Enteric glial NLRP3 inflammasome contributes to gut mucosal barrier alterations in a mouse model of diet-induced obesity.

AIM: In the present study, we investigated the involvement of NLRP3 inflammasome in the intestinal epithelial barrier (IEB) changes associated with obesity, and its role in the interplay between enteric glia and intestinal epithelial cells (IECs). METHODS: Wild-type C57BL/6J and NLRP3-KO (-/-) mice were fed with high-fat diet (HFD) or standard diet for 8 weeks. Colonic IEB integrity and inflammasome activation were assessed. Immunolocalization of colonic mucosal GFAP- and NLRP3-positive cells along with in vitro coculture experiments with enteric glial cells (EGCs) and IECs allowed to investigate the potential link between altered IEB, enteric gliosis, and NLRP3 activation. RESULTS: HFD mice showed increased body weight, altered IEB integrity, increased GFAP-positive glial cells, and NLRP3 inflammasome hyperactivation. HFD-NLRP3-/- mice showed a lower increase in body weight, an improvement in IEB integrity and an absence of enteric gliosis. Coculture experiments showed that palmitate and lipopolysaccharide contribute to IEB damage and promote enteric gliosis with consequent hyperactivation of enteric glial NLRP3/caspase-1/IL-1ß signaling. Enteric glial-derived IL-1ß release exacerbates the IEB alterations. Such an effect was abrogated upon incubation with anakinra (IL-1ß receptor antagonist) and with conditioned medium derived from silenced-NLRP3 glial cells. CONCLUSION: HFD intake elicits mucosal enteric gliotic processes characterized by a hyperactivation of NLRP3/caspase-1/IL-1ß signaling pathway, that contributes to further exacerbate the disruption of intestinal mucosal barrier integrity. However, we cannot rule out the contribution of NLRP3 inflammasome activation from other cells, such as immune cells, in IEB alterations associated with obesity. Overall, our results suggest that enteric glial NLRP3 inflammasome might represent an interesting molecular target for the development of novel pharmacological approaches aimed at managing the enteric inflammation and intestinal mucosal dysfunctions associated with obesity.

Abdominal Instillation of Crystalloid Fluid Decreases the Recurrence of Adhesive Small Bowel Obstruction.

Peritoneal adhesion is a common cause of small bowel obstruction (SBO). In this study, we included 40 adult patients who had SBO, or partial obstructive symptoms. In the abdominal instillation of crystalloid fluid (AICF) cohort, 16 patients underwent lysis of adhesions and abdominal crystalloid fluid instillation at the end of the procedure. In the control (CO) group, 24 patients received lysis of adhesions without fluid instillation. AICF was achieved by the abdominal instillation of 1864 ± 97.5 mL of crystalloid fluid. We analyzed the recurrence of peritoneal adhesions resulting in reoperation for SBO within the 64.3 ± 9.15 months of follow-up time for the CO and the 70.5 ± 13.16-month follow-up for the AICF group. The AICF group had a lower SBO recurrence rate of 12.5% compared to the CO group's 41.6% rate (P = .049). Taken together, AICF decreased the recurrence of SBO requiring reoperation secondary to adhesion formation compared to the lysis of adhesions alone, as seen in the CO group.

A Comparison of Clinical Outcomes of Colectomies for Pediatric and Adult Patients With Inflammatory Bowel Disease.

Background: Crohn's disease (CD) and ulcerative colitis (UC) are prevalent in adult and pediatric populations, but their differences are not well studied using national data. We compared the clinical outcomes of these patients using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) databases.Methods: Colectomy cases for CD and UC, the 2 major forms of inflammatory bowel disease (IBD), were compared between adult and pediatric patients using the 2017-2019 ACS NSQIP databases. Various clinical factors were analyzed, with postoperative complications being the primary outcome of interest.Results: We identified 542 pediatric and 5174 adult CD patients and 360 pediatric and 1292 adult UC patients. Adults with CD or UC were more likely to be on steroids preoperatively (CD: 60.15% vs 24.54%; UC: 65.63% vs 51.39%). Children with IBD were more likely to have preoperative transfusions (CD: 1.48% vs .33%; UC: 8.33% vs .62%), systemic inflammatory response syndrome (CD: 3.51% vs .93%; UC: 12.78% vs 3.10%), or sepsis (CD: 1.85% vs .66%; UC: 1.39% vs .31%). Unplanned reoperations were more common among pediatric patients in both disease states compared to adults (CD: 6.27% vs 4.10%; UC: 11.11% vs 4.26%), with P-values for all factors described as ≤.02. Multivariate logistic regression found pediatric age to be associated with higher odds of needing a reoperation among UC patients but not CD patients.Conclusion: Pediatric patients were sicker at the time of surgery, and those with either disease were more likely to require a reoperation within 30 days.

