Fibrinogen Inhibits Metalloproteinase-9 Activation and Syndecan-1 Cleavage to Protect Lung Function in ApoE Null Mice After Hemorrhagic Shock.

INTRODUCTION: Obesity is associated with higher mortality following trauma, although the pathogenesis is unclear. Both obesity and trauma are associated with syndecan-1 shedding and metalloproteinase-9 (MMP-9) activation, which can adversely affect endothelial cell function. We recently demonstrated that fibrinogen stabilizes endothelial cell surface syndecan-1 to reduce shedding and maintain endothelial barrier integrity. We thus hypothesized that MMP-9 activation and syndecan-1 shedding would be exacerbated by obesity after trauma but attenuated by fibrinogen-based resuscitation. MATERIALS AND METHODS: ApoE null (-/-) mice were fed a Western diet to induce obesity. Mice were subjected to hemorrhage shock and laparotomy then resuscitated with Lactated Ranger's (LR) or LR containing fibrinogen and compared to null and lean sham wild type mice. Mean arterial pressure (MAP) was monitored. Bronchial alveolar lavage protein as an indicator of permeability and lung histopathologic injury were assessed. Syndecan-1 protein and active MMP-9 protein were measured. RESULTS: MAP was similar between lean sham and ApoE-/- sham mice. However, following hemorrhage, ApoE-/- mice resuscitated with fibrinogen had significantly higher MAP than LR mice. Lung histopathologic injury and permeability were increased in LR compared to fibrinogen resuscitated animals. Compared with lean sham mice, both active MMP-9 and cleaved syndecan-1 level were significantly higher in ApoE-/- sham mice. Resuscitation with fibrinogen but not lactated Ringers largely reduced these changes. CONCLUSIONS: Fibrinogen as a resuscitative adjunct in ApoE-/- mice after hemorrhage shock augmented MAP and reduced histopathologic injury and lung permeability, suggesting fibrinogen protects the endothelium by inhibiting MMP-9-mediated syndecan-1 cleavage in obese mice.

Surgical Training for Civilian Surgeons Interested in Humanitarian Surgery: A Scoping Review.

INTRODUCTION: Humanitarian surgery is essential to surgical care in limited resource settings. The difficulties associated with resource constraints necessitate special training for civilian surgeons to provide care in these situations. Specific training or curricula for humanitarian surgeons are not well described in the literature. This scoping review summarizes the existing literature and identifies areas for potential improvement. METHODS: A review of articles describing established courses for civilian surgeons interested in humanitarian surgery, as well as those describing training of civilian surgeons in conflict zones, was performed. A total of 4808 abstracts were screened by two independent reviewers, and 257 abstracts were selected for full-text review. Articles describing prehospital care and military experience were excluded from the full-text review. RESULTS: Of the eight relevant full texts, 10 established courses for civilian surgeons were identified. Cadaver-based teaching combined with didactics were the most common course themes. Courses provided technical education focused on the management of trauma and burns as well as emergencies in orthopedics, neurosurgery, obstetrics, and gynecology. Other courses were in specialty surgery, mainly orthopedics. Two fellowship programs were identified, and these provide a different model for training humanitarian surgeons. CONCLUSIONS: Humanitarian surgery is often practiced in austere environments, and civilian surgeons must be adequately trained to first do no harm. Current programs include cadaver-based courses focused on enhancing trauma surgery and surgical subspecialty skills, with adjunctive didactics covering resource allocation in austere environments. Fellowships programs may serve as an avenue to provide a more standardized education and a reliable pipeline of global surgeons.

c-Jun-mediated miR-19b expression induces endothelial barrier dysfunction in an in vitro model of hemorrhagic shock.

