Background: A novel hydrophobically modified chitosan (hm-chitosan) polymer has been previously shown to improve survival in a non-compressible intra-abdominal bleeding model in swine. We performed a 28-day survival study to evaluate the safety of the hm-chitosan polymer in swine. Methods: Female Yorkshire swine (40-50 kg) were used. A mild, non-compressible, closed-cavity bleeding model was created with splenic transection. The hm-chitosan polymer was applied intraabdominally through an umbilical nozzle in the same composition and dose previously shown to improve survival. Animals were monitored intraoperatively and followed 28 days postoperatively for survival, signs of pain, and end-organ function. Gross pathological and microscopic evaluations were performed at the conclusion of the experiment. Results: A total of 10 animals were included (hm-chitosan = 8; control = 2). The 2 control animals survived through 28 days, and 7 of the 8 animals from the hm-chitosan group survived without any adverse events. One animal from the hm-chitosan group required early termination of the study for signs of pain, and superficial colonic ulcers were found on autopsy. Laboratory tests showed no signs of endorgan dysfunction after exposure to hm-chitosan after 28 days. On gross pathological examination, small (<0.5 cm) peritoneal nodules were noticed in the hm-chitosan group, which were consistent with giantcell foreign body reaction in microscopy, presumably related to polymer remnants. Microscopically, no signs of systemic polymer embolization or thrombosis were noticed. Conclusion: Prolonged intraperitoneal exposure to the hm-chitosan polymer was tolerated without any adverse event in the majority of animals. In the single animal that required early termination, the material did not appear to be associated with end-organ dysfunction in swine. Superficial colonic ulcers that would require surgical repair were identified in 1 out of 8 animals exposed to hm-chitosan. (c) 2023 Elsevier Inc. All rights reserved.

INTRODUCTION:Pancreas divisum (PD) is a common congenital anomaly of the pancreas, but its genetic basis remains unknown. The purpose of this genome-wide association study was to identify genetic loci associated with PD. METHODS:Using the Mass General Brigham Biobank, patients diagnosed with PD were identified. Quality control and imputation were performed using standard approaches. Single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥ 5% were tested for association with PD using mixed linear model-based association analysis. The significance threshold was set at 5 × 10-8. RESULTS:A total of 13,940 subjects were included, of which 251 (1.8%) were diagnosed with PD. A genetic locus in chromosome 3q29 was found to be associated with PD (lead SNP rs3850646, MAFPD = 34.6% vs. MAFcontrols = 26.4%, beta = 0.0106, P = 1.47 × 10-8). The identified locus is located in the phosphatidylinositol glycan anchor biosynthesis class Xand p21 activated kinase 2genes. The heritability of PD was estimated at 27.5%. (Expression quantitative trait loci) and chromatin interaction analysis found 12 genes whose expression may be regulated by SNPs in this genomic locus. CONCLUSIONS:The results of this study suggest that a genetic locus at 3q29 is associated with PD. This locus is in the phosphatidylinositol glycan anchor biosynthesis class X and p21 activated kinase 2 genes. Twelve candidate genes were identified whose expression may be regulated by this locus. These findings may help us understand both normal and aberrant pancreatic development and may aid in clinical evaluation and genetic counseling of patients with PD and associated diseases, such as acute pancreatitis.

