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Introduction Tranexamic acid (TXA) is a standard component of Tactical Combat Casualty Care. Recent retrospective studies have shown that TXA use is associated with a higher rate of venous thromboembolic (VTE) events in combat-injured patients. We aim to determine if selective administration should be considered in the prolonged field care environment. Materials and Methods We performed a systematic review using the 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Clinical trials and observational studies of combat casualties published between January 1, 1960, and June 20, 2022, were included. We analyzed survival and VTE outcomes in TXA recipients and non-recipients. We discussed the findings of each paper in the context of current and future combat environments. Results Six articles met criteria for inclusion. Only one study was powered to report mortality data, and it demonstrated a 7-fold increase in survival in severely injured TXA recipients. All studies reported an increased risk of VTE in TXA recipients, which exceeded rates in civilian literature. However, five of the six studies used overlapping data from the same registry and were limited by a high rate of missingness in pertinent variables. No VTE-related deaths were identified. Conclusions There may be an increased risk of VTE in combat casualties that receive TXA; however, this risk must be considered in the context of improved survival and an absence of VTE-associated deaths. To optimize combat casualty care during prolonged field care, it will be essential to ensure the timely administration of VTE chemoprophylaxis as soon as the risk of significant hemorrhage permits.

In the past year, we have become aware of a new mechanism of severe electrical injury ascribed to fractal wood art. This type of art has become increasingly popular and deadly due to exponential popularity in the use of Youtube type video teaching. This manuscript is one of the initial descriptions of the injury mode, presentation, treatment, and outcomes from four such cases treated at our institution. Additionally, we elicit a call for action in preventing further similar unnecessary injuries and deaths.

Purpose Microbial infection stimulates neutrophil/macrophage/monocyte extracellular trap formation, which leads to the release of citrullinated histone H3 (CitH3) catalyzed by peptidylarginine deiminase (PAD) 2 and 4. Understanding these molecular mechanisms in the pathogenesis of septic shock will be an important next step for developing novel diagnostic and treatment modalities. We sought to determine the expression of CitH3 in patients with septic shock, and to correlate CitH3 levels with PAD2/PAD4 and clinically relevant outcomes. Methods Levels of CitH3 were measured in serum samples of 160 critically ill patients with septic and non-septic shock, and healthy volunteers. Analyses of clinical and laboratory characteristics of patients were conducted. Results Levels of circulating CitH3 at enrollment were significantly increased in septic shock patients (n = 102) compared to patients hospitalized with non-infectious shock (NIC) (n = 32, p r = 0.36, p p p Conclusion CitH3 is increased in patients with septic shock. Its serum concentrations correlate with disease severity and prognosis, which may yield vital insights into the pathophysiology of sepsis.

The impact of injury mechanism on outcomes of pancreatic trauma has not been well studied, and current guidelines do not differentiate recommendations for blunt and penetrating injuries. The purpose of this study was to analyze interventions and outcomes as they relate to mechanism. We hypothesized that penetrating pancreatic trauma results in greater morbidity than blunt trauma because of more frequent operative exploration without imaging and thus more aggressive surgical management.Secondary analysis of a multicenter retrospective review of pancreatic injuries in patients 15 years and older from 2010 to 2018 was performed. Deaths within 24 hours of admission were excluded from analysis of the primary outcome, pancreas-related complications (PRCs). Data were analyzed by injury mechanism using various statistical tests where appropriate.Thirty-three centers reported on 1,240 patients (44% penetrating). Penetrating trauma patients were twice as likely to undergo resection (45% vs. 23%) and suffer PRCs (39% vs. 20%). However, differences varied widely based on injury grade and management. There were fewer resections and more nonoperative management in blunt grades I to III injury. Pancreas-related complications occurred in 40% of high-grade injuries with no difference between mechanisms and in 40% of patients after resection, regardless of mechanism or injury grade. High-grade pancreatic injury (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.55-3.67), penetrating injury (OR, 1.99; 95% CI, 1.31-3.05), and management in a low-volume center (i.e., five or fewer cases/year) (OR, 1.65; 95% CI, 1.16-2.35) were independent predictors of PRCs.Management of grades I to III, but not grades IV/V, pancreatic injuries varies based on mechanism. Penetrating injury is an independent risk factor for PRCs, but main pancreatic duct injury and resection are associated with high rates of PRCs regardless of the injury mechanism. Resection appears to offer better outcomes for grade IV/V injuries, and grade I and II injuries should be managed nonoperatively.Therapeutic/Care Management; Level III.

BACKGROUND Hemorrhage is a leading cause of maternal death worldwide, with increased risk in women with abnormal placentation. Aortic balloon occlusion (ABO), including resuscitative endovascular balloon occlusion (REBOA), has been used for obstetrical hemorrhage for 20 years, and is associated with decreased operative blood loss, fewer transfusions, and lower rates of hysterectomy. However, the effect of aortic occlusion on fetal/neonatal outcomes is not well known. METHODS A literature review on ABO for obstetrical or traumatic hemorrhage was performed. Cases were included if fetal/neonatal outcomes were reported. Data was collected on timing of balloon inflation (pre or post-delivery), fetal/neonatal mortality, and Apgar scores. Secondary maternal outcomes included blood loss, need for hysterectomy, ABO-related complications, and mortality. RESULTS Twenty-one reports of aortic balloon occlusion in 825 cases of obstetrical hemorrhage were reviewed (nine case reports/series and twelve comparative studies). 13.5% (111/825) had aortic occlusion prior to delivery of the fetus. Comparative cohorts included 448 patients who underwent iliac artery balloon occlusion (n = 219) or no vascular balloon occlusion (n = 229). The most common neonatal outcome reported was Apgar scores, with no difference in fetal/neonatal outcomes between ABO and non-ABO patients in any study. One neonatal mortality occurred in the sole reported case of ABO use in a pregnant trauma patient at 24 weeks gestation. One maternal mortality occurred due to aortic dissection. Five comparative studies reported significantly decreased blood loss in ABO patients compared to non-ABO patients and fourstudies reported significantly lower rates of hysterectomy in ABO patients. ABO-related complications were reported in 1.6% of patients (13/825). CONCLUSION Obstetrical hemorrhage is a devastating complication, and aortic balloon occlusion may potentially decrease blood loss and reduce the hysterectomy rate without compromising fetal and neonatal outcomes. Further research is needed to determine the safety of pre-delivery aortic occlusion as this occurred in 14% of cases. TYPE OF STUDY Review. LEVEL OF EVIDENCE IV.

