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Background: Heterotopic ossification frequently develops following high-energy blast injuries sustained in modern warfare. We hypothesized that differences in the population of progenitor cells present in a wound would correlate with the subsequent formation of heterotopic ossification.Methods: We obtained muscle biopsy specimens from military service members who had sustained high-energy wartime injuries and from patients undergoing harvest of a hamstring tendon autograft. Plastic-adherent cells were isolated in single-cell suspension and plated to assess the prevalence of colony-forming cells. Phenotypic characteristics were assessed with use of flow cytometry. Individual colony-forming units were counted after an incubation period of seven to ten days, and replicate cultures were incubated in lineage-specific induction media. Immunohistochemical staining was then performed to determine the percentage of colonies that had differentiated along an osteogenic lineage. Quantitative real-time reverse-transcription polymerase chain reaction was used to identify changes in osteogenic gene expression.Results: Injured patients had significantly higher numbers of muscle-derived connective-tissue progenitor cells per gram of tissue (p < 0.0001; 95% confidence interval [CI], 129,930 to 253,333), and those who developed heterotopic ossification had higher numbers of assayable osteogenic colonies (p < 0.016; 95% CI, 12,249 to 106,065). In the injured group, quantitative real-time reverse-transcription polymerase chain reaction performed on the in vitro expanded progeny of connective-tissue progenitors demonstrated upregulation of COL10A1, COL4A3, COMP, FGFR2, FLT1, IGF2, ITGAM, MMP9, PHEX, SCARB1, SOX9, and VEGFA in the patients with heterotopic ossification as compared with those without heterotopic ossification.Conclusions: Our study suggests that the number of connective-tissue progenitor cells is increased in traumatized tissue. Furthermore, wounds in which heterotopic ossification eventually forms have a higher percentage of connective-tissue progenitor cells committed to osteogenic differentiation than do wounds in which heterotopic ossification does not form. The early identification of heterotopic ossification-precursor cells and target genes in severe wounds not only may be an effective prognostic tool with which to assess whether heterotopic ossification will develop in a wound, but may also guide the future development of individualized prophylactic measures. [ABSTRACT FROM AUTHOR]

Benign pneumoperitoneum is asymptomatic free intraabdominal air and is reported to occur occasionally with colonoscopy. Management of benign pneumoperitoneum after colonoscopy is controversial and may depend on incidence or etiology. No previous studies prospectively investigated the incidence or inciting factors of benign pneumoperitoneum resulting from colonoscopy. In this study, 100 patients underwent colonoscopy and then radiography of the chest and abdomen to detect free air. The average age was 58 +/- 6.2 years, and 48 of the colonoscopies were therapeutic. No cases of benign pneumoperitoneum were detected, estimating the incidence at 0% to 3% for diagnostic and therapeutic colonoscopy. These data indicate that benign pneumoperitoneum attributable to colonoscopy is rare and possibly nonexistent. Given the paucity of data favoring the occurrence of benign pneumoperitoneum after colonoscopy, we advocate treating all cases of free intraabdominal air after colonoscopy as perforations. [ABSTRACT FROM AUTHOR]

Abstract: Background : Patients with sepsis-induced hypotension are generally treated with a combination of intravenous fluids and vasopressors. The attributes of patients receiving a liberal compared to a restrictive fluid strategy have not been fully characterized. We use machine learning (ML) techniques to identify key predictors of restrictive versus liberal fluids strategy, and the likelihood of receiving each strategy in distinct patient phenotypes. Methods: We performed a retrospective observational study of patients at Emory University Hospital from 2014 to 2021 that were hypotensive, met Sepsis-3 criteria, and received at least 1 L of intravenous crystalloid fluids. We excluded patients with nonseptic etiologies of hypotension. Supervised ML techniques were used to identify key predictors for the two strategies. Additionally, subset analyses were performed on patients with pneumonia, congestive heart failure (CHF), or chronic kidney disease (CKD). Using unsupervised ML techniques, we also identified three distinct sepsis-induced hypotension phenotypes and evaluated their likelihood of receiving either strategy. Results: We identified N = 15,292 patients and randomly split them into training (n = 12,233) and validation (n = 3,059) datasets. XGBoost was the most accurate model (AUC: 0.84) for predicting the strategies. While worse oxygenation was the strongest predictor of utilizing a restrictive fluid strategy, top predictors of a liberal fluid strategy included higher pulse and blood urea nitrogen. In subset analyses, CHF, CKD, and pneumonia were predictive of restrictive fluid strategy. We identified three distinct sepsis-induced hypotension phenotypes: 1) mild organ injury, 2) severe hypoxemia, and 3) renal dysfunction. Conclusions: We identified key predictors of restrictive versus liberal fluids strategy and distinct patient phenotypes for sepsis-induced hypotension., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Background and Objectives: Prediction of patient outcomes after severe traumatic brain injury (sTBI) is limited with current clinical tools. This study aimed to improve such prognostication by combining clinical data and serum inflammatory and neuronal proteins in patients with sTBI to develop predictive models for post-traumatic vasospasm (PTV) and mortality., Methods: Fifty-three adult civilian patients were prospectively enrolled in the sTBI arm of the Surgical Critical Care Initiative (SC2i). Clinical, serum inflammatory, and neuronal protein data were combined using the parsimonious machine learning methods of least absolute shrinkage and selection operator (LASSO) and classification and regression trees (CART) to construct parsimonious models for predicting development of PTV and mortality., Results: Thirty-six (67.9%) patients developed vasospasm and 10 (18.9%) died. The mean age was 39.2 years; 22.6% were women. CART identified lower IL9, lower presentation pulse rate, and higher eotaxin as predictors of vasospasm development (full data area under curve (AUC) = 0.89, mean cross-validated AUC = 0.47). LASSO identified higher Rotterdam computed tomography score and lower age as risk factors for vasospasm development (full data AUC 0.94, sensitivity 0.86, and specificity 0.94; cross-validation AUC 0.87, sensitivity 0.79, and specificity 0.93). CART identified high levels of eotaxin as most predictive of mortality (AUC 0.74, cross-validation AUC 0.57). LASSO identified higher serum IL6, lower IL12, and higher glucose as predictive of mortality (full data AUC 0.9, sensitivity 1.0, and specificity 0.72; cross-validation AUC 0.8, sensitivity 0.85, and specificity 0.79)., Conclusion: Inflammatory cytokine levels after sTBI may have predictive value that exceeds conventional clinical variables for certain outcomes. IL-9, pulse rate, and eotaxin as well as Rotterdam score and age predict development of PTV. Eotaxin, IL-6, IL-12, and glucose were predictive of mortality. These results warrant validation in a prospective cohort., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: Septic patients who develop acute respiratory failure (ARF) requiring mechanical ventilation represent a heterogenous subgroup of critically ill patients with widely variable clinical characteristics. Identifying distinct phenotypes of these patients may reveal insights about the broader heterogeneity in the clinical course of sepsis, considering multi-organ dynamics. We aimed to derive novel phenotypes of sepsis-induced ARF using observational clinical data and investigate the generalizability of the derived phenotypes., Methods: We performed a multi-center retrospective study of ICU patients with sepsis who required mechanical ventilation for ≥ 24 h. Data from two different high-volume academic hospital centers were used, where all phenotypes were derived in MICU of Hospital-I (N = 3225). The derived phenotypes were validated in MICU of Hospital-II (N = 848), SICU of Hospital-I (N = 1112), and SICU of Hospital-II (N = 465). Clinical data from 24 h preceding intubation was used to derive distinct phenotypes using an explainable machine learning-based clustering model interpreted by clinical experts., Results: Four distinct ARF phenotypes were identified: A (severe multi-organ dysfunction (MOD) with a high likelihood of kidney injury and heart failure), B (severe hypoxemic respiratory failure [median P/F = 123]), C (mild hypoxia [median P/F = 240]), and D (severe MOD with a high likelihood of hepatic injury, coagulopathy, and lactic acidosis). Patients in each phenotype showed differences in clinical course and mortality rates despite similarities in demographics and admission co-morbidities. The phenotypes were reproduced in external validation utilizing the MICU of Hospital-II and SICUs from Hospital-I and -II. Kaplan-Meier analysis showed significant difference in 28-day mortality across the phenotypes (p < 0.01) and consistent across MICU and SICU of both Hospital-I and -II. The phenotypes demonstrated differences in treatment effects associated with high positive end-expiratory pressure (PEEP) strategy., Conclusion: The phenotypes demonstrated unique patterns of organ injury and differences in clinical outcomes, which may help inform future research and clinical trial design for tailored management strategies., (© 2024. The Author(s).)