BACKGROUND: Our previous data demonstrated that miR-19b expression was increased in human lung microvascular endothelial cells in-vitro-, in-vivo and in patients with hemorrhagic shock, leading to a decrease in syndecan-1 mRNA and protein and resulting in loss of endothelial barrier function. However, the mechanism underlying increased miR-19b expression remains unclear. The objective of the current study was to determine if c-Jun mediates the early responsive microRNA, miR-19b, to cause endothelial barrier dysfunction. METHOD: Human lung microvascular endothelial cells (HLMEC) or HEK293T cells were transfected with c-Jun overexpressing vector, c-Jun siRNA, miR-19b promoter vector, miR-19b mutated promoter vector, miR-19b oligo inhibitor, then subjected to hypoxia/reoxygenation as in-vitro model of hemorrhagic shock. Levels of protein, miRNA, and luciferase activity were measured. Transwell permeability of endothelial monolayers were also determined. Plasma levels of c-Jun were measured in injured patients with hemorrhagic shock. RESULT: Hypoxia/reoxygenation induced primary (pri-)miR-19b, mature miR-19b, and c-Jun expression over time in a comparable timeframe. c-Jun silencing by transfection with its specific siRNA reduced both pri-miR-19b and mature miR-19b levels. Conversely, c-Jun overexpression enhanced H/R-induced pri-miR-19b. Studies using a luciferase reporter assay revealed that in cells transfected with vectors containing the wild-type miR-19b promoter and luciferase reporter, c-Jun overexpression or hypoxia/ reoxygenation significantly increased luciferase activity. c-Jun knockdown reduced the luciferase activity in these cells, suggesting that the miR-19b promoter is directly activated by c-Jun. Further, chromatin immunoprecipitation assay confirmed that c-Jun directly bound to the promoter DNA of miR-19b and hypoxia/reoxygenation significantly increased this interaction. Additionally, c-Jun silencing prevented cell surface syndecan-1 loss and endothelial barrier dysfunction in HLMECs after hypoxia/reoxygenation. Lastly, c-Jun was significantly elevated in patients with hemorrhagic shock compared to healthy controls. CONCLUSION: Transcription factor c-Jun is inducible by hypoxia/reoxygenation, binds to and activates the miR-19b promoter. Using an in-vitro model of hemorrhagic shock, our findings identified a novel cellular mechanism whereby hypoxia/ reoxygenation increases miR-19b transcription by inducing c-Jun and leads to syndecan-1 decrease and endothelial cell barrier dysfunction. This finding supports that miR-19b could be a potential therapeutic target for hemorrhage shock.

Patterns and Trends of Gun Violence Against Women in the United States.

OBJECTIVE: To examine patterns and trends of firearm injuries in a nationally representative sample of US women. SUMMARY OF BACKGROUND DATA: Gun violence in the United States exceeds rates seen in most other industrialized countries. Due to the paucity of data little is known regarding demographics and temporal variations in firearm injuries among women. METHODS: Data were extracted from the Centers for Disease Control and Prevention's Web-based Injury Statistics Query and Reporting System (2001-2017) for women 18 years and older. Number of nonfatal firearm assaults and homicide per year were extracted and crude population-based injury rates were calculated. Sub-stratification by age-group and time period were performed. RESULTS: Between 2001 and 2017, there were 88,823 nonfatal firearm assaults involving women and 29,106 firearm homicides. There were 4116 victims of nonfatal firearm assault in 2001 (3.8 per 105) and 12,959 by 2017 (10.0 per 105). Homicide rates were 1.5 per 105 in 2001 and 1.7 per 105 in 2017. Sub-stratification by age-group and time period showed that there were no significant changes in nonfatal firearm assault rates between 2001 and 2010 (P-trend = 0.132 in 18-44 yo; 0.298 in 45-64 yo). However between 2011 and 2017, nonfatal assault rates increased from 7.10 per 105 to 19.24 per 105 in 18-44 yo (P-trend = 0.013) and from 1.48 per 105 to 3.93 per 105 in 45-64 yo (P-trend = 0.003). Similar trends were seen with firearm homicide among 18-44 yo (1.91 per 105 to 2.47 per 105 in 2011-2017, P-trend = 0.022). However, the trends among 45-64 yo were not significant in both time periods. CONCLUSIONS: Female victims of gun violence are increasing and more recent years have been marked with higher rates of firearm injuries, particularly among younger women. These data suggest that improved public health strategies and policies may be beneficial in reducing gun violence against US women.

Coronary Artery Bypass Grafting Among Older Adults: Patterns, Outcomes, and Trends.

INTRODUCTION: Although the numbers of older adults in the US are rapidly increasing, there is sparse recent data on the use and outcomes of coronary artery bypass grafting (CABG) among this population. We aimed to evaluate the characteristics and outcomes of older adults undergoing CABG and to measure temporal trends. MATERIALS AND METHODS: Using data from the National Inpatient Sample (2005-2014), patients aged 85 y and older who underwent CABG were selected. Demographic, clinical, and hospital characteristics were extracted. Outcomes measured were hospital mortality, hospital length of stay, discharge home, and operative complications. Patients were grouped by 2-year increments. Differences in clinical characteristics and outcomes over time were evaluated using trend analyses. RESULTS: There were 60,124 patients included in the cohort. The mean age was 86.8 y with majority being men (61%), white (88%), and treated in teaching hospitals (61%). Over the study period, the annual surgical volume decreased from 6689 in 2005/06 to 5150 in 2013/14. Mortality decreased from 8.5% to 5.5% (P-trend <0.001) and mean hospital length of stay decreased from 13.9 d to 12.0 d (P-trend <0.001), whereas the rate of discharge home remained stable (14.1% versus 11.6%, P-trend = 0.056). Compared with patients in 2005/06, those in 2013/14 had higher comorbidities [diabetes: 27.6% versus 17.3%; chronic kidney disease: 29.8% versus 9.2%; peripheral artery disease: 7.5% versus 6.0%; and hypertension: 83.7% versus 64.5% (all P-trend <0.001)]. CONCLUSIONS: CABG volumes are decreasing among older adults, and comorbidity burden is increasing, but outcomes are improving. These data may indicate improved preoperative optimization and better perioperative care processes.

