The influence of microbial colonization on inflammatory versus pro-healing trajectories in combat extremity wounds.

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.

Developing the Ready Military Medical Force: military-specific training in Graduate Medical Education.

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.

ClotCatcher: a novel natural language model to accurately adjudicate venous thromboembolism from radiology reports.

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.

Targeted metagenomic assessment reflects critical colonization in battlefield injuries.

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.

Central role for neurally dysregulated IL-17A in dynamic networks of systemic and local inflammation in combat casualties.

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.

Development, refinement, and characterization of a nonhuman primate critical care environment.

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.

Evidence-based Surgical Competency Outcomes from the Clinical Readiness Program.

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.

Metagenomic features of bioburden serve as outcome indicators in combat extremity wounds.

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.

Cellular microRNAs correlate with clinical parameters in multiple injury patients.

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.

Patient-Specific Precision Injury Signatures to Optimize Orthopaedic Interventions in Multiply Injured Patients (PRECISE STUDY).

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.

Analysis of Surgical Volume in Military Medical Treatment Facilities and Clinical Combat Readiness of US Military Surgeons.

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.

There Is No Role for Damage Control Orthopedics Within the Golden Hour.

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.

Viral Micro-RNAs Are Detected in the Early Systemic Response to Injury and Are Associated With Outcomes in Polytrauma Patients.

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_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.

Tranexamic acid administration and pulmonary embolism in combat casualties with orthopaedic injuries.

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.

A Novel Paradigm for Surgical Skills Training and Assessment of Competency.

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.

Predicting the need for massive transfusion: Prospective validation of a smartphone-based clinical decision support tool.

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.

Association of a Network of Immunologic Response and Clinical Features With the Functional Recovery From Crotalinae Snakebite Envenoming.

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.

Clinical Readiness Program: Refocusing the Military Health System.

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.