Background: All military surgeons must maintain trauma capabilities for expeditionary care contexts, yet most are not trauma specialists. Maintaining clinical readiness for trauma and mass casualty care is a significant challenge for military and civilian surgeons. We examined the effect of a prescribed clinical readiness program for expeditionary trauma care on the surgical performance of 12 surgeons during a 60-patient mass-casualty situation (MASCAL)., Methods: The sample included orthopedic (four) and general surgeons (eight) who cared for MASCAL victims at Hamad Karzai International Airport, Kabul, Afghanistan, on August 26, 2021. One orthopedic and two general surgeons had prior deployment experience. The prescribed program included three primary measures of clinical readiness: 1, expeditionary knowledge (examination score); 2, procedural skills competencies (performance assessment score); and 3, clinical activity (operative practice profile metric). Data were attained from program records for each surgeon in the sample. Each of the 60 patient cases was reviewed and rated (performance score) by the Joint Trauma System's Performance Improvement Branch, a military-wide performance improvement organization. All scores were normalized to facilitate direct comparisons using effect size calculations between each predeployment measure and MASCAL surgical care., Results: Predeployment knowledge and clinical activity measures met program benchmarks. Baseline predeployment procedural skills competency scores did not meet program benchmarks; however, those gaps were closed through retraining, ensuring all surgeons met or exceeded the program benchmarks predeployment. There were very large effect sizes (Cohen's d ) between all program measures and surgical care score, confirming the relationship between the program measures and MASCAL trauma care provided by the 12 surgeons., Conclusion: The prescribed program measures ensured that all surgeons achieved predeployment performance benchmarks and provided high-quality trauma care to our nation's service members., Level of Evidence: Prognostic and Epidemiological; Level IV., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a "œwork of the United States Government"œ for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: The clinical demands of mass casualty events strain even the most well-equipped trauma centers and are especially challenging in resource-limited rural, remote, or austere environments. Gynecologists and urologists care for patients with pelvic and abdominal injuries, but the extent to which they are able to serve as "force multipliers" for trauma care is unclear. This study examined the abilities of urologists and gynecologists to perform 32 trauma procedures after mentored training by expert trauma educators to inform the potential for these specialists to independently care for trauma patients., Methods: Urological (6), gynecological surgeons (6), senior (postgraduate year 5) general surgery residents (6), and non-trauma-trained general surgeons (8) completed a rigorous trauma training program (Advanced Surgical Skills Exposure in Trauma Plus). All participants were assessed in their trauma knowledge and surgical abilities performing 32 trauma procedures before/after mentored training by expert trauma surgeons. Performance benchmarks were set for knowledge (80%) and independent accurate completion of all procedural components within a realistic time window (90%)., Results: General surgery participants demonstrated greater trauma knowledge than gynecologists and urologists; however, none of the specialties reached the 80% benchmark. Before training, general surgery, and urology participants outperformed gynecologists for overall procedural abilities. After training, only general surgeons met the 90% benchmark. Post hoc analysis revealed no differences between the groups performing most pelvic and abdominal procedures; however, knowledge associated with decision making and judgment in the provision of trauma care was significantly below the benchmark for gynecologists and urologists, even after training., Conclusion: For physiologically stable patients with traumatic injuries to the abdomen, pelvis, or retroperitoneum, these specialists might be able to provide appropriate care; however, they would best benefit trauma patients in the capacity of highly skilled assisting surgeons to trauma specialists. These specialists should not be considered for solo resuscitative surgical care., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Abstract: The last 20 years of sustained combat operations during the Global War on Terror generated significant advancements in combat casualty care. Improvements in point-of-injury care, en route care, and forward surgical care appropriately aligned with the survival, evacuation, and return to duty needs of the small-scale unconventional conflict. However, casualty numbers in large-scale combat operations have brought into focus the critical need for modernized casualty receiving and convalescence: Role 4 definitive care. Historically, World War II was the most recent conflict in which the United States fought in multiple operational theaters, with hundreds of thousands of combat casualties returned to the continental United States. These numbers necessitated the establishment of a "Zone of the Interior," which integrated military and civilian health care networks for definitive treatment and rehabilitation of casualties. Current security threats demand refocusing and bolstering the Military Health System's definitive care capabilities to maximize its force regeneration capacity in a similar fashion. Medical force generation, medical force sustainment and readiness, and integrated casualty care capabilities are three pillars that must be developed for Military Health System readiness of Role 4 definitive care in future large-scale contingencies against near-peer/peer adversaries., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: Top-tier general and specialty scientific journals serve as a bellwether for national research priorities. We hypothesize that military-relevant publications are underrepresented in the scientific literature and that such publications decrease significantly during peacetime., Methods: We identified high impact journals in the fields of Medicine, Surgery and Critical Care and developed Boolean searches for military-focused topics using National Library of Medicine Subject Headings terms. A PubMed search from 1950 to 2020 returned the number of research publications in relevant journals and the rate of military-focused publications by year. Rates of military publications were compared between peacetime and wartime. Publication rate trends were modeled with a quadratic function controlling for the start of active conflict and total casualty numbers. Baseline proportions of military physicians relative to the civilian sector served to estimate expected publication rates. Comparisons were performed using Pearson's χ 2 and Mann-Whitney U test, with p < 0.05 considered a significant difference., Results: From 1950 to 2020, a total of 716,340 manuscripts were published in the journals queried. Of these, military-relevant manuscripts totaled 4,052 (0.57%). We found a significant difference in the rate of publication during times of peace and times of war (0.40% vs. 0.69%, p < 0.001). Subgroup analysis found significantly reduced rates of publication in medical and critical care journals during peacetime. For each conflict, the percentage of military-focused publications peaked during periods of war but then receded below baseline levels within a median of 2.5 years (interquartile range, 1.5-3.8 years) during peacetime. The proportion of military-focused publications never reached the current proportion of military physicians in the workforce., Conclusion: There is marked reduction in rates of publication for military-focused articles in high impact journals during peacetime. Military-focused articles are underrepresented in high-impact journals. Investigators of military-relevant topics and editors of high-impact journals should seek to close this gap., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Mini abstract US military assets have been integral to the response to global pandemics, natural disasters, civilian casualties, and combat care. Strategies are being implemented to strengthen the military health care system and curtail the erosion of relevant surgical skills and knowledge during periods of low combat intensity. However, additional challenges remain. We describe these strategies and obstacles but also explore potential solutions that may strengthen the readiness of military surgeons and combat trauma teams., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

A combination of improved body armor, medical transportation, and treatment has led to the increased survival of warfighters from combat extremity injuries predominantly caused by blasts in modern conflicts. Despite advances, a high rate of complications such as wound infections, wound failure, amputations, and a decreased quality of life exist. To study the molecular underpinnings of wound failure, wound tissue biopsies from combat extremity injuries had RNA extracted and sequenced. Wounds were classified by colonization (colonized vs. non-colonized) and outcome (healed vs. failed) status. Differences in gene expression were investigated between timepoints at a gene level, and longitudinally by multi-gene networks, inferred proportions of immune cells, and expression of healing-related functions. Differences between wound outcomes in colonized wounds were more apparent than in non-colonized wounds. Colonized/healed wounds appeared able to mount an adaptive immune response to infection and progress beyond the inflammatory stage of healing, while colonized/failed wounds did not. Although, both colonized and non-colonized failed wounds showed increasing inferred immune and inflammatory programs, non-colonized/failed wounds progressed beyond the inflammatory stage, suggesting different mechanisms of failure dependent on colonization status. Overall, these data reveal gene expression profile differences in healing wounds that may be utilized to improve clinical treatment paradigms., (© 2024. The Author(s).)

