprising Black individuals, was associated with MSEs (β = 0.10; 95% CI, 0.05 to 0.14; P < .001). Segregation index (β = 0.02, 95% CI, -0.03 to 0.06; P = .53), children in a single-parent household (β = -0.04, 95% CI, -0.11 to 0.04; P = .28), and Gini income coefficient (β = -1.02; 95% CI, -11.97 to 9.93; P = .93) were not associated with MSEs on linear regression., Conclusions and Relevance: This study found that major US cities with higher populations of Black individuals are more likely to be affected by MSEs, suggesting that structural racism may have a role in their incidence. Public health initiatives aiming to prevent MSEs should target factors associated with structural racism to address gun violence.

Background: Growing epidemiological evidence suggests an adverse relationship between exposure to air pollutants and cognitive health, and this could be related to the effect of air pollution on vascular health., Objective: We aim to evaluate the association between air pollution exposure and a magnetic resonance imaging (MRI) marker of cerebral vascular burden, white matter hyperintensities (WMH)., Methods: This cross-sectional analysis used data from the French Three-City Montpellier study. Randomly selected participants 65-80 years of age underwent an MRI examination to estimate their total and regional cerebral WMH volumes. Exposure to fine particulate matter ( PM 2.5 ), nitrogen dioxide ( NO 2 ), and black carbon (BC) at the participants' residential address during the 5 years before the MRI examination was estimated with land use regression models. Multinomial and binomial logistic regression assessed the associations between exposure to each of the three pollutants and categories of total and lobar WMH volumes., Results: Participants' ( n = 582 ) median age at MRI was 70.7 years [interquartile range (IQR): 6.1], and 52% ( n = 300 ) were women. Median exposure to air pollution over the 5 years before MRI acquisition was 24.3 (IQR: 1.7) μ g / m 3 for PM 2.5 , 48.9 (14.6) μ g / m 3 for NO 2 , and 2.66 (0.60) 10 - 5 / m for BC. We found no significant association between exposure to the three air pollutants and total WMH volume. We found that PM 2.5 exposure was significantly associated with higher risk of temporal lobe WMH burden [odds ratio (OR) for an IQR increase = 1.82 (95% confidence interval: 1.41, 2.36) for the second volume tercile, 2.04 (1.59, 2.61) for the third volume tercile, reference: first volume tercile]. Associations for other regional WMH volumes were inconsistent., Conclusion: In this population-based study in older adults, PM 2.5 exposure was associated with increased risk of high WMH volume in the temporal lobe, strengthening the evidence on PM 2.5 adverse effect on the brain. Further studies looking at different markers of cerebrovascular damage are still needed to document the potential vascular effects of air pollution. https://doi.org/10.1289/EHP12231.

Objective: The effects of named weather storms on the rates of penetrating trauma is poorly understood with only case reports of single events currently guiding public health policy. This study examines whether tropical storms and hurricanes contribute to trauma services and volume., Methods: This was a cross-sectional review of tropical storms/hurricanes affecting New Orleans, Louisiana, during hurricane seasons (June 1-November 30) from 2010-2021, and their association with the rate of penetrating trauma. Authors sought to determine how penetrating trauma rates changed during hurricane seasons and associate them with demographic variables., Results: There were 5531 penetrating injuries, with 412 (7.4%) occurring during landfall and 554 (10.0%) in the aftermath. Black/African Americans were the most affected. There was an increase in the rate of penetrating events during landfall (3.4 events/day) and aftermath (3.5 events/day) compared to the baseline (2.8 events/day) ( P = < 0.001). Using multivariate analysis, wind speed was positively related to firearm injury, whereas the rainfall total was inversely related to firearm violence rates during landfall and aftermath periods. Self-harm was positively related to distance from the trauma center., Conclusions: Cities at risk for named weather storms may face increasing gun violence in the landfall and aftermath periods. Black/African Americans are most affected, worsening existing disparities. Self-harm may also increase following these weather events.

