Nationwide, County-Level Analysis of the Patterns, Trends, and System-Level Predictors of Opioid Prescribing in Surgery in the US: Social Determinants and Access to Mental Health Services Matter.

BACKGROUND: The diversion of unused opioid prescription pills to the community at large contributes to the opioid epidemic in the US. In this county-level population-based study, we aimed to examine the US surgeons' opioid prescription patterns, trends, and system-level predictors in the peak years of the opioid epidemic. STUDY DESIGN: Using the Medicare Part D database (2013 to 2017), the mean number of opioid prescriptions per beneficiary (OPBs) was determined for each US county. Opioid-prescribing patterns were compared across counties. Multivariable linear regression was performed to determine relationships between county-level social determinants of health (demographic, eg median age and education level; socioeconomic, eg median income; population health status, eg percentage of current smokers; healthcare quality, eg rate of preventable hospital stays; and healthcare access, eg healthcare costs) and OPBs. RESULTS: Opioid prescription data were available for 1,969 of 3,006 (65.5%) US counties, and opioid-related deaths were recorded in 1,384 of 3,006 counties (46%). Nationwide, the mean OPBs decreased from 1.08 ± 0.61 in 2013 to 0.87 ± 0.55 in 2017; 81.6% of the counties showed the decreasing trend. County-level multivariable analyses showed that lower median population age, higher percentages of bachelor's degree holders, higher percentages of adults reporting insufficient sleep, higher healthcare costs, fewer mental health providers, and higher percentages of uninsured adults are associated with higher OPBs. CONCLUSIONS: Opioid prescribing by surgeons decreased between 2013 and 2017. A county's suboptimal access to healthcare in general and mental health services in specific may be associated with more opioid prescribing after surgery.

Renal Sarcoma: A Population-Based Study.

INTRODUCTION: Renal sarcomas are exceedingly rare and lack a prognostic stage classification. We thus aimed to investigate the contemporary clinicopathologic characteristics and outcomes of renal sarcomas at a national level. PATIENTS AND METHODS: We utilized the Surveillance, Epidemiology, and End Results database to extract data on patients with renal sarcoma diagnosed between 2004 and 2015. We estimated median, 1-, 3-, and 5-year overall survival (OS) probabilities via Kaplan-Meier curves and used multivariable regression to compare OS between different patient groups. RESULTS: We identified 365 patients; at diagnosis, 104 patients (28.5%) had stage I disease (T1N0M0), 133 patients (36.4%) patients had stage II disease (T2-4N0M0), and 117 patients (32.1%) patients had stage III disease (any T, N1, or M1). Median survival was 105 months (interquartile range [IQR], 29 - not reached) for stage I disease, 46 months (IQR 14-118 months) for stage II disease, 8 months (IQR 3-28 months) for stage III disease, and 32 months (IQR, 8-116 months) for the entire cohort. Patient age (hazard ratio [HR] for death [per year] 1.02, 95% confidence interval [95% CI] 1.00-1.04), stage (II vs. I: HR 1.71, 95% CI 1.00-2.92; III vs. I: HR 4.93, 95% CI 2.68-9.05), grade (grade 3 vs. grade 1: 3.07, 95% CI 1.18-8.00; grade 4 vs. grade 1: HR 3.66, 95% CI 1.41-9.49), and possessing medical insurance (HR 0.40, 95% CI 0.16-0.94) were independently and significantly associated with OS. Performance of nephrectomy also trended towards independently improving OS (HR 0.23, 95% CI 0.05-1.09). CONCLUSION: A novel staging classification for renal sarcomas into a 3-stage system based on Tumor Node Metastasis (TNM) criteria produces distinct survival curves, although further studies are needed to robustly assess its validity.

Trauma patients with limited English proficiency: Outcomes from two level one trauma centers.

BACKGROUND: Outcomes for surgical patients with limited English proficiency (LEP) may be worse compared to patients with English proficiency. We sought to evaluate the association of LEP with outcomes for trauma patients. METHODS: Admitted adult patients on trauma service at two Level One trauma centers from 2015 to 2019 were identified. RESULTS: 12,562 patients were included in total; 7.3% had LEP. On multivariable analyses, patients with LEP had lower odds of discharge to post-acute care versus home compared to patients with English proficiency (OR 0.69; 95% CI 0.58-0.83; p < 0.001) but had similar length of stay (Beta coefficient 1.16; 95% CI 0.00-2.32; p = 0.05), and 30-day readmission (OR 1.08; 95% CI 0.87-1.35; p = 0.46). CONCLUSIONS: Trauma patients with LEP had comparable short-term outcomes to English proficient patients but were less likely to be discharged to post-acute care facilities. The role of structural barriers, family preferences, and other factors merit future investigation.