Introduction: Graduate Medical Education plays a critical role in training the next generation of military physicians, ensuring they are ready to uphold the dual professional requirements inherent to being both a military officer and a military physician. This involves executing the operational duties as a commissioned leader while also providing exceptional medical care in austere environments and in harm's way. The purpose of this study is to review prior efforts at developing and implementing military unique curricula (MUC) in residency training programs., Methods: We performed a literature search in PubMed (MEDLINE), Embase, Web of Science, and the Defense Technical Information Center through August 8, 2023, including terms "graduate medical education" and "military." We included articles if they specifically addressed military curricula in residency with terms including "residency and operational" or "readiness training", "military program", or "military curriculum"., Results: We identified 1455 articles based on title and abstract initially and fully reviewed 111. We determined that 64 articles met our inclusion criteria by describing the history or context of MUC, surveys supporting MUC, or military programs or curricula incorporated into residency training or military-specific residency programs., Conclusion: We found that although there have been multiple attempts at establishing MUC across training programs, it is difficult to create a uniform curriculum that can be implemented to train residents to a single standard across services and specialties., 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.)

Importance: Microbial contamination in combat wounds can lead to opportunistic infections and adverse outcomes. However, current microbiological detection has a limited ability to capture microbial functional genes. This work describes the application of targeted metagenomic sequencing to profile wound bioburden and capture relevant wound-associated signatures for clinical utility. Ultimately, the ability to detect such signatures will help guide clinical decisions regarding wound care and management and aid in the prediction of wound outcomes., Competing Interests: The authors declare no conflict of interest.

Introduction: Accurate identification of venous thromboembolism (VTE) is critical to develop replicable epidemiological studies and rigorous predictions models. Traditionally, VTE studies have relied on international classification of diseases (ICD) codes which are inaccurate - leading to misclassification bias. Here, we developed ClotCatcher, a novel deep learning model that uses natural language processing to detect VTE from radiology reports., Methods: Radiology reports to detect VTE were obtained from patients admitted to Emory University Hospital (EUH) and Grady Memorial Hospital (GMH). Data augmentation was performed using the Google PEGASUS paraphraser. This data was then used to fine-tune ClotCatcher, a novel deep learning model. ClotCatcher was validated on both the EUH dataset alone and GMH dataset alone., Results: The dataset contained 1358 studies from EUH and 915 studies from GMH (n = 2273). The dataset contained 1506 ultrasound studies with 528 (35.1%) studies positive for VTE, and 767 CT studies with 91 (11.9%) positive for VTE. When validated on the EUH dataset, ClotCatcher performed best (AUC = 0.980) when trained on both EUH and GMH dataset without paraphrasing. When validated on the GMH dataset, ClotCatcher performed best (AUC = 0.995) when trained on both EUH and GMH dataset with paraphrasing., Conclusion: ClotCatcher, a novel deep learning model with data augmentation rapidly and accurately adjudicated the presence of VTE from radiology reports. Applying ClotCatcher to large databases would allow for rapid and accurate adjudication of incident VTE. This would reduce misclassification bias and form the foundation for future studies to estimate individual risk for patient to develop incident VTE., (© 2023. The Author(s).)

Objectives: 1) Evaluate the value and strength of a competency framework for identifying and measuring performance requirements for expeditionary surgeons; 2) Verify psychometric integrity of assessment instrumentation for measuring domain knowledge and skills; 3) Identify gaps in knowledge and skills capabilities using assessment strategies; 4) Examine shared variance between knowledge and skills outcomes, and the volume and diversity of routine surgical practice., Background: Expeditionary military surgeons provide care for patients with injuries that extend beyond the care requirements of their routine surgical practice. The readiness of these surgeons to independently provide accurate care in expeditionary contexts is important for casualty care in military and civilian situations. Identifying and closing performance gap areas are essential for assuring readiness., Methods: We implemented evidence-based processes for identifying and measuring the essential performance competencies for expeditionary surgeons. All assessment instrumentation was rigorously examined for psychometric integrity. Performance outcomes were directly measured for expeditionary surgical knowledge and skills and gap areas were identified. Knowledge and skills assessment outcomes were compared, and also compared to the volume and diversity of routine surgical practice to determine shared variance., Results: Outcomes confirmed the integrity of assessment instrumentation and identified significant performance gaps for knowledge and skills in the domain., Conclusions: Identification of domain competencies and performance benchmarks, combined with best-practices in assessment instrumentation, provided a rigorous and defensible framework for quantifying domain competencies. By identifying and implementing strategies for closing performance gap areas, we provide a positive process for assuring surgical competency and clinical readiness., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Dynamic Network Analysis (DyNA) and Dynamic Hypergraphs (DyHyp) were used to define protein-level inflammatory networks at the local (wound effluent) and systemic circulation (serum) levels from 140 active-duty, injured service members (59 with TBI and 81 non-TBI). Interleukin (IL)-17A was the only biomarker elevated significantly in both serum and effluent in TBI vs. non-TBI casualties, and the mediator with the most DyNA connections in TBI wounds. DyNA combining serum and effluent data to define cross-compartment correlations suggested that IL-17A bridges local and systemic circulation at late time points. DyHyp suggested that systemic IL-17A upregulation in TBI patients was associated with tumor necrosis factor-α, while IL-17A downregulation in non-TBI patients was associated with interferon-γ. Correlation analysis suggested differential upregulation of pathogenic Th17 cells, non-pathogenic Th17 cells, and memory/effector T cells. This was associated with reduced procalcitonin in both effluent and serum of TBI patients, in support of an antibacterial effect of Th17 cells in TBI patients. Dysregulation of Th17 responses following TBI may drive cross-compartment inflammation following combat injury, counteracting wound infection at the cost of elevated systemic inflammation., (© 2023. The Author(s).)

