The Role of MAPRE2 and Microtubules in Maintaining Normal Ventricular Conduction.

BACKGROUND: Brugada syndrome is associated with loss-of-function SCN5A variants, yet these account for only ≈20% of cases. A recent genome-wide association study identified a novel locus within MAPRE2, which encodes EB2 (microtubule end-binding protein 2), implicating microtubule involvement in Brugada syndrome. METHODS: A mapre2 knockout zebrafish model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated protein 9) and validated by Western blot. Larval hearts at 5 days post-fertilization were isolated for voltage mapping and immunocytochemistry. Adult fish hearts were used for ECG, patch clamping, and immunocytochemistry. Morpholinos were injected into embryos at 1-cell stage for knockdown experiments. A transgenic zebrafish line with cdh2 tandem fluorescent timer was used to study adherens junctions. Microtubule plus-end tracking and patch clamping were performed in human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) with MAPRE2 knockdown and knockout, respectively. RESULTS: Voltage mapping of mapre2 knockout hearts showed a decrease in ventricular maximum upstroke velocity of the action potential and conduction velocity, suggesting loss of cardiac voltage-gated sodium channel function. ECG showed QRS prolongation in adult knockout fish, and patch clamping showed decreased sodium current density in knockout ventricular myocytes and arrhythmias in knockout iPSC-CMs. Confocal imaging showed disorganized adherens junctions and mislocalization of mature Ncad (N-cadherin) with mapre2 loss of function, associated with a decrease of detyrosinated tubulin. MAPRE2 knockdown in iPSC-CMs led to an increase in microtubule growth velocity and distance, indicating changes in microtubule dynamics. Finally, knockdown of ttl encoding tubulin tyrosine ligase in mapre2 knockout larvae rescued tubulin detyrosination and ventricular maximum upstroke velocity of the action potential. CONCLUSIONS: Genetic ablation of mapre2 led to a decrease in voltage-gated sodium channel function, a hallmark of Brugada syndrome, associated with disruption of adherens junctions, decrease of detyrosinated tubulin as a marker of microtubule stability, and changes in microtubule dynamics. Restoration of the detyrosinated tubulin fraction with ttl knockdown led to rescue of voltage-gated sodium channel-related functional parameters in mapre2 knockout hearts. Taken together, our study implicates microtubule dynamics in the modulation of ventricular conduction.

COVID-19 and Mortality in the Global Surgical Population: A Systematic Review and Meta-Analysis.

INTRODUCTION: To date, no systematic review or meta-analysis has comprehensively estimated the risk of mortality by surgery type on an international scale. We aim to delineate the risk of mortality in patients with COVID-19 who undergo surgery. METHODS: PubMed (MEDLINE), Scopus, OVID, the World Health Organization Global Literature on Coronavirus Disease, and Corona-Central databases were searched from December 2019 through January 2022. Studies providing data on mortality in patients undergoing surgery were included. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for abstracting data were followed and performed independently by two reviewers. The main outcome was mortality in patients with COVID-19. RESULTS: Of a total of 4023 studies identified, 46 studies with 80,015 patients met our inclusion criteria. The mean age was 67 y; 57% were male. Surgery types included general (14.9%), orthopedic (23.4%), vascular (6.4%), thoracic (10.6%), and urologic (8.5%). Patients undergoing surgery with COVID-19 elicited a nine-fold increased risk of mortality (relative risk [RR] 8.99, 95% confidence interval [CI] 4.96-16.32) over those without COVID-19. In low-income and middle-income countries (RR: 16.04, 95% CI: 4.59-56.12), the mortality risk was twice as high compared to high-income countries (RR: 7.50, 95% CI: 4.30-13.09). CONCLUSIONS: Mortality risk in surgical patients with COVID-19 compared to those without is increased almost 10-fold. The risk was highest in low-income and middle-income countries compared to high-income countries, suggesting a disproportionate effect of the pandemic on resource-constrained regions.

Use of Cold-Stored Whole Blood is Associated With Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study.

OBJECTIVE: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. BACKGROUND: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. METHODS: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. RESULTS: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P <0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients ( P <0.0001). CONCLUSIONS: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients.