Stem Cell Therapies for Gastrointestinal Anastomotic Healing: A Systematic Review and Meta-Analysis on Results from Animal Studies.

BACKGROUND: Despite considerable progress in surgical techniques, anastomotic leak (AL) is a common complication after gastrointestinal surgery. Stem cells are a promising therapy to improve healing and have been used in gastrointestinal anastomoses. In this study, we perform a systematic review and meta-analysis to evaluate the efficacy of stem cell therapies in preventing ALs among animal studies. METHODS: A systematic review of the literature was performed by searching PubMed, Web of Science, and the Cochrane Library. We considered all anastomoses of the gastrointestinal tract (excl. biliary) from the esophagus to the rectum. Outcomes included AL rates on postoperative day (POD) 7 and the latest time point reported. RESULTS: Fourteen studies were identified, evaluating stem cells in gastrointestinal anastomoses, of which 1 was on esophageal, 2 on gastric, 2 on small intestinal, and 9 on colorectal anastomoses. Meta-analysis did not show significant differences in AL rates on POD 7 (odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.04-3.15, p = 0.248, I2 = 34.1%, 95% CI: 0-75.2%, Q = 6.07, df = 4, p = 0.194), but there was a nonsignificant trend for lower AL rates at the latest time point reported (OR 0.28, 95% CI: 0.08-1.01, p = 0.052, I2 = 34%, 95% CI: 0-70.8%, Q = 10.6, df = 7, p = 0.157). CONCLUSION: Stem cell therapy may be associated with lower AL rates in gastrointestinal anastomoses, though meta-analysis is severely inhibited by heterogeneous study design. More studies are needed to determine the therapeutic potential of stem cells.

Do not forget the platelets: The independent impact of red blood cell to platelet ratio on mortality in massively transfused trauma patients.

BACKGROUND: Balanced blood component administration during massive transfusion is standard of care. Most literature focuses on the impact of red blood cell (RBC)/fresh frozen plasma (FFP) ratio, while the value of balanced RBC:platelet (PLT) administration is less established. The aim of this study was to evaluate and quantify the independent impact of RBC:PLT on 24-hour mortality in trauma patients receiving massive transfusion. METHODS: Using the 2013 to 2018 American College of Surgeons Trauma Quality Improvement Program database, adult patients who received massive transfusion (≥10 U of RBC/24 hours) and ≥1 U of RBC, FFP, and PLT within 4 hours of arrival were retrospectively included. To mitigate survival bias, only patients with consistent RBC:PLT and RBC:FFP ratios between 4 and 24 hours were analyzed. Balanced FFP or PLT transfusions were defined as having RBC:PLT and RBC:FFP of ≤2, respectively. Multivariable logistic regression was used to compare the independent relationship between RBC:FFP, RBC:PLT, balanced transfusion, and 24-hour mortality. RESULTS: A total of 9,215 massive transfusion patients were included. The number of patients who received transfusion with RBC:PLT >2 (1,942 [21.1%]) was significantly higher than those with RBC:FFP >2 (1,160 [12.6%]) (p < 0.001). Compared with an RBC:PLT ratio of 1:1, a gradual and consistent risk increase was observed for 24-hour mortality as the RBC:PLT ratio increased (p < 0.001). Patients with both FFP and PLT balanced transfusion had the lowest adjusted risk for 24-hour mortality. Mortality increased as resuscitation became more unbalanced, with higher odds of death for unbalanced PLT (odds ratio, 2.48 [2.18-2.83]) than unbalanced FFP (odds ratio, 1.66 [1.37-1.98]), while patients who received both FFP and PLT unbalanced transfusion had the highest risk of 24-hour mortality (odds ratio, 3.41 [2.74-4.24]). CONCLUSION: Trauma patients receiving massive transfusion significantly more often have unbalanced PLT rather than unbalanced FFP transfusion. The impact of unbalanced PLT transfusion on 24-hour mortality is independent and potentially more pronounced than unbalanced FFP transfusion, warranting serious system-level efforts for improvement. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Enteral nutrition is associated with high rates of pneumonia in intensive care unit (ICU) patients with acute pancreatitis.

