Early Chemoprophylaxis Against Venous Thromboembolism in Patients With Traumatic Brain Injury.

INTRODUCTION: Timing to start of chemoprophylaxis for venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) remains controversial. We hypothesize that early administration is not associated with increased intracranial hemorrhage. METHODS: A retrospective study of adult patients with TBI following blunt injury was performed. Patients with penetrating brain injury, any moderate/severe organ injury other than the brain, need for craniotomy/craniectomy, death within 24 hours of admission, or progression of bleed on 6 hour follow-up head computed tomography scan were excluded. Patients were divided into early (≤24 hours) and late (>24 hours) cohorts based on time to initiation of chemoprophylaxis. Progression of bleed was the primary outcome. RESULTS: 264 patients were enrolled, 40% of whom were in the early cohort. The average time to VTE prophylaxis initiation was 17 hours and 47 hours in the early and late groups, respectively (P < .0001). There was no difference in progression of bleed (5.6% vs. 7%, P = .67), craniectomy/-craniotomy rate (1.9% vs. 2.5%, P = .81), or VTE rate (0% vs. 2.5%, P = .1). CONCLUSION: Early chemoprophylaxis is not associated with progression of hemorrhage or need for neurosurgical intervention in patients with TBI and a stable head CT 7 hours following injury.

Characteristics of survivors of civilian public mass shootings: An Eastern Association for the Surgery of Trauma multicenter study.

BACKGROUND: Firearm injury remains a public health crisis. Whereas there have been studies evaluating causes of death in victims of civilian public mass shootings (CPMSs), there are no large studies evaluating injuries sustained and treatments rendered in survivors. The purpose of this study was to describe these characteristics to inform ideal preparation for these events. METHODS: A multicenter, retrospective study of CPMS survivors who were treated at designated trauma centers from July 1, 1999 to December 31, 2017, was performed. Prehospital and hospital variables were collected. Data are reported as median (25th percentile, 75th percentile interquartile range), and statistical analyses were carried out using Mann-Whitney U, χ2, and Kruskal-Wallis tests. Patients who died before discharge from the hospital were excluded. RESULTS: Thirty-one events involving 191 patients were studied. The median number of patients seen per event was 20 (5, 106), distance to each hospital was 6 (6, 10) miles, time to arrival was 56 (37, 90) minutes, number of wounds per patient was 1 (1, 2), and Injury Severity Score was 5 (1, 17). The most common injuries were extremity fracture (37%) and lung parenchyma (14%). Twenty-nine percent of patients did not receive paramedic-level prehospital treatment. Following arrival to the hospital, 27% were discharged from the emergency department, 32% were taken directly to the operating room/interventional radiology, 16% were admitted to the intensive care unit, and 25% were admitted to the ward. Forty percent did not require advanced treatment within 12 hours. The most common operations performed within 12 hours of arrival were orthopedic (15%) and laparotomy (15%). The most common specialties consulted were orthopedics (38%) and mental health (17%). CONCLUSION: Few CPMS survivors are critically injured. There is significant delay between shooting and transport. Revised triage criteria and a focus on rapid transport of the few severely injured patients are needed. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

The incidence of venous thromboembolic events in trauma patients after tranexamic acid administration: an EAST multicenter study.

To determine if there is a significant association between administration of tranexamic acid (TXA) in severely bleeding, injured patients, and venous thromboembolism (VTE), myocardial infarction (MI), or cerebrovascular accident (CVA). A multicenter, retrospective study was performed. Inclusion criteria were: age 18-80 years old and need for 5 units or more of blood in the first 24 h after injury. Exclusion criteria included: death within 24 h, pregnancy, administration of TXA more than 3 h following injury, and routine ultrasound surveillance for deep venous thrombosis. Incidence of VTE was the primary outcome. Secondary outcomes included MI, CVA, and death. A power analysis found that a total of 830 patients were needed to detect a true difference in VTE risk. 1333 patients (TXA = 887, No-TXA = 446 patients) from 17 centers were enrolled. There were no differences in age, shock index, Glasgow coma score, pelvis/extremity abbreviated injury score, or paralysis. Injury severity score was higher in the No-TXA group. Incidence of VTE, MI, or CVA was similar between the groups. The TXA group required significantly less transfusion (P < 0.001 for all products) and had a lower mortality [adjusted odds ratio 0.67 (95% confidence interval 0.45-0.98)]. Despite having a higher extremity/pelvis abbreviated injury score, results did not change when evaluating only patients with blunt injury. Use of TXA in bleeding, injured patients is not associated with VTE, MI, or CVA but is associated with a lower transfusion need and mortality.

