Safety of Bioplasma FDP and Hemopure in rhesus macaques after 30% hemorrhage.

Objectives: Prehospital transfusion can be life-saving when transport is delayed but conventional plasma, red cells, and whole blood are often unavailable out of hospital. Shelf-stable products are needed as a temporary bridge to in-hospital transfusion. Bioplasma FDP (freeze-dried plasma) and Hemopure (hemoglobin-based oxygen carrier; HBOC) are products with potential for prehospital use. In vivo use of these products together has not been reported. This study assessed the safety of intravenous administration of HBOC+FDP, relative to normal saline (NS), in rhesus macaques (RM). Methods: After 30% blood volume removal and 30 minutes in shock, animals were resuscitated with either NS or two units (RM size adjusted) each of HBOC+FDP during 60 minutes. Sequential blood samples were collected. After neurological assessment, animals were killed at 24 hours and tissues collected for histopathology. Results: Due to a shortage of RM during the COVID-19 pandemic, the study was stopped after nine animals (HBOC+FDP, seven; NS, two). All animals displayed physiologic and tissue changes consistent with hemorrhagic shock and recovered normally. There was no pattern of cardiovascular, blood gas, metabolic, coagulation, histologic, or neurological changes suggestive of risk associated with HBOC+FDP. Conclusion: There was no evidence of harm associated with the combined use of Hemopure and Bioplasma FDP. No differences were noted between groups in safety-related cardiovascular, pulmonary, renal or other organ or metabolic parameters. Hemostasis and thrombosis-related parameters were consistent with expected responses to hemorrhagic shock and did not differ between groups. All animals survived normally with intact neurological function. Level of evidence: Not applicable.

Aeromedical Evacuation, the Expeditionary Medicine Learning Curve, and the Peacetime Effect.

INTRODUCTION: Organizational proficiency increases with experience, which is known as a learning curve. A theoretical peacetime effect occurs when knowledge and skills degrade during peacetime. In this study, the intertheater evacuation system was examined for evidence of a military learning curve and peacetime effect. MATERIALS AND METHODS: Data on medical evacuations from U.S. Central Command occurring between January 1, 2003, and December 31, 2022, were acquired from the TRANSCOM Regulating and Command & Control Evacuation System. Priority mission evacuation time corresponding to peak periods of activity in Iraq and Afghanistan and minimal activity in Afghanistan was analyzed. Any reduction or increase in the delivery time of casualties would be considered a change in proficiency. RESULTS: There was a marginal monthly decline of 0.019 days (27.4 min) to perform a priority evacuation from Iraq (95% confidence interval [CI], 0.009 to 0.028 days, P < .001) and a decline of 0.010 days (14.4 min) from Afghanistan (95% CI, 0.003 to 0.016 days, P = .004) over 40 months from peak monthly average times. There was a monthly marginal increase in priority evacuation average time from Afghanistan of 0.008 days (11.5 min) (95% CI, 0.005 to 0.011, P < .001) between January 2013 and December 2020. The number of monthly evacuations estimated to maintain or improve monthly average evacuation time is approximately 50. CONCLUSIONS: An intertheater aeromedical evacuation system increased in proficiency during periods of conflict and declined during relative peacetime. There is evidence of a peacetime effect on intertheater aeromedical evacuation.

Evaluation of hemostatic devices in a randomized porcine model of junctional hemorrhage and 72-hour prolonged field care.