PURPOSE: Enteral nutrition is associated with improved outcomes in acute pancreatitis (AP), but previous studies have not focused on critically-ill patients. Our purpose was to determine the association between nutritional support and infectious complications in ICU-admitted patients with AP. METHODS: A retrospective analysis of patients with AP admitted in ICUs of 127 US hospitals from the eICU Collaborative were included. Patients were classified by type (initial and any use) of nutritional support they received: none (NN); oral (ON); enteral (EN); and parenteral nutrition (PN). RESULTS: 925 patients were identified. Length of stay was longer in the initial PN group (PN 21.3 ± 15.4 d, EN 19.1 ± 20.1 d, ON 8 ± 7.1 d, NN 6.6 ± 6.3 d, p < 0.001) and mortality was more common in the initial EN group (EN 16.7%, PN 8.9%, ON 2.7%, NN 10.9%, p < 0.001). Multivariate analysis found any EN use to be associated with infections (OR 2.12, 95% CI: 1.13-3.98, p = 0.019) and pneumonias (OR 2.04, 95% CI: 1.04-4.03, p = 0.039). CONCLUSION: EN was associated with an increased risk for pneumonias and overall infections in critically-ill patients with AP. More studies are needed to assess optimal nutritional approaches in critically-ill AP patients and patients who do not tolerate EN.

Intraoperative Deaths: Who, Why, and Can We Prevent Them?

INTRODUCTION: Intraoperative deaths (IODs) are rare but catastrophic. We systematically analyzed IODs to identify clinical and patient safety patterns. METHODS: IODs in a large academic center between 2015 and 2019 were included. Perioperative details were systematically reviewed, focusing on (1) identifying phenotypes of IOD, (2) describing emerging themes immediately preceding cardiac arrest, and (3) suggesting interventions to mitigate IOD in each phenotype. RESULTS: Forty-one patients were included. Three IOD phenotypes were identified: trauma (T), nontrauma emergency (NT), and elective (EL) surgery patients, each with 2 sub-phenotypes (e.g., ELm and ELv for elective surgery with medical arrests or vascular injury and bleeding, respectively). In phenotype T, cardiopulmonary resuscitation was initiated before incision in 42%, resuscitative thoracotomy was performed in 33%, and transient return of spontaneous circulation was achieved in 30% of patients. In phenotype NT, ruptured aortic aneurysms accounted for half the cases, and median blood product utilization was 2,694 mL. In phenotype ELm, preoperative evaluation did not include electrocardiogram in 12%, cardiac consultation in 62%, stress test in 87%, and chest x-ray in 37% of patients. In phenotype ELv, 83% had a single peripheral intravenous line, and vascular injury was almost always followed by escalation in monitoring (e.g., central/arterial line), alert to the blood bank, and call for surgical backup. CONCLUSIONS: We have created a framework for IOD that can help with intraoperative safety and quality analysis. Focusing on interventions that address appropriateness versus futility in care in phenotypes T and NT, and on prevention and mitigation of intraoperative vessel injury (e.g., intraoperative rescue team) or preoperative optimization in phenotype EL may help prevent IODs.

The Role of Transaminases in Predicting Choledocholithiasis. A Novel Predictive Composite Score Development in a Cohort of 1089 Patients Undergoing Laparoscopic Cholecystectomy.

BACKGROUND: Optimal use of interventional procedures and diagnostic tests for patients with suspected choledocholithiasis depends on accurate pretest risk estimation. We sought to define sensitivity/specificity of transaminases in identifying choledocholithiasis and to incorporate them into a biochemical marker composite score that could accurately predict choledocholithiasis. METHODS: All adult patients who underwent laparoscopic cholecystectomy by our Emergency Surgery Service between 2010 and 2018 were reviewed. Admission total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) was captured. Choledocholithiasis was confirmed via intraoperative cholangiogram, endoscopic retrograde cholangiopancreatography, or magnetic resonance cholangiopancreatography. Area under receiver operating characteristic curve (AUC) or C-statistic for AST, ALT, ALP, and TB as a measure of detecting choledocholithiasis was calculated. For score development, our database was randomly dichotomized to derivation and validation cohort and a score was derived. The score was validated by calculating its C-statistic. RESULTS: 1089 patients were included; 210 (20.3%) had confirmed choledocholithiasis. The AUC was .78 for TB, .77 for ALP and AST, and .76 for ALT. 545 and 544 patients were included in the derivation and the validation cohort, respectively. The elements of the derived score were TB, AST, and ALP. The score ranged from 0 to 4. The AUC was .82 in the derivation and .77 in the validation cohort. The probability of choledocholithiasis increased from 8% to 89% at scores 0 to 4, respectively. CONCLUSIONS: Aspartate aminotransferase predicted choledocholithiasis adequately and should be featured in choledocholithiasis screening algorithms. We developed a biochemical composite score, shown to be accurate in preoperative choledocholithiasis risk assessment in an emergency surgery setting.