Background: Systemic inflammatory response remains a poorly understood cause of morbidity and mortality after traumatic injury. Recent nonhuman primate (NHP) trauma models have been used to characterize the systemic response to trauma, but none have incorporated a critical care phase without the use of general anesthesia. We describe the development of a prolonged critical care environment with sedation and ventilation support, and also report corresponding NHP biologic and inflammatory markers., Methods: Eight adult male rhesus macaques underwent ventilation with sedation for 48-96 hours in a critical care setting. Three of these NHPs underwent "sham" procedures as part of trauma control model development. Blood counts, chemistries, coagulation studies, and cytokines/chemokines were collected throughout the study, and histopathologic analysis was conducted at necropsy., Results: Eight NHPs were intentionally survived and extubated. Three NHPs were euthanized at 72-96 hours without extubation. Transaminitis occurred over the duration of ventilation, but renal function, acid-base status, and hematologic profile remained stable. Chemokine and cytokine analysis were notable for baseline fold-change for Il-6 and Il-1ra (9.7 and 42.7, respectively) that subsequently downtrended throughout the experiment unless clinical respiratory compromise was observed., Conclusions: A NHP critical care environment with ventilation support is feasible but requires robust resources. The inflammatory profile of NHPs is not profoundly altered by sedation and mechanical ventilation. NHPs are susceptible to the pulmonary effects of short-term ventilation and demonstrate a similar bioprofile response to ventilator-induced pulmonary pathology. This work has implications for further development of a prolonged care NHP model., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Introduction: The pathophysiology of the inflammatory response after major trauma is complex, and the magnitude correlates with severity of tissue injury and outcomes. Study of infection-mediated immune pathways has demonstrated that cellular microRNAs may modulate the inflammatory response. The authors hypothesize that the expression of microRNAs would correlate to complicated recoveries in polytrauma patients (PtPs)., Methods: Polytrauma patients enrolled in the prospective observational Tissue and Data Acquisition Protocol with Injury Severity Score of >15 were selected for this study. Polytrauma patients were divided into complicated recoveries and uncomplicated recovery groups. Polytrauma patients' blood samples were obtained at the time of admission (T0). Established biomarkers of systemic inflammation, including cytokines and chemokines, were measured using multiplexed Luminex-based methods, and novel microRNAs were measured in plasma samples using multiplex RNA hybridization., Results: Polytrauma patients (n = 180) had high Injury Severity Score (26 [20-34]) and complicated recovery rate of 33%. MicroRNAs were lower in PtPs at T0 compared with healthy controls, and bivariate analysis demonstrated that variations of microRNAs correlated with age, race, comorbidities, venous thromboembolism, pulmonary complications, complicated recovery, and mortality. Positive correlations were noted between microRNAs and interleukin 10, vascular endothelial growth factor, Acute Physiology and Chronic Health Evaluation, and Sequential Organ Failure Assessment scores. Multivariable Lasso regression analysis of predictors of complicated recovery based on microRNAs, cytokines, and chemokines revealed that miR-21-3p and monocyte chemoattractant protein-1 were predictive of complicated recovery with an area under the curve of 0.78., Conclusion: Systemic microRNAs were associated with poor outcomes in PtPs, and results are consistent with previously described trends in critically ill patients. These early biomarkers of inflammation might provide predictive utility in early complicated recovery diagnosis and prognosis. Because of their potential to regulate immune responses, microRNAs may provide therapeutic targets for immunomodulation., Level of Evidence: Diagnostic Tests/Criteria; Level II., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Battlefield injury management requires specialized care, and wound infection is a frequent complication. Challenges related to characterizing relevant pathogens further complicates treatment. Applying metagenomics to wounds offers a comprehensive path toward assessing microbial genomic fingerprints and could indicate prognostic variables for future decision support tools. Wound specimens from combat-injured U.S. service members, obtained during surgical debridements before delayed wound closure, were subjected to whole metagenome analysis and targeted enrichment of antimicrobial resistance genes. Results did not indicate a singular, common microbial metagenomic profile for wound failure, instead reflecting a complex microenvironment with varying bioburden diversity across outcomes. Genus-level Pseudomonas detection was associated with wound failure at all surgeries. A logistic regression model was fit to the presence and absence of antimicrobial resistance classes to assess associations with nosocomial pathogens. A. baumannii detection was associated with detection of genomic signatures for resistance to trimethoprim, aminoglycosides, bacitracin, and polymyxin. Machine learning classifiers were applied to identify wound and microbial variables associated with outcome. Feature importance rankings averaged across models indicated the variables with the largest effects on predicting wound outcome, including an increase in P. putida sequence reads. These results describe the microbial genomic determinants in combat wound bioburden and demonstrate metagenomic investigation as a comprehensive tool for providing information toward aiding treatment of combat-related injuries., (© 2022. The Author(s).)