Novel cross-linked polysaccharide-polyelectrolyte hemostatic foam improves survival compared to CombatGauze in swine femoral artery hemorrhage model.

BACKGROUND: Uncontrolled hemorrhage is the leading cause of preventable death in combat and civilian trauma. Efficacious hemostatic agents in junctional hemorrhage can quell blood loss and improve survival. We hypothesized that a novel hemostatic foam of starch and chitosan would improve hemostasis, and thereby increase survival in a swine femoral artery hemorrhage model when compared with CombatGauze (CG). METHODS: A novel hemostatic foam of starch and chitosan was created and modified during the study period. Thirty pigs (four excluded) were assigned to treatment using either foam version 1 (FV1, n = 9) or 2 (FV2, n = 8), or (n = 9) in a standard swine femoral artery hemorrhage model. Animals were observed for 150 minutes. Outcomes assessed included hemostasis, survival, posttreatment blood loss, IV fluid volume, and hemodynamic and laboratory trends. RESULTS: Hemostasis prior to 150 minutes was similar with 44.4%, 77.8%, and 50% of swine treated with CG, FV1 and FV2, respectively (Kaplan-Meyer and log-rank test [KM-LR] p > 0.05). Survival to 150 minutes was improved in swine treated with FV1 (100%) compared with CG (55.6%) (KM-LR p = 0.02). Survival was similar between FV1 and FV2 (75%) (KM-LR p > 0.05), and between CG and FV2 (KM-LR p > 0.05). Using mixed model for longitudinal data, mean arterial pressure decreased significantly in CG- and FV2-treated swine, while there was no significant change in mean arterial pressure in FV1-treated swine. Trends in lactic acid, hematocrit, platelets, INR, and thrombelastography were more favorable for FV1 compared with CG. CONCLUSION: In this preclinical study of junctional hemorrhage, survival was improved in swine treated with version 1 of a novel chitosan/starch foam compared with CG. Trends in hemodynamics and laboratory data were also more favorable in the FV1-treated swine. This novel hemostatic foam may be an effective alternative to current hemostatic agents.

Breast Cancer Survival in Eastern Region of Ghana.

Objective: Five-year overall survival rate of breast cancer in low-income countries (LICs) is significantly lower than in high-resource countries. This study explored clinical and pathological factors influencing mortality in the Eastern region of Ghana. Methods: We performed a retrospective medical chart review for patients undergoing surgery and chemotherapy for breast cancer at a regional hospital in Ghana from January 2014 to January 2017. Descriptive and survival analysis was done. Results: One hundred and twenty-nine patients were included in the study. The median age at presentation was 51 years. Sixty percent of patients presented with poorly differential histological grade III. The most common histological type was invasive ductal carcinoma (83%). Based on stage assessment using only tumor size and lymph node status, 60% presented at stage 3. Only 25% were tested for hormone receptor proteins and HER2 status. Of these, 57% had triple-negative breast cancer (TNBC). The 3-year overall survival rate was only 52%. Conclusion: The cumulative 3-year survival was 52%. Despite success in reducing cancer mortality in northern Africa, survival in sub-Saharan Africa remains poor. A significantly higher percentage of GIII and TNBC is found in breast cancers seen in Ghana. When combined with limited capacity for accurate diagnosis, cancer subtype analysis, adequate therapy, and follow-up, late-stage presentation leads to poor outcomes. Future studies should emphasize the identification of barriers to care and opportunities for cost-effective and sustainable improvements in diagnosing and treating breast cancer in LICs.

Image-based assessment of sarcopenic obesity predicts mortality in major trauma.

BACKGROUND: Patients with obesity are also at risk for sarcopenia, which is difficult to recognize in this population. Our study examines whether sarcopenic-obesity (SO) is independently associated with mortality in trauma. METHODS: Using a retrospective database, we performed logistic regression analysis. . Admission CT scans were used to identify SO by calculating the visceral fat to skeletal muscle ratio >3.2. RESULTS: Of 883 patients, the prevalence of SO was 38% (333). Patients with SO were more likely to be male (79% versus 43%, p < 0.001), older (mean 66.5 years versus 46.3 years, p < 0.001), and less likely to have an injury severity score (ISS) ≥ 24 (43% versus 55%, p = 0.0003). Using multivariable logistic regression analysis, SO was independently associated with mortality (OR 2.8; 95% CI 1.6-4.8, p < 0.001). Causal mediation analysis found admission hyperglycemia as a mediator for mortality. CONCLUSIONS: Sarcopenic obesity is an independent predictor of mortality in major trauma.

