Objective The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels. Approach and Results We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the Four Core Genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male–female gonadal sex and XX–XY chromosome complement. Gonadectomy of adult mice revealed that the male–female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male–female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared to a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with two X chromosomes compared to mice with an X and Y chromosome. By generating mice with XX, XY and XXY chromosome complements, we determined that the presence of two X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration. Conclusions We demonstrate that having two X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels.

Gastrointestinal complications in critically ill patients during the COVID-19 pandemic pose a diagnostic and treatment dilemma. We present a case of a 74-year-old male who was brought to our emergency department with worsening shortness of breath, fever, and dry cough and was found to have COVID-19 pneumonia. Early in his hospital course, he was admitted to the intensive care unit, and was found to have significant abdominal distension with large amounts of simple fluid on bedside ultrasound. Bedside paracentesis returned succus and enteric feeds, and a methylene blue test confirmed a likely gastrointestinal perforation. The patients’ family refused surgical intervention and the patient underwent bedside drainage. This case represents several critical dilemmas clinicians faced during the recent surge of the COVID-19 pandemic.

Aim Minimally invasive approaches to proctocolectomy with ileal pouch anal anastomosis have become the standard of care with one benefit being the reduced risk of adhesion‐related complications. However, a lack of pouch adherence to the pelvis can lead to increased mobility as well as volvulization, placing pouch viability at risk. We aimed to describe our institutional experience with pouch volvulus. Methods Patients who presented with pouch volvulus from 1983 to 2020 were identified through a search of our pelvic pouch registry and enterprise‐wide electronic medical record. Pouch volvulus was defined as a reducible rotation of the J‐pouch on its mesenteric axis with evidence of a properly oriented ileo‐anal anastomosis. Patients with ‘twisted pouches’ were excluded. Results In total, 5760 patients underwent ileal pouch anal anastomosis from 1983 to 2020. Six patients (five women) were identified with a diagnosis of ‘pouch volvulus’ consistent with our definition. The six pouches were constructed utilizing laparoscopic techniques and the mean time from construction to volvulus was 2.36 years. All patients underwent urgent surgery, with a paucity of adhesions noted in five. Reduction and pouch pexy was performed in three and pouch excision in three, with immediate pouch reconstruction in two and end ileostomy creation in one. At a median follow‐up of 9 months, pouch survival was 50%. Conclusions Pelvic pouches constructed using minimally invasive techniques may be at risk of volvulus due to reduced adhesion development. A high index of suspicion is warranted in pouch patients with obstructive symptomatology. CT imaging may be diagnostic, and prompt surgical intervention may facilitate pouch salvage.

BACKGROUND:Redo ileocolic resection for recurrent Crohn's disease is associated with increased technical complexity and higher complication rates compared to primary resection. Literature concerning redo surgery for recurrent Crohn's disease is scarce and it is controversial whether a redo is a risk factor for postoperative anastomotic leak. OBJECTIVE:This study aimed to hypothesized that redo ileocolic resection for Crohn's disease is an independent risk factor for anastomotic leak.DESIGN: Retrospective, case-control study from 1994 to 2019 with multivariate analysis and propensity score weighting.SETTING: Quaternary, IBD-referral center.PATIENTS: Adult patients aged >18 years were included in the study. INTERVENTIONS:Primary or redo ileocolic resection with an anastomosis, with or without diverting ileostomy. MAIN OUTCOME MEASURES: Thirty-day anastomotic leak rate.RESULTS: A total of 991 patients (56% primary and 44% redo ileocolic resections) were included. Patients who underwent redo resection were significantly older with more comorbidities, fewer medications, and less fistulizing disease compared to the primary group. On univariate analysis, patients who underwent redo resection had more overall complications (50.5% vs 36.2%, p < 0.001), and the cumulative number of prior ileocolic resections was significantly associated with increased risk for overall morbidity (p < 0.001). There were 31 (3%) anastomotic leaks; leak rates did not differ between groups (p = 0.60). Multivariable analysis indicated that extensive adhesiolysis (p < 0.001), ileostomy omission (p = 0.009), and intraoperative abscess/fistula (p = 0.02) were independently associated with leaks but not redo resection (p = 0.27). Patients with 0, 1, 2, or 3 of these risk factors had observed leak rates of 1.1%, 1.3%, 6.0%, and 11.6.% (p = 0.03), respectively. LIMITATIONS:The limitations of this study were selection bias, referral bias, and single quaternary center.CONCLUSIONS: Compared to primary procedures, redo ileocolic resection for recurrent Crohn's disease is associated with increased overall morbidity but not anastomotic leak.

Background: Alpha-1-antitrypsin (AAT) is a protein that is the main inhibitor of neutrophil elastase and is released during inflammatory processes to reduce the activity of proteolytic enzymes in areas of inflammation. An indicator in the diagnosis of diseases of the small and large intestine. AAT plays an important role in the pathogenesis and regulation of the inflammatory process in inflammatory bowel diseases, can be used as diagnostic and prognostic markers in patients with intestinal lesions. The aim of the study was to determine the level of a-1-antitrypsin in the blood serum and in the feces in patients of UC with and without COVID-19 to assess the degree of inflammation activity and permeability in the intestine. Methods: Forty-two patients of UC with exacerbation of the disease without COVID-19 (Me age-32 years) with different disease activity according to the Meio activity index (group 1) and 23 UC patients with COVID-19 in the acute period (group 2) were examined. -a1-antitrypsin (AAT) (a1-Antitrypsin Clearance ELISA Immundiagnostik, Germany) was determined in blood serum and in feces. Statistical processing was carried out using the Statistica 6.0 program. Results: In the blood serum of UC patients with exacerbation of the disease without COVID-19, AAT fluctuations from 355 to 3056 mcg/l (norm 900-1800 mcg/l) were detected, the average value was 847.9616.5 mcg/l. In UC patients with exacerbation of the disease and the presence of COVID-19 in the acute period, AAT fluctuations from 645 to 4896 mcg/l (norm 900-1800 mcg/l), the average value is 2286.3 6181.4 mcg/l (P 5 0.000000). The range of AAT concentration in feces ranged from 55 to 625 ml/g of feces (norm 25-35 mg/g of feces), on average 364.9 6 11.4 ml/g of feces. The range of AAT concentration in feces ranged from 112 to 898 ml/g feces) (norm 25-35 mg/g feces), on average 539.6618.4 ml/g feces (P 5 0.000000). Conclusion(s):The increase in AAT in the blood serum and in the feces of patients with exacerbation of UC with the presence of COVID-19 infection in the acute period is significantly higher in patients with UC without COVID-19, which indicates a higher permeability of the intestinal wall.