Objectives: To evaluate early activation of latent viruses in polytrauma patients and consider prognostic value of viral micro-RNAs in these patients., Design: This was a subset analysis from a prospectively collected multicenter trauma database. Blood samples were obtained upon admission to the trauma bay (T0), and trauma metrics and recovery data were collected., Setting: Two civilian Level 1 Trauma Centers and one Military Treatment Facility., Patients: Adult polytrauma patients with Injury Severity Scores greater than or equal to 16 and available T0 plasma samples were included in this study. Patients with ICU admission greater than 14 days, mechanical ventilation greater than 7 days, or mortality within 28 days were considered to have a complicated recovery., Interventions: None., Measurements and Main Results: Polytrauma patients (n = 180) were identified, and complicated recovery was noted in 33%. Plasma samples from T0 underwent reverse transcriptase-quantitative polymerase chain reaction analysis for Kaposi's sarcoma-associated herpesvirus micro-RNAs (miR-K12&#95;10b and miRK-12-12) and Epstein-Barr virus-associated micro-RNA (miR-BHRF-1), as well as Luminex multiplex array analysis for established mediators of inflammation. Ninety-eight percent of polytrauma patients were found to have detectable Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus micro-RNAs at T0, whereas healthy controls demonstrated 0% and 100% detection rate for Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus, respectively. Univariate analysis revealed associations between viral micro-RNAs and polytrauma patients' age, race, and postinjury complications. Multivariate least absolute shrinkage and selection operator analysis of clinical variables and systemic biomarkers at T0 revealed that interleukin-10 was the strongest predictor of all viral micro-RNAs. Multivariate least absolute shrinkage and selection operator analysis of systemic biomarkers as predictors of complicated recovery at T0 demonstrated that miR-BHRF-1, miR-K12-12, monocyte chemoattractant protein-1, and hepatocyte growth factor were independent predictors of complicated recovery with a model complicated recovery prediction area under the curve of 0.81., Conclusions: Viral micro-RNAs were detected within hours of injury and correlated with poor outcomes in polytrauma patients. Our findings suggest that transcription of viral micro-RNAs occurs early in the response to trauma and may be associated with the biological processes involved in polytrauma-induced complicated recovery., Competing Interests: Dr. Schobel’s institution received funding from the Department of Defense Health Program (DOD DHP); he received support for article research from the DOD DHP. Drs. Anfossi, Shimizu, and Elster received support for article research from the National Institutes of Health (NIH). Drs. Lisboa, Davis, and Elster disclosed government work. Dr. Buchman’s institution received funding from the Uniformed Services University of the Health Sciences and/or the Henry M. Jackson Foundation, the Society of Critical Care Medicine, and Philips Corporation; he received support for article research from the Uniformed Services University of the Health Sciences; he disclosed that he is a Senior Advisor under an IPA tasked part-time to the Department of Health and Human Services/Office of the Assistant Secretary for Preparedness and Response/Biomedical Advanced Research and Development Authority/Division of Research, Innovation, and Ventures. Dr. Kirk’s institution received funding from the DOD. Dr. Calin is the Felix L. Haas Endowed Professor in Basic Science. Dr. Elster’s institution received funding from the DOD DHP – Joint Program Committee 6/Combat Casualty Care (USUHS HT9404-13-1-0032 and HU0001-15-2-0001), the NIH/the National Center for Advancing Translational Sciences grant UH3TR00943-01 through the NIH Common Fund, Office of Strategic Coordination, the National Cancer Institute grants 1R01 CA182905-01 and 1R01CA222007-01A1, the National Institute of General Medical Sciences 1R01GM122775-01 grant, a Team DOD (CA160445P1) grant, a Chronic Lymphocytic Leukemia Moonshot Flagship project, a CLL Global Research Foundation 2019 grant, a CLL Global Research Foundation 2020 grant, and donor support through Dr. Jaffer Ajani and the Estate of C. G. Johnson, Jr. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Introduction: Trauma systems within the United States have adapted the "golden hour" principle to guide prehospital planning with the goal to deliver the injured to the trauma facility in under 60 minutes. In an effort to reduce preventable prehospital death, in 2009, Secretary of Defense Robert M. Gates mandated that prehospital transport of injured combat casualties must be less than 60 minutes. The U.S. Military has implemented a 60-minute timeline for the transport of battlefield causalities to medical teams to include Forward Surgical Teams and Forward Resuscitative Surgical Teams. The inclusion of orthopedic surgeons on Forward Surgical Teams has been extrapolated from the concept of damage control orthopedics (DCO). However, it is not clear if orthopedic surgeons have yielded a demonstrable benefit in morbidity or mortality reduction. The purpose of this article is to investigate the function of orthopedic surgeons during the military "golden hour.", Materials and Methods: The English literature was reviewed for evidence supporting the use of orthopedic surgeons within the golden hour. Literature was reviewed in light of the 2009 golden hour mandate by Secretary Gates as well as those papers which highlighted the utility of DCO within the golden hour., Results: Evidence for orthopedic surgery within the "golden hour" or in the current conflicts when the United States enjoys air superiority was not identified., Conclusions: Within the military context, DCO, specifically pertaining to fracture fixation, should not be considered an element of golden hour planning and thus orthopedic surgeons are best utilized at more centralized Role 3 facility locations. The focus within the first hour after injury on the battlefield should be maintained on rapid and effective prehospital care combined with timely evacuation, as these are the most critical factors to reducing mortality., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Importance: Low surgical volume in the US Military Health System (MHS) has been identified as a challenge to military surgeon readiness. The Uniformed Services University of Health Sciences, in partnership with the American College of Surgeons, developed the Knowledge, Skills, and Abilities (KSA) Clinical Readiness Program that includes a tool for quantifying the clinical readiness value of surgeon workload, known as the KSA metric., Objective: To describe changes in US military general surgeon procedural volume and readiness using the KSA metric., Design, Setting, and Participants: This cohort study analyzed general surgery workload performed across the MHS, including military and civilian facilities, between fiscal year 2015 and 2019 and the calculated KSA metric value. The surgeon-level readiness among military general surgeons was calculated based on the KSA metric readiness threshold. Data were obtained from TRICARE, the US Department of Defense health insurance product., Main Outcomes and Measures: The main outcomes were general surgery procedural volumes and the KSA metric point value of those procedures across the MHS as well as the number of military general surgeons meeting the KSA metric readiness threshold. Aggregate facility and regional market-level claims data were used to calculate the procedural volumes and KSA metric readiness value of those procedures. Annual adjusted KSA metric points earned were used to determine the number of individual US military general surgeons meeting the readiness threshold., Results: The number of general surgery procedures generating KSAs in military hospitals decreased 25.6%, from 128 377 in 2015 to 95 461 in 2019, with a 19.1% decrease in the number of general surgeon KSA points (from 7 155 563 to 5 790 001). From 2015 to 2019, there was a 3.2% increase in both the number of procedures (from 419 980 to 433 495) and KSA points (from 21 071 033 to 21 748 984) in civilian care settings. The proportion of military general surgeons meeting the KSA metric readiness threshold decreased from 16.7% (n = 97) in 2015 to 10.1% (n = 68) in 2019., Conclusions and Relevance: This study noted that the number of KSA metric points and procedural volume in military hospitals has been decreasing since 2015, whereas both measures have increased in civilian facilities. The findings suggest that loss of surgical workload has resulted in further decreases in military surgeon readiness and may require substantial changes in patient care flow in the MHS to reverse the change.

Summary: Optimal timing and procedure selection that define staged treatment strategies can affect outcomes dramatically and remain an area of major debate in the treatment of multiply injured orthopaedic trauma patients. Decisions regarding timing and choice of orthopaedic procedure(s) are currently based on the physiologic condition of the patient, resource availability, and the expected magnitude of the intervention. Surgical decision-making algorithms rarely rely on precision-type data that account for demographics, magnitude of injury, and the physiologic/immunologic response to injury on a patient-specific basis. This study is a multicenter prospective investigation that will work toward developing a precision medicine approach to managing multiply injured patients by incorporating patient-specific indices that quantify (1) mechanical tissue damage volume; (2) cumulative hypoperfusion; (3) immunologic response; and (4) demographics. These indices will formulate a precision injury signature, unique to each patient, which will be explored for correspondence to outcomes and response to surgical interventions. The impact of the timing and magnitude of initial and staged surgical interventions on patient-specific physiologic and immunologic responses will be evaluated and described. The primary goal of the study will be the development of data-driven models that will inform clinical decision-making tools that can be used to predict outcomes and guide intervention decisions., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Sustainment of comprehensive procedural skills in trauma surgery is a particular problem for surgeons in rural, global, and combat settings. Trauma care often requires open surgical procedures for low-frequency/high-risk injuries at a time when open surgical experience is declining in general and trauma surgery training., Objective: To determine whether general surgeons participating in a 2-day standardized trauma skills course demonstrate measurable improvement in accuracy and independent performance of specific trauma skills., Design, Setting, and Participants: General surgeons in active surgical practice were enrolled from a simulation center with anatomic laboratory from October 2019 to October 2020. Differences in pretraining/training and posttraining performance outcomes were examined using (1) pretraining/posttraining surveys, (2) pretraining/posttraining knowledge assessment, and (3) training/posttraining faculty assessment. Analysis took place in November 2020., Interventions: A 2-day standardized, immersive, cadaver-based skills course, developed with best practices in instructional design, that teaches and assesses 24 trauma surgical procedures was used., Main Outcomes and Measures: Trauma surgery capability, as measured by confidence, knowledge, abilities, and independent performance of specific trauma surgical procedures; 3-month posttraining skill transfer., Results: The study cohort included 65 active-duty general surgeons, of which 16 (25%) were women and 49 (75%) were men. The mean (SD) age was 38.5 (4.2) years. Before and during training, 1 of 65 participants (1%) were able to accurately perform all 24 procedures without guidance. After course training, 64 participants (99%) met the benchmark performance requirements for the 24 trauma procedures, and 51 (78%) were able to perform them without guidance. Procedural confidence and knowledge increased significantly from before to after the course. At 3 months after training, 37 participants (56%) reported skill transfer to trauma or other procedures., Conclusions and Relevance: In this study, direct measurement of procedural performance following standardized training demonstrated significant improvement in skill performance in a broad array of trauma procedures. This model may be useful for assessment of procedural competence in other specialties.