Risk Factors Associated With Adverse Outcomes After Ventral Hernia Repair With Component Separation.

BACKGROUND: Over 350,000 surgeries are performed for ventral hernias (VHs) annually. Abdominal wall component separation has been more frequently used for the management of VHs. The goal of this study is to better understand factors associated with component separation complication rates. METHODS: The National Inpatient Sample (2005-2014) was used to identify all patients with an International Classification of Diseases ninth Revision diagnosis of VHs who underwent open VH repair with a pedicleor graft advancement flap. All cases included in this study were elective and not associated with additional procedures. Demographic, clinical, and hospital characteristics were extracted. Independent predictors of complications and outcomes were determined by multivariable regression analysis. RESULTS: Component separation was performed in 4346 patients. Mean age was 56; majority were female (55%) and white (80%). Most patients (73%) underwent surgery in an urban teaching hospital; mesh was used in 80% of cases and 11% were smokers. Hypertension was the most common comorbidity (50%), followed by obesity (26%), diabetes mellitus (DM) (23%), coronary artery disease (11%), and chronic obstructive pulmonary disease (COPD) (8%). Half of the patients (50%) had private insurance, and 35% had Medicare. Patients were distributed equally over household income quartiles. The mortality rate was 0.5%; median length of stay was 5 d. Overall complication rate was 25% (wound 11%, intraoperative 5%, infectious 11%, and pulmonary 8%). Mesh was associated with a lower rate of wound complications (10% versus 15%, P = 0.001). On multivariable analysis, patients with COPD (odds ratio: 2.02; 95% confidence interval: 1.58-2.59), obesity (1.37; 1.16-1.63), DM (1.3; 1.09-1.55), and those in the lowest income quartile (1.44; 1.06-1.96) had higher overall complication rates. CONCLUSIONS: Consistent with other studies, patients with COPD, Obesity, DM, and lower income status were associated with increased complications after component separation.

Trends in Firearm Injuries Among Children and Teenagers in the United States.

BACKGROUND: Gun violence among children and teenagers in the United States occurs at a magnitude many times that of other industrialized countries. The trends of injury in this age group relative to the adult population are not well studied. This study seeks to measure trends in pediatric firearm injuries in the United States. METHODS: Data from the National Trauma Data Bank (2010-2016) were used in selecting patients evaluated for firearm injury. Patients were classified as children and teenagers (<20 y) or adults (≥20 y). Changes in the proportion of firearm injuries among children and teenagers relative to the overall population (pediatric component) were determined using trend analyses. RESULTS: There were 240,510 firearm injuries with children and teenagers accounting for 45,075 of these injuries (pediatric component of 18.7%). Pediatric firearm injury was mostly among males (87.4%), Blacks (60.7%), and victims of assault (76.0%). The pediatric component of firearm injuries decreased from 21.7% in 2010 to 18.2% in 2016 (P-trend < 0.001). Although there was a decrease from 22.7% to 17.6% in the pediatric component of assault (P-trend < 0.001), there was an increase from 8.7% to 10.1% in the pediatric component of self-inflicted injuries (P-trend = 0.028). Substratification by race/ethnicity showed decrease in the pediatric component of firearm injuries among all groups (P-trend < 0.001) except Whites (P-trend = 0.847). CONCLUSIONS: Despite reductions in the pediatric component of firearm injuries, there remains a significant burden of injury in this group. Continued public health efforts are necessary to ensure safety and reduce firearm injuries among children and teenagers in the United States.

Are we doing too many non-therapeutic laparotomies in trauma? An analysis of the National Trauma Data Bank.