BACKGROUND: Hemorrhage control in prolonged field care (PFC) presents unique challenges that drive the need for enhanced point of injury treatment capabilities to maintain patient stability beyond the Golden Hour. To address this, two hemostatic agents, Combat Gauze (CG) and XSTAT, were evaluated in a porcine model of uncontrolled junctional hemorrhage for speed of deployment and hemostatic efficacy over 72 hours. METHODS: The left subclavian artery and subscapular vein were isolated in anesthetized male Yorkshire swine (70-85 kg) and injured via 50% transection, followed by 30 seconds of hemorrhage. Combat Gauze (n = 6) or XSTAT (n = 6) was administered until bleeding stopped and remained within subjects for observation over 72 hours. Physiologic monitoring, hemostatic efficacy, and hematological parameters were measured throughout the protocol. Gross necropsy and histology were performed following humane euthanasia. RESULTS: Both CG and XSTAT maintained hemostasis throughout the full duration of the protocol. There were no significant differences between groups in hemorrhage volume (CG: 1021.0 ± 183.7 mL vs. XSTAT: 968.2 ± 243.3 mL), total blood loss (CG: 20.8 ± 2.7% vs. XSTAT: 20.1 ± 5.1%), or devices used (CG: 3.8 ± 1.2 vs. XSTAT: 5.3 ± 1.4). XSTAT absorbed significantly more blood than CG (CG: 199.5 ± 50.3 mL vs. XSTAT: 327.6 ± 71.4 mL) and was significantly faster to administer (CG: 3.4 ± 1.6 minutes vs. XSTAT: 1.4 ± 0.5 minutes). There were no significant changes in activated clot time, prothrombin time, or international normalized ratio between groups or compared with baseline throughout the 72-hour protocol. Histopathology revealed no evidence of microthromboemboli or disseminated coagulopathies across evaluated tissues in either group. CONCLUSION: Combat Gauze and XSTAT demonstrated equivalent hemostatic ability through 72 hours, with no overt evidence of coagulopathies from prolonged indwelling. In addition, XSTAT offered significantly faster administration and the ability to absorb more blood. Taken together, XSTAT offers logistical and efficiency advantages over CG for immediate control of junctional noncompressible hemorrhage, particularly in a tactical environment. In addition, extension of indicated timelines to 72 hours allows translation to PFC.

Trauma and Critical Care Military-Civilian Publications Increased After the COVID-19 Pandemic: A Literature Review.

INTRODUCTION: There continues to be a growing demand for military-civilian partnerships (MCPs) in research collaborations developing medical trauma care in domestic and international affairs. The objective of this comprehensive review is to investigate the difference in the quantity of MCP trauma and critical care publications before and after the COVID-19 pandemic. METHODS: A systematic literature review was performed for the calendar years 2018 and 2021 utilizing MEDLINE, Cochrane, and EMBASE databases. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a three-tiered review of 603 English language articles to identify trauma-related military and/or civilian partners and describe the changes in geographical relationships. RESULTS: A total of 96 (2018) and 119 (2021) articles met screening criteria for trauma and critical care studies and were used for final data extraction. Ultimately, 59 (2018) and 71 (2021) papers met the inclusion criteria of identifying trauma/critical care MCPs and identified both military and civilian partners. There was also an increase from 10 (2018) to 17 (2021) publications that mentioned advocacy for MCP. Using the author affiliations, four regional MCP types were recorded: of 2018 articles, locoregional (3.4%), US-national (47.5%), single international country (42.4%), and between multiple countries (6.8%); of 2021 articles, locoregional (15.5%), US-national (38%), single international country (29.6%), and between multiple countries (16.9%). There has been an increase in the number of locoregional and multinational MCPs and an overall increase in the number of collaborative trauma publications and MCP advocacy papers. A national geographical heat map was developed to illustrate the changes from 2018 to 2021. CONCLUSIONS: There has been an increase in the number of recorded trauma and critical care MCP publications post-pandemic. The growth in the number of manuscripts in more regions post-pandemic suggests an increase in the recognition of collaborations that contribute not only to conflict readiness but also advancements in trauma and surgical care.

Optimizing combat readiness for military surgeons without trauma fellowship training: Engaging the "voluntary faculty" model.

BACKGROUND: Appropriate operative volume remains a critical component in mitigating surgical atrophy and maintaining clinical competency. The initiation of military-civilian surgical partnerships (MCPs) has been proposed for addressing knowledge, skills, and abilities (KSA) metrics to address concerns over operational readiness and the low acuity experienced by military surgeons. This study investigates the first partnership for Navy surgical staff at a nonacademic Military Treatment Facility (MTF) with a regional academic Army Military Treatment Facility (AMTF) and a civilian, nonacademic level II trauma center devised to improve operational readiness for attending surgeons. We hypothesize that a skill sustainment MCP will allow military surgeons to meet combat readiness standards as measured by the KSA metric. METHODS: A memorandum of understanding was initiated between the Navy Military Treatment Facility (NMTF), the AMTF, and the level II civilian trauma center (CTC). The single military surgeon in this study was classified as "voluntary faculty" at the CTC. Total case volume and acuity were recorded over an 11-month period. Knowledge, skills, and abilities metrics were calculated using the standard national provider identifier number and the novel case-log based method. RESULTS: A total of 156 cases were completed by a single surgeon over the study period, averaging 52 cases per institution. Significantly more KSAs were obtained at the CTC compared with NMTF (5,954 vs. 2,707; p < 0.001). Significantly more emergent cases were observed at the CTC compared with the MTFs (χ 2 = 7.1, n = 96, p < 0.05). At a single site, AMTF, a significant difference in the calculated KSA score, was observed between the national provider identifier and case-log methods (5,278 vs. 3,297; p = 0.04). CONCLUSION: The skill sustainment MCP between NMTF and CTC increased surgical readiness and exposed surgeons to increased operative acuity. The voluntary faculty model reduces direct litigation exposure and encourages clinical competency for military surgeons while remaining a deployable asset to the global military effort. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