Background: Improper or delayed activation of a massive transfusion protocol may have consequences to individuals and institutions. We designed a complex predictive algorithm that was packaged within a smartphone application. We hypothesized it would accurately assess the need for massive transfusion protocol activation and assist clinicians in that decision., Methods: We prospectively enrolled patients at an urban, level I trauma center. The application recorded the surgeon's initial opinion for activation and then prompted inputs for the model. The application provided a prediction and recorded the surgeon's final decision on activation., Results: Three hundred and twenty-one patients were enrolled (83% male; 59% penetrating; median Injury Severity Score 9; mean base deficit -4.11). Of 36 massive transfusion protocol activations, 26 had an app prediction of "high" or "moderate" probability. Of these, 4 (15%) patients received <10 u blood as a result of early hemorrhage control. Two hundred and eighty-five patients did not have massive transfusion protocol activated by the surgeon with 27 (9%) patients having "moderate" or "high" likelihood predicted by the application. Twenty-four of these did not require massive transfusion, and all patients had acidosis that unrelated to hemorrhagic shock. For 13 (50%) of the patients with "high" probability, the surgeon correctly altered their initial decision based on this information. The algorithm demonstrated an adjusted accuracy of 0.96 (95% confidence interval [0.93-0.98); P ≤ .001]), sensitivity = 0.99, specificity 0.72, positive predictive value 0.96, negative predictive value 0.99, and area under the receiver operating curve = 0.86., Conclusion: A smartphone-based clinical decision tools can aid surgeons in the decision to active massive transfusion protocol in real time, although it does not completely replace clinician judgment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In combat casualty care, tranexamic acid (TXA) is administered as part of initial resuscitation effort; however, conflicting data exist as to whether TXA contributes to increased risk of venous thromboembolism (VTE). The purpose of this study is to determine what factors increase risk of pulmonary embolism after combat-related orthopaedic trauma and whether administration of TXA is an independent risk factor for major thromboembolic events., Setting: United States Military Trauma Centers., Patients: Combat casualties with orthopaedic injuries treated at any US military trauma center for traumatic injuries sustained from January 2011 through December 2015. In total, 493 patients were identified., Intervention: None., Main Outcome Measures: Occurrence of major thromboembolic events, defined as segmental or greater pulmonary embolism or thromboembolism-associated pulseless electrical activity., Results: Regression analysis revealed TXA administration, traumatic amputation, acute kidney failure, and hypertension to be associated with the development of a major thromboembolic event for all models. Injury characteristics independently associated with risk of major VTE were Injury Severity Score 23 or greater, traumatic amputation, and vertebral fracture. The best performing model utilized had an area under curve  = 0.84, a sensitivity=0.72, and a specificity=0.84., Conclusions: TXA is an independent risk factor for major VTE after combat-related Orthopaedic injury. Injury factors including severe trauma, major extremity amputation, and vertebral fracture should prompt suspicion for increased risk of major thromboembolic events and increased threshold for TXA use if no major hemorrhage is present., Level of Evidence: III, Prognostic Study., Competing Interests: Each author certifies that neither he or she, nor any member of his or her immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. The authors have no conflicts of interest to disclose., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Background: The immunologic pathways activated during snakebite envenoming (SBE) are poorly described, and their association with recovery is unclear. The immunologic response in SBE could inform a prognostic model to predict recovery. The purpose of this study was to develop pre- and post-antivenom prognostic models comprised of clinical features and immunologic cytokine data that are associated with recovery from SBE., Materials and Methods: We performed a prospective cohort study in an academic medical center emergency department. We enrolled consecutive patients with Crotalinae SBE and obtained serum samples based on previously described criteria for the Surgical Critical Care Initiative (SC2i)(ClinicalTrials.gov Identifier: NCT02182180). We assessed a standard set of clinical variables and measured 35 unique cytokines using Luminex Cytokine 35-Plex Human Panel pre- and post-antivenom administration. The Patient-Specific Functional Scale (PSFS), a well-validated patient-reported outcome of functional recovery, was assessed at 0, 7, 14, 21 and 28 days and the area under the patient curve (PSFS AUPC) determined. We performed Bayesian Belief Network (BBN) modeling to represent relationships with a diagram composed of nodes and arcs. Each node represents a cytokine or clinical feature and each arc represents a joint-probability distribution (JPD)., Results: Twenty-eight SBE patients were enrolled. Preliminary results from 24 patients with clinical data, 9 patients with pre-antivenom and 11 patients with post-antivenom cytokine data are presented. The group was mostly female (82%) with a mean age of 38.1 (SD ± 9.8) years. In the pre-antivenom model, the variables most closely associated with the PSFS AUPC are predominantly clinical features. In the post-antivenom model, cytokines are more fully incorporated into the model. The variables most closely associated with the PSFS AUPC are age, antihistamines, white blood cell count (WBC), HGF, CCL5 and VEGF. The most influential variables are age, antihistamines and EGF. Both the pre- and post-antivenom models perform well with AUCs of 0.87 and 0.90 respectively., Discussion: Pre- and post-antivenom networks of cytokines and clinical features were associated with functional recovery measured by the PSFS AUPC over 28 days. With additional data, we can identify prognostic models using immunologic and clinical variables to predict recovery from SBE., Competing Interests: ES was employed by DecisionQ. CG receives grant funding from BTG Specialty Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gerardo, Silvius, Schobel, Eppensteiner, McGowan, Elster, Kirk and Limkakeng.)

Background: The National Surgical Quality Improvement Program (NSQIP) has become a prevalent tool for quality improvement. At our tertiary military hospital, NSQIP collects 20% of eligible cases. We implemented an emergency general surgery (EGS) registry to prospectively review all EGS cases. We compared our EGS registry with NSQIP, hypothesizing that NSQIP sampling under-represents EGS outcomes., Methods: A formal EGS Process Improvement Program was implemented in 2016. From 2016 to 2018, the four most common operations were laparoscopic appendectomy, laparoscopic cholecystectomy, surgery for small bowel obstruction, and nonelective hernia repair. Outcomes were compared between the EGS registry and NSQIP abstracted cases., Results: In 2016, the EGS registry identified 11/112 (9.8%) patients with a complication. National Surgical Quality Improvement Program abstracted 16% of EGS cases with 16.7% (3/18) of patients having a complication. In 2017, the EGS registry identified 10/87 (11.5%) cases with complications. National Surgical Quality Improvement Program abstracted 23% of EGS with zero complications. In 2018, the EGS registry identified 9.5% of 74 cases with complications. National Surgical Quality Improvement Program abstracted 15% of EGS cases with zero complications., Conclusions: National Surgical Quality Improvement Program did not capture many important EGS outcomes. In 2 of 3 years, NSQIP did not identify a single complication for EGS. National Surgical Quality Improvement Program alone may be insufficient to target EGS improvements., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 National Association for Healthcare Quality.)

Introduction: The Military Health System serves to globally provide health services and trained medical forces. Military providers possess variable levels of deployment preparedness. The aim of the Clinical Readiness Program is to develop and assess the knowledge, skills, and abilities (KSAs) needed for combat casualty care., Methods: The Clinical Readiness Program developed a KSA metric for general and orthopedic surgery. The KSA methodology underwent a proof of concept in six medical treatment facilities., Results: The KSA metric feasibly quantifies the combat relevance of surgical practice. Orthopedic surgeons are more likely than general surgeons to meet the threshold. Medical treatment facilities do not provide enough demand for general surgery services to achieve readiness., Conclusion: The Clinical Readiness Program identifies imbalances between the health care delivery and readiness missions. To close the readiness gap, the Military Health System needs to recapture high KSA value procedures, expand access to care, and/or partner with civilian institutions., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Abdominal pain is a common and functionally limiting complaint within the healthcare system linked to impaired quality of life and increased health care utilization. This chief complaint is associated with an extensive differential diagnosis leading to high utilization of diagnostic testing, increased healthcare cost, and delayed access to care. In patients presenting with acute or chronic abdominal pain, musculoskeletal pain often requires expensive testing, thereby delaying definitive care. An improved triage process is warranted. Performing a musculoskeletal examination to determine if pain patterns can be mechanically reproduced at the site of origin, or remote to the site of pain, warrants referral to a musculoskeletal specialist. In our young and healthy population, once the musculoskeletal mediated abdominal pain origin is determined, we see significant success in the application of a treatment approach consisting of manipulative therapy, exercise, and instrument-assisted soft tissue mobilization. A multimodal treatment approach for musculoskeletal-mediated abdominal pain has not been previously described. This case study outlines a novel management approach for musculoskeletal-mediated abdominal pain and provides an alternative diagnostic technique, when implemented early in the evaluation and management process of atypical abdominal pain, that improves the quality of life., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Scozzafava et al.)