Preoperative Factors Associated with Appendiceal Tumors in Nonelective Appendectomy.

Background: The rates of incidental appendiceal neoplasms after appendectomy performed for acute appendicitis is <2%. To date, no large studies have investigated the preoperative risk factors or imaging findings associated with incidental appendiceal tumors that present as appendicitis. Our study aims to identify preoperative factors that are associated with an increased risk of appendiceal tumors in patients who present with signs and symptoms of acute appendicitis. Materials and Methods: Using the targeted appendectomy American College of Surgeons National Surgical Quality Improvement Program database, we identified patients who underwent nonelective appendectomy for acute appendicitis in 2016. Patients with final pathology consistent with a tumor were compared with those with only appendicitis. A nonmatched case/control method was used to pull a random sample from the appendicitis cohort using a 1:4 ratio (tumor: acute appendicitis) to obtain adequate power for comparison. Preoperative patient variables and imaging findings were investigated using stepwise logistic regression to identify variables associated with appendiceal tumor. Results: Following multivariate analysis, preoperative imaging read of "indeterminate" and "not consistent with appendicitis," female gender, increased age, and lower preoperative white blood cell (WBC) count were significant predictors of tumor causing symptoms of appendicitis. The odds of having tumor pathology were significantly increased in patients with preoperative imaging of "indeterminate" and "not consistent with appendicitis." The odds of having tumor pathology were 82% higher for females than for males, increased by 2% for every 1-year increase in age, and increased by 3% for every one-unit decrease in WBC count. Conclusion: While incidental appendiceal tumors can present as acute appendicitis, 3 patient variables and one imaging finding were identified that may increase suspicion for appendiceal tumors. Consideration should be given to patients with these associated risk factors for additional preoperative consultation in addition to the potential for intraoperative pathology consultation.

Current Management of Gynecologic Trauma.

INTRODUCTION: To date, there are few reports describing the management of traumatic gynecologic injuries leaving physicians with little guidance. OBJECTIVE: Describe the injury patterns and the preferred management of these injuries. METHODS: A retrospective cohort study was performed using the National Trauma Data Bank (NTDB) from years 2011 to 2013. Female patients age 16 years and older with internal gynecologic injuries were identified based on diagnosis codes. Demographics, associated diagnoses and procedure codes were compiled for the cohort. RESULTS: 313 patients met inclusion criteria. The mechanism of injury was blunt in 236 (75%) patients, penetrating in 68 (21%), and other in 9 (4%). The mean Injury Severity Score was 16.6 ± 14.6. Mean age was 34 ± 21 years old. 226 (74.8%) patients had an ovarian and/or fallopian tube injury, 71 (25.2%) had a uterine injury, 8 (3%) had both, and 8 (3%) had injury to the ovarian or uterine vessels only. Of the 226 patients with ovarian and/or fallopian tube injury, 11(5%) underwent repair and 10 (4%) underwent salpingo-oophorectomy. Of the 71 uterine injuries, 15 (21%) underwent repair and 5 (7%) required a hysterectomy. CONCLUSIONS: Most traumatic internal gynecologic injuries result from blunt mechanism. Currently, these injuries are largely managed non-operatively. When surgery was performed, ovarian and uterine repair was more common than salpingo-oophorectomy and hysterectomy. Prospective large-scale studies are needed to establish a standard of treatment for the management of gynecologic trauma and to assess both short and long term outcomes and fertility rates.

National trends in total vs subtotal gastrectomy for middle and distal third gastric cancer.

BACKGROUND: To identify trends in total and subtotal gastrectomy for middle and distal third gastric adenocarcinoma in the U.S. METHODS: NCDB was queried for patients with stage 0-III middle or distal gastric adenocarcinoma treated with total or subtotal gastrectomy. Statistical analysis including cox proportional hazards model was performed to examine overall survival by stage. RESULTS: 1,628 (85%) underwent subtotal gastrectomy and 283 (15%) underwent total. 1113 patients (58%) had distal tumors and 798 (42%) had middle tumors. Total gastrectomy patients more often had poor tumor grade (60% vs 50%,p < 0.01), larger size (46.3 mm vs 37.8 mm,p < 0.0001), had positive nodes (3.6 ± 5.9 vs 2.2 ± 4.1,p < 0.0001), underwent chemoradiation (13% vs 6%,p < 0.0001), and were higher clinical stage (p < 0.05). An overall survival curve showed an adjusted HR of 2.7 for total vs subtotal gastrectomy at clinical stage 3 (p < 0.05). CONCLUSIONS: Total gastrectomy is performed for larger, more aggressive tumors with higher stage. Subtotal gastrectomy may have a survival benefit for stage III gastric cancers.