PREHOSPITAL PLASMA IS NONINFERIOR TO WHOLE BLOOD FOR RESTORATION OF CEREBRAL OXYGENATION IN A RHESUS MACAQUE MODEL OF TRAUMATIC SHOCK AND HEMORRHAGE.

ABSTRACT: Introduction: Traumatic shock and hemorrhage (TSH) is a leading cause of preventable death in military and civilian populations. Using a TSH model, we compared plasma with whole blood (WB) as prehospital interventions, evaluating restoration of cerebral tissue oxygen saturation (CrSO 2 ), systemic hemodynamics, colloid osmotic pressure (COP) and arterial lactate, hypothesizing plasma would function in a noninferior capacity to WB, despite dilution of hemoglobin (Hgb). Methods: Ten anesthetized male rhesus macaques underwent TSH before randomization to receive a bolus of O(-) WB or AB(+) plasma at T0. At T60, injury repair and shed blood (SB) to maintain MAP > 65 mm Hg began, simulating hospital arrival. Hematologic data and vital signs were analyzed via t test and two-way repeated measures ANOVA, data presented as mean ± SD, significance = P < 0.05. Results: There were no significant group differences for shock time, SB volume, or hospital SB. At T0, MAP and CrSO 2 significantly declined from baseline, though not between groups, normalizing to baseline by T10. Colloid osmotic pressure declined significantly in each group from baseline at T0 but restored by T30, despite significant differences in Hgb (WB 11.7 ± 1.5 vs. plasma 6.2 ± 0.8 g/dL). Peak lactate at T30 was significantly higher than baseline in both groups (WB 6.6 ± 4.9 vs. plasma 5.7 ± 1.6 mmol/L) declining equivalently by T60. Conclusions: Plasma restored hemodynamic support and CrSO 2 , in a capacity not inferior to WB, despite absence of additional Hgb supplementation. This was substantiated via return of physiologic COP levels, restoring oxygen delivery to microcirculation, demonstrating the complexity of restoring oxygenation from TSH beyond simply increasing oxygen carrying capacity.

Effects of hemodilution on coagulation function during prolonged hypotensive resuscitation in a porcine model of severe hemorrhagic shock.

Background: Although hemorrhage remains the leading cause of survivable death in casualties, modern conflicts are becoming more austere limiting available resources to include resuscitation products. With limited resources also comes prolonged evacuation time, leaving suboptimal prehospital field care conditions. When blood products are limited or unavailable, crystalloid becomes the resuscitation fluid of choice. However, there is concern of continuous crystalloid infusion during a prolonged period to achieve hemodynamic stability for a patient. This study evaluates the effect of hemodilution from a 6-hour prehospital hypotensive phase on coagulation in a porcine model of severe hemorrhagic shock. Methods: Adult male swine (n=5/group) were randomized into three experimental groups. Non-shock (NS)/normotensive did not undergo injury and were controls. NS/permissive hypotensive (PH) was bled to the PH target of systolic blood pressure (SBP) 85±5 mm Hg for 6 hours of prolonged field care (PFC) with SBP maintained via crystalloid, then recovered. Experimental group underwent controlled hemorrhage to mean arterial pressure 30 mm Hg until decompensation (Decomp/PH), followed by PH resuscitation with crystalloid for 6 hours. Hemorrhaged animals were then resuscitated with whole blood and recovered. Blood samples were collected at certain time points for analysis of complete blood counts, coagulation function, and inflammation. Results: Throughout the 6-hour PFC, hematocrit, hemoglobin, and platelets showed significant decreases over time in the Decomp/PH group, indicating hemodilution, compared with the other groups. However, this was corrected with whole blood resuscitation. Despite the appearance of hemodilution, coagulation and perfusion parameters were not severely compromised. Conclusions: Although significant hemodilution occurred, there was minimal impact on coagulation and endothelial function. This suggests that it is possible to maintain the SBP target to preserve perfusion of vital organs at a hemodilution threshold in resource-constrained environments. Future studies should address therapeutics that can mitigate potential hemodilutional effects such as lack of fibrinogen or platelets. Level of evidence: Not applicable-Basic Animal Research.