The cost of treatments for retained traumatic hemothorax: A decision analysis.

INTRODUCTION: Early video-assisted thorascopic surgery (VATS) is the recommended intervention for retained hemothorax in trauma patients. Alternative options, such as lytic therapy, to avoid surgery remain controversial. The purpose of this decision analysis was to assess expected costs associated with treatment strategies. METHODS: A decision tree analysis estimated the expected costs of three initial treatment strategies: 1) VATS, 2) intrapleural tissue plasminogen activator (TPA) lytic therapy, and 3) intrapleural non-TPA lytic therapy. Probability parameters were estimated from published literature. Costs were based on National Inpatient Sample data and published estimates. Our model compared overall expected costs of admission for each strategy. Sensitivity analyses were conducted to explore the impact of parameter uncertainty on the optimal strategy. RESULTS: In the base case analysis, using TPA as the initial approach had the lowest total cost (U.S. $37,007) compared to VATS ($38,588). TPA remained the optimal initial approach regardless of the probability of complications after VATS. TPA was an optimal initial approach if TPA success rate was >83% regardless of the failure rate with VATS. VATS was the optimal initial strategy if its total cost of admission was <$33,900. CONCLUSION: Lower treatment costs with lytic therapy does not imply significantly lower total cost of trauma admission. However, an initial approach with TPA lytic therapy may be preferred for retained traumatic hemothorax to lower the total cost of admission given its high probability of avoiding the operating room with its resultant increased costs. Future studies should identify differences in quality of life after recovery from competing interventions.

A porcine model for evaluating the management of noncompressible torso hemorrhage.

BACKGROUND: Noncompressible hemorrhage from central vascular injuries remains the leading cause of preventable death in modern combat. This report introduces a large animal model of noncompressible torso hemorrhage, which permits assessment of the various approaches to this problem. METHODS: Yorkshire swine were anesthetized and monitoring devices for central aortic pressure, carotid flow, and intracerebral and transcutaneous brain oximetry were applied. Class IV hemorrhagic shock was induced through an iliac arterial injury and animals were subjected to different vascular control methods including thoracic aortic clamping, supraceliac aortic clamping, direct vascular control, and proximal endovascular balloon occlusion. After vascular control, the injury was shunted, and damage control resuscitation was continued. Serum markers, intravenous fluid volumes, and vasopressor requirements were tracked over a subsequent resuscitation period. Postmortem tissue analysis was performed to compare levels of acute ischemic injury between groups. RESULTS: The protocol for animal preparation, hemorrhage volume, open surgical technique, and posthemorrhage resuscitation was developed using four animals. The endovascular approach was developed using two additional animals. After model development, treatment animals subsequently underwent noncompressible hemorrhage with thoracic aortic clamping, supraceliac aortic clamping, direct vascular control, and endovascular aortic occlusion. Premature death occurred in one animal in the direct vascular control group. CONCLUSION: This study presents a large animal model of class IV hemorrhagic shock from noncompressible hemorrhage, which permits comparison of various vascular control methods to address this challenging problem. Future studies using this model as the standard will allow further development of strategies for the management of noncompressible hemorrhage.

Direct vascular control results in less physiologic derangement than proximal aortic clamping in a porcine model of noncompressible extrathoracic torso hemorrhage.