BACKGROUND Artificial intelligence (AI) risk prediction algorithms such as the smartphone-available Predictive OpTimal Trees in Emergency Surgery Risk (POTTER) for emergency general surgery (EGS) are superior to traditional risk calculators because they account for complex nonlinear interactions between variables, but how they compare to surgeons’ gestalt remains unknown. Herein, we sought to: (1) compare POTTER to surgeons’ surgical risk estimation and (2) assess how POTTER influences surgeons' risk estimation. STUDY DESIGN A total of 150 patients who underwent EGS at a large quaternary care center between May 2018 and May 2019 were prospectively followed up for 30-day postoperative outcomes (mortality, septic shock, ventilator dependence, bleeding requiring transfusion, pneumonia), and clinical cases were systematically created representing their initial presentation. POTTER's outcome predictions for each case were also recorded. Thirty acute care surgeons with diverse practice settings and levels of experience were then randomized into two groups: 15 surgeons (SURG) were asked to predict the outcomes without access to POTTER's predictions while the remaining 15 (SURG-POTTER) were asked to predict the same outcomes after interacting with POTTER. Comparing to actual patient outcomes, the area under the curve (AUC) methodology was used to assess the predictive performance of (1) POTTER versus SURG, and (2) SURG versus SURG-POTTER. RESULTS POTTER outperformed SURG in predicting all outcomes (mortality—AUC: 0.880 vs. 0.841; ventilator dependence—AUC: 0.928 vs. 0.833; bleeding—AUC: 0.832 vs. 0.735; pneumonia—AUC: 0.837 vs. 0.753) except septic shock (AUC: 0.816 vs. 0.820). SURG-POTTER outperformed SURG in predicting mortality (AUC: 0.870 vs. 0.841), bleeding (AUC: 0.811 vs. 0.735), pneumonia (AUC: 0.803 vs. 0.753) but not septic shock (AUC: 0.712 vs. 0.820) or ventilator dependence (AUC: 0.834 vs. 0.833). CONCLUSION The AI risk calculator POTTER outperformed surgeons' gestalt in predicting the postoperative mortality and outcomes of EGS patients, and when used, improved the individual surgeons' risk prediction. Artificial intelligence algorithms, such as POTTER, could prove useful as a bedside adjunct to surgeons when preoperatively counseling patients. LEVEL OF EVIDENCE Prognostic and Epidemiological; Level II.

Background: Prospective, multicenter, single-arm study of antimicrobial-coated, noncrosslinked, acellular porcine dermal matrix (AC-PDM) in a cohort involving all centers for disease control and prevention wound classes in ventral/incisional midline hernia repair (VIHR). Materials and methods: Seventy-five patients (mean age 58.6±12.7 years; BMI 31.3±4.9 kg/m2) underwent ventral/incisional midline hernia repair with AC-PDM. Surgical site occurrence (SSO) was assessed in the first 45 days post-implantation. Length of stay, return to work, hernia recurrence, reoperation, quality of life, and SSO were assessed at 1, 3, 6, 12, 18, and 24 months. Results: 14.7% of patients experienced SSO requiring intervention within 45 days post-implantation, and 20.0% thereafter (>45 d post-implantation). Recurrence (5.8%), definitely device-related adverse events (4.0%), and reoperation (10.7%) were low at 24 months; all quality-of-life indicators were significantly improved compared to baseline. Conclusion: AC-PDM exhibited favourable results, including infrequent hernia recurrence and definitely device-related adverse events, with reoperation and SSO comparable to other studies, and significantly improved quality of life.

BACKGROUND:Opioid overprescription in trauma contributes to the opioid epidemic through diversion of unused pills. Through our study, we sought to do the following: (1) understand the variation in opioid prescription after injury and its relationship to patient and/or clinical variables, and (2) study the relationship between opioid prescribing and long-term pain and analgesic use. METHOD:Trauma patients with an injury severity score ≥9 admitted to 3 level 1 trauma centers were screened for chronic pain and analgesic use 6 to 12 months postinjury. First, multivariable linear regression models were constructed with "oral morphine equivalents" and "number of opioid pills prescribed" at discharge as dependent variables. The coefficients of determination were calculated to determine how much of the variation in opioid prescription was explained by patient and clinical variables. Second, a multivariable logistic regression analysis was created to study the association between opioid prescription at discharge and chronic pain/analgesic use at 6 to 12 months. Analyses were adjusted for patient demographics, socioeconomics, comorbidities, injury parameters, and hospital course. RESULTS:Of the 2,702 patients included (mean [standard deviation] age: 61.0 [21.5]; 55% males), 74% were prescribed opioids at discharge (mean number of pills [standard deviation]: 24.0 [26.5]; mean oral morphine equivalent [standard deviation]: 204.8 [348.1]). The adjusted coefficients of determination for oral morphine equivalents and number of pills was 0.12 and 0.21, respectively, suggesting that the measured patient and clinical factors explain <21% of the variation in opioid prescribing in trauma. Patients prescribed opioids were more likely to have chronic pain (odds ratio [95%] confidence interval: 1.34 [1.05-1.71]) and use analgesics daily (odds ratio [95%] confidence interval: 1.86 [1.25-2.77]) 6 to 12 months postinjury. CONCLUSION:The variation in opioid prescription after traumatic injury is more affected by system and provider level rather than clinical or patient-related factors, and opioid prescribing correlates independently with long-term chronic pain and continued analgesic use postinjury. Efforts to decrease opioid use should prioritize standardizing prescription practices after traumatic injury.

