Cytokine Profile of Adipose-Derived Stem Cells From Patients With Burn Injuries and Infection.

INTRODUCTION: Adipose-derived stem cells (ASCs) are multipotent stem cells capable of differentiating into many cell lineages. They play an important role in wound healing by secreting cytokines. Prior studies have demonstrated the presence of proinflammatory cytokines in burn wounds. However, no studies have been performed evaluating the cytokines released by burn wounds with infections. We hypothesized that there is an alteration in the paracrine factors secreted by ASCs in burn wounds with concomitant infections. METHODS: Adipose tissue was collected from patients with burn injuries at their index operation. ASCs were extracted and grown under standard tissue culture techniques. The supernatant was extracted. Cytokine analyses were performed with multiplex assays. Infection was determined using a burn sepsis protocol. The cytokine profiles of the two groups were compared using a Mann-Whitney U test. RESULTS: Sixteen patients were enrolled in the study, 50% with bacterial infection (n = 8). There was no significant difference in the baseline demographics of the two groups (P > 0.05). There were significantly lower concentrations of interleukin 13 and interferon gamma (P < 0.05) in burn patients with concomitant infections. CONCLUSIONS: ASCs are critical to burn wound healing. This study demonstrated diminished production of interleukin 13, an immunoregulatory cytokine involved in the antiinflammatory pathway by downregulating macrophage activity. This study also demonstrated significantly lower levels of interferon gamma in patient with burns and concomitant infection. This cytokine is crucial for antimicrobial defenses.

Chronic psychiatric diagnoses increase emergency department utilization following bariatric surgery.

INTRODUCTION: This study aims to evaluate the impact mental health disorders have on emergency department (ED) utilization following bariatric surgery. We hypothesize that the presence of preexisting psychiatric diagnoses is predictive of increased post-bariatric surgical ED usage as compared to a matched cohort without psychiatric comorbidities. METHODS AND PROCEDURES: We utilized the Colorado All Payers Claim Database to identify patients undergoing laparoscopic sleeve gastrectomy, gastric band, or gastric bypass, (N = 5393). Patients with preexisting diagnoses of schizophrenia or bipolar disorder (PSY), and no concomitant mental health diagnosis were included (N = 427). Patients without a psychiatric diagnosis (CON) were used for comparison. Propensity score matching in a 1:1 ratio was done matching for age, sex, BMI, procedure type, and comorbidities. Baseline ED utilization was calculated over the year preceding surgery. RESULTS: A total of 240 patients with bipolar disorder or schizophrenia were identified. After matching, baseline ED utilization was 62% higher in the PSY group (ED visits per person per month (EDVPP) of 0.17 (95%CI 0.16-0.18) in the PSY group compared to 0.10 (95%CI 0.09-0.12) in the CON group). ED utilization increased dramatically in the month following surgery for both PSY and CON groups (EDVPP 0.58 (95%CI 0.52-0.65) vs 0.34 (95%CI 0.28-0.41)), but visits returned to baseline for the CON but not PSY patients by three months after surgery (11% vs 60% above baseline, respectively). In the PSY group, ED utilization remained elevated at 18% above baseline for two years post-surgery (EDVPP 0.20 (95%CI 0.19-0.22). CONCLUSIONS: Bariatric patients with schizophrenia or bipolar disorder have higher baseline ED usage compared to a matched cohort. ED usage increases post-operatively in all patients but to a greater extent in patients with these diagnoses. Such patients would benefit from intensive outpatient follow-up to limit ED visits.

Demographic factors as determinant of selection of sleeve gastrectomy or gastric bypass for surgical weight loss.