Trauma during pregnancy is the leading non-obstetric cause of morbidity and mortality, and accounts for five per 1000 fetal deaths. Direct fetal injury due to trauma during pregnancy is rare, and limited information is available about how to optimize fetal outcomes after injury. Early recognition and appropriate management of direct fetal trauma may improve outcomes for the fetus. There are currently no available guidelines to direct management of the injured fetus. We provide a detailed literature review of the management and outcomes of direct fetal injury following blunt and penetrating injury during pregnancy, and describe a suggested initial approach to the injured pregnant patient with a focus on evaluation for fetal injury. We identified 45 reported cases of blunt trauma resulting in direct fetal injury, with 21 surviving past the neonatal period, and 33 of penetrating trauma resulting in direct fetal injury, with 24 surviving past the neonatal period. Prenatal imaging identified fetal injury in 19 cases of blunt trauma and was used to identify bullet location relative to the fetus in 6 cases. These reports were used to develop management algorithms for the injured fetus.

BACKGROUND Trauma is a leading cause of death, and traumatic brain injury is one of the hallmark injuries of current military conflicts. Valproic acid (VPA) administration in high doses (300-400 mg/kg) improves survival in lethal trauma models, but effectiveness of lower doses on survival is unknown. This information is essential for properly designing the upcoming clinical trials. We, therefore, performed the current study to determine the lowest dose at which VPA administration improves survival in a model of lethal injuries. METHODS Swine were subjected to traumatic brain injury (10-mm cortical impact), 40% blood volume hemorrhage, and multiple trauma (femur fracture, rectus crush, and Grade V liver laceration). After 1 hour of shock, animals were randomized (n = 6/group) to four groups: normal saline (NS) resuscitation; or NS with VPA doses of 150 mg/kg (VPA 150) or 100 mg/kg (VPA 100) administered over 3 hours or 100 mg/kg over 2 hours (VPA 100 over 2 hours). Three hours after shock, packed red blood cells were given, and animals were monitored for another 4 hours. Survival was assessed using Kaplan-Meier and log-rank test. RESULTS Without resuscitation, all of the injured animals died within 5 hours. Similar survival rates were observed in the NS (17%) and VPA 100 (0%) resuscitation groups. Survival rates in the 100-mg/kg VPA groups were significantly (p < 0.05) better when it was given over 2 hours (67%) compared to 3 hours (0%). 83% of the animals in the VPA 150 group survived, which was significantly higher than the NS and VPA 100 over 3 hours groups (p < 0.05). CONCLUSION A single dose of VPA (150 mg/kg) significantly improves survival in an otherwise lethal model of multiple injuries. This is a much lower dose than previously shown to have a survival benefit and matches the dose that is tolerated by healthy human subjects with minimal adverse effects. LEVEL OF EVIDENCE Therapeutic, level V.

For monitoring of concussion, brain function, organ condition and other medical applications, what is needed is a non-invasive method of monitoring tissue metabolism. MRI-based functional imaging technology detects changes in blood oxygenation, a correlate of neural activity, and thus may offer a prediction of prognosis in cases of concussion and other cerebral traumas. Yet, potential relationships between perturbations to cerebral metabolism and patient outcomes cannot be effectively exploited clinically because we lack a practical, low-cost, non-invasive means to monitor cerebral oxygenation and metabolism in the emergency department, operating room, or medical facilities. We have developed a device to optically assay the redox state of Cytochrome-C-Oxidase (CCO), the mitochondrial enzyme responsible for the last step of the electron transport chain. Changes in CCO redox reflect changes in respiratory flux, and thus changes in the rate of oxidative adenosine triphosphate (ATP) synthesis. In other words, changes in CCO reflect brain cell’s metabolic activity more directly than the traditional blood oxygenation measurement methods. To non-invasively measure changes in CCO as well as blood oxygenation, we have developed a Super-Continuum Infrared Spectroscopy of Cytochrome-C-Oxidase (SCISCCO) system that uses an all-fiber integrated, super-continuum light source to simultaneously measure both of the new (CCO) and the traditional (blood oxygenation) markers of neural metabolism. The SCISCCO system is validated by confirming the near-infrared spectrum of CCO in vitro. To demonstrate in vivo feasibility, the measured responses of oxygenation and CCO responses to acute ischemia (e.g., blood pressure tests) in human participants are compared to data from the literature. Furthermore, we show that the new device’s measurements of oxygenated (HbO) and deoxygenated (HbR) hemoglobin in response to breath hold challenges are principled and consistent with previously reported findings. The validated SCISCCO system is finally applied to measure cerebral oxygenation and the redox state of CCO in participants during an attention test protocol. Twenty-five healthy adults completed an attention task that included nine 60-second periods of attention task, interleaved with 60-s periods of resting baseline. It has been well established that the frontal lobe of the human brain is active during tasks of attention. We therefore predicted that attention task should elicit an increase in HbO concentration accompanied by a decrease in redox state of CCO (e.g., ratio of oxidized CCO to reduced CCO) in frontal lobe brain regions as measured with the SCISCCO system. Our findings are consistent with our predictions: HbO concentration increases while CCO concentration decreases during the attention blocks relative to the resting baseline, thereby indicating an increase in oxidative metabolism of the frontal lobe brain regions of interest. Our systematic, multi-method approach thus validates the new device as well as the validity of the metabolic biomarkers that it measures. The SCISCCO system could be a new tool for monitoring brain and organ metabolism, which could be invaluable for screening concussion patients or use in an operating or emergency room to gauge patient’s organ response to treatments.