Effects of Preoperative COVID-19 Status on Emergent or Urgent Colectomy Outcomes.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 has been described as eliciting a powerful immune response. The association of coronavirus disease 2019 (COVID-19) infection with diseases requiring emergent or urgent colectomies may exacerbate the risk of surgical complications. We investigated the effect of preoperative COVID-19 infection on the clinical outcomes of patients who underwent a nonelective colectomy in 2021. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program Targeted Colectomy database for all of the patients who underwent a colectomy in 2021 and filtered for patients classified as "Urgent" or "Emergent." Two groups were created based on preoperative COVID-19 status: COVID+ (n = 242) and COVID- cohorts (n = 11,049). Several clinical variables were compared. RESULTS: Before filtering for urgent/emergent operations, a large percentage of COVID+ patients were found to have undergone an urgent or emergency colectomy (68.36% vs 25.05%). Preoperatively, these patients were more likely to be taking steroids (21.49% vs 12.41%) or have a bleeding issue requiring a transfusion (19.42% vs 11.00%). A larger percentage of infected patients returned to the operating room (14.05% vs 8.13%) and had a hospital stay >30 days (18.18% vs 5.35%). COVID-19 infection was associated with a higher rate of mortality (14.05% vs 8.08%) but did not independently predict it (odds ratio 1.25, P = 0.233), with all P ≤ 0.001. CONCLUSIONS: Urgent or emergent colectomy patients who were COVID-19+ preoperatively were more likely to present with comorbidities, which, along with the recent viral infection, contributed to markedly worse clinical outcomes, including an increased rate of mortality.

Effects of COVID-19 Status on Hip Fracture Surgical Outcomes: An ACS NSQIP Study.

BACKGROUND: Studies have indicated that patients infected with the SARS-CoV-2 virus fare worse clinically after a traumatic injury, especially those who are older and have other comorbidities. OBJECTIVE: This study aims to understand the effects of Corona Virus Disease 19 (COVID-19) diagnosis on patients undergoing surgery for hip fractures. METHODS: This is a retrospective review of the 2021 American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Targeted Hip Fracture database for patients who underwent surgery. Two cohorts were formed based on patients' preoperative COVID-19 status, as tested within 14 days prior to the operation. Several clinical factors were compared. RESULTS: The COVID-positive cohort consisted of 184 patients, all of whom had a laboratory-confirmed or clinically suspected SARS-CoV-2 infection, while the COVID-negative cohort consisted of 12,211 patients with no infection. A lower proportion of COVID-positive patients had an emergent operation compared to the COVID-negative cohort (58.70% vs. 73.09%, p < .001). Preoperatively, the COVID-positive cohort showed higher rates of coagulopathy/bleeding disorders (22.83% vs. 14.12%), congestive heart failure (16.30% vs. 9.84%), diabetes mellitus (28.26% vs. 19.24%), and dementia (42.39% vs. 28.07%), with p ≤ .005 for all. Postoperatively, a higher proportion of COVID-positive patients died (9.78% vs. 5.40%) or had pneumonia (8.70% vs. 3.65%), hospital readmission within 30 days (10.87% vs. 6.76%), and pressure sores (8.15% vs. 4.55%), with p ≤ .033 for all. CONCLUSION: The diagnosis of COVID-19 in hip fracture patients was associated with higher rates of postoperative complications, including mortality, when compared to COVID-negative patients, indicating the severity of the viral infection.

Effects of the COVID-19 Pandemic on Colectomy Outcomes for Inflammatory Bowel Disease.