Background: Extending the time to definitive hemorrhage control in noncompressible torso hemorrhage (NCTH) is of particular importance in the battlefield where transfer times are prolonged and NCTH remains the leading cause of death. While resuscitative endovascular balloon occlusion of the aorta is widely practiced as an initial adjunct for the management of NCTH, concerns for ischemic complications after 30 minutes of compete aortic occlusion deters many from zone 1 deployment. We hypothesize that extended zone 1 occlusion times will be enabled by novel purpose-built devices that allow for titratable partial aortic occlusion., Methods: This is a cross-sectional analysis describing pREBOA-PRO zone 1 deployment characteristics at seven level 1 trauma centers in the United States and Canada (March 30, 2021, and June 30, 2022). To compare patterns of zone 1 aortic occlusion, the AORTA registry was used. Data were limited to adult patients who underwent successful occlusion in zone 1 (2013-2022)., Results: One hundred twenty-two patients pREBOA-PRO patients were included. Most catheters were deployed in zone 1 (n = 89 [73%]) with a median zone 1 total occlusion time of 40 minutes (interquartile range, 25-74). A sequence of complete followed by partial occlusion was used in 42% (n = 37) of zone 1 occlusion patients; a median of 76% (interquartile range, 60-87%) of total occlusion time was partial occlusion in this group. As was seen in the prospectively collected data, longer median total occlusion times were observed in the titratable occlusion group in AORTA compared with the complete occlusion group., Conclusion: Longer zone 1 aortic occlusion times seen with titratable aortic occlusion catheters appear to be driven by the feasibility of controlled partial occlusion. The ability to extend safe aortic occlusion times may have significant impact to combat casualty care where exsanguination from NCTH is the leading source of potentially preventable deaths., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Introduction: Endothelial glycocalyx damage occurs in numerous pathological conditions and results in endotheliopathy. Extracellular vesicles, including exosomes and microvesicles, isolated from adipose-derived mesenchymal stem cells (ASCs) have therapeutic potential in multiple disease states; however, their role in preventing glycocalyx shedding has not been defined. We hypothesized that ASC-derived exosomes and microvesicles would protect the endothelial glycocalyx from damage by LPS injury in cultured endothelial cells. Methods : Exosomes and microvesicles were collected from ASC conditioned media by centrifugation (10,000 g for microvesicles, 100,000 g for exosomes). Human umbilical vein endothelial cells (HUVECs) were exposed to 1 μg/mL lipopolysaccharide (LPS). LPS-injured cells (n = 578) were compared with HUVECS with concomitant LPS injury plus 1.0 μg/mL of exosomes (n = 540) or microvesicles (n = 510) for 24 hours. These two cohorts were compared with control HUVECs that received phosphate-buffered saline only (n = 786) and HUVECs exposed to exosomes (n = 505) or microvesicles (n = 500) alone. Cells were fixed and stained with FITC-labeled wheat germ agglutinin to quantify EGX. Real-time quantitative reverse-transcription polymerase chain reaction was used on HUVECs cell lystate to quantify hyaluron synthase-1 (HAS1) expression. Results: Exosomes alone decreased endothelial glycocalyx staining intensity when compared with control (4.94 vs. 6.41 AU, P < 0.001), while microvesicles did not cause a change glycocalyx staining intensity (6.39 vs. 6.41, P = 0.99). LPS injury resulted in decreased glycocalyx intensity as compared with control (5.60 vs. 6.41, P < 0.001). Exosomes (6.85 vs. 5.60, P < 0.001) and microvesicles (6.35 vs. 5.60, P < 0.001) preserved endothelial glycocalyx staining intensity after LPS injury. HAS1 levels were found to be higher in the exosome (1.14 vs. 3.67 RE, P = 0.02) and microvesicle groups (1.14 vs. 3.59 RE, P = 0.02) when compared with LPS injury. Hyaluron synthase-2 and synthase-3 expressions were not different in the various experimental groups. Conclusions: Exosomes alone can damage the endothelial glycocalyx. However, in the presence of LPS injury, both exosomes and microvesicles protect the glycocalyx layer. This effect seems to be mediated by HAS1. Level of Evidence : Basic science study., (Copyright © 2023 by the Shock Society.)

Acute hemorrhage commonly leads to coagulopathy and organ dysfunction or failure. Recent evidence suggests that damage to the endothelial glycocalyx contributes to these adverse outcomes. The physiological events mediating acute glycocalyx shedding are undefined, however. Here, we show that succinate accumulation within endothelial cells drives glycocalyx degradation through a membrane reorganization-mediated mechanism. We investigated this mechanism in a cultured endothelial cell hypoxia-reoxygenation model, in a rat model of hemorrhage, and in trauma patient plasma samples. We found that succinate metabolism by succinate dehydrogenase mediates glycocalyx damage through lipid oxidation and phospholipase A2-mediated membrane reorganization, promoting the interaction of matrix metalloproteinase 24 (MMP24) and MMP25 with glycocalyx constituents. In a rat hemorrhage model, inhibiting succinate metabolism or membrane reorganization prevented glycocalyx damage and coagulopathy. In patients with trauma, succinate levels were associated with glycocalyx damage and the development of coagulopathy, and the interaction of MMP24 and syndecan-1 was elevated compared to healthy controls.