Background Administering antithrombotics (AT) to the multiply injured patient with blunt cerebrovascular injury (BCVI) requires a thoughtful assessment of the risk of stroke and death associated with nontreatment. Large, multicenter analysis of outcomes stratified by injury grade and vessel injured is needed to inform future recommendations. Methods Nine hundred and seventy-one BCVIs were identified from the PROspective Vascular Injury Treatment registry in this retrospective analysis. Using multivariate analysis, we identified predictors of BCVI-related stroke and death. We then stratified these risks by injury grade and vessel injured. We compared the risk of adverse outcomes in the nontreatment group with those treated with antiplatelet agents and/or anticoagulants. Results Stroke was identified in 7% of cases. Overall mortality was 12%. Both increased with increasing BCVI grade. Treatment with ATs was associated with lower mortality and was not significantly affected by the choice of agent. Withholding ATs was associated with an increased risk of stroke and/or death across all subgroups (Grade I/II: odds ratio [OR], 4.66; 95% confidence interval [CI], 2.48-8.75; Grade III: OR, 7.0; 95% CI, 2.01-24.5; Grade IV: OR, 4.43; 95% CI, 1.76-11.1) even after controlling for covariates. Predictors of death included more severe trauma, Grade IV injury, and the occurrence of stroke. Arterial occlusion, hypotension, and endovascular intervention were significant predictors of stroke. Patients that experienced a BCVI-related stroke were at a 4.2× increased risk of death. The data set lacked the granularity necessary to evaluate AT timing or dosing regimen, which limited further analysis of stroke prevention strategies. Conclusion Stroke and death remain significant risks for all BCVI grades regardless of the vessel injured. Antithrombotics represent the only management strategy that is consistently associated with a lower incidence of stroke and death in all BCVI categories. In the multi-injured BCVI patient with a high risk of bleeding on anticoagulation, antiplatelet agents are an efficacious alternative. Given the 40% mortality rate in patients who survived their initial trauma and developed a BCVI-related stroke, nontreatment may no longer be a viable option. Level of evidence Epidemiological III; Therapeutic IV.

BACKGROUND Noncompressible torso hemorrhage is a leading cause of preventable death on the battlefield. Intra-aortic balloon occlusion was first used in combat in the 1950s, but military use was rare before Operation Iraqi Freedom and Operation Enduring Freedom. During these wars, the combination of an increasing number of deployed vascular surgeons and a significant rise in deaths from hemorrhage resulted in novel adaptations of resuscitative endovascular balloon occlusion of the aorta (REBOA) technology, increasing its potential application in combat. We describe the background of REBOA development in response to a need for minimally invasive intervention for hemorrhage control and provide a detailed review of all published cases (n = 47) of REBOA use for combat casualties. The current limitations of REBOA are described, including distal ischemia and reperfusion injury, as well as ongoing research efforts to adapt REBOA for prolonged use in the austere setting. LEVEL OF EVIDENCE Level V.

The Bowel Injury Prediction Score (BIPS) is a tool for identifying patients at risk for blunt bowel and mesenteric injury (BBMI) requiring surgery. BIPS is calculated by assigning one point for each of the following: (1) WBC ≥ 17,000, (2) abdominal tenderness, and (3) injury grade ≥ 4 (mesenteric contusion or hematoma with bowel wall thickening or adjacent interloop fluid collection) on CT scan. A total score ≥ 2 is associated with BBMI requiring surgery. We aimed to validate the BIPS as a predictor for patients with BBMIs requiring operative intervention in a multi-center prospective study.Patients were prospectively enrolled at 15 U.S. trauma centers following blunt trauma with suspicion of BBMI on CT scan between July 1, 2018 and July 31, 2019. The BIPS was calculated for each patient enrolled in the study.Of 313 patients, 38% had BBMI requiring operative intervention. Patients were significantly more likely to require surgery in the presence of abdominal tenderness (OR, 3.6; 95% CI, 1.6-8.0) and CT grade ≥ 4 (OR, 11.7; 95% CI, 5.7-23.7). Patients with a BIPS ≥ 2 were more than ten times more likely to require laparotomy than those with a BIPS 2 (OR, 10.1; 95% CI, 5.0-20.4). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a BIPS ≥ 2 for BBMI requiring surgery was 72% (CI 0.6-0.8), 78% (CI 0.7-0.8), 67% (CI 0.6-0.8), and 82% (CI 0.8-0.9), respectively. The AUROC curve for BIPS ≥ 2 was 0.75. The sensitivity, specificity, PPV, and NPV of a BIPS ≥ 2 for BBMI requiring surgery in patients with severe alteration in mental status (GCS 3-8) was 70% (CI 0.5-0.9), 92% (CI 0.8-1.0), 82% (CI 0.6-1.0), and 86% (CI 0.7-1.0), respectively.This prospective multi-center trial validates BIPS as a predictor of BBMI requiring surgery. Calculation of BIPS during the initial evaluation of trauma patients is a useful adjunct to help general surgeons taking trauma call determine operative versus non-operative management of patients with BBMI including those with severe alteration in mental status.

Background Hemorrhage is a leading cause of mortality in trauma. Resuscitative endovascular balloon occlusion of the aorta (REBOA) can control hemorrhage, but distal ischemia, subsequent reperfusion injury, and the need for frequent balloon titration remain problems. Improved device design can allow for partial REBOA (pREBOA) that may provide hemorrhage control while also perfusing distally without need for significant provider titration. Methods Female Yorkshire swine (N = 10) were subjected to 40% hemorrhagic shock for 1 hour (mean arterial pressure [MAP], 28-32 mm Hg). Animals were then randomized to either complete aortic occlusion (ER-REBOA) or partial occlusion (novel pREBOA-PRO) without frequent provider titration or distal MAP targets. Detection of a trace distal waveform determined partial occlusion in the pREBOA-PRO arm. After 2 hours of zone 1 occlusion, the hemorrhaged whole blood was returned. After 50% autotransfusion, the balloon was deflated over a 10-minute period. Following transfusion, the animals were survived for 2 hours while receiving resuscitation based on objective targets: lactated Ringer's fluid boluses (goal central venous pressure, ≥ 6 mm Hg), a norepinephrine infusion (goal MAP, 55-60 mm Hg), and acid-base correction (goal pH, >7.2). Hemodynamic variables, arterial lactate, lactate dehydrogenase, aspartate aminotransferase, and creatinine levels were measured. Results All animals survived throughout the experiment, with similar increase in proximal MAPs in both groups. Animals that underwent partial occlusion had slightly higher distal MAPs. At the end of the experiment, the partial occlusion group had lower end levels of serum lactate (p = 0.006), lactate dehydrogenase (p = 0.0004) and aspartate aminotransferase (p = 0.004). Animals that underwent partial occlusion required less norepinephrine (p = 0.002), less bicarbonate administration (p = 0.006), and less fluid resuscitation (p = 0.042). Conclusion Improved design for pREBOA can decrease the degree of distal ischemia and reperfusion injury compared with complete aortic occlusion, while providing a similar increase in proximal MAPs. This can allow pREBOA zone-1 deployment for longer periods without the need for significant balloon titration.