Necrotizing Soft Tissue Infection in the Elderly: Effect of Pre-Operative Factors on Mortality and Discharge Disposition.

Background: Necrotizing soft tissue infections (NSTIs) are rapidly progressing, life-threatening diseases associated with substantial morbidity and mortality, especially in patients 65 years or older. We aimed to evaluate clinical factors associated with mortality and discharge disposition after NSTIs in elderly patients. Patients and Methods: Retrospective data were obtained from the 2007-2017 American College of Surgeons-National Surgical Quality (ACS-NSQIP) database. Patients aged 65 years or older with a post-operative diagnosis of an NSTI (defined as gas gangrene, necrotizing fasciitis, or Fournier gangrene) were included. Univariable and multivariable analyses were performed to identify independent clinical and demographic factors associated with mortality and with discharge disposition. Results: A total of 1,460 patients were included. Median age was 71 years, 43% were females. Overall, 30-day mortality was 18.5% and 30-day morbidity was 63.6%. The most important predictors of mortality included pre-operative septic shock (odds ratio [OR], 6.36; 95% confidence interval [CI], 3.61-11.18), pre-operative dialysis dependence (OR, 2.99; 95% CI, 1.77-5.05), coagulopathy (international normalized ratio [INR], >1.5, OR, 2.25; 95% CI, 1.51-3.37), hepatobiliary disease (bilirubin >1.0 mg/dL; OR, 2.05; 95% CI, 1.38-3.04) and aged 80 years or older (OR, 3.36; 95% CI, 2.08-5.44). Patients without any of these risk factors had a mortality of 7.3%. Predictors of discharge to inpatient rehabilitation or skilled care included age 80 years or older (OR, 2.49; 95% CI, 1.44-4.30), American Society of Anesthesiologists (ASA) ≥3 (OR, 2.05; 95% CI, 1.03-4.05)] and amputation as opposed to debridement (OR, 2.53; 95% CI,1.48-4.32). Conclusions: We identified several pre-operative clinical factors that were associated with increased post-operative mortality and discharge to post-acute care. The next steps should focus on determining if optimization of modifiable predictors would improve mortality.

Lower Mortality with Cryoprecipitate During Massive Transfusion in Penetrating but Not Blunt Trauma.

BACKGROUND: Balanced blood product transfusion improves the outcomes of trauma patients with exsanguinating hemorrhage, but it remains unclear whether administering cryoprecipitate improves mortality. We aimed to examine the impact of early cryoprecipitate transfusion on the outcomes of the trauma patients needing massive transfusion (MT). METHODS: All MT patients 18 years or older in the 2017 Trauma Quality Improvement Program (TQIP) were retrospectively reviewed. MT was defined as the transfusion of ≥10 units of blood within 24 hours. Propensity score analysis (PSA) was used to 1:1 match then compare patients who received and those who did not receive cryoprecipitate in the first 4 hours after injury. Outcomes included in-hospital mortality, 1-day mortality, in-hospital complications and transfusion needs at 24 hours. RESULTS: Of 1,004,440 trauma patients, 1,454 MT patients received cryoprecipitate and 2,920 did not. After PSA, 877 patients receiving cryoprecipitate were matched to 877 patients who did not. In-hospital mortality was lower among patients who received cryoprecipitate (49.4% v. 54.9%, P = 0.022), as was 1-day mortality. Sub-analyses showed that mortality was lower with cryoprecipitate in patients with penetrating (37.5% versus. 48%, adjusted P = 0.008), but not blunt trauma (58.5% versus. 59.8%, adjusted P = 1.000). In penetrating trauma, the cryoprecipitate group also had lower 1-day mortality (21.8% versus. 38.6%, P <0.001) and a higher rate of hemorrhage control surgeries performed within 24 hours (71.4% versus. 63.3%, P = 0.018). CONCLUSIONS: Cryoprecipitate in MT is associated with improved survival in penetrating, but not blunt, trauma. Randomized trials are needed to better define the role of cryoprecipitate in MT.

National adherence to the ASGE-SAGES guidelines for managing suspected choledocholithiasis: An EAST multicenter study.