INTRODUCTION: Use of sleeve gastrectomy (SG) for weight loss has grown exponentially; however, clear indications for SG versus Roux-en-Y gastric bypass (RNYGB) are lacking. Certain populations may be more likely to undergo SG due to its simpler technique and without clear clinical indications. We aim to examine underlying predictors of patients undergoing SG vs RNY across a single state. METHODS: We queried the Colorado All Payers Claim Database for patients undergoing laparoscopic SG or RNY. Patient-level variables included patient demographics, comorbidities, distance traveled for surgery, and distressed communities index (DCI), a zip code-based measure of socioeconomic status. Hospital-level variables included annual bariatric surgery volume, academic status, and whether hospitals were a bariatric Center of Excellence. We performed mixed-effects logistic regression adjusting for demographics, insurance coverage, and comorbidities to compare odds of undergoing SG vs RNY, with a random effect for hospital. RESULTS: 5,017 patients were included with 3,042 (60.6%) undergoing SG and 1,975 (39.4%) undergoing RNY. On multivariable analysis, patients with a high DCI were not more likely to undergo a SG (OR 1.18, CI 0.89-1.55, p = 0.25). However, patients who underwent surgery at hospitals serving the greatest proportion of those from highly distressed communities were significantly more likely to undergo SG (OR 4.22, CI 1.38-12.96, p = 0.01). Patients managed at Bariatric Centers of Excellence were less likely to undergo SG (OR 0.22, CI 0.07-0.62, p = 0.005). Patients with higher BMI, diabetes, or GERD were all more likely to undergo RNY. CONCLUSION: While patients with high DCI were more likely to undergo SG on univariate analysis, these associations disappeared after addition of a hospital-level random effect, suggesting that disparities may be due access to surgeons or systems with preference for one procedure. However, hospitals serving a higher proportion of high-DCI patients are more likely to utilize SG.

Intermuscular adipose tissue directly modulates skeletal muscle insulin sensitivity in humans.

Intermuscular adipose tissue (IMAT) is negatively related to insulin sensitivity, but a causal role of IMAT in the development of insulin resistance is unknown. IMAT was sampled in humans to test for the ability to induce insulin resistance in vitro and characterize gene expression to uncover how IMAT may promote skeletal muscle insulin resistance. Human primary muscle cells were incubated with conditioned media from IMAT, visceral (VAT), or subcutaneous adipose tissue (SAT) to evaluate changes in insulin sensitivity. RNAseq analysis was performed on IMAT with gene expression compared with skeletal muscle and SAT, and relationships to insulin sensitivity were determined in men and women spanning a wide range of insulin sensitivity measured by hyperinsulinemic-euglycemic clamp. Conditioned media from IMAT and VAT decreased insulin sensitivity similarly compared with SAT. Multidimensional scaling analysis revealed distinct gene expression patterns in IMAT compared with SAT and muscle. Pathway analysis revealed that IMAT expression of genes in insulin signaling, oxidative phosphorylation, and peroxisomal metabolism related positively to donor insulin sensitivity, whereas expression of macrophage markers, inflammatory cytokines, and secreted extracellular matrix proteins were negatively related to insulin sensitivity. Perilipin 5 gene expression suggested greater IMAT lipolysis in insulin-resistant individuals. Combined, these data show that factors secreted from IMAT modulate muscle insulin sensitivity, possibly via secretion of inflammatory cytokines and extracellular matrix proteins, and by increasing local FFA concentration in humans. These data suggest IMAT may be an important regulator of skeletal muscle insulin sensitivity and could be a novel therapeutic target for skeletal muscle insulin resistance.

Pharmacokinetic and Pharmacodynamic Evaluation of a Weight-Based Dosing Regimen of Cefoxitin for Perioperative Surgical Prophylaxis in Obese and Morbidly Obese Patients.

The objective of this study was to determine the pharmacokinetics and pharmacodynamics (PK/PD) of a weight-based cefoxitin dosing regimen for surgical prophylaxis in obese patients. Patients received a single dose of cefoxitin at 40 mg/kg based on total body weight. Cefoxitin samples were obtained over 3 h from serum and adipose tissue, and concentrations were determined by validated high-performance liquid chromatography. Noncompartmental pharmacokinetic analysis was performed, followed by Monte Carlo simulations to estimate probability of target attainment (PTA) for Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis over 4-h periods postdose. Thirty patients undergoing bariatric procedures were enrolled. The body mass index (mean ± standard deviation [SD])was 45.9 ± 8.0 kg/m(2) (range, 35.0 to 76.7 kg/m(2)); the median cefoxitin dose was 5 g (range, 4.0 to 7.5 g). The mean maximum concentrations were 216.15 ± 41.80 µg/ml in serum and 12.62 ± 5.89 in tissue; the mean tissue/serum ratio was 8% ± 3%. In serum, weight-based regimens achieved ≥90% PTA (goal time during which free [unbound] drug concentrations exceed pathogen MICs [fT>MIC] of 100%) for E. coli and S. aureus over 2 h and for B. fragilis over 1 h; in tissue this regimen failed to achieve goal PTA at any time point. The 40-mg/kg regimens achieved higher PTAs over longer periods in both serum and tissue than did the standard 2-g doses. However, although weight-based cefoxitin regimens were better than fixed doses, achievement of desired pharmacodynamic targets was suboptimal in both serum and tissue. Alternative dosing regimens and agents should be explored in order to achieve more favorable antibiotic performance during surgical prophylaxis in obese patients.