Objective Valproic acid (VPA) treatment improves survival in animal models of injuries on doses higher than those allowed by Food and Drug Administration (FDA). We investigated the proteomic alterations induced by a single high-dose (140mg/kg) of VPA (VPA140) compared to the FDA-approved dose of 30mg/kg (VPA30) in healthy humans. We also describe the proteomic and transcriptomic changes induced by VPA140 in an injured patient. We hypothesized that VPA140 would induce cytoprotective changes in the study participants. Methods Serum samples were obtained from healthy subjects randomized to two groups; VPA140 and VPA30 at 3 timepoints: 0h(baseline), 2h, and 24h following infusion(n = 3/group). Samples were also obtained from an injured patient that received VPA140 at 0h, 6h and 24h following infusion. Proteomic analyses were performed using liquid chromatography-mass spectrometry (LC-MS/MS), and transcriptomic analysis was performed using RNA-sequencing. Differentially expressed (DE) proteins and genes were identified for functional annotation and pathway analysis using iPathwayGuide and gene set enrichment analysis (GSEA), respectively. Results For healthy individuals, a dose comparison was performed between VPA140 and VPA30 groups at 2 and 24 h. Functional annotation showed that top biological processes in VPA140 versus VPA30 analysis at 2 h included regulation of fatty acid (P = 0.002) and ATP biosynthesis (P = 0.007), response to hypoxia (P = 0.017), cell polarity regulation (P = 0.031), and sequestration of calcium ions (P = 0.031). Top processes at 24 h in VPA140 versus VPA30 analysis included amino acid metabolism (P = 0.023), collagen catabolism (P = 0.023), and regulation of protein breakdown (P = 0.023). In the injured patient, annotation of the DE proteins in the serum showed that top biological processes at 2 h included neutrophil chemotaxis (P = 0.002), regulation of cellular response to heat (P = 0.008), regulation of oxidative stress (P = 0.008) and regulation of apoptotic signaling pathway (P = 0.008). Top biological processes in the injured patient at 24 h included autophagy (P = 0.01), glycolysis (P = 0.01), regulation of apoptosis (P = 0.01) and neuron apoptotic processes (P = 0.02). Conclusions VPA140 induces cytoprotective changes in human proteome not observed in VPA30. These changes may be responsible for its protective effects in response to injuries.

Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) has become a standard adjunct for the management of life-threatening truncal hemorrhage, but the technique is limited by the sequalae of ischemia distal to occlusion. Partial REBOA addresses this limitation, and the recent Food and Drug Administration approval of a device designed to enable partial REBOA will broaden its application. We conducted a systematic review of the available animal and clinical literature on the methods, impacts, and outcomes associated with partial REBOA as a technique to enable targeted proximal perfusion and limit distal ischemic injury. We hypothesize that a systematic review of the published animal and human literature on partial REBOA will provide actionable insight for the use of partial REBOA in the context of future wider clinical implementation of this technique. Methods Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols guidelines, we conducted a search of the available literature which used partial inflation of a REBOA balloon catheter. Findings from 22 large animal studies and 14 clinical studies met inclusion criteria. Results Animal and clinical results support the benefits of partial REBOA including extending the resuscitative window extended safe occlusion time, improved survival, reduced proximal hypertension, and reduced resuscitation requirements. Clinical studies provide practical physiologic targets for partial REBOA including a period of total occlusion followed by gradual balloon deflation to achieve a target proximal pressure and/or target distal pressure. Conclusions Partial REBOA has several benefits which have been observed in animal and clinical studies, most notably reduced ischemic insult to tissues distal to occlusion and improved outcomes compared with total occlusion. Practical clinical protocols are available for the implementation of partial REBOA in cases of life-threatening torso hemorrhage.

Background Current resuscitative endovascular balloon occlusion of the aorta (REBOA) literature focuses on improving outcomes through careful patient selection, diligent catheter placement, and expeditious definitive hemorrhage control. However, the detection and treatment of post-REBOA ischemia-reperfusion injury (IRI) remains an area for potential improvement. Herein, we provide a review of the metabolic derangements that we have encountered while managing post-REBOA IRI in past swine experiments. We also provide data-driven clinical recommendations to facilitate resuscitation post-REBOA deflation that may be translatable to humans. Methods We retrospectively reviewed the laboratory data from 25 swine across three varying hemorrhagic shock models that were subjected to complete REBOA of either 45 minutes, 60 minutes, or 90 minutes. In each model the balloon was deflated gradually following definitive hemorrhage control. Animals were then subjected to whole blood transfusion and critical care with frequent electrolyte monitoring and treatment of derangements as necessary. Results Plasma lactate peaked and pH nadired long after balloon deflation in all swine in the 45-minute, 60-minute, and 90-minute occlusion models (onset of peak lactate, 32.9 ± 6.35 minutes, 38.8 ± 10.55 minutes, and 49.5 ± 6.5 minutes; pH nadir, 4.3 ± 0.72 minutes, 26.9 ± 12.32 minutes, and 42 ± 7.45 minutes after balloon deflation in the 45-, 60-, and 90-minute occlusion models, respectively). All models displayed persistent hypoglycemia for more than an hour following reperfusion (92.1 ± 105.5 minutes, 125 ± 114.9 minutes, and 96 ± 97.8 minutes after balloon deflation in the 45-, 60-, and 90-minute occlusion groups, respectively). Hypocalcemia and hyperkalemia occurred in all three groups, with some animals requiring treatment more than an hour after reperfusion. Conclusion Metabolic derangements resulting from REBOA use are common and may worsen long after reperfusion despite resuscitation. Vigilance is required to detect and proactively manage REBOA-associated IRI. Maintaining a readily available "deflation kit" of pharmacological agents needed to treat common post-REBOA electrolyte abnormalities may facilitate management. Level of evidence Level V.