Background: ATLS suggests simple thoracostomy (ST) after failure of needle thoracostomy (NT) in thoracic trauma. Some EMS agencies have adopted ST into their practice. We sought to describe our experience implementing ST in the prehospital setting, hypothesizing that prehospital ST would reduce failure rates and improve outcomes compared to NT., Methods: This was a retrospective review of adult trauma patients who received prehospital ST or NT from 2017 to 2020., Results: There were 48 patients with 64 procedures included. 83.7% were male and 65.8% injured by penetrating mechanism and of median (IQR) age of 31 (25-46) years. 28 (43.8%) procedures were NT and 36 (56.3%) were ST. Rates of improved patient response ( P = .15), noted return of blood/air ( P = .19), and return of spontaneous circulation ( P = .62) did not differ. On-scene times were higher for ST (16.8 vs 11.5 minutes; P < .02). Overall mortality did not differ between ST and NT (68.2% vs 46.4%, respectively; P = .125). For patients that survived beyond the ED, procedure-related complication rates were 2 of 21 patients (9.5%) in ST and 1 of 12 (8.3%) in NT. In penetrating trauma, simple thoracostomy had longer on-scene time and total prehospital time., Discussion: ST did not improve success rates of ROSC and was associated with prolonged prehospital times, especially in penetrating trauma patients. Given the benefit of "scoop and run" in urban penetrating trauma, consideration should be given to direct transport in lieu of ST. Use of ST in blunt trauma should be evaluated prospectively.

Introduction: Trauma represents the leading cause of nonobstetrical maternal death. How in-hospital outcomes of acutely injured pregnant patients (PP) compares to that of similarly aged nonpregnant control groups (CGs) has not been described. We hypothesized that PPs suffering acute traumatic injuries would have worse outcomes compared to a matched CG., Materials and Methods: The American College of Surgeons Trauma Quality Improvement Program (TQIP) was used to identify traumatically injured females between 2017 and 2019. Propensity score matching on age, race, injury severity score , and type of trauma (blunt, penetrating, or other) was used to compare PPs and the CG. Primary outcomes were mortality, disposition, length of stay (LOS), and complications., Results: A total of 1078 traumatically injured pregnant females were identified. Propensity score matching resulted in 990 patients in the PP and CG cohorts. After matching, PPs were more likely to be assault victims (11% versus 6%, P < 0.001), had longer length of stay (LOS) (5 versus 3 d, P < 0.001), and were more likely to require mechanical ventilation (26% versus 16%, P < 0.001) or intensive care unit (ICU) admission (44% versus 32%, P < 0.001). PPs were more likely to proceed directly to the operating room (OR)(34% versus 15%, P < 0.001) and less likely to be discharged home from the emergency department (ED) (1% versus 12%, P < 0.001). Complications and mortality rates were similar among PPs., Conclusions: After acute trauma, PPs did not have increased mortality or complications when compared to matched controls, although they were more likely to be victims of assault, directly proceed to the OR, require mechanical ventilation or ICU admission, and have longer LOSs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Blunt cerebrovascular injury (BCVI) is a significant cause of morbidity and mortality after blunt trauma. Numerous screening strategies exist, although which is used is institution- and physician-dependent. We sought to identify the most cost-effective screening strategy for BCVI, hypothesizing that universal screening would be optimal among the screening strategies studied., Study Design: A Markov decision analysis model was used to compare the following screening strategies for identification of BCVI: (1) no screening; (2) Denver criteria; (3) extended Denver criteria; (4) Memphis criteria; and (5) universal screening. The base-case scenario modeled 50-year-old patients with blunt traumatic injury excluding isolated extremity injures. Patients with BCVI detected on imaging were assumed to be treated with antithrombotic therapy, subsequently decreasing risk of stroke and mortality. One-way sensitivity analyses were performed on key model inputs. A single-year horizon was used with an incremental cost-effectiveness ratio threshold of $100,000 per quality-adjusted life-year., Results: The most cost-effective screening strategy for patients with blunt trauma among the strategies analyzed was universal screening. This method resulted in the lowest stroke rate, mortality, and cost, and highest quality-adjusted life-year. An estimated 3,506 strokes would be prevented annually as compared with extended Denver criteria (incremental cost-effectiveness ratio of $71,949 for universal screening vs incremental cost-effectiveness ratio of $12,736 for extended Denver criteria per quality-adjusted life-year gained) if universal screening were implemented in the US. In 1-way sensitivity analyses, universal screening was the optimal strategy when the incidence of BCVI was greater than 6%., Conclusions: This model suggests universal screening may be the cost-effective strategy for BCVI screening in blunt trauma for certain trauma centers. Trauma centers should develop institutional protocols that take into account individual BCVI rates., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Continuous prediction surveillance modeling is an emerging tool giving dynamic insight into conditions with potential mitigation of adverse events (AEs) and failure to rescue. The Epic electronic medical record contains a Deterioration Index (DI) algorithm that generates a prediction score every 15 min using objective data. Previous validation studies show rapid increases in DI score (≥14) predict a worse prognosis. The aim of this study was to demonstrate the utility of DI scores in the trauma intensive care unit (ICU) population., Methods: A prospective, single-center study of trauma ICU patients in a Level 1 trauma center was conducted during a 3-mo period. Charts were reviewed every 24 h for minimum and maximum DI score, largest score change (Δ), and AE. Patients were grouped as low risk (ΔDI <14) or high risk (ΔDI ≥14)., Results: A total of 224 patients were evaluated. High-risk patients were more likely to experience AEs (69.0% versus 47.6%, P = 0.002). No patients with DI scores <30 were readmitted to the ICU after being stepped down to the floor. Patients that were readmitted and subsequently died all had DI scores of ≥60 when first stepped down from the ICU., Conclusions: This study demonstrates DI scores predict decompensation risk in the surgical ICU