Declining Military Surgical Cases and the Impact on Military Surgical Graduate Medical Education.

BACKGROUND: Several studies have indicated a decline in the number, types, and complexity of surgical procedures within military treatment facilities (MTFs). This study aims to determine what effect, if any, these downward trends have had on the relationship between the military health system (MHS) and surgical graduate medical education. METHODS: Graduating chief resident final ACGME case logs from 4 of thirteen military general surgery programs were evaluated from 2015 to 2020. The proportion of total cases performed by residents at military institutions were compared on a year over year basis. RESULTS: The proportion of cases performed within the military hospitals declined 3.27% each year between 2015 and 2020 (P < .0001) in 4 MTFs. All individual hospitals had significant declines in case volume except one (William Beaumont Army Medical Center) which increased 6.05% with each year, but also increased the number of MTF partnerships within its program (P < .0001). CONCLUSIONS: There has been a statistically significant decline over time in the proportion of cases logged by residents within the studied military treatment facilities. Investment into military hospitals to increase case numbers, case diversity, and complexity and/or acceptance of this gradual decline with greater shifting of educational workload onto civilian hospitals is required.

Perception of Treatment Success and Impact on Function with Antibiotics or Appendectomy for Appendicitis: A Randomized Clinical Trial with an Observational Cohort.

OBJECTIVE: To compare secondary patient reported outcomes of perceptions of treatment success and function for patients treated for appendicitis with appendectomy vs. antibiotics at 30 days. SUMMARY BACKGROUND DATA: The Comparison of Outcomes of antibiotic Drugs and Appendectomy trial found antibiotics noninferior to appendectomy based on 30-day health status. To address questions about outcomes among participants with lower socioeconomic status, we explored the relationship of sociodemographic and clinical factors and outcomes. METHODS: We focused on 4 patient reported outcomes at 30 days: high decisional regret, dissatisfaction with treatment, problems performing usual activities, and missing >10 days of work. The randomized (RCT) and observational cohorts were pooled for exploration of baseline factors. The RCT cohort alone was used for comparison of treatments. Logistic regression was used to assess associations. RESULTS: The pooled cohort contained 2062 participants; 1552 from the RCT. Overall, regret and dissatisfaction were low whereas problems with usual activities and prolonged missed work occurred more frequently. In the RCT, those assigned to antibiotics had more regret (Odd ratios (OR) 2.97, 95% Confidence intervals (CI) 2.05-4.31) and dissatisfaction (OR 1.98, 95%CI 1.25-3.12), and reported less missed work (OR 0.39, 95%CI 0.27-0.56). Factors associated with function outcomes included sociodemographic and clinical variables for both treatment arms. Fewer factors were associated with dissatisfaction and regret. CONCLUSIONS: Overall, participants reported high satisfaction, low regret, and were frequently able to resume usual activities and return to work. When comparing treatments for appendicitis, no single measure defines success or failure for all people. The reported data may inform discussions regarding the most appropriate treatment for individuals. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02800785.

An Analysis of Head and Neck Surgical Workload During Recent Combat Operations From 2002 to 2016.

INTRODUCTION: In battle-injured U.S. service members, head and neck (H&N) injuries have been documented in 29% who were treated for wounds in deployed locations and 21% who were evacuated to a Role 4 MTF. The purpose of this study is to examine the H&N surgical workload at deployed U.S. military facilities in Iraq and Afghanistan in order to inform training, needed proficiency, and MTF manning. MATERIALS AND METHODS: A retrospective analysis of the DoD Trauma Registry was performed for all Role 2 and Role 3 MTFs, from January 2002 to May 2016; 385 ICD-9 CM procedure codes were identified as H&N surgical procedures and were stratified into eight categories. For the purposes of this analysis, H&N procedures included dental, ophthalmologic, airway, ear, face, mandible maxilla, neck, and oral injuries. Traumatic brain injuries and vascular injuries to the neck were excluded. RESULTS: A total of 15,620 H&N surgical procedures were identified at Role 2 and Role 3 MTFs. The majority of H&N surgical procedures (14,703, 94.14%) were reported at Role 3 facilities. Facial bone procedures were the most common subgroup across both roles of care (1,181, 75.03%). Tracheostomy accounted for 16.67% of all H&N surgical procedures followed by linear repair of laceration of eyelid or eyebrow (8.23%) and neck exploration (7.41%). H&N caseload was variable. CONCLUSIONS: H&N procedures accounted for 8.25% of all surgical procedures performed at Role 2 and Role 3 MTFs; the majority of procedures were eye (40.54%) and airway (18.50%). These data can be used as planning tools to help determine the medical footprint and also to help inform training and sustainment requirements for deployed military general surgeons especially if future contingency operations are more constrained in terms of resources and personnel.