BACKGROUND: The optimal method of vascular control and resuscitation in patients with life-threatening, extrathoracic torso hemorrhage remains debated. Guidelines recommend emergency department thoracotomy (EDT) with aortic clamping, although transabdominal aortic clamping followed by vascular control and direct vascular control (DVC) without aortic clamping are alternatives. The objective of this study is to compare the effectiveness of three approaches to extrathoracic torso hemorrhage in a large animal model. METHODS: Adolescent swine (Sus Scrofa) (mean weight = 80.9 kg) were randomized into three groups all of which had class IV shock established by hemorrhage from an iliac artery injury. Group 1: EDT with thoracic aortic clamping (N = 6); group 2: transabdominal supraceliac aortic clamping (SCC; N = 6); and group 3: DVC of bleeding site without aortic clamping (N = 6). After hemorrhage, EDT or SCC was performed in groups 1 and 2, respectively, with subsequent exploration of the bleeding site and placement of a temporary vascular shunt (TVS). Group 3 (DVC) underwent direct exploration of the injury and placement of a TVS. All groups were resuscitated to predefined physiologic endpoints over 6 hours with repeated measures of central and cerebral perfusion and end-organ function at standardized time points. Postmortem tissue analysis was performed to quantify injury to critical tissue beds. RESULTS: There was no difference in mortality among the groups and no TVS failures. Central aortic pressure, carotid flow, and partial pressure brain tissue oximetry, all demonstrated increases in EDT and SCC after application of the aortic clamp relative to DVC (p < 0.05). During resuscitation, serum lactate levels were higher in EDT compared with SCC and DVC (6.85 vs. 3.08 and 2.15, respectively; p < 0.05) and serum pH in EDT reflected greater acidosis than SCC and DVC (7.24 vs. 7.36 and 7.39, respectively; p < 0.05). EDT and SCC required more intravenous fluid than DVC (2,166 mL and 2,166 mL vs. 667 mL, respectively; p < 0.05) and more vasopressors were used in EDT and SCC compared with DVC (52.1 µg and 43.5 µg vs. 12.4 µg, respectively; p < 0.05). Brain and myocardial tissue stains demonstrated the same degree of acute ischemic changes in all groups. CONCLUSION: Although aortic clamping increases central and cerebral perfusion, DVC results in less physiologic derangement. The optimal method of aortic control would incorporate the benefits of maintained central pressure with less associated morbidity. Clinical studies evaluating DVC are warranted.

Closing the "care in the air" capability gap for severe lung injury: the Landstuhl Acute Lung Rescue Team and extracorporeal lung support.

BACKGROUND: The success of US Air Force Critical Care Air Transport Teams (CCATT) in transporting critically ill and injured patients enabled changes in military medical force deployment and casualty care practice. Even so, a subset of casualties remains who exceed even CCATT capabilities for movement. These patients led to the creation of the Landstuhl Acute Lung Rescue Team (ALeRT) to close the "care in the air" capability gap. METHODS: The ALeRT Registry was queried for the period between November 1, 2005, and June 30, 2010. Additionally, Landstuhl Regional Medical Center critical care patient transfers to host nation medical centers were reviewed for cases using extracorporeal lung support systems. RESULTS: For the review period, US Central Command activated the ALeRT on 40 occasions. The ALeRT successfully evacuated patients on 24 of 27 missions launched (89%). Three patients were too unstable for ALeRT evacuation. Of the 13 remaining activations, four patients died and nine patients improved sufficiently for standard CCATT movement. The ALeRT initiated pumpless extracorporeal lung assistance six times, but only once to facilitate evacuation. Two patients were supported with full extracorporeal membrane oxygenation support after evacuation due to progressive respiratory failure. CONCLUSIONS: ALeRT successfully transported 24 casualties from the combat zones to Germany. Without the ALeRT, these patients would have remained in the combat theater as significant consumers of limited deployed medical resources. Pumpless extracorporeal lung assistance is already within the ALeRT armamentarium, but has only been used for one aeromedical evacuation. Modern extracorporeal membrane oxygenation systems hold promise as a feasible capability for aeromedical evacuation.

Short-term and Long-term Rates of Postacute Sequelae of SARS-CoV-2 Infection: A Systematic Review.