OBJECTIVES: Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD) and ulcerative colitis (UC). These two chronic inflammatory conditions can differ in severity, presentation, and anatomical localization, and can greatly affect quality of life if not managed properly. Given the many healthcare challenges during the coronavirus disease 2019 pandemic, we studied the effects of the pandemic and corresponding changes to medical resources on surgical outcomes for patients with IBD. METHODS: Deidentified data from patients who underwent a colectomy for CD or UC were collected from the National Surgical Quality Improvement Program database of the American College of Surgeons. We analyzed clinical factors and surgical outcomes between 2019 and 2020. RESULTS: Patients with IBD were more likely to have lost >10% of their body mass before the operation in 2020. Operations for patients with UC were significantly shorter in the first year of the pandemic. Patients with CD were less likely to have a urinary tract infection or sepsis postoperatively in 2020, whereas patients with UC were more likely to require a repeat operation. Interestingly, both patient populations were less likely to undergo an emergency operation in 2020 than in 2019. CONCLUSIONS: Colectomy outcomes for patients with CD in 2020 were similar or improved in comparison with those seen in 2019, whereas colectomies for UC saw a statistically but not clinically significant increase in the rate of repeat operations. Overall, these patients seem to have been well managed despite the coronavirus disease 2019 pandemic-induced strain on the healthcare system.

EVALUATION OF COMPONENTS OF THE EXTRACELLULAR PURINERGIC SIGNALING SYSTEM IN HUMAN SEPSIS.

ABSTRACT: Objective: Extracellular purines such as adenosine triphosphate (ATP), uridine triphosphate (UTP), and uridine diphosphate (UDP) and the ATP degradation product adenosine are biologically active signaling molecules, which accumulate at sites of metabolic stress in sepsis. They have potent immunomodulatory effects by binding to and activating P1 or adenosine and P2 receptors on the surface of leukocytes. Here we assessed the levels of extracellular purines, their receptors, metabolic enzymes, and cellular transporters in leukocytes of septic patients. Methods: Peripheral blood mononuclear cells (PBMCs), neutrophils, and plasma were isolated from blood obtained from septic patients and healthy control subjects. Ribonucleic acid was isolated from cells, and mRNA levels for purinergic receptors, enzymes, and transporters were measured. Adenosine triphosphate, UTP, UDP, and adenosine levels were evaluated in plasma. Results: Adenosine triphosphate levels were lower in septic patients than in healthy individuals, and levels of the other purines were comparable between the two groups. Levels of P1 and P2 receptors did not differ between the two patient groups. mRNA levels of ectonucleoside triphosphate diphosphohydrolase (NTPDase) 1 or CD39 increased, whereas those of NTPDase2, 3, and 8 decreased in PBMCs of septic patients when compared with healthy controls. CD73 mRNA was lower in PBMCs of septic than in healthy individuals. Equilibrative nucleoside transporter (ENT) 1 mRNA concentrations were higher and ENT2, 3, and 4 mRNA concentrations were lower in PBMCs of septic subjects when compared with healthy subjects. Concentrative nucleoside transporter (CNT) 1 mRNA levels were higher in PBMCs of septic versus healthy subjects, whereas the mRNA levels of CNT2, 3, and 4 did not differ. We failed to detect differences in mRNA levels of purinergic receptors, enzymes, and transporters in neutrophils of septic versus healthy subjects. Conclusion: Because CD39 degrades ATP to adenosine monophosphate (AMP), the lower ATP levels in septic individuals may be the result of increased CD39 expression. This increased degradation of ATP did not lead to increased adenosine levels, which may be explained by the decreased expression of CD73, which converts AMP to adenosine. Altogether, our results demonstrate differential regulation of components of the purinergic system in PBMCs during human sepsis.

How the COVID-19 pandemic affected the severity and clinical presentation of diverticulitis.