The leading causes of death in military conflicts continue to be hemorrhagic shock (HS) and traumatic brain injury (TBI). Most of the mortality is a result of patients not surviving long enough to obtain surgical care. As a result, there is a significant unmet need for a therapy that stimulates a "prosurvival phenotype" that counteracts the cellular pathophysiology of HS and TBI to prolong survival. Valproic acid (VPA), a well-established antiepileptic therapy for more than 50 years, has shown potential as one such prosurvival therapy. This review details how VPA's role as a nonselective histone deacetylase inhibitor induces cellular changes that promote survival and decrease cellular pathways that lead to cell death. The review comprehensively covers more than two decades worth of studies ranging from preclinical (mice, swine) to recent human clinical trials of the use of VPA in HS and TBI. Furthermore, it details the different mechanisms in which VPA alters gene expression, induces cytoprotective changes, attenuates platelet dysfunction, provides neuroprotection, and enhances survival in HS and TBI. Valproic acid shows real promise as a therapy that can induce the prosurvival phenotype in those injured during military conflict.

Introduction Low distal aortic flow via partial aortic occlusion (AO) may mitigate ischemia induced by resuscitative endovascular balloon occlusion of the aorta (REBOA). We compared endocrine effects of a novel simulated partial AO strategy, endovascular variable aortic control (EVAC), with simulated REBOA in a swine model. Materials and methods Aortic flow in 20 swine was routed from the supraceliac aorta through an automated extracorporeal circuit. Following liver injury-induced hemorrhagic shock, animals were randomized to control (unregulated distal flow), simulated REBOA (no flow, complete AO), or simulated EVAC (distal flow of 100-300 mL/min after 20 minutes of complete AO). After 90 minutes, damage control surgery, resuscitation, and full flow restoration ensued. Critical care was continued for 4.5 hours or until death. Results Serum angiotensin II concentration was higher in the simulated EVAC (4,769 ± 624 pg/mL) than the simulated REBOA group (2649 ± 429) (p = 0.01) at 180 minutes. There was no detectable difference in serum renin [simulated REBOA: 231.3 (227.9-261.4) pg/mL; simulated EVAC: 294.1 (231.2-390.7) pg/mL; p = 0.27], aldosterone [simulated EVAC: 629 (454-1098), simulated REBOA: 777 (575-1079) pg/mL, p = 0.53], or cortisol (simulated EVAC: 141 ± 12, simulated REBOA: 127 ± 9 ng/mL, p = 0.34) concentrations between groups. Conclusions Simulated EVAC was associated with higher serum angiotensin II, which may have contributed to previously reported cardiovascular benefits. Future studies should evaluate the renal effects of EVAC and the concomitant therapeutic use of angiotensin II.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a hemorrhage control technique that is increasingly being adopted for the management of noncompressible bleeding. In addition to limiting hemorrhage, REBOA increases blood flow to the heart, lungs, and brain. A small number of case reports and animal studies describe the use of REBOA to increase coronary perfusion during cardiopulmonary resuscitation. We report a case in which REBOA may have reversed ST-segment abnormalities during a Type II non-ST elevation myocardial infarction (NSTEMI) in a patient with previous trauma. We describe the presentation, course, and decision making that contributed to the use of REBOA in this case. Additionally, we will present a review of the literature on the effects of REBOA on coronary perfusion.

A reproducible, lethal noncompressible torso hemorrhage model is important to civilian and military trauma research. Current large animal models balancing clinical applicability with standardization and internal validity. As such, large animal models of trauma vary widely in the surgical literature, limiting comparisons. Our aim was to create and validate a porcine model of uncontrolled hemorrhage that maximizes reproducibility and standardization.Seven Yorkshire-cross swine were anesthetized, instrumented, and splenectomized. A simple liver tourniquet was applied before injury to prevent unregulated hemorrhage while creating a traumatic amputation of 30% of the liver. Release of the tourniquet and rapid abdominal closure following injury provided a standardized reference point for the onset and duration of uncontrolled hemorrhage. At the moment of death, the liver tourniquet was quickly reapplied to provide accurate quantification of intra-abdominal blood loss. Weight and volume of the resected and residual liver segments were measured. Hemodynamic parameters were recorded continuously throughout each experiment.This liver injury was rapidly and universally lethal (11.2 ± 4.9 min). The volume of hemorrhage (35.8% ± 6% of total blood volume) and severity of uncontrolled hemorrhage (100% of animals deteriorated to a sustained mean arterial pressure35 mmHg for 5 min) were consistent across all animals. Use of the tourniquet effectively halted preprocedure and postprocedure blood loss allowing for accurate quantification of amount of hemorrhage over a defined period. In addition, the tourniquet facilitated the creation of a consistent liver resection weight (0.0043 ± 0.0003 liver resection weight: body weight) and as a percentage of total liver resection weight (27% ± 2.2%).This novel tourniquet-assisted noncompressible torso hemorrhage model creates a standardized, reproducible, highly lethal, and clinically applicable injury in swine. Use of the tourniquet allowed for consistent liver injury and precise control over hemorrhage. Recorded blood loss was similar across all animals. Improving reproducibility and standardization has the potential to offer improvements in large animal translational models of hemorrhage.Level I.

BACKGROUNDDespite clinical reports of poor outcomes, the degree to which resuscitative endovascular balloon occlusion of the aorta (REBOA) exacerbates traumatic brain injury (TBI) is not known. We hypothesized that combined effects of increased proximal mean arterial pressure (pMAP), carotid blood f

BACKGROUND Although damage control resuscitation (DCR) is routinely performed for short durations, prolonged DCR may be required in military conflicts as a component of prolonged field care. Valproic acid (VPA) has been shown to have beneficial properties in lethal hemorrhage/trauma models. We sought to investigate whether the addition of a single dose of VPA to a 72-hour prolonged DCR protocol would improve clinical outcomes. METHODS Fifteen Yorkshire swine (40-45 kg) were subjected to lethal (50% estimated total blood volume) hemorrhagic shock (HS) and randomized to three groups: (1) HS, (2) HS-DCR, (3) HS-DCR-VPA (150 mg/kg over 3 hours) (n = 5/cohort). In groups assigned to receive DCR, Tactical Combat Casualty Care guidelines were applied (1 hour into the shock period), targeting a systolic blood pressure of 80 mm Hg. At 72 hours, surviving animals were given transfusion of packed red blood cells, simulating evacuation to higher echelons of care. Survival rates, physiologic parameters, resuscitative fluid requirements, and laboratory profiles were used to compare the clinical outcomes. RESULTS This model was 100% lethal in the untreated animals. DCR improved survival to 20%, although this was not statistically significant. The addition of VPA to DCR significantly improved survival to 80% (p < 0.01). The VPA-treated animals also had significantly (p < 0.05) higher systolic blood pressures, lower fluid resuscitation requirements, higher hemoglobin levels, and lower creatinine and potassium levels. CONCLUSION VPA administration improves survival, decreases resuscitation requirements, and improves hemodynamic and laboratory parameters when added to prolonged DCR in a lethal hemorrhage model.