Importance: Short-term and long-term persistent postacute sequelae of COVID-19 (PASC) have not been systematically evaluated. The incidence and evolution of PASC are dependent on time from infection, organ systems and tissue affected, vaccination status, variant of the virus, and geographic region. Objective: To estimate organ system-specific frequency and evolution of PASC. Evidence Review: PubMed (MEDLINE), Scopus, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases were searched from December 2019 through March 2021. A total of 2100 studies were identified from databases and through cited references. Studies providing data on PASC in children and adults were included. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for abstracting data were followed and performed independently by 2 reviewers. Quality was assessed using the Newcastle-Ottawa Scale for cohort studies. The main outcome was frequency of PASC diagnosed by (1) laboratory investigation, (2) radiologic pathology, and (3) clinical signs and symptoms. PASC were classified by organ system, ie, neurologic; cardiovascular; respiratory; digestive; dermatologic; and ear, nose, and throat as well as mental health, constitutional symptoms, and functional mobility. Findings: From a total of 2100 studies identified, 57 studies with 250 351 survivors of COVID-19 met inclusion criteria. The mean (SD) age of survivors was 54.4 (8.9) years, 140 196 (56%) were male, and 197 777 (79%) were hospitalized during acute COVID-19. High-income countries contributed 45 studies (79%). The median (IQR) proportion of COVID-19 survivors experiencing at least 1 PASC was 54.0% (45.0%-69.0%; 13 studies) at 1 month (short-term), 55.0% (34.8%-65.5%; 38 studies) at 2 to 5 months (intermediate-term), and 54.0% (31.0%-67.0%; 9 studies) at 6 or more months (long-term). Most prevalent pulmonary sequelae, neurologic disorders, mental health disorders, functional mobility impairments, and general and constitutional symptoms were chest imaging abnormality (median [IQR], 62.2% [45.8%-76.5%]), difficulty concentrating (median [IQR], 23.8% [20.4%-25.9%]), generalized anxiety disorder (median [IQR], 29.6% [14.0%-44.0%]), general functional impairments (median [IQR], 44.0% [23.4%-62.6%]), and fatigue or muscle weakness (median [IQR], 37.5% [25.4%-54.5%]), respectively. Other frequently reported symptoms included cardiac, dermatologic, digestive, and ear, nose, and throat disorders. Conclusions and Relevance: In this systematic review, more than half of COVID-19 survivors experienced PASC 6 months after recovery. The most common PASC involved functional mobility impairments, pulmonary abnormalities, and mental health disorders. These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low- and middle-income countries.

Gun violence incidence during the COVID-19 pandemic is higher than before the pandemic in the United States.

During the coronavirus disease 2019 (COVID-19) pandemic, gun violence (GV) in the United States (U.S.) was postulated to increase strain on already taxed healthcare resources, such as blood products, intensive care beds, personal protective equipment, and even hospital staff. This report aims to estimate the relative risk of GV in the U.S. during the pandemic compared to before the pandemic. Daily police reports corresponding to gun-related injuries and deaths in the 50 states and the District of Columbia from February 1st, 2019, to March 31st, 2021 were obtained from the GV Archive. Generalized linear mixed-effects models in the form of Poisson regression analysis were utilized to estimate the state-specific rates of GV. Nationally, GV rates were 30% higher between March 01, 2020, and March 31, 2021 (during the pandemic), compared to the same period in 2019 (before the pandemic) [intensity ratio (IR) = 1.30; 95% CI 1.29, 1.32; p < 0.0001]. The risk of GV was significantly higher in 28 states and significantly lower in only one state. National and state-specific rates of GV were higher during the COVID-19 pandemic compared to the same timeframe 1 year prior. State-specific steps to mitigate violence, or at a minimum adequately prepare for its toll during the COVID-19 pandemic, should be taken.

Renin-angiotensin-aldosterone system inhibitors and the risk of mortality in patients with hypertension hospitalised for COVID-19: systematic review and meta-analysis.