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. (c) 2022 Published by Elsevier Inc.

BACKGROUND:In military combat settings, noncompressible closed cavity exsanguination is the leading cause of potentially survivable deaths, with no effective treatment available at point of injury. The aim of this study was to assess whether an expanding foam based on hydrophobically modified chitosan (hm-chitosan) may be used as a locally injectable hemostatic agent for the treatment of noncompressible bleeding in a swine model. METHODS:A closed-cavity, grade V hepato-portal injury was created in all animals resulting in massive noncoagulopathic, noncompressible bleeding. Animals received either fluid resuscitation alone (control, n = 8) or fluid resuscitation plus intraperitoneal hm-chitosan agent through an umbilical port (experimental, n = 18). The experiment was terminated at 180 minutes or death (defined as end-tidal CO2 <8mmHg or mean arterial pressure [MAP] <15mmHg), whichever came first. RESULTS:All animals had profound hypotension and experienced a near-arrest from hypovolemic shock (mean MAP = 24 mmHg at 10 minutes). Mean survival time was higher than 150 minutes in the experimental arm versus 27 minutes in the control arm (P < .001). Three-hour survival was 72% in the experimental group and 0% in the control group (P = .002). Hm-chitosan stabilized rising lactate, preventing acute lethal acidosis. MAP improved drastically after deployment of the hm-chitosan and was preserved at 60 mmHg throughout the 3 hours. Postmortem examination was performed in all animals and the hepatoportal injuries were anatomically similar. CONCLUSION:Intraperitoneal administration of hm-chitosan-based foam for massive, noncompressible abdominal bleeding improves survival in a lethal, closed-cavity swine model. Chronic safety and toxicity studies are required.

Background: Socioeconomic status (SES) is defined as a total measure of an individual's economic or social position in relation to others. Income and educational level are often used as quantifiable objective measures of SES but are inherently limited. Perceived SES (p-SES), refers to an individual's perception of their own SES. Herein, we assess the cor-relation between objective SES (o-SES) as defined by income and educational level and p-SES after injury and compare their associations with long-term outcomes after injury. Methods: Moderate-to-severely injured patients admitted to a Level 1 trauma center were asked to complete a phone-based survey assessing functional and mental health out-comes, social dysfunction, chronic pain, and return to work/school 6-12 mo postinjury. o-SES was determined by income and educational level (low educational level: high school or lower; low income: live in zip code with median income/household lower than the national median). p-SES was determined by asking patients to categorize their SES. The correlation coefficient between o-SES and p-SES was calculated. Multivariate logistic regression models were built to determine the associations between o-SES and p-SES and long-term outcomes.Results: A total of 729 patients were included in this study. Patients who reported a low p -SES were younger, more likely to suffer penetrating injuries, and to have a weak social support network. Twenty-one percent of patients with high income and high educational level classified their p-SES as low or mid-low, and conversely, 46% of patients with low education and low income classified their p-SES as high or mid-high. The correlation coefficient between p-SES and o-SES was 0.2513. After adjusting for confounders, p-SES was a stronger predictor of long-term outcomes, including functional limitations, social dysfunction, mental health outcomes, return to work/school, and chronic pain than was oSES.Conclusions: Patient-reported p-SES correlates poorly with o-SES indicating that the commonly used calculation of income and education may not accurately capture an individuals' SES. Furthermore, we found p-SES to be more strongly correlated with long-term outcome measures than o-SES. As we strive to improve long-term outcomes after injury, pSES may be an important variable in the early identification of individuals who are likely to suffer from worse long-term outcomes after injury. 2022 Published by Elsevier Inc.