population, which may otherwise go unnoticed in real time. This can identify patients at risk of AE when transferred to the floor. Using the DI model could alert providers to increase surveillance in high-risk patients to mitigate unplanned returns to the ICU and failure to rescue., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Abstract: The original guidelines of cardiopulmonary resuscitation focused on the establishment of an airway and rescue breathing before restoration of circulation through cardiopulmonary resuscitation. As a result, the airway-breathing-circulation approach became the central guiding principle of resuscitation. Despite new guidelines by the American Heart Association for a circulation-first approach, Advanced Trauma Life Support guidelines continue to advocate for the airway-breathing-circulation sequence. Although definitive airway management is often necessary for severely injured patients, endotracheal intubation (ETI) before resuscitation in patients with hemorrhagic shock may worsen hypotension and precipitate cardiac arrest. In severely injured patients, a paradigm shift should be considered, which prioritizes restoration of circulation before ETI and positive pressure ventilation while maintaining a focus on basic airway assessment and noninvasive airway interventions. For this patient population, the most reasonable current strategy may be to target a simultaneous resuscitation approach, with immediate efforts to control hemorrhage and provide basic airway interventions while prioritizing volume resuscitation with blood products and deferring ETI until adequate systemic perfusion has been attained. We believe that a circulation-first sequence will improve both survival and neurologic outcomes for a traumatically injured patient and will continue to advocate this approach, as additional clinical evidence is generated to inform how to best tailor circulation-first resuscitation for varied injury patterns and patient populations., (Copyright © 2022 by the Shock Society.)

Background: Patient selection for resuscitative endovascular balloon occlusion of the aorta (REBOA) has evolved during the last decade. A recent multicenter collaboration to implement the newest generation REBOA balloon catheter identified variability in patient selection criteria. The aims of this systematic review were to compare recent REBOA patient selection guidelines and to identify current areas of consensus and variability., Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic review of clinical practice guidelines for REBOA patient selection in trauma. Published algorithms from 2015 to 2022 and institutional guidelines from a seven-center REBOA collaboration were compiled and synthesized., Results: Ten published algorithms and seven institutional guidelines on REBOA patient selection were included. Broad consensus exists on REBOA deployment for blunt and penetrating trauma patients with non-compressible torso hemorrhage refractory to blood product resuscitation. Algorithms diverge on precise systolic blood pressure triggers for early common femoral artery access and REBOA deployment, as well as the use of REBOA for traumatic arrest and chest or extremity hemorrhage control., Conclusion: Although our convenience sample of institutional guidelines likely underestimates patient selection variability, broad consensus exists in the published literature regarding REBOA deployment for blunt and penetrating trauma patients with hypotension not responsive to resuscitation. Several areas of patient selection variability reflect individual practice environments., Level of Evidence: Level 5, systematic review., Competing Interests: Competing interests: JJM receives honoraria for lectures from Prytime Medical and is a member of the Prytime Medical Clinical Advisory Board. All authors voluntarily participate in a collaborative group of centers organized by Prytime Medical that share clinical experiences with the pREBOA-PRO device, but none receives compensation for participation., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Tranexamic acid (TXA) protects the vasculature endothelium after hemorrhage, resulting in a decreased capillary leak. These properties may protect patients receiving TXA from acute respiratory distress syndrome (ARDS), however, clinical studies have yet to examine this topic. We hypothesized that trauma patients receiving TXA would have lower incidence of ARDS., Methods: This was a retrospective review of adult (18+ y) patients who presented to a large Level I trauma center with an injury severity score ≥ 16 from admit years 2012-2020. Propensity matching was employed to examine how TXA administration is associated with ARDS., Results: There were a total of 2751 patients meeting study criteria, with 162 (5.9%) received TXA. Of the 162 patients that received TXA, only 12 (7.4%) received pre-hospital TXA, while 4 (2.5%) received TXA both pre-hospital and in hospital. Of the 63 patients developing ARDS, 62 (98.4%) did not receive TXA. After propensity matching, 304 patients remained, with 152 in each cohort. The incidence of ARDS (P = 0.08), pneumonia (P = 0.68), any pulmonary complication (P = 0.33), and mortality (P = 0.37) were not different in patients receiving TXA on propensity matching., Conclusions: TXA did not protect trauma patients from pulmonary complications; however, nearly all patients developing ARDS did not receive TXA. Larger studies should examine this relationship to improve understanding of therapies that may prevent ARDS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: No evidence exists about the impact of air pollution reduction on incidence of dementia. The aim of this study was to quantify how air quality improvement leads to dementia-incidence benefits., Methods: In the French Three-City cohort (12 years of follow-up), we used parametric g-computation to quantify the expected number of prevented dementia cases under different hypothetical interventions with particulate matter measuring <2.5 μm (PM 2.5 ) reductions., Results: Among 7051 participants, 789 participants developed dementia. The median PM 2.5 reduction between 1990 and 2000 was 12.2 (μg/m 3 ). Such a reduction reduced the risk of all-cause dementia (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.76 to 0.95). If all study participants were enjoying a hypothetical reduction of more than 13.10 μg/m 3 (median reduction observed in the city of Montpellier), the rate difference was -0.37 (95% CI, -0.57 to -0.17) and the rate ratio was 0.67 (95% CI, 0.50 to 0.84)., Discussion: These findings highlight the possible substantial benefits of reducing air pollution in the prevention of dementia., (© 2022 the Alzheimer's Association.)