OBJECTIVE: The association between the use of renin-angiotensin-aldosterone (RAAS) inhibitors and the risk of mortality from COVID-19 is unclear. We aimed to estimate the association of RAAS inhibitors, including ACE inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) with COVID-19 mortality risk in patients with hypertension. METHODS: PubMed (MEDLINE) SCOPUS, OVID, Cochrane Library databases and medrxiv.org were searched from 1 January 2020 to 1 September 2020. Studies reporting the association of RAAS inhibitors (ACEi or ARBs) and mortality in patients with hypertension, hospitalised for COVID-19 were extracted. Two reviewers independently extracted appropriate data of interest and assessed the risk of bias. All analyses were performed using random-effects models on log-transformed risk ratio (RR) estimates, and heterogeneity was quantified. RESULTS: Fourteen studies were included in the systematic review (n=73,073 patients with COVID-19; mean age 61 years; 53% male). Overall, the between-study heterogeneity was high (I2=80%, p<0.01). Patients with hypertension with prior use of RAAS inhibitors were 35% less likely to die from COVID-19 compared with patients with hypertension not taking RAAS inhibitors (pooled RR 0.65, 95% CI 0.45 to 0.94). The quality of evidence by Grading of Recommendations, Assessment, Development and Evaluations was graded as 'moderate' quality. CONCLUSIONS: In this meta-analysis, with prior use of RAAS inhibitors was associated with lower risk mortality from COVID-19 in patients with hypertension. Our findings suggest a potential protective effect of RAAS-inhibitors in COVID-19 patients with hypertension. PROSPERO REGISTRATION NUMBER: The present study has been registered with PROSPERO (registration ID: CRD 42020187963).

Risk factors of perioperative mortality from complicated peptic ulcer disease in Africa: systematic review and meta-analysis.

Introduction: In 2013, peptic ulcer disease (PUD) caused over 300 000 deaths globally. Low-income and middle-income countries are disproportionately affected. However, there is limited information regarding risk factors of perioperative mortality rates in these countries. Objective: To assess perioperative mortality rates from complicated PUD in Africa and associated risk factors. Design: We performed a systematic review and a random-effect meta-analysis of literature describing surgical management of complicated PUD in Africa. We used subgroup analysis and meta-regression analyses to investigate sources of variations in the mortality rates and to assess the risk factors contributing to mortality. Results: From 95 published reports, 10 037 patients underwent surgery for complicated PUD. The majority of the ulcers (78%) were duodenal, followed by gastric (14%). Forty-one per cent of operations were for perforation, 22% for obstruction and 9% for bleeding. The operations consisted of vagotomy (38%), primary repair (34%), resection and reconstruction (12%), and drainage procedures (6%). The overall PUD mortality rate was 6.6% (95% CI 5.4% to 8.1%). It increased to 9.7% (95% CI 7.1 to 13.0) when we limited the analysis to studies published after the year 2000. The correlation was higher between perforated PUD and mortality rates (r=0.41, p<0.0001) than for bleeding PUD and mortality rates (r=0.32, p=0.001). Non-significant differences in mortality rates existed between sub-Saharan Africa (SSA) and North Africa and within SSA. Conclusion: Perioperative mortality rates from complicated PUD in Africa are substantially high and could be increasing over time, and there are possible regional differences.

Trauma Embolic Scoring System in military trauma: a sensitive predictor of venous thromboembolism.

INTRODUCTION: Clinical decision support tools capable of predicting which patients are at highest risk for venous thromboembolism (VTE) can assist in guiding surveillance and prophylaxis decisions. The Trauma Embolic Scoring System (TESS) has been shown to model VTE risk in civilian trauma patients. No such support tools have yet been described in combat casualties, who have a high incidence of VTE. The purpose of this study was to evaluate the utility of TESS in predicting VTE in military trauma patients. METHODS: A retrospective cohort study of 549 combat casualties from October 2010 to November 2012 admitted to a military treatment facility in the USA was performed. TESS scores were calculated through data obtained from the Department of Defense Trauma Registry and chart reviews. Univariate analysis and multivariate logistic regression were performed to evaluate risk factors for VTE. Receiver operating characteristic (ROC) curve analysis of TESS in military trauma patients was also performed. RESULTS: The incidence of VTE was 21.7% (119/549). The median TESS for patients without VTE was 8 (IQR 4-9), and the median TESS for those with VTE was 10 (IQR 9-11). On multivariate analysis, Injury Severity Score (ISS) (OR 1.03, p=0.007), ventilator days (OR 1.05, p=0.02), and administration of tranexamic acid (TXA) (OR 1.89, p=0.03) were found to be independent risk factors for development of VTE. On ROC analysis, an optimal high-risk cut-off value for TESS was ≥7 with a sensitivity of 0.92 and a specificity of 0.53 (area under the curve 0.76, 95% CI 0.72 to 0.80, p<0.0001). CONCLUSIONS: When used to predict VTE in military trauma, TESS shows moderate discrimination and is well calibrated. An optimal high-risk cut-off value of ≥7 demonstrates high sensitivity in predicting VTE. In addition to ISS and ventilator days, TXA administration is an independent risk factor for VTE development. LEVEL OF EVIDENCE: Level III.