BACKGROUND: Exploratory laparotomy (EL) has been the definitive diagnostic and therapeutic modality for operative abdominal trauma in the US. Recently, many trauma centers have started using diagnostic laparoscopy (DL) in stable trauma patients in an effort to reduce the incidence of non-therapeutic laparotomy (NL). We aim to evaluate the incidence of NL in the trauma population in the US and compare the outcomes between DL and NL. METHODS: Using ICD-9 codes, the National Trauma Data Bank (2010-2015) was queried for patients undergoing any abdominal surgical intervention. Patients were divided into two groups: diagnostic laparoscopy (DL) and exploratory laparotomy (EL). Hemodynamically unstable patients on arrival and patients with abbreviated injury score (AIS) > 3 were excluded. Patients in EL group without any codes for gastrointestinal, diaphragmatic, hepatic, splenic, vascular, or urological procedures were considered to have undergone NL. After excluding patients who were converted to open from the DL group, multivariate regression models were used to analyze the outcomes of DL vs NL group with respect to mortality, length of stay, and complications. RESULTS: A total of 3197 patients underwent NL vs 1323 patients who underwent DL. Compared to DL group, the NL group were older (mean age: 35 vs. 31, P < 0.01). Rate of penetrating injury was 77% vs 86% for patients in NL vs DL. On multivariate analysis, NL was associated with increased mortality (OR 4.5, 95% CI 2.1-9.7), higher rate of complications (OR 2.2, 95% CI 1.4-3.3), and a longer hospital stay (OR 2.7, 95% CI 2.1-3.5). NL was also associated with higher rates of pneumonia, VTE, ARDS, and cardiac arrest. CONCLUSION: With increasing experience in minimally invasive surgery, DL should be a part of the armamentarium of trauma surgeons. This study supports that in well-selected trauma patients DL has favorable outcomes compared to NL. These findings warrant further investigation.

Less is more: Outcomes of surgical approaches to rectal prolapse in patients with cirrhosis.

BACKGROUND: Patients with cirrhosis have increased risk of perioperative complications, and surgical management of concomitant rectal prolapse poses a challenge in these patients. Given the paucity of data informing this, our study aimed to evaluate postoperative outcomes. METHODS: The National Surgical Quality Improvement Program database was queried for patients undergoing rectal prolapse repair from 2011 to 2019. Patients were stratified by cirrhosis (Model for End-Stage Liver Disease ≥10) and no cirrhosis. Bivariate and multivariable regression analyses were used to compare comorbidities, repair types, and identify predictors of postoperative outcomes. RESULTS: We identified 2,234 patients: 332 patients with cirrhosis (Model for End-Stage Liver Disease 14 [10-34]). Patients with cirrhosis were older (76 ± 12 years vs 69 ± 17, P < .001) with increased comorbidities (eg, heart failure, lung disease), greater mortality (3.6% vs 0.8%, P < .001), and complication rates compared with patients without cirrhosis. Readmission rates and longer hospital stays also were observed in patients with cirrhosis. A total of 52% of NCPs underwent abdominal repair compared with 62% of patients with cirrhosis who received perineal repair; greater complication rates were observed for abdominal repairs in both groups (patients without cirrhosis 11.4%, patients with cirrhosis 25%). Predictors of greater complication rates in patients with cirrhosis included abdominal repair (odds ratio 2.7, 95% confidence interval 1.4-5, P = .002) and presence of ascites (odds ratio 4.6, 95% confidence interval 1.1-20, P = .04). CONCLUSION: Overall, abdominal repairs have greater complication rates even when controlling for Model for End-Stage Liver Disease score and presence of ascites. The Delorme procedure had the lowest complication rates. Additional evidence is needed to recommend a preferred surgical approach to rectal prolapse repair in patients with cirrhosis.

Early Cholecystectomy in Patients with Sickle Cell Disease with Uncomplicated Cholelithiasis Is Associated with Better Outcomes.

BACKGROUND: Up to 85% of patients with sickle cell disease (SCD) will develop gallstones by their third decade. Cholecystectomy is the most commonly performed procedure in these patients. Cholecystectomy is recommended for patients with SCD with symptomatic cholelithiasis and leads to lower morbidity. No contemporary large studies have evaluated this recommendation or associated clinical outcomes. This study evaluates clinical outcomes after cholecystectomy in patients with SCD and cholelithiasis with specific advanced clinical presentations. STUDY DESIGN: The Nationwide Inpatient Sample was queried for patients with SCD and gallbladder disease between 2006 and 2015. Patients were divided into groups based on their disease presentation, including uncomplicated cholelithiasis, acute and chronic cholecystitis, and gallstone pancreatitis. Clinical outcomes associated with disease presentation were analyzed. Statistical analysis was performed using the Student's t -test, chi-square test, ANOVA, and logistic regression. RESULTS: There were 6,662 patients with SCD who presented with cholelithiasis. Median age was 20 (interquartile range 16 to 34) years and 54% were female patients. Cholecystectomy was performed in 1,779 patients with SCD with the most common indication being chronic cholecystitis (44%), followed by uncomplicated cholelithiasis (27%), acute cholecystitis (21%), and choledocholithiasis or gallstone pancreatitis (8%). On multivariable regression, advanced clinical presentation was the strongest predictor of perioperative vaso-occlusive crisis, which was the most common complication. Patients undergoing cholecystectomy for uncomplicated cholelithiasis were at lower risk than those with acute cholecystitis (odds ratio [OR] 2.37; 95% CI 1.64 to 3.41), chronic cholecystitis (OR 1.74; 95% CI 1.26 to 2.4), and choledocholithiasis or gallstone pancreatitis (OR 2.24; 95% CI 1.41 to 3.57). CONCLUSIONS: Seventy-three percent of patients with SCD have advanced clinical presentation at the time of their cholecystectomy. After cholecystectomy, perioperative vaso-occlusive events were significantly increased in patients with advanced clinical presentation. These data support screening abdominal ultrasounds and early cholecystectomy for cholelithiasis in patients with SCD.