BACKGROUND/AIMS: Single-institution studies showed that patients presented with more severe diverticulitis and underwent more emergency operations during the coronavirus disease 2019 (COVID-19) pandemic. Therefore, we studied this trend using nationwide data from the American College of Surgeons National Surgical Quality Improvement Program database. METHODS: Patients (n = 23,383) who underwent a colectomy for diverticulitis in 2018 (control year) and 2020 (pandemic year) were selected. We compared these groups for differences in disease severity, comorbidities, perioperative factors, and complications. RESULTS: During the pandemic, colonic operations for diverticulitis decreased by 13.14%, but the rates of emergency operations (17.31% vs. 20.04%, P< 0.001) and cases with a known abscess/perforation (50.11% vs. 54.55%, P< 0.001) increased. Likewise, the prevalence of comorbidities, such as congestive heart failure, acute renal failure, systemic inflammatory response syndrome, and septic shock, were higher during the pandemic (P< 0.05). During this same period, significantly more patients were classified under American Society of Anesthesiologists classes 3, 4, and 5, suggesting their preoperative health states were more severe and life-threatening. Correspondingly, the average operation time was longer (P< 0.001) and complications, such as organ space surgical site infection, wound disruption, pneumonia, acute renal failure, septic shock, and myocardial infarction, increased (P< 0.05) during the pandemic. CONCLUSIONS: During the pandemic, surgical volume decreased, but the clinical presentation of diverticulitis became more severe. Due to resource reallocation and possibly patient fear of seeking medical attention, diverticulitis was likely underdiagnosed, and cases that would have been elective became emergent. This underscores the importance of monitoring patients at risk for diverticulitis and intervening when criteria for surgery are met.

COVID-19 Pandemic Effects on Clinical Outcomes of Hip Fractures Among Pediatric and Adult Patients.

BACKGROUND: Little is known about the distribution and outcomes of hip fractures in pediatric patients during the COVID-19 pandemic. OBJECTIVE: To study the clinical outcomes of both pediatric and adult patients who underwent hip fracture surgeries and determine the effects of changes surrounding the COVID-19 pandemic. METHODS: Both pediatric and adult surgical hip fracture cases were analyzed from the pandemic year (2020) and the control year (2019) using the American College of Surgeons National Surgical Quality Improvement Program database. RESULTS: Between the prepandemic (control) and pandemic years, a total of 2,438 pediatric and 28,180 adult cases were compared. Pediatric patients had similar perioperative characteristics and outcomes between the two years. Significantly fewer hip fractures were reported among adults during the pandemic (p < .001). Preoperatively, more adult patients had ventilator dependence (p = .020), transfusions (p = .029), and systemic inflammatory response syndrome (p < .001) in 2020. Adult operations were more likely to be emergent in 2020 (p < .001) and adults had more severe disease states. Length of stay (p < .001) and the time from operation to discharge (p < .001) were significantly longer for the adult cohort in 2020. Mortality was also higher for adults during the first year of the pandemic (p = .003), and superficial surgical site infections became more common (p = .036). CONCLUSION: Pediatric hip fracture patients had similar clinical outcomes between 2019 and 2020. Adults with hip fractures presented in more serious clinical conditions, which resulted in higher mortality in 2020. Further studies could better clarify the reasons as to why adult hip fracture patients had markedly worse clinical course during the COVID year than pediatric patients.

Racial Disparities in Clinical Outcomes of Emergency Colectomies for Diverticulitis.

OBJECTIVES: The literature suggests that there are ongoing racial disparities in healthcare outcomes between patients in White and non-White populations. As such, we examined the outcomes of patients who underwent an emergency colectomy for diverticulitis. METHODS: We identified 4841 White and 590 non-White patients, which include Black/African American and Asian patients, using the 2016-2019 American College of Surgeons National Surgical Quality Improvement Program databases. We compared Black/African American and Asian patients with White patients for differences in surgical outcomes. RESULTS: Non-White patients had more comorbidities than White patients (P < 0.05). These patients underwent longer operations, developed more postoperative complications, and were more likely to have lengths of stay >30 days. When controlling for all of the covariates in multivariate logistic regression models, White race was independently associated with a 22.14% lower odds of a hospital stay >30 days compared with non-White patients (P = 0.001). CONCLUSIONS: In this study, non-White patients developed more complications than did White patients and had longer hospitalizations. These disparities represent a more complex societal issue that cannot be managed perioperatively alone.