Evaluating Thera-101 as a Low-Volume Resuscitation Fluid in a Model of Polytrauma.

Traumatic brain injury (TBI) and hemorrhage remain challenging to treat in austere conditions. Developing a therapeutic to mitigate the associated pathophysiology is critical to meet this treatment gap, especially as these injuries and associated high mortality are possibly preventable. Here, Thera-101 (T-101) was evaluated as low-volume resuscitative fluid in a rat model of TBI and hemorrhage. The therapeutic, T-101, is uniquely situated as a TBI and hemorrhage intervention. It contains a cocktail of proteins and microvesicles from the secretome of adipose-derived mesenchymal stromal cells that can act on repair and regenerative mechanisms associated with poly-trauma. T-101 efficacy was determined at 4, 24, 48, and 72 h post-injury by evaluating blood chemistry, inflammatory chemo/cytokines, histology, and diffusion tensor imaging. Blood chemistry indicated that T-101 reduced the markers of liver damage to Sham levels while the levels remained elevated with the control (saline) resuscitative fluid. Histology supports the potential protective effects of T-101 on the kidneys. Diffusion tensor imaging showed that the injury caused the most damage to the corpus callosum and the fimbria. Immunohistochemistry suggests that T-101 may mitigate astrocyte activation at 72 h. Together, these data suggest that T-101 may serve as a potential field deployable low-volume resuscitation therapeutic.

Cerebral Regional Tissue Oxygenation as Surrogate for Blood Loss in Nonhuman Primate Models of Shock.

INTRODUCTION: Hemorrhage is the leading cause of preventable death, with a majority of mortalities in the prehospital setting. Current hemorrhage resuscitation guidelines cannot predict the critical point of intervention to activate massive transfusion (MT) and prevent cardiovascular decompensation. We hypothesized that cerebral regional tissue oxygenation (CrSO2) would indicate MT need in nonhuman primate models of hemorrhagic shock. METHODS: Nineteen anesthetized male rhesus macaques underwent hemorrhage via a volume-targeted (VT) or pressure-targeted (PT) method. VT animals were monitored for 30 min following 30% blood volume hemorrhage. PT animals were hemorrhaged to mean arterial pressure (MAP) of 20 mmHg and maintained for at least 60 min until decompensation. Statistics for MAP, heart rate (HR), end tidal carbon dioxide (EtCO2), and CrSO2 were analyzed via one- or two-way repeated-measures analysis of variance, Pearson's R, and receiver-operator curve. A P < 0.05 is considered significant. RESULTS: Following initial hemorrhage (S0), there were no significant differences between groups. After cessation of hemorrhage in the VT group, MAP and EtCO2 returned to baseline while CrSO2 plateaued. The PT group maintained model-defined low MAP, suppressing EtCO2, and significantly decreased CrSO2 compared to the VT group by S25. Linear regression of CrSO2versus shed blood volume demonstrated R2 = 0.7539. CrSO2 of 47% was able to detect >40% blood loss with an area under the curve of 0.9834 at 92.3% (66.7%-99.6%) sensitivity and 95.5% (84.9%-99.2%) specificity. CONCLUSIONS: Regardless of hemorrhage modality and compensatory response, CrSO2 correlated strongly with shed blood volume. Analysis demonstrated that CrSO2 values below 49% indicate Advanced Trauma Life Support class IV shock (blood loss>40%). CrSO2 at the point of care may help indicate MT need earlier and more accurately than traditional markers.

Analysis of Outcomes Associated With Outpatient Management of Nonoperatively Treated Patients With Appendicitis.