BACKGROUND: The American Society for Gastrointestinal Endoscopy and Society of American Gastrointestinal and Endoscopic Surgeons provide guidelines for managing suspected common bile duct (CBD) stones. We sought to evaluate adherence to the guidelines among patients with choledocholithiasis and/or acute biliary pancreatitis (ABP) and to evaluate the ability of these guidelines to predict choledocholithiasis. METHODS: We prospectively identified patients undergoing same-admission cholecystectomy for choledocholithiasis and/or ABP from 2016 to 2019 at 12 United States medical centers. Predictors of suspected CBD stones were very strong (CBD stone on ultrasound; bilirubin >4 mg/dL), strong (CBD > 6 mm; bilirubin ≥1.8 to ≤4 mg/dL), or moderate (abnormal liver function tests other than bilirubin; age >55 years; ABP). Patients were grouped by probability of CBD stones: high (any very strong or both strong predictors), low (no predictors), or intermediate (any other predictor combination). The management of each probability group was compared with the recommended management in the guidelines. RESULTS: The cohort was comprised of 844 patients. High-probability patients had 64.3% (n = 238/370) deviation from guidelines, intermediate-probability patients had 29% (n = 132/455) deviation, and low-probability patients had 78.9% (n = 15/19) deviation. Acute biliary pancreatitis increased the odds of deviation for the high- (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.06-2.8; p = 0.03) and intermediate-probability groups (OR, 1.6; 95% CI, 1.07-2.42; p = 0.02). Age older than 55 years (OR, 2.19; 95% CI, 1.4-3.43; p < 0.001) also increased the odds of deviation for the intermediate group. A CBD greater than 6 mm predicted choledocholithiasis in the high (adjusted OR (aOR), 2.16; 95% CI, 1.17-3.97; p = 0.01) and intermediate group (aOR, 2.78; 95% CI, 1.59-4.86; p < 0.001). Any very strong predictor (aOR, 2.43; 95% CI, 1.76-3.37; p < 0.0001) and both strong predictors predicted choledocholithiasis (aOR, 2; 95% CI, 1.35-2.96; p < 0.001). CONCLUSION: Almost 45% of patients with suspected CBD stones were managed discordantly from the American Society for Gastrointestinal Endoscopy and Society of American Gastrointestinal and Endoscopic Surgeons guidelines. We believe these guidelines warrant revision to better reflect the ability of the clinical variables at predicting choledocholithiasis. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Early versus late enteral nutrition in critically ill patients receiving vasopressor support.

BACKGROUND: Outcomes of early enteral nutrition (EEN) in critically ill patients on vasoactive medications remain unclear. We aimed to compare in-hospital outcomes for EEN vs late EN (LEN) in mechanically ventilated patients receiving vasopressor support. METHODS: This was a retrospective study using the national eICU Collaborative Research Database. Adult patients requiring vasopressor support and mechanical ventilation within 24 h of admission and for ≥2 days were included. Patients with an admission diagnosis that could constitute a contraindication for EEN (eg, gastrointestinal [GI] perforation, GI surgery) and patients with an intensive care unit (ICU) length of stay (LOS) <72 h were excluded. EEN and LEN were defined as tube feeding within 48 h and between 48 h and 1 week (nothing by mouth during the first 48 h) of admission, respectively. Propensity score matching was performed to derive two cohorts receiving EEN and LEN that were comparable for baseline patient characteristics. RESULTS: Among 1701 patients who met the inclusion criteria (EEN: 1001, LEN: 700), 1148 were included in propensity score-matched cohorts (EEN: 574, LEN: 574). Median time to EN was 29 vs 79 h from admission in the EEN and LEN groups, respectively. There was no significant difference in mortality or hospital LOS between the two nutrition strategies. EEN was associated with shorter ICU LOS, lower need for renal replacement therapy, and lower incidence of electrolyte abnormalities. CONCLUSION: This study showed no difference in 28-day mortality between EEN and LEN in critically ill patients receiving vasopressor support.

Low-Molecular Weight Heparin is Superior to Unfractionated Heparin for Elderly Trauma Patients.

BACKGROUND: Several studies have demonstrated that low-molecular weight heparin (LMWH) is superior to unfractionated heparin (UFH) in trauma patients. The superiority of either one has not been established for the elderly. In this study, we compared LMWH to UFH in elderly trauma patients. METHODS: A retrospective analysis of the American College of Surgeons' Trauma Quality Improvement Program database was performed for patients aged ≥65 y. Propensity score matching was performed to minimize confounders between the two groups. Outcomes included venous thromboembolic (VTE) and bleeding events. RESULTS: Overall, 93,987 patients were identified (mean age 77.1 ± 7.3 y, females 55,035 [58.6%]), of which 67,738 (72.1%) patients received LMWH and 26,249 (27.9%) received UFH. After Propensity score matching, LMWH was associated with a lower incidence of deep venous thrombosis (1.7% versus 2.1%, P = 0.007) and pulmonary embolisms (0.6% versus 1%, P< 0.001). LMWH was also associated with fewer bleeding complications (transfusions: 2.8% versus 3.5%, P< 0.001, procedures: 0.7% versus 0.9%, P = 0.007). Sub-analyses showed that differences in VTE rates were identified in patients with mild injuries (Injury Severity Score [ISS] <16, 0.6% versus 1.9%, P< 0.001). Differences in bleeding complications were identified in patients with injuries of mild (ISS <16, transfusions: 3% versus 3.8%, P< 0.001, surgeries: 0.3% versus 0.4%, P= 0.015) and moderate severity (ISS 16-24, transfusions: 1.9% versus 2.7%, P= 0.038, surgeries: 1% versus 1.7%, P= 0.013). CONCLUSION: LMWH prophylaxis is superior to UFH for VTE prevention among elderly trauma patients. LMWH prophylaxis is associated with fewer bleeding complications compared to UFH in patients with injuries of mild or moderate severity.