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. (C) 2021 Elsevier Inc. All rights reserved.

BACKGROUND:Prehospital tourniquet (PHT) utilization has increased in response to mass casualty events. We aimed to describe the incidence, therapeutic effectiveness, and morbidity associated with tourniquet placement in all patients treated with PHT application.METHODS:A retrospective observational cohort study was performed to evaluate all adults with a PHT who presented at two Level I trauma centers between January 2015 and December 2019. Medically trained abstractors determined if the PHT was clinically indicated (placed for limb amputation, vascular hard signs, injury requiring hemostasis procedure, or significant documented blood loss). Prehospital tourniquets were further designated as appropriately or inappropriately applied (based on PHT anatomic placement location, occurrence of a venous tourniquet, or ischemic time defined as >2 hours). Statistical analyses were performed to generate primary and secondary results.RESULTS:A total of 147 patients met study inclusion criteria, of which 70% met the criteria for trauma registry inclusion. Total incidence of PHT utilization increased from 2015 to 2019, with increasing proportions of PHTs placed by nonemergency medical service personnel. Improvised PHTs were frequently used. Prehospital tourniquets were clinically indicated in 51% of patients. Overall, 39 (27%) patients had a PHT that was inappropriately placed, five of which resulted in significant morbidity.CONCLUSION:In summary, prehospital tourniquet application has become widely adopted in the civilian setting, frequently performed by civilian and nonemergency medical service personnel. Of PHTs placed, nearly half had no clear indication for placement and over a quarter of PHTs were misapplied with notable associated morbidity. Results suggest that the topics of clinical indication and appropriate application of tourniquets may be important areas for continued focus in future tourniquet educational programs, as well as future quality assessment efforts.LEVEL OF EVIDENCE:Epidemiological, level III; Therapeutic, level IV.

In resource-limited countries, open appendectomy is still performed under general anesthesia (GA) or neuraxial anesthesia (NA). We sought to compare the postoperative outcomes of appendectomy under NA versus GA. We conducted a post hoc analysis of the International Patterns of Opioid Prescribing (iPOP) multicenter study. All patients ≥ 16 years-old who underwent an open appendectomy between October 2016 and March 2017 in one of the 14 participating hospitals were included. Patients were stratified into two groups: NA—defined as spinal or epidural—and GA. All-cause morbidity, hospital length of stay (LOS), and pain severity were assessed using univariate analysis followed by multivariable logistic regression adjusting for the following preoperative characteristics: age, gender, body mass index (BMI), smoking, history of opioid use, emergency status, and country. A total of 655 patients were included, 353 of which were in the NA group and 302 in the GA group. The countries operating under NA were Colombia (39%), Thailand (31%), China (23%), and Brazil (7%). Overall, NA patients were younger (mean age (SD): 34.5 (14.4) vs. 40.7 (17.9), p-value < 0.001) and had a lower BMI (mean (SD): 23.5 (3.8) vs. 24.3 (5.2), p-value = 0.040) than GA patients. On multivariable analysis, NA was independently associated with less postoperative complications (OR, 95% CI: 0.30 [0.10–0.94]) and shorter hospital LOS (LOS > 3 days, OR, 95% CI: 0.47 [0.32–0.68]) compared to GA. There was no difference in postoperative pain severity between the two techniques. Open appendectomy performed under NA is associated with improved outcomes compared to that performed under GA. Further randomized controlled studies should examine the safety and value of NA in lower abdominal surgery.

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 Pro-gram 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 charac-teristic 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%) un-derwent laparoscopic cholecystectomy, and 35,152 (7.5%) patients underwent surgery for SBO. The ESS correlated extremely well with mortality for patients who underwent lapa-roscopic 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. (c) 2020 Elsevier Inc. All rights reserved.