Importance: In the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which found antibiotics to be noninferior, approximately half of participants randomized to receive antibiotics had outpatient management with hospital discharge within 24 hours. If outpatient management is safe, it could increase convenience and decrease health care use and costs. Objective: To assess the use and safety of outpatient management of acute appendicitis. Design, Setting, and Participants: This cohort study, which is a secondary analysis of the CODA trial, included 776 adults with imaging-confirmed appendicitis who received antibiotics at 25 US hospitals from May 1, 2016, to February 28, 2020. Exposures: Participants randomized to antibiotics (intravenous then oral) could be discharged from the emergency department based on clinician judgment and prespecified criteria (hemodynamically stable, afebrile, oral intake tolerated, pain controlled, and follow-up confirmed). Outpatient management and hospitalization were defined as discharge within or after 24 hours, respectively. Main Outcomes and Measures: Outcomes compared among patients receiving outpatient vs inpatient care included serious adverse events (SAEs), appendectomies, health care encounters, satisfaction, missed workdays at 7 days, and EuroQol 5-dimension (EQ-5D) score at 30 days. In addition, appendectomy incidence among outpatients and inpatients, unadjusted and adjusted for illness severity, was compared. Results: Among 776 antibiotic-randomized participants, 42 (5.4%) underwent appendectomy within 24 hours and 8 (1.0%) did not receive their first antibiotic dose within 24 hours, leaving 726 (93.6%) comprising the study population (median age, 36 years; range, 18-86 years; 462 [63.6%] male; 437 [60.2%] White). Of these participants, 335 (46.1%; site range, 0-89.2%) were discharged within 24 hours, and 391 (53.9%) were discharged after 24 hours. Over 7 days, SAEs occurred in 0.9 (95% CI, 0.2-2.6) per 100 outpatients and 1.3 (95% CI, 0.4-2.9) per 100 inpatients; in the appendicolith subgroup, SAEs occurred in 2.3 (95% CI, 0.3-8.2) per 100 outpatients vs 2.8 (95% CI, 0.6-7.9) per 100 inpatients. During this period, appendectomy occurred in 9.9% (95% CI, 6.9%-13.7%) of outpatients and 14.1% (95% CI, 10.8%-18.0%) of inpatients; adjusted analysis demonstrated a similar difference in incidence (-4.0 percentage points; 95% CI, -8.7 to 0.6). At 30 days, appendectomies occurred in 12.6% (95% CI, 9.1%-16.7%) of outpatients and 19.0% (95% CI, 15.1%-23.4%) of inpatients. Outpatients missed fewer workdays (2.6 days; 95% CI, 2.3-2.9 days) than did inpatients (3.8 days; 95% CI, 3.4-4.3 days) and had similar frequency of return health care visits and high satisfaction and EQ-5D scores. Conclusions and Relevance: These findings support that outpatient antibiotic management is safe for selected adults with acute appendicitis, with no greater risk of complications or appendectomy than hospital care, and should be included in shared decision-making discussions of patient preferences for outcomes associated with nonoperative and operative care. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

PEGylated Polyester Nanoparticles Trigger Adverse Events in a Large Animal Model of Trauma and in Naïve Animals: Understanding Cytokine and Cellular Correlations with These Events.

Intravenously infusible nanoparticles to control bleeding have shown promise in rodents, but translation into preclinical models has been challenging as many of these nanoparticle approaches have resulted in infusion responses and adverse outcomes in large animal trauma models. We developed a hemostatic nanoparticle technology that was screened to avoid one component of the infusion response: complement activation. We administered these hemostatic nanoparticles, control nanoparticles, or saline volume controls in a porcine polytrauma model. While the hemostatic nanoparticles promoted clotting as marked by a decrease in prothrombin time and both the hemostatic nanoparticles and controls did not active complement, in a subset of the animals, hard thrombi were found in uninjured tissues in both the hemostatic and control nanoparticle groups. Using data science methods that allow one to work across heterogeneous data sets, we found that the presence of these thrombi correlated with changes in IL-6, INF-alpha, lymphocytes, and neutrophils. While these findings might suggest that this formulation would not be a safe one for translation for trauma, they provide guidance for developing screening tools to make nanoparticle formulations in the complex milieux of trauma as well as for therapeutic interventions more broadly. This is important as we look to translate intravenously administered nanoparticle formulations for therapies, particularly considering the vascular changes seen in a subset of patients following COVID-19. We need to understand adverse events like thrombi more completely and screen for these events early to make nanomaterials as safe and effective as possible.