Association Between NEDD4L Variation and the Genetic Risk of Acute Appendicitis: A Multi-institutional Genome-Wide Association Study.

Importance: The familial aspect of acute appendicitis (AA) has been proposed, but its hereditary basis remains undetermined. Objective: To identify genomic variants associated with AA. Design, Setting, and Participants: This genome-wide association study, conducted from June 21, 2019, to February 4, 2020, used a multi-institutional biobank to retrospectively identify patients with AA across 8 single-nucleotide variation (SNV) genotyping batches. The study also examined differential gene expression in appendiceal tissue samples between patients with AA and controls using the GSE9579 data set in the National Institutes of Health's Gene Expression Omnibus repository. Statistical analysis was conducted from October 1, 2019, to February 4, 2020. Main Outcomes and Measures: Single-nucleotide variations with a minor allele frequency of 5% or higher were tested for association with AA using a linear mixed model. The significance threshold was set at P = 5 × 10-8. Results: A total of 29 706 patients (15 088 women [50.8%]; mean [SD] age at enrollment, 60.1 [17.0] years) were included, 1743 of whom had a history of AA. The genomic inflation factor for the cohort was 1.003. A previously unknown SNV at chromosome 18q was found to be associated with AA (rs9953918: odds ratio, 0.99; 95% CI, 0.98-1.00; P = 4.48 × 10-8). This SNV is located in an intron of the NEDD4L gene. The heritability of appendicitis was estimated at 30.1%. Gene expression data from appendiceal tissue donors identified NEDD4L to be among the most differentially expressed genes (14 of 22 216 genes; ß [SE] = -2.71 [0.44]; log fold change = -1.69; adjusted P = .04). Conclusions and Relevance: This study identified SNVs within the NEDD4L gene as being associated with AA. Nedd4l is involved in the ubiquitination of intestinal ion channels and decreased Nedd4l activity may be implicated in the pathogenesis of AA. These findings can improve the understanding of the genetic predisposition to and pathogenesis of AA.

Rhabdomyolysis in Severe COVID-19: Male Sex, High Body Mass Index, and Prone Positioning Confer High Risk.

BACKGROUND: Bedside experience and studies of critically ill patients with coronavirus disease 2019 (COVID-19) indicate COVID-19 to be a devastating multisystem disease. We aim to describe the incidence, associated variables, and outcomes of rhabdomyolysis in critically ill COVID-19 patients. MATERIALS AND METHODS: Data for all critically ill adult patients (≥18 years old) admitted to the ICU at a large academic medical center with confirmed COVID-19 between March 13, 2020 and April 18, 2020 were prospectively collected. Patients with serum creatine kinase (CK) concentrations greater than 1000 U/L were diagnosed with rhabdomyolysis. Patients were further stratified as having moderate (serum CK concentration 1000-4999 U/L) or severe (serum CK concentration ≥5000 U/L) rhabdomyolysis. Univariate and multivariate analyses were performed to identify outcomes and variables associated with the development of rhabdomyolysis. RESULTS: Of 235 critically ill COVID-19 patients, 114 (48.5%) met diagnostic criteria for rhabdomyolysis. Patients with rhabdomyolysis more often required mechanical ventilation (P < 0.001), prone positioning (P < 0.001), pharmacological paralysis (P < 0.001), renal replacement therapy (P = 0.010), and extracorporeal membrane oxygenation (ECMO) (P = 0.025). They also had longer median ICU length of stay (LOS) (P < 0.001) and hospital LOS (P < 0.001). No difference in mortality was observed. Male sex, patients with morbid obesity, SOFA score, and prone positioning were independently associated with rhabdomyolysis. CONCLUSIONS: Nearly half of critically ill COVID-19 patients in our cohort met diagnostic criteria for rhabdomyolysis. Male sex, morbid obesity, SOFA score, and prone position were independently associated with rhabdomyolysis.