The endothelial glycocalyx (EGX) contributes to the permeability barrier of vessels and regulates the coagulation cascade. EGX damage, which occurs in numerous disease states, including sepsis and trauma, results in endotheliopathy. While influenza and other viral infections are known to cause endothelial dysfunction, their effect on the EGX has not been described. We hypothesized that the H1N1 influenza virus would cause EGX degradation. Human umbilical vein endothelial cells (HUVECs) were exposed to varying multiplicities of infection (MOI) of the H1N1 strain of influenza virus for 24 hours. A dose-dependent effect was examined by using an MOI of 5 (n = 541), 15 (n = 714), 30 (n = 596), and 60 (n = 653) and compared to a control (n = 607). Cells were fixed and stained with FITC-labelled wheat germ agglutinin to quantify EGX. There was no difference in EGX intensity after exposure to H1N1 at an MOI of 5 compared to control (6.20 vs. 6.56 Arbitrary Units (AU), p = 0.50). EGX intensity was decreased at an MOI of 15 compared to control (5.36 vs. 6.56 AU, p<0.001). The degree of EGX degradation was worse at higher doses of the H1N1 virus; however, the decrease in EGX intensity was maximized at an MOI of 30. Injury at MOI of 60 was not worse than MOI of 30. (4.17 vs. 4.47 AU, p = 0.13). The H1N1 virus induces endothelial dysfunction by causing EGX degradation in a dose-dependent fashion. Further studies are needed to characterize the role of this EGX damage in causing clinically significant lung injury during acute viral infection., Competing Interests: The authors have declared that no competing interests exist.

Abstract: Introduction: Time is an essential element in outcomes of trauma patients. The relationship of time to treatment in management of noncompressible torso hemorrhage (NCTH) with resuscitative endovascular balloon occlusion of the aorta (REBOA) or resuscitative thoracotomy (RT) has not been previously described. We hypothesized that shorter times to intervention would reduce mortality. Methods: A review of the Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery registry from 2013 to 2022 was performed to identify patients who underwent emergency department aortic occlusion (AO). Multivariate logistic regression was used to examine the impact of time to treatment on mortality. Results: A total of 1,853 patients (1,245 [67%] RT, 608 [33%] REBOA) were included. Most patients were male (82%) with a median age of 34 years (interquartile range, 30). Median time from injury to admission and admission to successful AO were 31 versus 11 minutes, respectively. Patients who died had shorter median times from injury to successful AO (44 vs. 72 minutes, P &lt; 0.001) and admission to successful AO (10 vs. 22 minutes, P &lt; 0.001). Multivariate logistic regression demonstrated that receiving RT was the strongest predictor of mortality (odds ratio [OR], 6.6; 95% confidence interval [CI], 4.4-9.9; P &lt; 0.001). Time from injury to admission and admission to successful AO were not significant. This finding was consistent in subgroup analysis of RT-only and REBOA-only populations. Conclusions: Despite expedited interventions, time to aortic occlusion did not significantly impact mortality. This may suggest that rapid in-hospital intervention was often insufficient to compensate for severe exsanguination and hypovolemia that had already occurred before emergency department presentation. Selective prehospital advanced resuscitative care closer to the point of injury with "scoop and control" efforts including hemostatic resuscitation warrants special consideration., Competing Interests: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)

Background: Combat applications of tourniquets for extremity trauma have led to increased civilian prehospital tourniquet use. Studies have demonstrated that appropriate prehospital tourniquet application can decrease the incidence of arrival in shock without increasing limb complications. The aim of this study was to examine outcomes of prehospital tourniquet placement without definitive vascular injury., Methods: Retrospective review was performed of a prospectively maintained database by the American Association for the Surgery of Trauma from 29 trauma centers. Patients in this subset analysis did not have a significant vascular injury as determined by imaging or intra-operatively. Patients who received prehospital tourniquets (PHTQ) were compared to patients without prehospital tourniquets (No-PHTQ). Outcomes were amputation rates, nerve palsy, compartment syndrome, and in-hospital mortality., Results: A total of 622 patients had no major vascular injury. The incidence of patients without major vascular injury was higher in the PHTQ group (n = 585/962, 60.8 vs n = 37/88, 42.0%, P < .001). Cohorts were similar in age, gender, penetrating mechanism, injury severity scores (ISS), abbreviated injury score (AIS), and mortality ( P > .05). Amputation rates were 8.3% (n = 49/585) in the PHTQ group compared to 0% (n = 0/37) in the No-PHTQ group. Amputation rates were higher in PHTQ than No-PHTQ with similar ISS and AIS ( P = .96, P = .59). The incidence of nerve palsy and compartment syndrome was not different ( P > .05)., Conclusions: This study showed a significant amount of prehospital tourniquets are being placed on patients without vascular injuries. Further studies are needed to elucidate the appropriateness of prehospital tourniquets, including targeted education of tourniquet placement.