Military physicians have amassed tremendous experience treating children with combat-related injuries in Iraq and Afghanistan. This review will present several treatment principles adapted from adult trauma care that were applied to children in war and consider their selective application in civilian practice. Many standard practices of adult trauma care were applied to the management of war-injured children. Initial reports of tourniquet use, tranexamic acid administration, and balanced blood transfusion suggest a benefit to the pediatric population. Constraints of providing intensive care in an austere environment required a shift in management toward aggressive limb salvage over amputation, and early palliation for severe brain injury or extensive burns. Despite the obstacles that may limit the direct translation of trauma care principals to civilian settings, these wartime experiences offer robust and excellent preliminary data that might inform future investigations in the field of pediatric trauma care.

Management of non-compressible torso hemorrhage (NCTH) remains a challenge despite continued advancements in trauma resuscitation. Resuscitative thoracotomy with aortic cross-clamping and recent advances in endovascular aortic occlusion, including resuscitative endovascular occlusion of the aorta (REBOA), have finite durations of therapy due to the inherent physiologic stressors that accompany complete occlusion. Here we attempt to illuminate the current state of aortic occlusion for trauma resuscitation including: 1) explanation of the deleterious consequences of complete occlusion, 2) potential methods and limitations of existing technology to overcome these consequences, 3) a description of innovative methods to improve the resuscitation of NCTH. By explaining the complexity and potential deleterious effects of resuscitation augmented with aortic occlusion, our goal is to provide practitioners with a real-world perspective on current endovascular technology and to encourage the continued innovation required to overcome existing obstacles.

The duration of use and efficacy of resuscitative endovascular balloon occlusion of the aorta (REBOA) is limited by distal ischemia. We developed a hybrid endovascular-extracorporeal circuit variable aortic control (VAC) device to extend REBOA duration in a lethal model of hemorrhagic shock to serve as an experimental surrogate to further the development of endovascular VAC (EVAC) technologies.Nine Yorkshire-cross swine were anesthetized, instrumented, splenectomized, and subjected to 30% liver amputation. Following a short period of uncontrolled hemorrhage, REBOA was instituted for 20 minutes. Automated variable occlusion in response to changes in proximal mean arterial pressure was applied for the remaining 70 minutes of the intervention phase using the automated extracorporeal circuit. Damage-control surgery and whole blood resuscitation then occurred, and the animals were monitored for a total of 6 hours.Seven animals survived the initial surgical preparation. After 20 minutes of complete REBOA, regulated flow was initiated through the extracorporeal circuit to simulate VAC and provide perfusion to distal tissue beds during the 90-minute intervention phase. Two animals required circuit occlusion for salvage, while five animals tolerated sustained, escalating restoration of distal blood flow before surgical hemorrhage control. Animals tolerating distal flow had preserved renal function, maintained proximal blood pressure, and rapidly weaned from complete REBOA.We combined a novel automated, extracorporeal circuit with complete REBOA to achieve EVAC in a swine model of uncontrolled hemorrhage. Our approach regulated proximal aortic pressure, alleviated supranormal values above the balloon, and provided controlled distal aortic perfusion that reduced ischemia without inducing intolerable bleeding. This experimental model serves as a temporary surrogate to guide future EVAC catheter designs that may provide transformational approaches to hemorrhagic shock.

BACKGROUND Combat-injured patients may require rapid and sustained support during transport; however, the prolonged aortic occlusion produced by conventional resuscitative endovascular balloon occlusion of the aorta (REBOA) may lead to substantial morbidity. Partial REBOA (P-REBOA) may permit longer periods of occlusion by allowing some degree of distal perfusion. However, the ability of this procedure to limit exsanguination is unclear. We evaluated the impact of P-REBOA on immediate survival and ongoing hemorrhage in a highly lethal swine liver injury model. METHODS Fifteen Yorkshire-cross swine were anesthetized, instrumented, splenectomized, and subjected to rapid 10% total blood loss followed by 30% liver amputation. Coagulopathy was created through colloid hemodilution. Randomized swine received no intervention (control), P-REBOA, or complete REBOA (C-REBOA). Central mean arterial pressure (cMAP), carotid blood flow, and blood loss were recorded. Balloons remained inflated in the P-REBOA and C-REBOA groups for 90 minutes followed by graded deflation. The study ended at 180 minutes from onset of hemorrhage or death of the animal. Survival analysis was performed, and data were analyzed using repeated-measures analysis of variance with post hoc pairwise comparisons. RESULTS Mean survival times in the control, P-REBOA, and C-REBOA groups were, 25 ± 21, 86 ± 40, and 163 ± 20 minutes, respectively (p < 0.001). Blood loss was greater in the P-REBOA group than the C-REBOA or control groups, but this difference was not significant (4,722 ± 224, 3,834 ± 319, 3,818 ± 37 mL, respectively, p = 0.10). P-REBOA resulted in maintenance of near-baseline carotid blood flow and cMAP, while C-REBOA generated extreme cMAP and prolonged supraphysiologic carotid blood flow. Both experimental groups experienced profound decreases in cMAP following balloon deflation. CONCLUSION In the setting of severe ongoing hemorrhage, P-REBOA increased survival time beyond the golden hour while maintaining cMAP and carotid flow at physiologic levels.

Care during mass casualty events (MCE) has improved during the last 15 years. Military and civilian collaboration has led to partnerships which augment the response to MCE. Much has been written about strategies to deliver care during an MCE, but there is little about how to transition back to normal operations after an event. A panel discussion entitled The Day(s) After: Lessons Learned from Trauma Team Management in the Aftermath of an Unexpected Mass Casualty Event at the 76th Annual American Association for the Surgery of Trauma meeting on September 13, 2017 brought together a cadre of military and civilian surgeons with experience in MCEs. The events described were the First Battle of Mogadishu (1993), the Second Battle of Fallujah (2004), the Bagram Detention Center Rocket Attack (2014), the Boston Marathon Bombing (2013), the Asiana Flight 214 Plane Crash (2013), the Baltimore Riots (2015), and the Orlando Pulse Night Club Shooting (2016). This article focuses on the lessons learned from military and civilian surgeons in the days after MCEs.