INTRODUCTION Psychoactive drug use (PDU) is reported in up to 40% of trauma patients and is associated with a higher rate of in-hospital complications. However, little is known about its long-term impact on trauma patients. We aimed to assess the long-term functional, mental, and psychosocial outcomes of PDU in trauma patients 6 to 12 months after injury. METHODS Trauma patients with moderate to severe injuries (Injury Severity Score, >9) who had a toxicology screen upon admission to one of three level 1 trauma centers were contacted by phone 6 to 12 months postinjury. Psychoactive drug use was defined as the presence of a psychoactive, nonprescribed substance on toxicology screen including amphetamine, barbiturate, benzodiazepine, cannabinoid, methamphetamine, methadone, opioid, oxycodone, methylenedioxymethamphetamine (ecstasy), phencyclidine, tricyclic antidepressant, and cocaine. The interviews systematically evaluated functional limitations, social functioning, chronic pain, and mental health (posttraumatic stress disorder, depression, anxiety). Patients with a score of <= 47 on the Short-Form Health Survey version 2.0 social functioning subdomain were considered to have social dysfunction. Multivariable regression models were built to determine the independent association between PDU and long-term outcomes. RESULTS Of the 1,699 eligible patients, 571 (34%) were included in the analysis, and 173 (30.3%) screened positive for PDU on admission. Patients with PDU were younger (median age [interquartile range], 43 [28-55] years vs. 66 [46-78] years, p < 0.001), had more penetrating injuries (8.7% vs. 4.3%, p = 0.036), and were less likely to have received a college education (41.3% vs. 54.5%, p = 0.004). After adjusting for patients' characteristics including the presence of a baseline psychiatric comorbidity, patients with PDU on admission were more likely to suffer from daily chronic pain, mental health disorders, and social dysfunction 6 to 12 months after injury. There was no difference in the functional limitations between patients with and without PDU. CONCLUSION On the long term, PDU in trauma patients is strongly and independently associated with worse mental health, more chronic pain, and severe impairment in social functioning. A trauma hospitalization presents an opportunity to identify patients at risk and to mitigate the long-term impact of PDU on recovery.

Background: Body mass index (BMI) does not reliably predict Surgical site infections (SSI). We hypothesize that abdominal wall thickness (AWT) would serve as a better predictor of SSI for patients undergoing emergency colon operations. Methods: We retrospectively evaluated our Emergency Surgery Database (2007-2018). Emergency colon operations for any indication were included. AWT was measured by pre-operative CT scans at 5 locations. Only superficial and deep SSIs were considered as SSI in the analysis. Univariate then multivariable analyses were used to determine predictors of SSI. Results: 236 patients met inclusion criteria. The incidence of post-operative SSI was 25.8% and the median BMI was 25.8kg/m(2) [22.5-30.1]. The median AWT between patients with and without SSI was significantly different (2.1cm [1.4, 2.8] and 1.8cm [1.2, 2.5], respectively). A higher BMI trended toward increased rates of SSI, but this was not statistically significant. In overweight (BMI 25-29.9kg/m(2)) and obese (BMI >= 30kg/m(2)) patients, SSI versus no SSI rates were (50.0% versus 41.9% and 47.4% versus 36.4%, P = 0.365 and 0.230) respectively. The incidence of SSI in patients with an average AWT < 1.8cm was 20% and 30% for patients with average AWT >= 1.8cm. On multivariable analysis, AWT >= 1.8cm at 2cm inferior to umbilicus was an independent predictor of SSI (OR 2.98, 95%CI 1.34-6.63, P = 0.007). Conclusions: AWT is a better predictor of SSI than BMI. Preoperative imaging of AWT may direct intraoperative decisions regarding wound management. Future clinical outcomes research in emergency surgery should include abdominal wall thickness as an important patient variable. (C) 2021 Elsevier Inc. All rights reserved.

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 dif ference 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. (c) 2021 Published by Elsevier Inc.