Advanced bleeding control in combat casualty care: An international, expert-based Delphi consensus.

BACKGROUND: Hemorrhage from truncal and junctional injuries is responsible for the vast majority of potentially survivable deaths in combat casualties, causing most of its fatalities in the prehospital arena. Optimizing the deployment of the advanced bleeding control modalities required for the management of these injuries is essential to improve the survival of severely injured casualties. This study aimed to establish consensus on the optimal use and implementation of advanced bleeding control modalities in combat casualty care. METHODS: A Delphi method consisting of three rounds was used. An international expert panel of military physicians was selected by the researchers to complete the Delphi surveys. Consensus was reached if 70% or greater of respondents agreed and if 70% or greater responded. RESULTS: Thirty-two experts from 10 different nations commenced the process and reached consensus on which bleeding control modalities should be part of the standard equipment, that these modalities should be available at all levels of care, that only trained physicians should be allowed to apply invasive bleeding control modalities, but all medical and nonmedical personnel should be allowed to apply noninvasive bleeding control modalities, and on the training requirements for providers. Consensus was also reached on the necessity of international registries and guidelines, and on certain indications and contraindications for resuscitative endovascular balloon occlusion of the aorta (REBOA) in military environments. No consensus was reached on the role of a wound clamp in military settings and the indications for REBOA in patients with chest trauma, penetrating axillary injury or penetrating neck injury in combination with thoracoabdominal injuries. CONCLUSION: Consensus was reached on the contents of a standard bleeding control toolbox, where it should be available, providers and training requirements, international registries and guidelines, and potential indications for REBOA in military environments.

Military deployment's impact on the surgeon's practice.

BACKGROUND: As the United States withdraws from overseas conflicts, general surgeons remain deployed in support of global operations. Surgeons and surgical teams are foundational to combat casualty care; however, currently, there are few casualty producing events. Low surgical volume and acuity can have detrimental effects on surgical readiness for those frequently deployed. The surgical team cycle of deployment involves predeployment training, drawdown of clinical practice, deployment, postdeployment reintegration, and rebuilding of a patient panel. This study aims to assess these effects on typical general surgeon practices. Quantifying the overall impact of deployment may help refine and implement measures to mitigate the effects on skill retention and patient care. METHODS: Surgeon case logs of eligible surgeons deploying between January 1, 2017, and January 1, 2020, were included from participating military treatment facilities. Eligible surgeons were surgeons whose case logs were primarily at a single military treatment facility 26 weeks before and after deployment and whose deployment duration, location, and number of deployed cases were obtainable. RESULTS: Starting 26 weeks prior to deployment, analyzing in 1-week intervals toward deployment time, case count decreased by 4.8% (p < 0.0001). With each 1-week interval, postdeployment up to the 26-week mark, case count increased by 6% (p < 0.0001). Cases volumes most prominently drop 3 weeks prior to deployment and do not reach normal levels until approximately 7 weeks postdeployment. Case volumes were similar across service branches. CONCLUSION: There is a significant decrease in the number of cases performed before deployment and increase after return regardless of military branch. The perideployment surgical volume decline should be understood and mitigated appropriately; predeployment training, surgical skill retention, and measures to safely reintegrate surgeons back into their practice should be further developed and implemented. LEVEL OF EVIDENCE: Economic/Decision, Level III.

Therapeutic cardiac arrest as an adjunct to resuscitative endovascular balloon occlusion of the aorta: Bridging the gap from fatal hemorrhage to definitive surgical control in swine.