Background: Food insecurity (FI) is an important social determinant of health that is associated with many forms of violence. We hypothesized that FI would be associated with gun violence., Methods: Firearm injury data was collected from 2016 to 2020 (n = 3115) at a single institution that serves as the only Level I trauma center in a major southern US city. The data were linked with Map the Meal Gap data, a publicly available data set, which estimates rates of county-level FI based on state-level FI and social determinants, including unemployment, poverty, disability, and other factors. Regression analysis was utilized to examine the relationship between FI with rates of overall gun trauma and odds of gun-related violence. Food insecurity by county of patient residence was categorized by rates less than the national average of 11.5% (low), between the national and state average (16.5%) (moderate), and greater than the state average (high). Out of state residents were excluded from the analyses., Results: Of the 3,115 patients with firearm injuries identified, 138 (4.4%) resided in counties with low FI rates, 1048 (33.6%) in moderate FI, and 1929 (62.0%) in counties with high FI. Patients in regions of high FI were more likely to be a Level I trauma activation, a victim of assault, and have Medicaid or be self-pay. There was no significant difference in mortality by levels of FI. Food insecurity was significantly associated with firearm injury, with each percent increase in FI being related to approximately 56 additional gun-related injuries per 100,000 people (95% confidence interval, 54-59) and increased odds of the injury classified as assault (odds ratio, 1.13; 95% confidence interval, 1.07-1.19)., Conclusion: Violence prevention initiatives targeting food insecure communities may help alleviate the US gun violence epidemic. Further, trauma center screening for household FI and in-hospital interventions addressing FI may help reduce gun violence recidivism., Level of Evidence: Prognostic and Epidemiologic; Level IV., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Traumatic brain injury (TBI) is a significant source of morbidity and mortality in the United States. Recent shifts in state legislation have increased the use of recreational and medical marijuana. While cannabinoids and tetrahydrocannabinol (THC) have known anti-inflammatory effects, the impact of preinjury THC use on clinical outcomes in the setting of severe TBI is unknown. We hypothesized that preinjury THC use in trauma patients suffering TBI would be associated with decreased thromboembolic events and adverse outcomes., Methods: The American College of Surgeons Trauma Quality Improvement Program was used to identify patients aged ≥18 y with TBI and severe injury (Injury Severity Score ≥ 16) in admit year 2017. Patients with smoking or tobacco history or missing or positive toxicology tests for drug and/or alcohol use other than THC were excluded. Propensity score matching was used to compare THC+ patients to similar THC- patients., Results: A total of 13,266 patients met inclusion criteria, of which 1669 were THC+. A total of 1377 THC+ patients were matched to 1377 THC- patients. No significant differences were found in in-hospital outcomes, including mortality, length of stay, cardiac arrest, pulmonary embolism, deep vein thrombosis, or acute respiratory distress syndrome. No patients had ischemic stroke, and THC+ patients had significantly decreased rates of hemorrhagic stroke (0.5% versus 1.5%, P = 0.02, odds ratio 0.41 [95% confidence interval 0.18-0.86])., Conclusions: Preinjury THC use may be associated with decreased hemorrhagic stroke in severely injured patients with TBI, but there was no difference in thromboembolic outcomes. Further research into pathophysiological mechanisms related to THC are needed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Succinate (SI) is a citric acid cycle metabolite that accumulates in tissues during hemorrhagic shock (HS) due to electron transport chain uncoupling. Dimethyl malonate (DMM) is a competitive inhibitor of SI dehydrogenase, which has been shown to reduce SI accumulation and protect against reperfusion injury. Whether DMM can be therapeutic after severe HS is unknown. We hypothesized that DMM would prevent SI buildup during resuscitation (RES) in a swine model of HS, leading to better physiological recovery after RES., Methods: The carotid arteries of Yorkshire pigs were cannulated with a 5-Fr catheter. After placement of a Swan-Ganz catheter and femoral arterial line, the carotid catheters were opened and the animals were exsanguinated to a mean arterial pressure (MAP) of 45 mm. After 30 minutes in the shock state, the animals were resuscitated to a MAP of 60 mm using lactated ringers. A MAP above 60 mm was maintained throughout RES. One group received 10 mg/kg of DMM (n = 6), while the control received sham injections (n = 6). The primary end-point was SI levels. Secondary end-points included cardiac function and lactate., Results: Succinate levels increased from baseline to the 20-minute RES point in control, while the DMM cohort remained unchanged. The DMM group required less intravenous