Despite technological advancements, REBOA is associated with significant risks due to complications of vascular access and ischemia-reperfusion. The inherent morbidity and mortality of REBOA is often compounded by coexisting injury and hemorrhagic shock. Additionally, the potential for REBOA-related injuries is exaggerated due to the growing number of interventions being performed by providers who have limited experience in endovascular techniques, inadequate resources, minimal training in the technique, and who are performing this maneuver in emergency situations. In an effort to ultimately improve outcomes with REBOA, we sought to compile a list of complications that may be encountered during REBOA usage. To address the current knowledge gap, we assembled a list of anecdotal complications from high-volume REBOA users internationally. More importantly, through a consensus model, we identify contributory factors that may lead to complications and deliberate on how to recognize, mitigate, and manage such events. An understanding of the pitfalls of REBOA and strategies to mitigate their occurrence is of vital importance to optimize patient outcomes.

To avoid potential cardiovascular collapse after resuscitative endovascular balloon occlusion of the aorta (REBOA), current guidelines recommend methodically deflating the balloon for 5 minutes to gradually reperfuse distal tissue beds. However, anecdotal evidence suggests that this approach may still result in unpredictable aortic flow rates and hemodynamic instability. We sought to characterize aortic flow dynamics following REBOA as the balloon is deflated in accordance with current practice guidelines.Eight Yorkshire-cross swine were splenectomized, instrumented, and subjected to rapid 25% total blood volume hemorrhage. After 30 minutes of shock, animals received 60 minutes of Zone 1 REBOA with a low-profile REBOA catheter. During subsequent resuscitation with shed blood, the aortic occlusion balloon was gradually deflated in stepwise fashion at the rate of 0.5 mL every 30 seconds until completely deflated. Aortic flow rate and proximal mean arterial pressure (MAP) were measured continuously over the period of balloon deflation.Graded balloon deflation resulted in variable initial return of aortic flow (median, 78 seconds; interquartile range [IQR], 68-105 seconds). A rapid increase in aortic flow during a single-balloon deflation step was observed in all animals (median, 819 mL/min; IQR, 664-1241 mL/min) and corresponded with an immediate decrease in proximal MAP (median, 30 mm Hg; IQR, 14.5-37 mm Hg). Total balloon volume and time to return of flow demonstrated no correlation (r = 0.016).This study is the first to characterize aortic flow during balloon deflation following REBOA. A steep inflection point occurs during balloon deflation that results in an abrupt increase in aortic flow and a concomitant decrease in MAP. Furthermore, the onset of distal aortic flow was inconsistent across study animals and did not correlate with initial balloon volume or relative deflation volume. Future studies to define the factors that affect aortic flow during balloon deflation are needed to facilitate controlled reperfusion following REBOA.

The transition from complete aortic occlusion during resuscitative endovascular balloon occlusion of the aorta can be associated with hemodynamic instability. Technique refinements and new technologies have been proposed to minimize this effect. In order to inform new techniques and technology, we examined the relationship between blood pressure and aortic flow during the restoration of systemic circulation following aortic occlusion at progressive levels of hemorrhage.An automated supraceliac aortic clamp, capable of continuously variable degrees of occlusion, was applied in seven swine. The swine underwent stepwise removal of 40% of their total blood volume in four equal aliquots. After each aliquot, progressive luminal narrowing to the point of complete aortic occlusion was achieved over 5 minutes, sustained for 5 minutes, and then released over 5 minutes. Proximal and distal blood pressure and distal aortic flow were continuously recorded throughout the study.Upon release of the clamp, hyperemic aortic flow was observed following 10% and 20% hemorrhage (1,599 ± 785 mL/min, p0.01; and 1,070 ± 396 mL/min, p0.01, respectively). Proximal blood pressure exhibited a nonlinear relationship to aortic flow during clamp removal; however, distal blood pressure increased linearly with distal flow upon clamp opening across all hemorrhage volumes.Hyperemic blood flow following return of circulation may contribute to cardiovascular collapse. Reintroduction of systemic blood flow after aortic occlusion should be guided by distal blood pressure rather than proximal pressure. Awareness of hemodynamic physiology during aortic occlusion is of paramount importance to the clinical implementation of next-generation resuscitative endovascular balloon occlusion of the aorta techniques and technologies.

BACKGROUND Future endovascular hemorrhage control devices will require features that mitigate the adverse effects of vessel occlusion. Permissive regional hypoperfusion (PRH) with variable aortic control (VAC) is a novel strategy to minimize hemorrhage and reduce the ischemic burden of complete aortic occlusion (AO). The objective of this study was to compare PRH with VAC to AO in a lethal model of hemorrhage. METHODS Twenty-five swine underwent cannulation of the supraceliac aorta, with diversion of aortic flow through an automated extracorporeal circuit. After creation of uncontrolled liver hemorrhage, animals were randomized to 90 minutes of treatment: Control (full, unregulated flow; n = 5), AO (no flow; n = 10), and PRH with VAC (dynamic distal flow initiated after 20 minutes of AO; n = 10). In the PRH group, distal flow rates were regulated between 100 and 300 mL/min based on a desired, preset range of proximal mean arterial pressure (MAP). At 90 minutes, damage control surgery, resuscitation, and restoration of full flow ensued. Critical care continued for 4.5 hours or until death. Hemodynamic parameters and markers of ischemia were recorded. RESULTS Study survival was 0%, 50%, and 90% for control, AO, and VAC, respectively (p < 0.01). During intervention, VAC resulted in more physiologic proximal MAP (84 ± 18 mm Hg vs. 105 ± 9 mm Hg, p < 0.01) and higher renal blood flow than AO animals (p = 0.02). During critical care, VAC resulted in higher proximal MAP (73 ± 8 mm Hg vs. 50 ± 6 mm Hg, p < 0.01), carotid and renal blood flow (p < 0.01), lactate clearance (p < 0.01), and urine output (p < 0.01) than AO despite requiring half the volume of crystalloids to maintain proximal MAP ≥50 mm Hg (p < 0.01). CONCLUSION Permissive regional hypoperfusion with variable aortic control minimizes the adverse effects of distal ischemia, optimizes proximal pressure to the brain and heart, and prevents exsanguination in this model of lethal hemorrhage. These findings provide foundational knowledge for the continued development of this novel paradigm and inform next-generation endovascular designs.