Background: Trauma patients are at a significant risk of venous thromboembolism (VTE), with lower extremity fractures (LEF) being independent risk factors. Use of direct oral anticoagusants (DOACs) for VTE prophylaxis is effective in elective orthopedic surgery, but currently not approved for trauma patients. The primary objective of this study was to compare the effectiveness and safety of thromboprophylaxis of DOACs with lowmolecular-weight heparin (LMWH) in trauma patients sustaining LEF. Materials and methods: We included adult trauma patients admitted to trauma quality improvement program participating trauma centers (between 2013 and 2016), who sustained LEF and were started on DOACs or LMWH for thromboprophylaxis after admission. Propensity score matching was performed to compare symptomatic VTE and bleeding control interventions between the groups. Results: Of 1,009,922 patients in trauma quality improvement program, 167,640 met inclusion criteria (165,009 received LMWH and 2631 received DOACs). After propensity score matching, 2280 predominantly elderly (median age: 67 y) isolated femur fracture patients (median ISS: 10) were included in each group (4560 patients in total). Symptomatic VTE occurred in 1.4% of patients in both matched groups (P = 0.992). Bleeding control interventions occurred less often in the DOAC group, albeit statistically insignificant (5.8% versus 6.0%, P = 0.772). Conclusions: This study found similar rates of VTE and bleeding control measures for thromboprophylaxis with DOACs or LMWH in matched trauma patients with LEF. Further prospective research is warranted to consolidate the safety of DOAC thromboprophylaxis in trauma patients with LEF. Favorable oral administration and likely increased adherence could benefit this high-risk population. (C) 2020 The Authors. Published by Elsevier Inc.

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; β [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.

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.

BACKGROUND:Decision making regarding the optimal timing for initiating thromboprophylaxis in patients with blunt abdominal solid organ injuries (BSOIs) remains ill-defined, with no guidelines defining optimal timing. In this study, we aimed to evaluate the relationship of the timing of thromboprophylaxis with thromboembolic and bleeding complications in the setting of BSOIs. METHODS:A retrospective analysis of the Trauma Quality Improvement Program database was performed between 2013 and 2016. All patients with isolated BSOIs (liver, spleen, pancreas, or kidney, Abbreviated Injury Scale score, <3 in other regions) who underwent initial nonoperative management (NOM) were included. Patients were divided into three groups (early, <48 hours; intermediate, 48-72 hours; and late, >72 hours) based on timing of thromboprophylaxis initiation. Primary outcomes were rates of thromboembolism and bleeding after thromboprophylaxis initiation. RESULTS:Of the 25,118 patients with isolated BSOIs, 3,223 met the inclusion criteria (age, 38.7 ± 17.3 years; males, 2.082 [64.6%]), among which 1,832 (56.8%) received early thromboprophylaxis, 703 (21.8%) received intermediate thromboprophylaxis, and 688 (21.4%) received late thromboprophylaxis. Late thromboprophylaxis initiation was independently associated with a higher likelihood of both deep vein thrombosis (odds ratio [OR], 3.15; 95% confidence interval [CI], 1.68-5.91, p < 0.001) and pulmonary embolism (OR, 4.29; 95% CI, 1.95-9.42; p < 0.001). Intermediate thromboprophylaxis initiation was independently associated with a higher likelihood of deep venous thrombosis (OR, 2.38; 95% CI, 1.20-4.74; p = 0.013), but not pulmonary embolism (p = 0.960) compared with early initiation. Early (but not intermediate) thromboprophylaxis initiation was independently associated with a higher likelihood of bleeding (OR, 2.05; 95% CI, 1.11-2.18; p = 0.023), along with a history of diabetes mellitus, splenic, and high-grade liver injuries. CONCLUSION:Early thromboprophylaxis should be considered in patients with BSOIs undergoing nonoperative management who are at low likelihood of bleeding. An intermediate delay (48-72 hours) of thromboprophylaxis should be considered for patients with diabetes mellitus, splenic injuries, and Grades 3 to 5 liver injuries. LEVEL OF EVIDENCE:Therapeutic, Level IV.