Incidence and Cause of Potentially Preventable Death after Civilian Public Mass Shooting in the US.

BACKGROUND: The incidence and severity of civilian public mass shooting (CPMS) events continue to rise. Understanding the wounding pattern and incidence of potentially preventable death (PPD) after CPMS is key to updating prehospital response strategy. METHODS: A retrospective study of autopsy reports after CPMS events identified via the Federal Bureau of Investigation CPMS database from December 1999 to December 31, 2017 was performed. Sites of injury, fatal injury, and incidence of PPD were determined independently by a multidisciplinary panel composed of trauma surgery, emergency medicine, critical care paramedicine, and forensic pathology. RESULTS: Nineteen events including 213 victims were reviewed. Mean number of gunshot wounds per victim was 4.1. Sixty-four percent of gunshots were to the head and torso. The most common cause of death was brain injury (52%). Only 12% (26 victims) were transported to the hospital and the PPD rate was 15% (32 victims). The most commonly injured organs in those with PPD were the lung (59%) and spinal cord (24%). Only 6% of PPD victims had a gunshot to a vascular structure in an extremity. CONCLUSIONS: The PPD rate after CPMS is high and is due mostly to non-hemorrhaging chest wounds. Prehospital care strategy should focus on immediate point of wounding care by both laypersons and medical personnel, as well as rapid extrication of victims to definitive medical care.

The Effect of Pancreaticojejunostomy Technique on Fistula Formation Following Pancreaticoduodenectomy in the Soft Pancreas.

INTRODUCTION: A soft pancreas has been associated with an increased risk of post-operative pancreatic fistula formation. Few studies have evaluated the effect of anastomotic technique (duct to mucosa vs invagination) on fistula formation. This study aims to compare the effect of anastomotic technique on fistula formation among patients with a soft pancreas in a large multiinstitutional database. METHODS: The targeted pancreas module of the American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) Database was used. All patients with a soft pancreas who underwent pancreaticoduodenectomy from 2014 to 2015 were identified. Demographic data, comorbid conditions, operative variables, and 30-day outcomes were compared using univariate and multivariable analyses. RESULTS: A total of 975 patients met inclusion criteria. Eight-hundred fifty four (88%) underwent a duct to mucosa pancreaticojejunostomy technique and 121 (12%) underwent invagination. Patients who underwent invagination had higher 30-day mortality (5.8% vs 1.4%, p < 0.01), higher fistula formation (38% vs 25%, p < 0.01), and more often had percutaneous drain placement post-operatively (27% vs 14%, p < 0.01). Following multivariable analysis, invagination remained associated with pancreatic fistula formation (OR 2.5, CI 1.4-4.3) and post-operative percutaneous drain placement (OR 1.8, CI 1.1-2.9). CONCLUSION: Invagination technique for pancreaticojejunostomy in patients with a soft pancreas is associated with increased rates of pancreatic fistula. Surgeons should consider utilizing a duct to mucosa technique when feasible to decrease morbidity following pancreaticoduodenectomy in this patient population.

Barriers to bariatric surgery: Factors influencing progression to bariatric surgery in a U.S. metropolitan area.