The positive effect of eugenol on acute pancreatic tissue injury: a rat experimental model.

INTRODUCTION: we present a rat experimental model used to evaluate the possible reduction in the extent of pancreatic tissue injury in acute pancreatitis cases, after administration of eugenol. METHODS: one hundred and twenty Wistar rats were used, which were randomly assigned in 3 groups: sham (n=20), control (n=50) and eugenol (n=50). Acute pancreatitis was induced by biliopancreatic ligation in the control and eugenol groups, but not in the Sham group. In the eugenol group, eugenol was administered per-os. Five histopathological parameters, such as edema, inflammatory infiltration, duct dilatation, hemorrhage and acinar necrosis were evaluated. RESULTS: at 72 h from acute pancreatitis induction, the total histological score was diminished in the eugenol group (p<0.0005) and duct dilatation and inflammatory infiltration were reduced compared to the control group (p<0.05). In addition, at 72 h, eugenol reduced pancreatic myeloperoxidase activity (p<0.0005). CONCLUSION: eugenol, a highly free radical scavenger agent, may have a preventive role in acute pancreatic injury, as it was evident in our rat experimental model.

Multisystem outcomes and predictors of mortality in critically ill patients with COVID-19: Demographics and disease acuity matter more than comorbidities or treatment modalities.

BACKGROUND: We sought to describe characteristics, multisystem outcomes, and predictors of mortality of the critically ill COVID-19 patients in the largest hospital in Massachusetts. METHODS: This is a prospective cohort study. All patients admitted to the intensive care unit (ICU) with reverse-transcriptase-polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 14, 2020, and April 28, 2020, were included; hospital and multisystem outcomes were evaluated. Data were collected from electronic records. Acute respiratory distress syndrome (ARDS) was defined as PaO2/FiO2 ratio of ≤300 during admission and bilateral radiographic pulmonary opacities. Multivariable logistic regression analyses adjusting for available confounders were performed to identify predictors of mortality. RESULTS: A total of 235 patients were included. The median (interquartile range [IQR]) Sequential Organ Failure Assessment score was 5 (3-8), and the median (IQR) PaO2/FiO2 was 208 (146-300) with 86.4% of patients meeting criteria for ARDS. The median (IQR) follow-up was 92 (86-99) days, and the median ICU length of stay was 16 (8-25) days; 62.1% of patients were proned, 49.8% required neuromuscular blockade, and 3.4% required extracorporeal membrane oxygenation. The most common complications were shock (88.9%), acute kidney injury (AKI) (69.8%), secondary bacterial pneumonia (70.6%), and pressure ulcers (51.1%). As of July 8, 2020, 175 patients (74.5%) were discharged alive (61.7% to skilled nursing or rehabilitation facility), 58 (24.7%) died in the hospital, and only 2 patients were still hospitalized, but out of the ICU. Age (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.04-1.12), higher median Sequential Organ Failure Assessment score at ICU admission (OR, 1.24; 95% CI, 1.06-1.43), elevated creatine kinase of ≥1,000 U/L at hospital admission (OR, 6.64; 95% CI, 1.51-29.17), and severe ARDS (OR, 5.24; 95% CI, 1.18-23.29) independently predicted hospital mortality.Comorbidities, steroids, and hydroxychloroquine treatment did not predict mortality. CONCLUSION: We present here the outcomes of critically ill patients with COVID-19. Age, acuity of disease, and severe ARDS predicted mortality rather than comorbidities. LEVEL OF EVIDENCE: Prognostic, level III.

Low-molecular-weight heparin versus unfractionated heparin in pediatric traumatic brain injury.