fluid to maintain a MAP above 60 (450.0 vs. 229.0 mL; p = 0.01). The DMM group had higher pulmonary capillary wedge pressure at the 20-minute and 40-minute RES points. The DMM group had better recovery of cardiac output and index during RES, while the control had no improvement. While lactate levels were similar, DMM may lead to increased ionized calcium levels., Discussion: Dimethyl malonate slows SI accumulation during HS and helps preserve cardiac filling pressures and function during RES. In addition, DMM may protect against depletion of ionized calcium. Dimethyl malonate may have therapeutic potential during HS., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Tourniquet use for extremity hemorrhage control has seen a recent increase in civilian usage. Previous retrospective studies demonstrated that tourniquets improve outcomes for major extremity trauma (MET). No prospective study has been conducted to date. The objective of this study was to evaluate outcomes in MET patients with prehospital tourniquet use. We hypothesized that prehospital tourniquet use in MET decreases the incidence of patients arriving to the trauma center in shock., Methods: Data were collected prospectively for adult patients with MET at 26 Level I and 3 Level II trauma centers from 2015 to 2020. Limbs with tourniquets applied in the prehospital setting were included in the tourniquet group and limbs without prehospital tourniquets were enrolled in the control group., Results: A total of 1,392 injured limbs were enrolled with 1,130 tourniquets, including 962 prehospital tourniquets. The control group consisted of 262 limbs without prehospital tourniquets and 88 with tourniquets placed upon hospital arrival. Prehospital improvised tourniquets were placed in 42 patients. Tourniquets effectively controlled bleeding in 87.7% of limbs. Tourniquet and control groups were similarly matched for demographics, Injury Severity Score, and prehospital vital signs (p > 0.05). Despite higher limb injury severity, patients in the tourniquet group were less likely to arrive in shock compared with the control group (13.0% vs. 17.4%, p = 0.04). The incidence of limb complications was not significantly higher in the tourniquet group (p > 0.05)., Conclusion: This study is the first prospective analysis of prehospital tourniquet use for civilian extremity trauma. Prehospital tourniquet application was associated with decreased incidence of arrival in shock without increasing limb complications. We found widespread tourniquet use, high effectiveness, and a low number of improvised tourniquets. This study provides further evidence that tourniquets are being widely and safely adopted to improve outcomes in civilians with MET., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2022 American Association for the Surgery of Trauma.)

Modelling how a pandemic is spreading over time is a challenging issue. The new coronavirus disease called COVID-19 does not escape this rule as it has embraced over two hundred countries. As for previous pandemics, several studies have attempted to model the occurrence of cases caused by COVID-19. However, no study has succeeded in accurately modelling the impact of the infectious agent. Here we show that COVID-19 daily case distribution in humans obeys a Gamma law, which two new parameters can describe without any adjustment. Though the Gamma law has been exploited for nearly two centuries to describe the statistical distribution of spatial or temporal quantities, the goodness-of-fit rationale using two or three parameters has remained enigmatic. The new Gamma law approach we demonstrate here emerges from actual data and sheds light on the underlying mechanisms of the observed phenomenon. This finding has promising applicability in the epidemiological domain and in all disciplines involving branching systems, for which our Gamma law approach may bring a solution to hitherto unsolved problems., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Introduction: Trauma patients receiving massive transfusion protocol (MTP) are at risk of citrate-induced hypocalcemia and hyperkalemia. Here we evaluate potassium (K), ionized calcium (iCa), and K/iCa ratio as predictors of mortality., Methods: This retrospective study includes all adult trauma patients who received MTP within 1 h at our level I trauma center between 2014 and 2019. Receiver operating characteristic curve analysis assessed predictive accuracy of K/iCa ratio at admission on 120-day mortality., Results: Of 614 patients, 146 received MTP within 1 h and 38 expired. Patients who expired had higher K/iCa ratio than survivors (median [IQR] = 5.7 [3.8-7.2] vs 3.7 [3.1-4.9], p < 0.001). Area under the curve of K/iCa was 0.72 (95%CI = 0.62-0.82, p < 0.001) with sensitivity = 63.2% and specificity = 77.6%. At the optimum K/iCa cutoff (5.07), patients with high ratios had 4 times higher mortality risk (HR = 3.97, 95%CI = 1.89-8.32, p < 0.001)., Conclusion: Elevated K/iCa ratio was an independent predictor of mortality in trauma patients managed with MTP., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Death from noncompressible torso hemorrhage (NCTH) may be preventable with improved