Tissue storage ex vivo significantly increases vascular fusion bursting pressure.

INTRODUCTION: Harvested biological tissue is a common medium for surgical device assessment in a laboratory setting; this study aims to differentiate between surgical device performance in the clinical and laboratory environments prior to and following tissue storage. Vascular tissue fusion devices are sensitive to tissue-device temperature gradients, tissue pre-stretch in vivo and tissue water content, each of which can vary during tissue storage. In this study, we compare the results of tissue fusion prior to and following storage using a standardized bursting pressure protocol. METHODS: Epigastric veins from seven porcine models were subject to identical bursting pressure protocols after fusion. One half of each vein was fused in vivo, harvested and immediately analyzed for burst pressure; the remainder was stored (0.9% Phosphate Buffered Saline, 24h, 4 °C) and then analyzed ex vivo. Histological slides were prepared for qualitative analysis of in versus ex vivo fusions. RESULTS: Bursting pressures of vessels fused ex vivo (514.7 ± 187.0 mmHg) were significantly greater than those of vessels fused in vivo (310 ± 127.7 mmHg, p = 2.06 E-10). Histological imaging of venous axial cross-sections indicated the lamination of adventitia and media layers ex vivo, whereas in vivo samples consisted only of adventitia. CONCLUSION: These findings suggest that the fusion of porcine venous tissue ex vivo may overestimate the clinical performance of fusion devices. Prior work has indicated that increased tissue hydration and the lamination of tissue layers both positively affect arterial fusion bursting pressures. The bursting pressure increase observed herein may therefore be due to storage-induced alterations in tissue composition and mechanics of the fusion interface. While harvested tissue provides an accessible medium for comparative study, the fusion of vascular tissue in vivo may avoid storage-induced biomechanical alterations and is likely a better indicator of fusion device performance in a clinical setting.

The Burden of Burns: An Analysis of Public Health Measures.

Accurate analysis of injuries is paramount when allocating resources for prevention, research, education, and legislation. As burn mortality has improved over recent decades, the societal burden of burn injuries has grown ambiguous to the public while a scarcity of investigational funding for survivors has led to a gap in understanding lifelong sequela. We aim to compare national references reporting the incidence of burn injuries in the United States. The American Burn Association Burn Injury Summary Report (ABA-BISR), American Burn Association Fact Sheet, Centers for Disease Control and Prevention (CDC) Web-based Injury Statistics Query and Reporting (WISQARS) database, the CDC National Center for Health Statistics' National Hospital Ambulatory Medical Care Survey (NHAMCS), National Inpatient Sample (NIS), National Emergency Department Sample (NEDS), and commercially available claims databases were queried for 2020 or the most recent data available. The BISR estimated 30,135 burn admissions in 2022. The 2016 ABA Fact Sheet reported 486,000 burns presented to US emergency departments (ED). In 2020, CDC's WISQARS database reported 3,529 fatal, and 287,926 non-fatal, burn injuries. The 2020 NEDS reported 438,185 ED visits while the 2020 NIS estimated 103,235 inpatients. The NHAMCS reported 359,000 ED visits for burn injuries in the same period, and an analysis of ICD-10 burn codes demonstrated over 698,555 claims. Our study demonstrates a large variability in the reported incidence of burn injury by the ABA, CDC, national samples, and claims databases. Per our analyses, we estimate that 600,000 individuals annually suffer a burn injury which merits emergent care in the United States.

The Impact of Pre-Trauma Steroid Use on Wound Healing and Outcomes.

This study presents data on pre-trauma steroid use, a topic underrepresented in the trauma literature. Long-term steroid use has been linked to impaired wound healing, compromised immune responses, and hindrance of bone healing, alongside the potential for adrenal insufficiency during traumatic events. The aim of this study was to conduct a retrospective analysis of clinical outcomes for trauma patients with chronic steroid use. Examining adult trauma cases with pre-trauma steroid use at a level 1 trauma center (January 2016-September 2023), we identified 18 patients (58.6 ± 19.4 years, 55.6% males). All were on prednisone prior to trauma activation and 66.7% had autoimmune disease. Complications included orthopedic fractures (72.2%), ICU admissions (16.7%), and low mortality (5.6%). Future larger, multi-center studies are needed to determine the impact of immunosuppression and pre-trauma steroids on clinical outcomes.