BACKGROUND: Bariatric surgery is an effective and durable treatment for obesity. However, the number of patients that progress to bariatric surgery after initial evaluation remains low. OBJECTIVES: The purpose of this study was to identify factors influencing a qualified patient's successful progression to surgery in a U.S. metropolitan area. SETTING: Academic, university hospital. METHODS: A single-institution retrospective chart review was performed from 2003 to 2016. Patient demographics and follow-up data were compared between those who did and did not progress to surgery. A follow-up telephone survey was performed for patients who failed to progress. Univariate analyses were performed and statistically significant variables of interest were analyzed using a multivariable logistic regression model. RESULTS: A total of 1102 patients were identified as eligible bariatric surgery candidates. Four hundred ninety-eight (45%) patients progressed to surgery and 604 (55%) did not. Multivariable analysis showed that patients who did not progress were more likely male (odds ratio [OR] 2.2 confidence interval [CI]: 1.2-4.2, P < .05), smokers (OR 2.4 CI: 1.1-5.4, P < .05), attended more nutrition appointments (OR 2.1 CI: 1.5-2.8, P < .0001), attended less total preoperative appointments (OR .41 CI: .31-.55, P < .0001), and resided in-state compared with out of state (OR .39 CI: .22-.68, P < .05). The top 3 patient self-reported factors influencing nonprogression were fear of complication, financial hardship, and insurance coverage. CONCLUSIONS: Multiple patient factors and the self-reported factors of fear of complication and financial hardship influenced progression to bariatric surgery in a U.S. metropolitan population. Bariatric surgeons and centers should consider and address these factors when assessing patients.

The association of IVC filter placement with the incidence of postoperative pulmonary embolism following laparoscopic bariatric surgery: an analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Project.

BACKGROUND: Venous thromboembolism, including pulmonary embolism (PE) and deep venous thrombosis, is a leading cause of morbidity and mortality after bariatric surgery. Inferior vena cava filters (IVCFs) have been used as a method to reduce the incidence of clinically significant PEs after bariatric surgery. OBJECTIVES: To compare the incidence of postoperative PEs in patients with IVCFs with those in patients without IVCFs at the time of bariatric surgery. SETTING: American College of Surgeons Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program. METHODS: All patients undergoing laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy from 2015 to 2016 were identified within the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database. Patients with an IVCF present at the time of surgery were compared with those patients without an IVCF present at the time of surgery with respect to preoperative patient variables, operative variables, incidence of 30-day PE, deep venous thrombosis, and additional 30-day morbidity and mortality. RESULTS: A total of 286,704 patients met the inclusion criteria; 2512 (.9%) patients had an IVCF present at the time of surgical intervention, of which 1747 (69.5%) were placed within 30 days of bariatric surgery. Patients with an IVCF were higher-risk patients as determined by previously established risk factors for venous thromboembolism events. When a subgroup matched analysis using variables associated with the risk of venous thromboembolism events was performed looking at higher-risk patients only, there was no statistically significant difference in the incidence of PE based on the presence of an IVCF. CONCLUSION: IVCFs are being selectively placed in higher-risk patients. Despite their selective use, IVCFs do not appear to have a protective benefit with respect to the incidence of postoperative PE events.

Older Age Confers a Higher Risk of 30-Day Morbidity and Mortality Following Laparoscopic Bariatric Surgery: an Analysis of the Metabolic and Bariatric Surgery Quality Improvement Program.

INTRODUCTION: There is a paucity of literature describing the association of age with the risk of adverse events following bariatric surgery. The purpose of this study is to investigate the association of age with 30-day morbidity and mortality following laparoscopic bariatric surgery using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database. METHODS: All adult patients undergoing laparoscopic Roux-en-Y gastric bypass (RNGYB) or sleeve gastrectomy (SG) were identified within the MBSAQIP database. Patients were divided into five equal age quintiles. Binary outcomes of interest, including cardiac, pulmonary, wound, septic, clotting, and renal events, in addition to the incidence of related 30-day unplanned reintervention, related 30-day mortality, and a composite morbidity and mortality outcome were compared across the age quintiles and procedures. RESULTS: A total of 266,544 patients met inclusion criteria. Older age was associated with an increased risk of all morbidity outcomes except venous thromboembolism events, 30-day mortality, and the composite morbidity and mortality outcome. Patients who underwent Roux-en-Y gastric bypass had worse outcomes per quintile for almost every outcome of interest when compared to patients who underwent sleeve gastrectomy. CONCLUSION: Older patients and patients who undergo Roux-en-Y gastric bypass are at an increased risk of perioperative morbidity and mortality following laparoscopic bariatric surgery. Additional studies are needed to determine the association of age with long-term weight loss and cardiometabolic comorbidity resolution following bariatric surgery in order to determine if the increased perioperative risk is offset by improved long-term outcomes in older patients undergoing bariatric surgery.

Successful Surgical Stabilization of Rib Fractures Despite Candida Colonization of the Mediastinum.

Pleural space or chest wall infection is a contraindication to surgical stabilization of rib fractures (SSRF) because of the risk of hardware infection. However, the exact degree of risk is uncertain. SSRF is associated with a decreased need for mechanical ventilation and pneumonia. This case report describes a patient with polytrauma and Candida colonization of the mediastinum who successfully underwent SSRF.