Background: Post-traumatic acute kidney injury has occurred in every major military conflict since its initial description during World War II. To ensure the proper treatment of combat casualties, early detection is critical. This study therefore aimed to investigate combat-related post-traumatic acute kidney injury in recent military conflicts, used machine learning algorithms to identify clinical and biomarker variables associated with the development of post-traumatic acute kidney injury, and evaluated the effects of post-traumatic acute kidney injury on wound healing and nosocomial infection., Methods: We conducted a retrospective clinical cohort review of 73 critically injured US military service members who sustained major combat-related extremity wounds and had collected injury characteristics, assayed serum and tissue biopsy samples for the expression of protein and messenger ribonucleic acid biomarkers. Bivariate analyses and random forest recursive feature elimination classification algorithms were used to identify associated injury characteristics and biomarker variables., Results: The incidence of post-traumatic acute kidney injury was 20.5%. Of that, 86% recovered baseline renal function and only 2 (15%) of the acute kidney injury group required renal replacement therapy. Random forest recursive feature elimination algorithms were able to estimate post-traumatic acute kidney injury with the area under the curve of 0.93, sensitivity of 0.91, and specificity of 0.91. Post-traumatic acute kidney injury was associated with injury severity score, serum epidermal growth factor, and tissue activin A type receptor 1, matrix metallopeptidase 10, and X-C motif chemokine ligand 1 expression. Patients with post-traumatic acute kidney injury exhibited poor wound healing and increased incidence of nosocomial infections., Conclusion: The occurrence of acute kidney injury in combat casualties may be estimated using injury characteristics and serum and tissue biomarkers. External validations of these models are necessary to generalize for all trauma patients., (Published by Elsevier Inc.)

Objective: Scope evidence on technical performance metrics for open emergency surgery. Identify surgical performance metrics and procedures used in trauma training courses., Design: Structured literature searches of electronic databases were conducted from January 2010 to December 2019 to identify systematic reviews of tools to measure surgical skills employed in vascular or trauma surgery evaluation and training., Setting and Participants: Faculty of Shock Trauma Anesthesiology Research Center, University of Maryland School of Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland and Implementation Science, King's College, London., Results: The evidence from 21 systematic reviews including over 54,000 subjects enrolled into over 840 eligible studies, identified that the Objective Structured Assessment of Technical Skill was used for elective surgery not for emergency trauma and vascular control surgery procedures. The Individual Procedure Score (IPS), used to evaluate emergency trauma procedures performed before and after training, distinguished performance of residents from experts and practicing surgeons. IPS predicted surgeons who make critical errors and need remediation interventions. No metrics showed Kirkpatrick's Level 4 evidence of technical skills training benefit to emergency surgery outcomes., Conclusions: Expert benchmarks, errors, complication rates, task completion time, task-specific checklists, global rating scales, Objective Structured Assessment of Technical Skills, and IPS were found to identify surgeons, at all levels of seniority, who are in need of remediation of technical skills for open surgical hemorrhage control. Large-scale, multicenter studies are needed to evaluate any benefit of trauma technical skills training on patient outcomes., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study was to evaluate the utilization of pelvic binders, the proper placement of binders, and to determine any differences in blood product transfusions between combat casualties with and without a pelvic binder identified on initial imaging immediately after the injury., Methods: We conducted a retrospective review of all combat-injured patients who arrived at our military treatment hospital between 2010 and 2012 with a documented pelvic fracture. Initial imaging (X-ray or computed tomography) immediately after injury were evaluated by 2 independent radiologists. Young-Burgess (YB) classification, pelvic diastasis, correct binder placement over the greater trochanters, and the presence of a pelvic external fixator (ex-fix) was recorded. Injury severity score (ISS), whole blood, and blood component therapy administered within the first 24-hours after injury were compared between casualties with and without a pelvic binder., Results: 39 casualties had overseas imaging to confirm and radiographically classify a YB pelvic ring injury. The most common fracture patterns were anteroposterior (53%) and lateral compression (28%). 49% (19/39) did not have a binder or ex-fix identified on initial imaging or in any documentation after injury. Ten patients had a binder, with 30% positioned incorrectly over the iliac crest. ISS (34 ± 1.6) was not statistically different between the binder and the no-binder group. Pubic symphysis diastasis was significantly lower in the binder group (1.4 ± 0.2 vs 3.7 ± 0.5, P < .001). There was a trend toward decreased 24-hour total blood products between the binder and no-binder groups (75 ± 11 vs 82 ± 13, P = .67). This was due to less cryoprecipitate in the binder group (6 ± 2 vs 19 ± 5, P = .01)., Conclusions: Pelvic binder placement in combat trauma may be inconsistent and an important area for continued training. While 24-hour total transfusions do not appear to be different, no-binder patients received significantly more cryoprecipitate.

Background: Tranexamic acid (TXA) may be a useful adjunct for military patients with severe traumatic brain injury (TBI). These patients are often treated in austere settings without immediate access to neurosurgical intervention. The purpose of this study was to evaluate any association between TXA use and progression of intracranial hemorrhage (ICH), neurologic outcomes, and venous thromboembolism (VTE) in TBI., Methods: This was a retrospective cohort study of military casualties from October 2010 to December 2015 who were transferred to a military treatment facility (MTF) in the United States. Data collected included: demographics, types of injuries, initial and interval head computerized tomography (CT) scans, Glasgow Coma Scores (GCS), and six-month Glasgow Outcome Scores (GOS). Results were stratified based on TXA administration, progression of ICH, and VTE., Results: Of the 687 active duty service members reviewed, 71 patients had ICH (10.3%). Most casualties were injured in a blast (80.3%), with 36 patients (50.7%) sustaining a penetrating TBI. Mean ISS was 28.2 ± 12.3. Nine patients (12.7%) received a massive transfusion within 24 h of injury, and TXA was administered to 14 (19.7%) casualties. Patients that received TXA had lower initial reported GCS (9.2 ± 4.4 vs. 12.5 ± 3.4, p = 0.003), similar discharge GCS (13.3 ± 4.0 vs. 13.8 ± 3.2, p = 0.58), and a larger improvement between initial and discharge GCS (3.7 ± 3.9 vs. 1.3 ± 3.1, p = 0.02). However, there was no difference in mortality (7.1% vs. 7.0%, p = 1.00), progression of ICH (45.5% vs. 14.7%, p = 0.09), frequency of cranial decompression (50.0% vs. 42.1%, p = 0.76), or mean GOS (3.5 ± 0.9 vs. 3.8 ± 1.0, p = 0.13). Patients administered TXA had a higher rate of VTE (35.7% vs. 7.0%, p = 0.01). On multivariate analysis, however, TXA was not independently associated with VTE., Conclusions: Patients that received TXA were associated with an improvement in GCS but not in progression of ICH or GOS. TXA was not independently associated with VTE, although this may be related to a paucity of patients receiving TXA. Decisions about TXA administration in military casualties with ICH should be considered in the context of the availability of neurosurgical intervention as well as severity of extracranial injuries and need for massive transfusion.