OBJECTIVE: The incidence of venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) has increased significantly. The Eastern Association for the Surgery of Trauma recommends using low-molecular-weight heparin (LMWH) over unfractionated heparin (UH) in pediatric patients requiring VTE prophylaxis, although this strategy is unsupported by the literature. In this study, the authors compare the outcomes of pediatric TBI patients receiving LMWH versus UH. METHODS: The authors performed a 4-year (2014-2017) analysis of the pediatric American College of Surgeons Trauma Quality Improvement Program. All trauma patients (age ≤ 18 years) with TBI requiring thromboprophylaxis with UH or LMWH were potentially eligible for inclusion. Patients who had been transferred, had died in the emergency department, or had penetrating trauma were excluded. Patients were stratified into either the LMWH or the UH group on the basis of the prophylaxis they had received. Patients were matched on the basis of demographics, injury characteristics, vital signs, and transfusion requirements using propensity score matching (PSM). The study endpoints were VTE, death, and craniotomy after initiation of prophylaxis. Univariate analysis was performed after PSM to compare outcomes. RESULTS: A total of 2479 patients met the inclusion criteria (mean age 15.5 ± 3.7 years and 32.0% female), of which 1570 (63.3%) had received LMWH and 909 (36.7%) had received UH. Before PSM, patients receiving UH were younger, had a lower Glasgow Coma Scale score, and had a higher Injury Severity Score. Patients treated in pediatric hospitals were more likely to receive UH (12.9% vs 9.0%, p < 0.001) than patients treated in adult hospitals. Matched patients receiving UH had a higher incidence of VTE (5.1% vs 2.9%, p = 0.03). CONCLUSIONS: LMWH prophylaxis in pediatric TBI appears to be more effective than UH in preventing VTE. Large, multicenter prospective studies are warranted to confirm the superiority of LMWH over UH in pediatric patients with TBI. Moreover, outcomes of VTE prophylaxis in the very young remain understudied; therefore, dedicated studies to evaluate this population are needed.

Performance of the Emergency Surgery Score (ESS) Across Different Emergency General Surgery Procedures.

BACKGROUND: The Emergency Surgery Score (ESS) has been previously validated as a reliable tool to predict postoperative outcomes in emergency general surgery (EGS). The purpose of this study is to assess the differential performance of the ESS in specific EGS procedures. METHODS: The American College of Surgeons' National Surgical Quality Improvement Program database was retrospectively analyzed for patients undergoing EGS between 2007 and 2017. Patients who underwent the following EGS procedures were identified: laparoscopic appendectomy, laparoscopic cholecystectomy, surgery for small bowel obstruction (SBO), colectomy, and incarcerated ventral or inguinal hernia repair. The performance of the ESS in predicting mortality in each procedure was assessed using receiver operating characteristic analyses. RESULTS: A total of 467,803 patients underwent EGS (mean age 50 ± 19.9 y, females 241,330 [51.6%]), of which 191,930 (41%) underwent laparoscopic appendectomy, 40,353 (8.6%) underwent laparoscopic cholecystectomy, and 35,152 (7.5%) patients underwent surgery for SBO. The ESS correlated extremely well with mortality for patients who underwent laparoscopic appendectomy (area under the curve (AUC) 0.91), laparoscopic cholecystectomy (AUC 0.91), lysis of adhesions for SBO (AUC 0.83), colectomy (AUC 0.83), and incarcerated hernia repair (AUC 0.85). CONCLUSIONS: ESS performance accurately predicts mortality across a wide range of EGS procedures, and its use should be encouraged for preoperative patient counseling and for nationally benchmarking the quality of care of EGS.

Outcomes of same admission cholecystectomy and endoscopic retrograde cholangiopancreatography for common bile duct stones: A post hoc analysis of an Eastern Association for the Surgery of Trauma multicenter study.

BACKGROUND: The optimal timing for cholecystectomy after endoscopic retrograde cholangiopancreatography (ERCP) for common bile duct (CBD) stones is unknown. We hypothesized that a delay between procedures would correlate with more biliary complications and longer hospitalizations. METHODS: We prospectively identified patients who underwent same admission cholecystectomy after ERCP for CBD stones from 2016 to 2019 at 12 US medical centers. The cohort was stratified by time between ERCP and cholecystectomy: ≤24 hours (immediate), >24 to ≤72 hours (early), and >72 hours (late). Primary outcomes included operative duration, postoperative length of stay, (LOS), and hospital LOS. Secondary outcomes included rates of open conversion, CBD explorations, biliary complications, and in-hospital complications. RESULTS: For the 349 patients comprising the study cohort, 33.8% (n = 118) were categorized as immediate, 50.4% (n = 176) as early, and 15.8% (n = 55) as late. Rates of CBD explorations were lower in the immediate group compared with the late group (0.9% vs. 9.1%, p = 0.01). Rates of open conversion were lower in the immediate group compared with the early group (0.9% vs. 10.8%, p < 0.01) and in the immediate group compared with the late group (0.9% vs. 10.9%, p < 0.001). On a mixed-model regression analysis, an immediate cholecystectomy was associated with a significant reduction in postoperative LOS (ß = 0.79; 95% confidence interval, 0.65-0.96; p = 0.02) and hospital LOS (ß = 0.68; 95% confidence interval, 0.62-0.75; p < 0.0001). CONCLUSION: An immediate cholecystectomy following ERCP correlates with a shorter postoperative LOS and hospital LOS. Rates of CBD explorations and conversion to open appear more common after 24 hours. LEVEL OF EVIDENCE: Therapeutic, level III.