Neoadjuvant Radiation Is Associated with Fistula Formation Following Pancreaticoduodenectomy.

BACKGROUND: Post-operative pancreatic fistulas remain a significant source of morbidity following pancreatic surgery. Few studies have evaluated the effect of neoadjuvant chemotherapy and radiation on this adverse outcome. This study aims to evaluate the effects of neoadjuvant therapy on 30-day morbidity and mortality following pancreaticoduodenectomy. STUDY DESIGN: A retrospective analysis was performed utilizing the targeted pancreas module of the National Surgical Quality Improvement Project (NSQIP) from 2014 to 2015 for patients undergoing pancreaticoduodenectomy with pancreaticojejunal reconstruction. A fistula was defined according to the NSQIP definition. Patient demographics, operative variables, and 30-day outcomes were compared between those who received no neoadjuvant therapy, chemoradiation, chemotherapy alone, and radiation alone. Univariate analysis was completed using chi-square, Fisher exact test, Student's t test, and Mann-Whitney U test where appropriate. Independent predictors of fistula formation were established using multivariable regression. A P value < 0.05 was considered significant. RESULTS: Three thousand one hundred fourteen patients were included of which 559 patients (18%) developed a pancreatic fistula. Two thousand six hundred thirty-five (85%) patients did not undergo neoadjuvant therapy, 207 (6.6%) had chemoradiation, 256 (8.2%) had chemotherapy alone, and 16 (0.5%) had radiation alone. Patients who developed a fistula had increased 30-day mortality (4.9 vs. 1.7%, P < .001) and major morbidities. Following multivariable analysis, neoadjuvant radiation (OR 2.1, 95% CI 1.0-4.5) was associated with increased fistula formation while neoadjuvant chemotherapy (OR 0.5, 95% CI 0.3-0.9) was protective. CONCLUSION: Neoadjuvant chemotherapy provides protection against the development of pancreatic fistulas while neoadjuvant radiation potentiates formation likely due to their effects on the texture of the pancreatic gland. Given the morbidity of pancreatic fistula formation, these factors should be considered in neoadjuvant regimens.

Sepsis Rapid Response Teams.

Sepsis rapid response teams are being incorporated into hospitals around the world. Based on the concept of the medical emergency team, the sepsis rapid response team consists of a specifically trained team of health care providers educated in the early recognition, diagnosis, and treatment of patients at risk of having or who have sepsis. Using hospital-wide initiatives consisting of multidisciplinary education, training, and specific resource utilization, such teams have been found to improve patient outcomes.

Inhibition of CDK-mediated phosphorylation of Smad3 results in decreased oncogenesis in triple negative breast cancer cells.

Breast cancer onset and disease progression have been linked to members of the TGFß superfamily and their downstream signaling components, the Smads. Alterations in Smad3 signaling are associated with the dichotomous role of TGFß in malignancy, mediating both tumor suppressant and pro-metastatic behaviors. Overexpression of cell cycle regulators, cyclins D and E, renders cyclin-dependent kinases (CDKs) 4/2 hyperactive. Noncanonical phosphorylation of Smad3 by CDK4/2 inhibits tumor suppressant actions of Smad3. We hypothesized that CDK inhibition (CDKi) would restore Smad3 action and help promote cancer cell regression. Treatment of triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, MDA-MB-436, Hs578T) with CDK2i or CDK4i resulted in increased Smad3 activity and decreased cell migration. Transfection with a 5M Smad3 construct containing inhibitory mutations in 5 CDK phosphorylation sites also resulted in decreased TNBC cell migration and invasion. MDA-MB-231 cells treated with CDK2i or CDK4i resulted in decreased Smad3 protein phosphorylation at the CDK phosphorylation T179 site, decreased MMP2 and c-myc expression, and increased p15 and p21 expression. Using a novel transfected cell array, we found that CDK2i treatment decreased activity of the epithelial-to-mesenchymal transition related transcription factors Snail and Twist. In vivo studies in an MDA-MB-231 tumor model showed that individual and combination treatment with paclitaxel and CDK2i resulted in decreased tumor volume and Ki67 staining. Collectively, these data support further investigation of targeted CDK inhibitors as a promising therapeutic strategy for TNBC, a breast cancer subtype with limited treatment options.