Imperforate hymen and leaking hematosalpinx mimicking acute appendicitis: A report of a rare case and a review of literature.

INTRODUCTION: Cases of imperforate hymen with leaking hematosalpinx into the peritoneum are rare. We present a case of imperforate hymen mimicking acute appendicitis creating diagnostic challenges with a near miss diagnosis. CASE: A 12-year-old premenarchal female presented with severe pain that migrated from the epigastrium to the right lower quadrant. Physical examination revealed an ill-defined non-tender mass in the right lower quadrant on deep palpation, without signs of peritonitis. We made a diagnosis of an appendiceal mass and the patient underwent an appendectomy. We found approximately 200 mL of dark blood in the peritoneum and an inflamed appendix. After the appendectomy we noticed an engorged right fallopian tube leaking into the peritoneum and a bulky pelvic mass in the lower segment of the uterus. Perineal examination revealed a slightly bulging imperforate hymen. Hymenectomy was performed and 500 mL of viscous old blood was drained. On follow-up, the hymen was still open. DISCUSSION: Imperforate hymen commonly presents with cyclic abdominal pain and enlarging mass in premenarchal females, it is rare to present with hemoperitoneum and mimicking acute appendicitis. CONCLUSION: Although rare, imperforate hymen with retrograde menstruation that causes dilatation of the vagina and uterus (i.e., hematocolpometra) is an important consideration in the differential diagnosis of abdominal pain in premenarchal females with abdominal pain. It is easily diagnosed by physical examination. However, if patient or parents refuse genital exam evaluation, imaging studies can greatly help with diagnosis. Ultrasound will show an echogenic fluid accumulation in the vagina that can extend to uterus.

Regional, racial, gender, and tumor biology disparities in breast cancer survival rates in Africa: A systematic review and meta-analysis.

BACKGROUND: The survival rates from breast cancer in Africa are poor and yet the incidence rates are on the rise. In this study, we hypothesized that, in Africa, a continent with great disparities in socio-economic status, race, tumor biology, and cultural characteristics, the survival rates from breast cancer vary greatly based on region, tumor biology (hormone receptor), gender, and race. We aimed to conduct the first comprehensive systematic review and meta-analysis on region, gender, tumor-biology and race-specific 5-year breast cancer survival rates in Africa and compared them to 20-year survival trends in the United States. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library to identify studies on breast cancer survival in African published before October 17, 2018. Pooled 5-year survival rates of breast cancer were estimated by random-effects models. We explored sources of heterogeneity through subgroup meta-analyses and meta-regression. Results were reported as absolute difference (AD) in percentages. We compared the survival rates of breast cancer in Africa and the United States. FINDINGS: There were 54 studies included, consisting of 18,970 breast cancer cases. There was substantial heterogeneity in the survival rates (mean 52.9%, range 7-91%, I2 = 99.1%; p for heterogeneity <0.0001). Meta-regression analyses suggested that age and gender-adjusted 5-year survival rates were lower in sub-Saharan Africa compared to north Africa (AD: -25.4%; 95% CI: -34.9 - -15.82%), and in predominantly black populations compared to predominantly non-black populations (AD: -25.9%; 95% CI: 35.40 - -16.43%). Survival rates were 10 percentage points higher in the female population compared to male, but the difference was not significant. Progesterone and estrogen receptor-positive breast cancer subtypes were positively associated with survival (r = 0.39, p = 0.08 and r = 0.24, p = 0.29 respectively), but triple-negative breast cancer was negatively associated with survival. Survival rates are increasing over time more in non-black Africans (55% in 2000 versus 65% in 2018) compared to black Africans (33% in 2000 versus 40% in 2018); but, the survival rates for Africans are still significantly lower when compared to black (76% in 2015) and white (90% in 2015) populations in the United States. CONCLUSION: Regional, sub-regional, gender, and racial disparities exist, influencing the survival rates of breast cancer in Africa. Therefore, region and race-specific public health interventions coupled with prospective genetic studies are urgently needed to improve breast cancer survival in this region.