prehospital care and shorter in-hospital times to hemorrhage control. We hypothesized that shorter times to surgical intervention for hemorrhage control would decrease mortality in hypotensive patients with NCTH., Methods: This was an AAST-sponsored multicenter, prospective analysis of hypotensive patients aged 15+ years who presented with NCTH from May 2018 to December 2020. Hypotension was defined as an initial systolic blood pressure (SBP) ≤ 90 mm Hg. Primary outcomes of interest were time to surgical intervention and in-hospital mortality., Results: There were 242 hypotensive patients, of which 48 died (19.8%). Nonsurvivors had higher mean age (47.3 vs. 38.8; p = 0.02), higher mean New Injury Severity Score (38 vs. 29; p < 0.001), lower admit systolic blood pressure (68 vs. 79 mm Hg; p < 0.01), higher incidence of vascular injury (41.7% vs. 21.1%; p = 0.02), and shorter median (interquartile range, 25-75) time from injury to operating room start (74 minutes [48-98 minutes] vs. 88 minutes [61-128 minutes]; p = 0.03) than did survivors. Multivariable Cox regression showed shorter time from emergency department arrival to operating room start was not associated with improved survival (p = 0.04)., Conclusion: Patients who died arrived to a trauma center in a similar time frame as did survivors but presented in greater physiological distress and had significantly shorter times to surgical hemorrhage intervention than did survivors. This suggests that even expediting a critically ill patient through the current trauma system is not sufficient time to save lives from NCTH. Civilian prehospital advance resuscitative care starting from the patient first contact needs special consideration., Level of Evidence: Prognostic/Epidemiologic, Level III., (Copyright © 2022 American Association for the Surgery of Trauma.)

Background: Gun violence, particularly in the form of mass shooting events (MSE), is a growing, significant public health crisis in the US. Whether stricter gun laws decrease MSE is not known. We hypothesized that stronger state gun laws would be associated with lower MSE incidence., Study Design: Mass shooting events, defined as at least 4 people injured in a single event, and state gun law grade data for years 2014 through 2021 were obtained from the Gun Violence Archive and Giffords Law Center, respectively. An A grade indicated strictest gun control laws, and F indicated the weakest. US 2020 Census data were used to estimate MSE per million per state. The number of MSE per million was examined for association with gun law grades., Results: From 2014 through 2020, there were a total of 2,736 recorded MSE, with at least a 2-fold increase in incidence from 272 in 2014 to 626 in 2020. Concomitantly, the number of F grade states decreased from 27 to 21 (22%). The MSE mean (SD) per F state increased from 4.0 (5.1) in 2014 to 9.7 (10.3) in 2020 (p = 0.03). No differences were found in unadjusted number of MSE per year by gun law grade for any study year examined (p = 0.67). After adjusting for population, this finding of no difference persisted., Conclusions: Strength of state gun law grades does not affect MSE incidence, even after correction for population size. This suggests that legislation by itself is not an effective prevention measure and other broader and meaningful primary gun violence interventions are needed., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Viscoelastic tests including thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are being used in patients with severe hemorrhage at trauma centers to guide resuscitation. Several recent studies demonstrated hypercoagulability in female trauma patients that was associated with a survival advantage. The objective of our study was to elucidate the effects of gender differences in TEG/ROTEM values on survival in trauma patients with severe hemorrhage., Methods: A retrospective review of consecutive adult patients receiving massive transfusion protocol (MTP) at 7 Level I trauma centers was performed from 2013 to 2018. Data were stratified by gender and then further examined by TEG or ROTEM parameters. Results were analyzed using univariate and multi-variate analyses., Results: A total of 1565 patients were included with 70.9% male gender (n = 1110/1565). Female trauma patients were older than male patients (43.5 ± .9 vs 41.1 ± .6 years, P = .01). On TEG, females had longer reaction times (6.1 ± .9 min vs 4.8 ± .2 min, P = .03), increased alpha angle (68.6 ± .8 vs 65.7 ± .4, P < .001), and higher maximum amplitude (59.8 ± .8 vs 56.3 ± .4, P < .001). On ROTEM, females had significantly longer clot time (99.2 ± 13.7 vs 75.1 ± 2.6 sec, P = .09) and clot formation time (153.6 ± 10.6 sec vs 106.9 ± 3.8 sec, P < .001). When comparing by gender, no difference for in-hospital mortality was found for patients in the TEG or ROTEM group ( P > .05). Multivariate analysis showed no survival difference for female patients (OR 1.11, 95% CI .83-1.50, P = .48)., Conclusions: Although a difference between male and females was found on TEG/ROTEM for certain clotting parameters, no difference in mortality was observed. Prospective multi-institutional studies are needed.