Immediate use cryoprecipitate products provide lasting organ protection in a rodent model of trauma/hemorrhagic shock and prolonged hypotensive resuscitation.

BACKGROUND: Cryoprecipitate (CP) can augment hemostasis after hemorrhagic shock (HS). Similar to fresh frozen plasma (FFP), CP may provide short-term endothelial protection. We tested a new 5-day postthaw CP (5-day pathogen-reduced cryoprecipitate [5PRC]) and lyophilized pathogen-reduced cryoprecipitate (LPRC) to overcome challenges of early administration and hypothesized that 5PRC and LPRC would provide lasting organ protection in a rodent model of HS. METHODS: Mice underwent trauma/HS (laparotomy then HS), mean arterial pressure (MAP) 35 × 90 minutes, and then 6 hours of hypotensive resuscitation (MAP, 55-60 mm Hg) with lactated Ringer's solution (LR), FFP, CP, 5PRC, or LPRC and compared with shams. Animals were followed for 72 hours. Organs and blood were collected. Data are presented as mean ± SD and analysis of variance with Bonferroni post hoc. RESULTS: Mean arterial pressure was comparable between experimental groups at baseline, preresuscitation, and 6 hours per protocol. However, volume needed to resuscitate to target MAP over 6 hours was less than half for CP, 5PRC, LPRC, and FFP compared with LR, suggesting that CP products can serve as effective resuscitative agents. Mean arterial pressure at 72 hours was also significantly higher in the CP, 5PRC, and FFP groups compared with LR. Resuscitation with CP, 5PRC, and LPRC provided lasting protection from gut injury and enhanced syndecan immunostaining comparable with FFP, while LR mice demonstrated persistent organ dysfunction. Sustained endothelial protection was demonstrated by lessened lung permeability, while cystatin C was an indicator of kidney function, and liver aspartate aminotransferase and alanine transaminase returned to sham levels in all groups. CONCLUSION: Cryoprecipitate products can provide lasting organ protection comparable with FFP in a sustained rodent model of trauma/HS and hypotensive resuscitation. The availability of 5PRC and LPRC will allow for investigation into the immediate use of cryoprecipitate for severely injured patients. As lyophilized products such as cryoprecipitate become available clinically, their use has important implications for prehospital, rural, and battlefield usage.

Disfiguring Firearm Injuries in Children in the United States.

Firearms are a leading cause of injury and death among children in the United States. Most gun violence studies highlight mortality, but few have examined the morbidity in disfiguring injuries suffered by children. Using National Trauma Data Bank 2007-2015, children who suffered gunshot injuries and underwent procedures with lasting physical disfigurement formed the cohort of this study. We identified 28 593 children as victims of firearm injuries. Most were aged 13-18 (84%). There was a preponderance of male gender (86%) and black race/ethnicity (57%). Total mortality was 3774 (13%), and 1500 (5.4%) were identified with one or more disfigurements: 220 amputations, 191 craniectomy, 100 enucleation, 533 ileostomy/colostomy, and 557 tracheostomies. This report highlights the large toll firearm injuries take on American children, specifically in non-concealable disfigurements. These injuries are very impactful to their education and overall socialization and therefore must be a part of the discussion of gun violence in the United States.

Early lyophilized cryoprecipitate enhances the ADAMTS13/VWF ratio to reduce systemic endotheliopathy and lessen lung injury in a mouse multiple-trauma hemorrhage model.