Risk Factors for Empyema Following Penetrating Diaphragmatic Injuries.

Empyema resulting as a complication of penetrating diaphragmatic injuries is a subject that requires further investigation, and the aim of this study was to determine the risk factors associated with empyema in patients with penetrating trauma. Consecutive adult trauma patients from a level 1 trauma center were searched for penetrating diaphragm injuries. Data were collected on patient demographics, pre-existing conditions, injury type and severity, hospital interventions, in-hospital complications, and outcomes. Patients were stratified by empyema formation and univariant analyses were performed. 164 patients were identified, and 17 patients (10.4%) developed empyema. Empyema was associated with visible abdominal contamination (35.3% vs 15%, P = .04), thoracotomy (35.5% vs 13.6%, P = .03), pneumonia (41.2% vs 14.3%, P = .01), sepsis (35.3% vs 8.8%, P = .006), increased hospital length of stay (25.5 vs 10.1 days, p =<.001), increased intensive care unit length of stay (9.6 vs 4.3 days, P = .01), and decreased in-hospital mortality (0% vs 20.4%, P = .04).

Venovenous Extracorporeal Membrane Oxygenation Usage Following Bullet Embolism to the Pulmonary Artery.

Background: Pulmonary artery embolus is a rare complication following gunshot wounds that creates a unique and serious challenge for trauma surgeons. While the majority of bullets that embolize through the vascular system end in the peripheral circulation, approximately one-third enter the central venous circulation. Case Report: We present the case of a bullet embolus to the left pulmonary artery following gunshot wounds to the right chest and the abdomen, with the abdominal ballistic traversing the liver before entering the vena cava and embolizing. The patient's course was complicated by the development of severe acute respiratory distress syndrome that was successfully managed by venovenous extracorporeal membrane oxygenation. Conclusion: Venovenous extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome after bullet embolization to the pulmonary tree and surgical embolectomy is a viable option in appropriately selected patients.

Discrepancies in Mass Shootings and Access to Trauma Care Across the United States, 2014-2018.

INTRODUCTION: The United States has one of the highest rates of gun violence and mass shootings. Timely medical attention in such events is critical. The objective of this study was to assess geographic disparities in mass shootings and access to trauma centers. METHODS: Data for all Level I and II trauma centers were extracted from the American College of Surgeons and the Trauma Center Association of America registries. Mass shooting event data (4+ individuals shot at a single event) were taken from the Gun Violence Archive between 2014 and 2018. RESULTS: A total of 564 trauma centers and 1672 mass shootings were included. Ratios of the number of mass shootings vs trauma centers per state ranged from 0 to 11.0 mass shootings per trauma center. States with the greatest disparity (highest ratio) included Louisiana and New Mexico. CONCLUSION: States in the southern regions of the US experience the greatest disparity due to a high burden of mass shootings with less access to trauma centers. Interventions are needed to increase access to trauma care and reduce mass shootings in these medically underserved areas.

Chest Tube Size Selection: Evaluating Provider Practices, Treatment Efficacy, and Complications in Management of Thoracic Trauma.

BACKGROUND: The standard for managing traumatic pneumothorax (PTX), hemothorax (HTX), and hemopneumothorax (HPTX) has historically been large-bore (LB) chest tubes (>20-Fr). Previous studies have shown equal efficacy of small-bore (SB) chest tubes (≤19-Fr) in draining PTX and HTX/HPTX. This study aimed to evaluate provider practice patterns, treatment efficacy, and complications related to the selection of chest tube sizes for patients with thoracic trauma. METHODS: A retrospective chart review was performed on adult patients who underwent tube thoracostomy for traumatic PTX, HTX, or HPTX at a Level 1 Trauma Center from January 2016 to December 2021. Comparison was made between SB and LB thoracostomy tubes. The primary outcome was indication for chest tube placement based on injury pattern. Secondary outcomes included retained hemothorax, insertion-related complications, and duration of chest tube placement. Univariate and multivariate analyses were performed. RESULTS: Three hundred and forty-one patients were included and 297 (87.1%) received LB tubes. No significant differences were found between the groups concerning tube failure and insertion-related complications. LB tubes were more frequently placed in patients with penetrating MOI, higher average ISS, and higher average thoracic AIS. Patients who received LB chest tubes experienced a higher incidence of retained HTX. DISCUSSION: In patients with thoracic trauma, both SB and LB chest tubes may be used for treatment. SB tubes are typically placed in nonemergent situations, and there is apparent provider bias for LB tubes. A future randomized clinical trial is needed to provide additional data on the usage of SB tubes in emergent situations.