Adult Intussusception due to Gastrointestinal Stromal Tumor: A Rare Case Report, Comprehensive Literature Review, and Diagnostic Challenges in Low-Resource Countries.

We present a rare case of gastrogastric intussusception due to gastrointestinal stromal tumor (GIST) and the largest comprehensive literature review of published case reports on gastrointestinal (GI) intussusception due to GIST in the past three decades. We found that the common presenting symptoms were features of gastrointestinal obstruction and melena. We highlight the diagnostic challenges faced in low-resource countries. Our findings emphasize the importance of early clinical diagnosis in low-resource settings in order to guide timely management. In addition, histological analysis of the tumor for macroscopic and microscopic characteristics including mitotic index and c-Kit/CD117 status should be obtained to guide adjuvant therapy with imatinib mesylate. Periodic follow-up to access tumor recurrence is fundamental and should be the standard of care.

The pediatric resuscitative thoracotomy during combat operations in Iraq and Afghanistan - A retrospective cohort study.

BACKGROUND: Combat zone trauma poses a unique set of challenges and injury patterns not seen in the civilian setting. The role of the pediatric resuscitative thoracotomy in combat zones remains unclear given a paucity of data regarding procedure outcomes in this setting. We compare outcomes among children in traumatic arrest undergoing resuscitative thoracotomy versus cardiopulmonary (CPR) resuscitation only. METHODS: We queried the Department of Defense Trauma Registry (DODTR) from 2007 to 2016 for all pediatric subjects that underwent a resuscitative thoracotomy or CPR in the prehospital or emergency department setting during operations in Iraq or Afghanistan. We removed CPR subjects with mechanisms of injury not matched in the thoracotomy cohort. RESULTS: During the study period, there were 3439 pediatric encounters. We identified 13 subjects who underwent a resuscitative thoracotomy and 66 subjects who underwent CPR without thoracotomy with matching mechanisms of injury. When comparing the two cohorts those in the thoracotomy group had higher median thorax body region scores (median 3 versus 0, p = .001), but a trend towards higher rates of survival to discharge (31% versus 9%, p = .108). The youngest survivor in the thoracotomy cohort was less than 1 year old. CONCLUSIONS: We observed a trend towards higher survival among subjects that underwent a resuscitative thoracotomy survived to hospital discharge compared to subjects undergoing CPR without thoracotomy. The literature will benefit from further data to confirm an association between this procedure and a survival benefit among pediatric subjects in the resource limited setting. Furthermore, improvements in documentation will guide equipping and training providers expected to care for pediatric trauma patients.

Development of an emergency general surgery process improvement program.

BACKGROUND: The Joint Trauma System has demonstrated improved outcomes through coordinated research and process improvement programs. With fewer combat trauma patients, our military American College of Surgeons level 2 trauma center's ability to maintain a strong trauma Process Improvement (PI) program has become difficult. As emergency general surgery (EGS) patients are similar to trauma patients, our Trauma and Acute Care Surgery (TACS) service developed an EGS PI program analogous to what is done in trauma. We describe the implementation of our novel EGS PI program and its effect on institutional PI proficiency. METHODS: An EGS registry was developed in 2013. Inclusion criteria were based on AAST published literature. In 2015, EGS registrar and PI coordinator positions were developed and filled with existing trauma staff. A formal EGS PI program began January 1, 2016. Pre- and post-program data was compared to determine the effect including EGS PI events had on increasing yield into our trauma PI program. RESULTS: In 2016, TACS saw 1001 EGS consults. Four hundred forty-four met criteria for registry inclusion. Eighty-two patients had 131 PI events; re-admission within 30 days, unplanned therapeutic intervention, and unplanned ICU admission were the most common events. Capture of EGS PI events yielded a 49% increase compared with 2015. CONCLUSION: Overall patient volume and PI events post EGS PI program initiation exceeded those prior to implementation. These data suggest that extending trauma PI principles to EGS may be beneficial in maintaining inter-war military and/or lower volume trauma center readiness.