Importance: Armed conflict in the 21st century poses new challenges to a humanitarian surgical response, including changing security requirements, access to patients, and communities in need, limited deployable surgical assets, resource constraints, and the requirement to address both traumatic injuries as well as emergency surgical needs of the population. At the same time, recent improvements in trauma care and systems have reduced injury-related mortality. This combination of new challenges and medical capabilities warrants reconsideration of long-standing humanitarian surgery protocols., Objective: To describe a consensus framework for surgical care designed to respond to this emerging need., Design, Setting, and Participants: An international group of 35 representatives from humanitarian agencies, US military, and academic trauma programs was invited to the Stanford Humanitarian Surgical Response in Conflict Working Group to engage in a structured process to review extant trauma protocols and make recommendations for revision., Main Outcomes and Measures: The working group's method adapted core elements of a modified Delphi process combined with consensus development conference from August 3 to August 5, 2018., Results: Lessons from civilian and military trauma systems as well as recent battlefield experiences in humanitarian settings were integrated into a tiered continuum of response from point of injury through rehabilitation. The framework addresses the security and medical requirements as well as ethical and legal principles that guide humanitarian action. The consensus framework includes trained, lay first responders; far-forward resuscitation/stabilization centers; rapid damage control surgical access; and definitive care facilities. The system also includes nontrauma surgical care, injury prevention, quality improvement, data collection, and predeployment training requirements., Conclusions and Relevance: Evidence suggests that modern trauma systems save lives. However, the requirements of providing this standard of care in insecure conflict settings places new burdens on humanitarian systems that must provide both emergency and trauma surgical care. This consensus framework integrates advances in trauma care and surgical systems in response to a changing security environment. It is possible to reduce disparities and improve the standard of care in these settings.

Introduction: Clinical decision support tools capable of predicting which patients are at highest risk for venous thromboembolism (VTE) can assist in guiding surveillance and prophylaxis decisions. The Trauma Embolic Scoring System (TESS) has been shown to model VTE risk in civilian trauma patients. No such support tools have yet been described in combat casualties, who have a high incidence of VTE. The purpose of this study was to evaluate the utility of TESS in predicting VTE in military trauma patients., Methods: A retrospective cohort study of 549 combat casualties from October 2010 to November 2012 admitted to a military treatment facility in the USA was performed. TESS scores were calculated through data obtained from the Department of Defense Trauma Registry and chart reviews. Univariate analysis and multivariate logistic regression were performed to evaluate risk factors for VTE. Receiver operating characteristic (ROC) curve analysis of TESS in military trauma patients was also performed., Results: The incidence of VTE was 21.7% (119/549). The median TESS for patients without VTE was 8 (IQR 4-9), and the median TESS for those with VTE was 10 (IQR 9-11). On multivariate analysis, Injury Severity Score (ISS) (OR 1.03, p=0.007), ventilator days (OR 1.05, p=0.02), and administration of tranexamic acid (TXA) (OR 1.89, p=0.03) were found to be independent risk factors for development of VTE. On ROC analysis, an optimal high-risk cut-off value for TESS was ≥7 with a sensitivity of 0.92 and a specificity of 0.53 (area under the curve 0.76, 95% CI 0.72 to 0.80, p<0.0001)., Conclusions: When used to predict VTE in military trauma, TESS shows moderate discrimination and is well calibrated. An optimal high-risk cut-off value of ≥7 demonstrates high sensitivity in predicting VTE. In addition to ISS and ventilator days, TXA administration is an independent risk factor for VTE development., Level of Evidence: Level III., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Critical errors increase postoperative morbidity and mortality. A trauma readiness index was used to evaluate critical errors in 4 trauma procedures. In comparison to practicing and expert surgeon benchmarks, we hypothesized that pretraining trauma readiness index including both vascular and nonvascular trauma surgical procedures can identify residents who will make critical errors., Methods: In a prospective study, trained evaluators used a standardized script to evaluate performance of brachial, axillary, and femoral artery exposure and proximal control and lower-extremity fasciotomy on unpreserved cadavers. Forty residents were evaluated before and immediately after Advanced Surgical Skills for Exposure in Trauma training, and 38 were re-evaluated 14 months later. Residents were compared to 34 practicing surgeons evaluated once 30 months after training, and 10 experts., Results: Resident trauma readiness index increased with training (P < .001), remained unchanged 14 month later and was higher, with lower variance than practicing surgeons (P < .05). Expert trauma readiness index was higher than residents (P < .004) and practicing surgeons (P < .001). Resident training decreased critical errors when evaluated immediately and 14 months after Advanced Surgical Skills for Exposure in Trauma training. Practicing surgeons had more critical errors and performance variability than residents or experts. Experts had 5 to 7 times better error recovery than practicing surgeons or residents. Trauma readiness index area under the receiver operating curve with Youden Index <0.60 or <6 decile in their cohort, predicts a surgeon will make a critical error., Conclusion: Low trauma readiness index was associated with critical errors occurring in all surgeon cohorts and can identify surgeons in need of remedial intervention., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Background: Both the frequency and high complication rates associated with extremity wounds in recent military conflicts have highlighted the need for clinical decision support tools (CDST) to decrease time to wound closure and wound failure rates., Methods: Machine learning was used to estimate both successful wound closure (based on penultimate debridement biomarker data) and the necessary number of surgical debridements (based on presentation biomarkers) in 73 service members treated according to military guidelines based on clinical data and the local/systemic level of 32 cytokines. Models were trained to estimate successful closure including an additional 8 of 80 civilian patients with similar injury patterns. Previous analysis has demonstrated the potential to reduce the number of operative debridements by 2, with resulting decreases in ICU and hospital LOS, while decreasing the rate of wound failure., Results: Analysis showed similar cytokine responses when civilians followed a military-like treatment schedule with surgical debridements every 24 to 72 hours. A model estimating successful closure had AUC of 0.89. Model performance in civilians degraded when these had a debridement interval > 72 hours (73 of the 80 civilians). A separate model estimating the number of debridements required to achieve successful closure had a multiclass AUC of 0.81., Conclusion: CDSTs can be developed using biologically compatible civilian and military populations as cytokine response is highly influenced by surgical treatment. Our CDSTs may help identify who may require serial debridements versus early closure, and precisely when traumatic wounds should optimally be closed.

Multiple organ failure (MOF) is the leading cause of late mortality and morbidity in patients who are admitted to intensive care units (ICUs). However, there is an epidemiologic discrepancy in the mechanism of underlying immunologic derangement dependent on etiology between sepsis and trauma patients in MOF. We hypothesized that damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), while both involved in the development of MOF, contribute differently to the systemic innate immune derangement and coagulopathic changes. We found that DAMPs not only produce weaker innate immune activation than counterpart PAMPs, but also induce less TLR signal desensitization, contribute to less innate immune cell death, and propagate more robust systemic coagulopathic effects than PAMPs. This differential contribution to MOF provides further insight into the contributing factors to late mortality in critically ill trauma and sepsis patients. These findings will help to better prognosticate patients at risk of MOF and may provide future therapeutic molecular targets in this disease process.

In an effort to improve surgical quality and reduce clinical variability, the Military Health System (MHS) expanded its participation in the National Surgical Quality Improvement Program to all military hospitals beginning in 2015. This expansion and a partnership with the American College of Surgeons laid the foundation for a surgical quality collaborative in the MHS. We review the history of the program in the MHS and the activities that have contributed to developing the collaborative. We also report promising trends in surgical outcomes at hospitals that were already participating in the program in 2014, when a critical MHS review identified areas for improvement in surgical care. We conclude with a discussion of possible lessons for other health systems and challenges ahead for the MHS, now that full enrollment in the program has been completed.