Does the use of double hormone replacement therapy for trauma patient organ donors improve organ recovery for transplant.

BACKGROUND: With an ongoing demand for transplantable organs, optimization of donor management protocols, specifically in trauma populations, is important for obtaining a high yield of viable organs per patient. Endocrine management of brain-dead potential organ donors (BPODs) is controversial, leading to heterogeneous clinical management approaches. Previous studies have shown that when levothyroxine was combined with other treatments, including steroids, vasopressin, and insulin, BPODs had better organ recovery and survival outcomes were increased for transplant recipients. AIM: To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients. METHODS: A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed. Exclusion criteria included patients who were not solid organ donors, patients who were not declared brain dead (donation after circulatory death), and patients who did not receive steroids in their hospital course. Levothyroxine and steroid administration, the number of organs donated, the types of organs donated, and demographic information were recorded. Univariate analyses were performed with P < 0.05 considered to be statistically significant. RESULTS: A total of 88 patients met inclusion criteria, 69 (78%) of whom received levothyroxine and steroids (ST/LT group) vs 19 (22%) receiving steroids without levothyroxine (ST group). No differences were observed between the groups for gender, race, pertinent injury factors, age, or other hormone therapies used (P > 0.05). In the ST/LT group, 68.1% (n = 47) donated a high yield (3-5) of organ types per donor compared to 42.1% (n = 8) in the ST group (P = 0.038). There was no difference in the total number of organ types donated between the groups (P = 0.068). CONCLUSION: This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population. Limitations to this study include the retrospective design and the relatively small number of organ donors who met inclusion criteria. This study is unique in that it mitigates steroid administration as a confounding variable and focuses specifically on the adjunctive use of levothyroxine.

Traumatic Abdominal Wall Hernia: Management Using a Standardized Approach.

Traumatic abdominal wall hernias are a rare complication of high energy blunt trauma. There exist several studies evaluating and outlining potential management options but still no generalized consensus on management. This series was meant to evaluate the diagnosis and management of traumatic abdominal wall hernias. A prospectively maintained database was used to identify patients with TAWH from 2021 to 2022. The primary outcome was operative management. Secondary outcomes included: time to diagnosis and post-operative outcomes. Of the 19 patients in this case series, 100% (n = 19/19) were secondary to blunt trauma with a mean ISS of 21. Exploratory laparotomy was performed in 17 cases. 14 cases had concomitant traumatic injuries to visceral structures. Complications were found in nearly half of the patients with 3 experiencing wound dehiscence. Future studies should be aimed at standardizing management approach taking into account nature of the mechanism and concomitant injuries.

Reflux and Barrett's esophagus after sleeve gastrectomy: analysis of a statewide database.

BACKGROUND: Recent studies have suggested that sleeve gastrectomy (SG) is associated with the development of Barrett esophagus (BE) even in the absence of gastroesophageal reflux disease (GERD) symptoms. OBJECTIVE: The aim of this study was to assess the rates of upper endoscopy and incidence of new BE diagnoses in patients undergoing SG. SETTING: This was a claims-data study of patients who underwent SG between 2012 and 2017 while enrolled in a U.S. statewide database. METHODS: Diagnostic claims data were used to identify pre- and postoperative rates of upper endoscopy, GERD, reflux esophagitis, and BE. Time-to-event analysis using a Kaplan-Meier approach was performed to estimate the cumulative postoperative incidence of these conditions. RESULTS: We identified 5562 patients who underwent SG between 2012 and 2017. Of these, 1972 patients (35.5%) had at least 1 diagnostic record of upper endoscopy. The preoperative incidences of a diagnosis of GERD, esophagitis, and BE were 54.9%, 14.6%, and .9%, respectively. The predicted postoperative incidences of GERD, esophagitis, and BE, respectively, were 18%, 25.4%, and 1.6% at 2 years and 32.1%, 85.0%, and 6.4% at 5 years. CONCLUSIONS: In this large statewide database, rates of esophagogastroduodenoscopy remained low after SG, but the incidence of a new postoperative esophagitis or BE diagnosis in patients who underwent esophagogastroduodenoscopy was higher than in the general population. Patients undergoing SG may have a disproportionately high risk of developing reflux complications including BE after surgery.