BACKGROUND: Recent studies in severely injured patients suggest an important role of von Willebrand Factor (VWF) and ADAMTS13 in the endotheliopathy of trauma (EoT). We hypothesized that the early use of cryoprecipitate would be effective as an endothelial protector by supplementing physiologic VWF and ADAMTS13 to reverse the EoT. We tested a pathogen-reduced lyophilized cryoprecipitate (LPRC) that could expedite the early administration of cryoprecipitate in the battlefield. METHODS: A mouse multiple-trauma model with uncontrolled hemorrhage (UCH) from liver injury was utilized followed by hypotensive resuscitation (mean arterial pressure, 55-60) × 3 hours with lactated Ringer's (LR), fresh frozen plasma (FFP), conventional pathogen-reduced cryoprecipitate (CC), and LPRC. Blood was collected for measurement of syndecan-1, VWF, and ADAMTS13 by ELISA. Lungs were stained for histopathologic injury and syndecan-1 and bronchial alveolar lavage (BAL) fluid harvested for protein as an indicator of permeability. Statistical analysis was by ANOVA followed by Bonferroni correction. RESULTS: Following multiple trauma and UCH, blood loss was similar across groups. Mean volume of resuscitation was higher in the LR group compared with the other resuscitation groups. Lung histopathologic injury, syndecan-1 immunostaining and BAL protein were higher with LR compared with resuscitation with FFP and CC, while LPRC further reduced BAL compared with FFP and CC. The ADAMTS13/VWF ratio was significantly lower in LR but improved with FFP and CC, comparable to shams while LPRC further increased this ratio. CONCLUSION: The protective effects of CC and LPRC were comparable to FFP in ameliorating the EoT in our murine multiple trauma and UCH model. Lyophilized cryoprecipitate may also provide additional benefit by enhancing the ADAMTS13/VWF ratio. These data provide evidence of the safety and efficacy of LPRC and warrants further investigation for its potential application in military settings once approved for human administration.

Contemporary management and outcomes of penetrating colon injuries: Validation of the 2020 AAST Colon Organ Injury Scale.

INTRODUCTION: The American Association for the Surgery of Trauma Colon Organ Injury Scale (OIS) was updated in 2020 to include a separate OIS for penetrating colon injuries and included imaging criteria. In this multicenter study, we describe the contemporary management and outcomes of penetrating colon injuries and hypothesize that the 2020 OIS system correlates with operative management, complications, and outcomes. METHODS: This was a retrospective study of patients presenting to 12 Level 1 trauma centers between 2016 and 2020 with penetrating colon injuries and Abbreviated Injury Scale score of <3 in other body regions. We assessed the association of the new OIS with surgical management and clinical outcomes and the association of OIS imaging criteria with operative criteria. Bivariate analysis was done with χ 2 , analysis of variance, and Kruskal-Wallis, where appropriate. Multivariable models were constructed in a stepwise selection fashion. RESULTS: We identified 573 patients with penetrating colon injuries. Patients were young and predominantly male; 79% suffered a gunshot injury, 11% had a grade V destructive injury, 19% required ≥6 U of transfusion, 24% had an Injury Severity Score of >15, and 42% had moderate-to-large contamination. Higher OIS was independently associated with a lower likelihood of primary repair, higher likelihood of resection with anastomosis and/or diversion, need for damage-control laparotomy, and higher incidence of abscess, wound infection, extra-abdominal infections, acute kidney injury, and lung injury. Damage control was independently associated with diversion and intra-abdominal and extra-abdominal infections. Preoperative imaging in 152 (27%) cases had a low correlation with operative findings ( κ coefficient, 0.13). CONCLUSION: This is the largest study to date of penetrating colon injuries and the first multicenter validation of the new OIS specific to these injuries. While imaging criteria alone lacked strong predictive value, operative American Association for the Surgery of Trauma OIS colon grade strongly predicted type of interventions and outcomes, supporting use of this grading scale for research and clinical practice. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Validation of the American Association for the Surgery of Trauma Organ Injury Scale for Penetrating Colon Injuries.

In 2020, the American Association for the Surgery of Trauma (AAST) published a revision of the organ injury scale (OIS) for bowel injuries. The update included for the first time a separate OIS for penetrating colon injuries as well as imaging criteria. To validate the new OIS and its correlation with outcomes, we performed a retrospective review of patients with penetrating colon injuries (AIS<3 in other body regions) between 2016 and 2020 at a single institution. Sixty-six patients met inclusion criteria. Most were young (29 years median) and male (90%). All underwent operative intervention and 23 (34%) had pre-operative imaging. Imaging grade was higher than operative grade in 11 patients (48%). Higher AAST operative grade was associated with a higher likelihood of resection and anastomosis or colostomy, need for damage control laparotomy, and development of intra-abdominal abscess and acute kidney injury. A multicenter study is underway to confirm these findings.

Biomarkers of endothelial cell dysfunction persist beyond resuscitation in patients with hemorrhagic shock.