BackgroundComplete resuscitative endovascular balloon occlusion of the aorta (C-REBOA) increases proximal mean arterial pressure (MAP) at the cost of distal organ ischemia, limiting the duration of intervention. We hypothesized that partial aortic occlusion (P-REBOA) would maintain a more physiologic proximal MAP and reduce distal tissue ischemia. We investigated the hemodynamic and physiologic effects of P-REBOA vs C-REBOA.Study DesignFifteen swine were anesthetized, instrumented, splenectomized, and subjected to rapid 25% blood volume loss. They were randomized to C-REBOA, P-REBOA, or no intervention (controls). Partial REBOA was created by partially inflating an aortic balloon catheter to generate a 50% blood pressure gradient across the balloon. Hemodynamics were recorded and serum makers of ischemia and inflammation were measured. After 90 minutes of treatment, balloons were deflated to evaluate the immediate effects of reperfusion. End organs were histologically examined.ResultsComplete REBOA produced supraphysiologic increases in proximal MAP after hemorrhage compared with more modest augmentation in the P-REBOA group (p < 0.01), with both groups significantly greater than controls (p < 0.01). Less rebound hypotension after balloon deflation was seen in the P-REBOA compared with C-REBOA groups. Complete REBOA resulted in higher serum lactate than both P-REBOA and controls (p < 0.01). Histology revealed early necrosis and disruption of duodenal mucosa in all C-REBOA animals, but none in P-REBOA animals.ConclusionsIn a porcine hemorrhagic shock model, P-REBOA resulted in more physiologically tolerable hemodynamic and ischemic changes compared with C-REBOA. Additional work is needed to determine whether the benefits associated with P-REBOA can both extend the duration of intervention and increase survival.

A 28-year-old man with multiple gunshot wounds to the chest and upper extremities was transported by private vehicle to a community hospital with limited trauma capabilities. On arrival he developed pulseless electrical activity and cardiopulmonary resuscitation was initiated. He was intubated, transfused with 4 units of packed red blood cells, and resuscitated with 2 L of crystalloid prior to regaining spontaneous circulation. Left-sided tube thoracostomy immediately drained 1600 mL of bright red blood. He was transiently stable for a short transport to the nearest level 1 trauma center. On arrival the patient was normotensive with tachycardia. Chest X-ray demonstrated persistent left-sided hemothorax despite a well-positioned chest tube. Focused Assessment with Sonography for Trauma (FAST) examination was negative for pericardial fluid, but positive for intra-abdominal fluid. During the secondary examination the patient became hypotensive with systolic blood pressure (SBP) in the 70 s. A massive transfusion protocol was initiated, tranexamic acid was administered, and the patient was promptly transported to the operating room. The patient transiently responded to the massive transfusion. While instruments were being opened in the operating room, he again became hypotensive with SBP in the 50 s. The patient was acidotic (pH of 6.87, base excess −14.6), coagulopathic (international normalized ratio of 1.5) and …

Background Evacuation of traumatic hemothorax (HTx) is typically accomplished with large-bore (28-40 Fr) chest tubes, often resulting in patient discomfort. Management of HTx with smaller (14 Fr) pigtail catheters has not been widely adopted because of concerns about tube occlusion and blood evacuation rates. We compared pigtail catheters with chest tubes for the drainage of acute HTx in a swine model. Methods Six Yorkshire cross-bred swine (44-54 kg) were anesthetized, instrumented, and mechanically ventilated. A 32 Fr chest tube was placed in one randomly assigned hemithorax; a 14 Fr pigtail catheter was placed in the other. Each was connected to a chest drainage system at -20 cm H2O suction and clamped. Over 15 minutes, 1,500 mL of arterial blood was withdrawn via femoral artery catheters. Seven hundred fifty milliliters of the withdrawn blood was instilled into each pleural space, and fluid resuscitation with colloid was initiated. The chest drains were then unclamped. Output from each drain was measured every minute for 5 minutes and then every 5 minutes for 40 minutes. The swine were euthanized, and thoracotomies were performed to quantify the volume of blood remaining in each pleural space and to examine the position of each tube. Results Blood drainage was more rapid from the chest tube during the first 3 minutes compared with the pigtail catheter (348 ± 109 mL/min vs. 176 ± 53 mL/min), but this difference was not statistically significant (p = 0.19). Thereafter, the rates of drainage between the two tubes were not substantially different. The chest tube drained a higher total percentage of the blood from the chest (87.3% vs. 70.3%), but this difference did not reach statistical significance (p = 0.21). Conclusion We found no statistically significant difference in the volume of blood drained by a 14 Fr pigtail catheter compared with a 32 Fr chest tube.

Background A clear command structure ensures quality patient care despite overwhelmed resources during a mass casualty incident (MCI). The American College of Surgeons has stated that surgeons should strive to occupy these leadership roles. Objective We sought to identify whether surgeons, as compared to emergency physicians, are sufficiently prepared to assume command in the event of a mass disaster. Methods We surveyed hospital-affiliated surgeons and emergency physicians to assess their knowledge of MCI response principles and to gauge opinions regarding who should be in charge during a disaster. Results One hundred and forty-nine (58%) surveys were completed, 78 by surgeons and 71 by emergency physicians. Both groups demonstrated a critical lack of knowledge regarding fundamental principles and key logistical components of preparedness and MCI response. Surgeons as a group were even less prepared than emergency physicians. Of those surgeons who had reviewed their hospital's disaster plan, half (50%) still did not know where to report for an MCI activation. Nonetheless, both groups believed they had sufficient training and both asserted they ought to occupy command positions during a disaster scenario. Conclusions Errors in disaster triage have been known to increase mortality as well as the monetary cost of disaster response. Funding exists to improve hospital preparedness, but surgeons are lagging behind emergency physicians in taking advantage of these opportunities. Overall, it is imperative that physicians improve their understanding of the MCI response protocols they will be tasked to implement should disaster strike.

This case outlines the emergency department and surgical course of a 63-year-old male presenting with acute onset abdominal pain. Appendicitis was high on the differential for the treating physician, but after the computed tomography and laboratory evaluation were unremarkable, the patient was discharged only to return the next day. What ensued was one of the rarest cases of missed appendicitis documented in the medical literature. [West J Emerg Med. 2014;15(7):-0.]