Factors Associated with Weight Loss After Endoscopic Transoral Outlet Reduction (TORe).

INTRODUCTION: Endoscopic transoral outlet reduction (TORe) has emerged as a safe and effective treatment option for weight regain after Roux-en-Y Gastric Bypass (RYGB). Factors that predict successful weight loss after TORe are incompletely understood. The aims of this study were to evaluate procedural factors and patient factors that may affect percent total body weight loss (%TBWL) after TORe. METHODS: A retrospective cohort study was performed on patients after TORe. The primary outcomes were %TBWL at 6 and 12 months based on four procedural factors: purse-string (PS) vs. non-purse-string (NPS) suture pattern, gastric pouch sutures (N), change in the diameter of the gastrojejunal anastomosis, and change in the length of the gastric pouch. Secondary outcomes included patient factors that affected weight loss. RESULTS: Fifty-one patients underwent TORe. Weight loss for completers was 11.3 ± 7.6% and 12.2 ± 9.2% at 6 and 12 months. There was a correlation between %TBWL and change in pouch length at 6 and 12 months and number of sutures in the pouch at 6 months. The difference in %TBWL between PS and NPS groups at 6 months (PS, n=21, 12.3 ± 8.5% and NPS, n=8, 8.7 ± 3.7%) and 12 months (PS, n=21, 13.5 ± 9.2% and NPS, n=5, 7.0 ± 7.9%) did not reach statistical significance. For secondary outcomes, depression was associated with %TBWL. CONCLUSION: Change in pouch length and number of sutures in the pouch correlated positively while depression correlated negatively with weight loss after TORe. Further studies are needed to understand these effects.

Perioperative Fluid Management in Surgical Patients: A Review.

Intravenous (IV) fluids are one of the most widely prescribed medications. Despite their frequent usage, IV fluids are often not used appropriately. High-quality evidence to guide the surgeon in the perioperative period is sparse. A plethora of choices for IV fluids exists with limited evidence to help guide the surgeon in specific patient populations and situations. To address this, the authors have set out to provide a critical review of commonly used IV fluids to treat surgical patients. Gaps in the existing literature for the surgical population will also be discussed as potential target areas for future research.

Comparison of rampage and non-rampage mass shootings in the U.S.: A 5-year demographic analysis.

BACKGROUND: Rampage mass shootings (RMS) are a subset of mass shootings occurring in public involving random victims. Due to rarity, RMS are not well-characterized. We aimed to compare RMS and NRMS. We hypothesized that RMS and NRMS would be significantly different with respect to time/season, location, demographics, victim number/fatality rate, victims being law enforcement, and firearm characteristics. STUDY DESIGN: Mass shootings (4 or more victims shot at a single event) from 2014-2018 were identified in the Gun Violence Archive (GVA). Data were collected from the public domain (e.g. news). Crude comparisons between NRMS and RMS were performed using Chi-squared or Fisher's exact tests. Parametric models of victim and perpetrator characteristics were conducted at the event level using negative binomial regression and logistic regression. RESULTS: There were 46 RMS and 1626 NRMS. RMS occurred most in businesses (43.5%), whereas NRMS occurred most in streets (41.1%), homes (28.6%), and bars (17.9%). RMS were more likely to occur between 6AM-6PM (OR=9.0 (4.8-16.8)). RMS had more victims per incident (23.6 vs. 4.9, RR: 4.8 (4.3,5.4)). Casualties of RMS were more likely to die (29.7% vs. 19.9%, OR: 1.7 (1.5,2.0)). RMS were more likely to have at least one police casualty (30.4% versus 1.8%, OR: 24.1 (11.6,49.9)) or police death (10.9% versus 0.6%, OR: 19.7 (6.4,60.3)). RMS had significantly greater odds that casualties were adult (OR: 1.3 (1.0,1.6)) and female (OR: 1.7 (1.4,2.1)). Deaths in RMS were more likely to be female (OR: 2.0 (1.5,2.5)) and White (OR: 8.6 (6.2,12.0) and less likely to be children (OR: 0.4 (0.2,0.8)). Perpetrators of RMS were more likely to die by suicide (34.8%), be killed by police (28.3%), or be arrested at the scene (26.1%), while more than half of perpetrators from NRMS escaped without death or apprehension (55.8%). Parametric models of perpetrator demographics indicated significant increases in the odds that a RMS shooter was White (OR: 13.9 (7.3,26.6)) or Asian (OR: 16.9 (3.7,78.4)). There was no significant difference in weapon type used (p=0.35). CONCLUSION: The demographics, temporality, and location differ between RMS and NRMS, suggesting that they are dissimilar and require different preventive approaches.