BACKGROUND: Uncontrolled hemorrhage is the leading cause of potentially survivable combat casualty mortality, with 86.5% of cases resulting from noncompressible torso hemorrhage. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive technique used to stabilize patients with noncompressible torso hemorrhage; however, its application can take an average of 8 minutes to place. One therapeutic capable of bridging this gap is adenosine-lidocaine-magnesium (ALM), which at high doses induces a reversible cardioplegia. We hypothesize by using ALM as an adjunct to REBOA, the ALM-induced cardiac arrest will temporarily halt exsanguination and reduce blood loss, allowing for REBOA placement and control of bleeding. METHODS: Male Yorkshire swine (60-80 kg) were randomly assigned to REBOA only or ALM-REBOA (n = 8/group). At baseline, uncontrolled hemorrhage was induced via a 1.5-cm right femoral arteriotomy, and hemorrhaged blood was quantified. One minute after injury (S1), ALM was administered, and 7 minutes later (T0), zone 1 REBOA inflation occurred. If cardiac arrest ensued, cardiac function either recovered spontaneously or advanced life support was initiated. At T30, surgical hemostasis was obtained, and REBOA was deflated. Animals were resuscitated until they were humanely euthanized at T90. RESULTS: During field care phase, heart rate and end-tidal CO2 of the ALM-REBOA group were significantly lower than the REBOA only group. While mean arterial pressure significantly decreased from baseline, no significant differences between groups were observed throughout the field care phase. There was no significant difference in survival between the two groups (ALM-REBOA = 89% vs. REBOA only = 100%). Total blood loss was significantly decreased in the ALM-REBOA group (REBOA only = 24.32 ± 1.89 mL/kg vs. ALM-REBOA = 17.75 ± 2.04 mL/kg, p = 0.0499). CONCLUSION: Adenosine-lidocaine-magnesium is a novel therapeutic, which, when used with REBOA, can significantly decrease the amount of blood loss at initial presentation, without compromising survival. This study provides proof of concept for ALM and its ability to bridge the gap between patient presentation and REBOA placement.

Noninvasive Cerebral Perfusion and Oxygenation Monitoring Augment Prolonged Field Care in a Non-Human Primate Model of Decompensated Hemorrhage and Resuscitation.

BACKGROUND: Decompensated hemorrhagic shock (DHS) is the leading cause of preventable death in combat casualties. "Golden hour" resuscitation effects on cerebral blood flow and perfusion following DHS in prolonged field care (PFC) are not well investigated. Using an established non-human primate model of DHS, we hypothesized noninvasive regional tissue oxygenation (rSO2) and Transcranial Doppler (TCD) would correlate to the invasive measurement of partial pressure of oxygen (PtO2) and mean arterial pressure (MAP) in guiding hypotensive resuscitation in a PFC setting. METHODS: Ten rhesus macaques underwent DHS followed by a 2 h PFC phase (T0-T120), and subsequent 4 h hospital resuscitation phase (T120-T360). Invasive monitoring (PtO2, MAP) was compared against noninvasive monitoring systems (rSO2, TCD). Results were analyzed using t tests and one-way repeated measures ANOVA. Linear correlation was determined via Pearson r. Significance = P < 0.05. RESULTS: MAP, PtO2, rSO2, and mean flow velocity (MFV) significantly decreased from baseline at T0. MAP and PtO2 were restored to baseline by T15, while rSO2 was delayed through T30. At T120, MFV returned to baseline, while the Pulsatility Index significantly elevated by T120 (1.50 ±â€Š0.31). PtO2 versus rSO2 (R2 = 0.2099) and MAP versus MFV (R2 = 0.2891) shared very weak effect sizes, MAP versus rSO2 (R2 = 0.4636) displayed a low effect size, and PtO2 versus MFV displayed a moderate effect size (R2 = 0.5540). CONCLUSIONS: Though noninvasive monitoring methods assessed here did not correlate strongly enough against invasive methods to warrant a surrogate in the field, they do effectively augment and direct resuscitation, while potentially serving as a substitute in the absence of invasive capabilities.

Cost and benefit of military quarantine policies.

The initial response to COVID-19 included quarantine policies. This study aims to determine the infection containment proportions and cost of two variations of quarantine policies based on geographic travel and close contact with infected individuals within deployed US military populations. Special Operations Command Africa (SOCAF) records of individuals quarantined between March 1, 2020 and June 1, 2020 were examined. The infection containment proportion and cost in containment hours were compared between types of quarantine and between geographic areas. Geographic quarantine contained 2 cases out of 63 quarantined individuals in West Africa (3.2%) compared to 0 out of 221 in East Africa (p = 0.0486). Close contact quarantine contained 3 cases out of 31 quarantined individuals in West Africa compared to 4 out of 55 in East Africa (7.3%, p = 0.6989). Total confinement was 42,048 h for each contained infection using geographic quarantine compared to 4076 h using close contact quarantine. In the US military population deployed to Africa for COVID-19, quarantining based on geographic movement is an order of magnitude more costly in terms of time for each contained infection then quarantining based on close contact with infected individuals. There is not a statistical difference between East and West Africa. The associated costs of quarantine must be carefully weighed against the risk of disease spread.