BACKGROUND: It has been shown that microRNA-19b (miR-19b) binds to and degrades syndecan-1 after hemorrhagic shock (HS) and contributes to endothelial dysfunction in vitro and in vivo. The objective of the current study was to assess longitudinal changes in miR-19b and syndecan-1 in HS patients. METHODS: Blood samples from HS patients (blood pressure <90 mm Hg and ≥2 U blood) were collected upon admission, completion of hemostasis, and after 24 hours for miR-19b (quantitative reverse transcription PCR) and syndecan-1 (enzyme-linked immunosorbent assay) and compared with controls and minimally injured (Injury Severity Score, ≤9). Inflammatory cytokines were measured (Luminex [Thermo Fisher, Waltham, MA]). Correlations between syndecan-1, miR-19b, inflammatory markers, and patient outcomes were performed. Logistic regression models were developed for outcomes. RESULTS: Thirty-four HS patients were studied: age, 46 (19-89) years; male, 82%; penetrating, 35%; Injury Severity Score, 24 ± 10; and blood products at 24 hours, 21 ± 19 U. MicroRNA-19b was increased upon arrival and further increased over time: 4.6 → 6.7 → 24.1-fold change compared with 0.1 and 1.2 for minimally injured patients and controls, respectively. Syndecan-1 was increased to 42.6 → 50 → 51.5 ng/mL over time compared with 14.7 and 23.5 for minimally injured and controls, respectively. Values for both biomarkers remained significantly increased through 24 hours and were associated with a persistent increase in inflammatory cytokines. Admission syndecan-1 significantly predicted mortality, coagulopathy, and massive transfusion. CONCLUSION: We have shown for the first time that miR-19b and syndecan-1 were biomarkers for endothelial dysfunction independent of resuscitation. MicroRNA-19b did not demonstrate a strong correlation with syndecan-1 nor outcomes. Admission syndecan-1, however, remains a strong prognostic marker, but its elevation over time suggests a versatile role following HS that requires further investigation. LEVEL OF EVIDENCE: Prognostic/Epidemiological; Level II.

TRAUMA-DERIVED EXTRACELLULAR VESICLES ARE SUFFICIENT TO INDUCE ENDOTHELIAL DYSFUNCTION AND COAGULOPATHY.

ABSTRACTINTRODUCTION: Although a number of studies have demonstrated increased release of extracellular vesicles (EVs) and changes in their origin differentials after trauma, the biologic significance of EVs is not well understood. We hypothesized that EVs released after trauma/hemorrhagic shock (HS) contribute to endotheliopathy and coagulopathy. To test this hypothesis, adoptive transfer experiments were performed to determine whether EVs derived from severely injured patients in shock were sufficient to induce endothelial dysfunction and coagulopathy. Methods: Total EVs were enriched from plasma of severely injured trauma/HS patients or minimally injured patients by ultracentrifugation and characterized for size and numbers. Under isoflurane anesthesia, noninjured naive C57BL/6J mice were administered EVs at varying concentrations and compared with mice receiving equal volume vehicle (phosphate-buffered saline (PBS)) or to mice receiving EVs from minimally injured patients. Thirty minutes after injection, mice were sacrificed, and blood was collected for thrombin generation (thrombin-antithrombin, thrombin-antithrombin complex [TAT] assay) and syndecan-1 by enzyme-linked immunoabsorbent assay (ELISA). Lungs were harvested for examination of histopathologic injury and costained with von Willebrand factor and fibrin to identify intravascular coagulation. Bronchial alveolar lavage fluid was aspirated from lungs for protein measurement as an indicator of the endothelial permeability. Data are presented as mean ± SD, P < 0.05 was considered significant, and t test was used. Results: An initial proof-of-concept experiment was performed in naive mice receiving EVs purified from severely injured trauma/HS patients (Injury Severity Score [ISS], 34 ± 7) at different concentrations (5 × 106 to 3.1 × 109/100 µL/mouse) and compared with PBS (control) mice. Neither TAT nor syndecan-1 levels were significantly different between groups at 30 minutes after EV infusion. However, lung vascular permeability and histopathologic injury were significantly higher in the EV group, and lung tissues demonstrated intravascular fibrin deposition. Based on these data, EVs from severely injured trauma/HS patients (ISS, 32 ± 6) or EVs from minimally injured patients (ISS, 8 ± 3) were administered to naive mice at higher concentrations (1 × 109 to 1 × 1010 EV/100 µL/mouse). Compared with mice receiving EVs from minimally injured patients, plasma TAT and syndecan-1 levels were significantly higher in the trauma/HS EV group. Similarly, bronchial alveolar lavage protein and lung histopathologic injury were higher in the trauma/HS EV group, and lung tissues demonstrated enhanced intravascular fibrin deposition. Conclusion: These data demonstrate that trauma/HS results in the systemic release of EVs, which are capable of inducing endotheliopathy as demonstrated by elevated syndecan-1 and increased permeability and coagulopathy as demonstrated by increased TAT and intravascular fibrin deposition. Targeting trauma-induced EVs may represent a novel therapeutic strategy.