Glycerol as a precursor for hepatic de novo glutathione synthesis in human liver.

BACKGROUND: Glycerol is a substrate for gluconeogenesis and fatty acid esterification in the liver, processes which are upregulated in obesity and may contribute to excess fat accumulation. Glycine and glutamate, in addition to cysteine, are components of glutathione, the major antioxidant in the liver. In principle, glycerol could be incorporated into glutathione via the TCA cycle or 3-phosphoglycerate, but it is unknown whether glycerol contributes to hepatic de novo glutathione biosynthesis. METHODS: Glycerol metabolism to hepatic metabolic products including glutathione was examined in the liver from adolescents undergoing bariatric surgery. Participants received oral [U-13C3]glycerol (50 mg/kg) prior to surgery and liver tissue (0.2-0.7g) was obtained during surgery. Glutathione, amino acids, and other water-soluble metabolites were extracted from the liver tissue and isotopomers were quantified with nuclear magnetic resonance spectroscopy. RESULTS: Data were collected from 8 participants (2 male, 6 female; age 17.1 years [range 14-19]; BMI 47.4 kg/m2 [range 41.3-63.3]). The concentrations of free glutamate, cysteine, and glycine were similar among participants, and so were the fractions of 13C-labeled glutamate and glycine derived from [U-13C3]glycerol. The signals from all component amino acids of glutathione - glutamate, cysteine and glycine - were strong and analyzed to obtain the relative concentrations of the antioxidant in the liver. The signals from glutathione containing [13C2]glycine or [13C2]glutamate derived from the [U-13C3]glycerol drink were readily detected, and 13C-labelling patterns in the moieties were consistent with the patterns in corresponding free amino acids from the de novo glutathione synthesis pathway. The newly synthesized glutathione with [U-13C3]glycerol trended to be lower in obese adolescents with liver pathology. CONCLUSIONS: This is the first report of glycerol incorporation into glutathione through glycine or glutamate metabolism in human liver. This could represent a compensatory mechanism to increase glutathione in the setting of excess glycerol delivery to the liver.

The COVID-19 pandemic and its impacts on mass shootings in six major US cities.

BACKGROUND: The COVID-19 pandemic has significant impacts on the US socioeconomic structure. Gun violence is a major public health issue and the effects on this area have not been well-elucidated. The objective of this study was to determine the impacts of the pandemic on mass shootings in six major United States cities with historically high rates of gun violence. METHODS: Mass shooting data were extracted from an open-source database, Gun Violence Archive. Mass shooting was defined as four or more people shot at a single event. Data from six cities with the highest incidence of mass shootings were analyzed in 2019 versus 2020 (Baltimore, Chicago, Detroit, New Orleans, Philadelphia, and St. Louis). Geographic data were examined to assess changes in each city's mass shooting geographic distribution over time. Quantitative changes were assessed using the Area Deprivation Index (ADI), and qualitative data were assessed using ArcGIS. RESULTS: In 2020, the overall percentage of mass shootings increased by 46.7% though there was no change in the distribution of these events when assessed quantitatively (no change in average ADI) nor qualitatively (using ArcGIS). In the six cities analyzed, the total proportion of mass shooting events was unchanged during the pandemic (21.8% vs 20.6%, p = 0.64). Chicago, the US city with the highest incidence of mass shootings, did not experience a significant change in 2020 (n = 34/91, 37.3% vs. n = 53/126, 42.1%, p = 0.57). Baltimore had a significant decrease in mass shooting events (n = 18/91, 19.8% vs. 10/126, 7.9%, p = 0.01). The other four cities had no significant change in the number of mass shootings (p>0.05). CONCLUSION: This study is the first to use ArcGIS technology to describe the patterns of mass shooting in six major US cities during the COVID-19 pandemic. The number of mass shootings in six US cities remained largely unchanged which suggests that changes in mass shootings is likely occurring in smaller cities. Future studies should focus on the changing patterns of homicides in at-risk communities and other possible social influences.