Diversity, Equity, and Inclusion: A Current Analysis of General Surgery Residency Programs.

BACKGROUND: Local, regional, and national diversity, equity, and inclusion (DEI) initiatives have been established to combat barriers to entry and promote retention in surgery residency programs. Our study evaluates changes in diversity in general surgery residency programs. We hypothesize that diversity trends have remained stable nationally and regionally. MATERIALS AND METHODS: General surgery residents in all postgraduate years were queried regarding their self-reported sex, race, and ethnicity following the 2020 ABSITE. Residents were then grouped into geographic regions. Data were analyzed utilizing descriptive statistics, Kruskal-Wallis test, and chi-square analyses. RESULTS: A total of 9276 residents responded. Nationally, increases in female residents were noted from 38.0 to 46.0% (P < .001) and in Hispanic or Latinx residents from 7.3 to 8.3% (P = .031). Across geographic regions, a significant increase in female residents was noted in the Northwest (51.9 to 58.3%, P = .039), Midwest (36.9 to 43.3%, P = .006), and Southwest (35.8 to 47.5%, P = .027). A significant increase in black residents was only noted in the Northwest (0 to 15.8%, P = .031). The proportion of white residents decreased nationally by 8.9% and in the Mid-Atlantic, Southeast, and Southwest between 5.5 and 15.9% (P < .05). DISCUSSION: In an increasingly diverse society, expanding the numbers of underrepresented surgeons in training, and ultimately in practice, is a necessity. This study shows that there are region-specific increases in diversity, despite minimal change on a national level. This finding may suggest the need for region-specific DEI strategies and initiatives. Future studies will seek to evaluate individual programs with DEI plans and determine if there is a correlation to changing demographics.

A 20-year review of surgical training case logs: Is general surgery still general?

BACKGROUND: Surgical training has undergone many facets of restructuring over the most recent decades, with critiques of the quality and variability of training as well as the competency of recent graduates. This study examines the changes in surgical training in operative volume and breadth in the past 2 decades. METHODS: The Accreditation Council for Graduate Medical Education Case Log Statistics Reports from 1999 to 2019 were reviewed. Case logs were grouped into defined case categories and group levels of postgraduate training. Descriptive analyses and multiple linear regressions were performed. RESULTS: General surgery residents are graduating with 10.7% more cases, owing to increases in mostly junior year cases (P < .001). The breadth of specialty cases has decreased, while there was an increase in alimentary and abdominal cases to 58.4% from 47.2% 20 years ago. A decrease in vascular surgery cases from 19.9% to 10.7% of all cases was noted. Analysis of the distribution of defined categories showed right skewness in many categories with mode being much lower than reported mean. CONCLUSION: Evaluation of trends, despite residents graduating with higher case volume than the minimum required, shows that the breadth and variety of cases has narrowed significantly in the past 20 years, providing a case for general surgery training restructuring.

Role of Von Willebrand Factor after Injury: It May Do More Than We Think.

ABSTRACT: Acute traumatic coagulopathy is a complex phenomenon following injury and a main contributor to hemorrhage. It remains a leading cause of preventable death in trauma patients. This phenomenon is initiated by systemic injury to the vascular endothelium that is exacerbated by hypoperfusion, acidosis, and hypothermia and leads to systemic activation of the coagulation cascades and resultant coagulopathy. Many previous studies have focused on endotheliopathy with targeted markers such as syndecan-1, soluble thrombomodulin, and plasma adrenaline as potential culprits for initiation and propagation of this state. However, in more recent studies, hyperadhesive von Willebrand factor (VWF), which is released following endothelial injury, and its cleaving metalloprotease ADAMTS13 have emerged as significant targets of the downstream effect of endothelial breakdown and coagulation dysregulation. Elucidation of the mechanism by which the dysregulated VWF-ADAMTS13 axis leads to endothelial dysfunction and coagulopathy after trauma can help identify new targets for therapy and sites for intervention. Much of what is known mechanistically regarding VWF stems from work done in traumatic brain injury. Following localized brain injury, brain-derived extracellular vesicles are released into circulation where they induce a hypercoagulable state that rapidly turns into consumptive coagulopathy. VWF released from injured endothelial cells binds to these extracellular vesicles to enhance their activity in promoting coagulopathy and increasing endothelial permeability. However, there are numerous gaps in our knowledge of VWF following injury, providing a platform for further investigation.