Intestinal discontinuity may be associated with worse outcomes in damage control laparotomy for trauma: An American association for the surgery of trauma prospective multicenter observational study.

Abstract INTRODUCTION The utilization of glucagon-like peptide 1 receptor agonists (GLP-1RA) is rising for the treatment of obesity, with emerging data to suggest that they may also exert anti-inflammatory effects beyond weight loss. As the prevalence of obesity rises in patients with inflammatory bowel disease (IBD), there is mounting interest in understanding the effect that GLP-1RAs have on IBD-associated outcomes. METHODS Utilizing the Mayo Clinic Platform, which provides de-identified clinical data on approximately 8 million patients, we performed a case-control study to evaluate the impact that use of GLP-1RAs had on IBD-specific outcomes of corticosteroid use, emergency department (ED) visits, hospitalizations, intestinal surgery, and mortality in patients with ulcerative colitis (UC) and Crohn’s disease (CD). Patients were included if a diagnosis code for CD or UC occurred at least 4 times. GLP-1RA exposure was defined as having a GLP-1RA (liraglutide, semaglutide, tirzepatide) ordered or administered at least twice. IBD cases with GLP-1RA exposure were propensity score matched on age, sex, type 2 diabetes mellitus, and body mass index (BMI). RESULTS In total, there were 580 patients with IBD identified who were treated with a GLP-1RA (322 UC, 258 CD) who were matched to controls with IBD who were not treated with GLP-1RA. Of the 322 individuals with UC, the rates of corticosteroid use (46.6% vs 85.1%, OR 0.15, 95% CI 0.11-0.22, p < 0.001), hospitalization (40.9% vs 65.9%; OR 0.35, 95% CI 0.25-0.48, p< 0.001), intestinal resection (6.5% vs 20.8%; OR 0.27, 95% CI 0.16-0.45, p< 0.001) and mortality (4.6% vs 22%; OR 0.17, 95% CI 0.10-0.30, p< 0.001) were lower in the GLP-1RA treated patients as compared to controls (Figure 1). Frequency of ED visits was similar between groups (51.9% vs 56.5%; OR 0.73, 95% CI 0.52-1.00, p = 0.048). In patients with CD, rates of corticosteroid use (39.9% vs 76.0%, RR 0.53), ED visits (41.9% vs 52.7%, RR 0.80), hospitalization (30.6% vs 55.8%, RR 0.55), intestinal resection (17.8% vs 53.9%, RR 0.33), and mortality (5.8% vs 10.9%, RR 0.53). CONCLUSIONS The use of GLP-1 receptor analogs was associated with improved IBD-specific outcomes in patients with UC and CD. Further study is needed to better define the true impact of GLP1RA on IBD-specific outcomes, ideally with more granular measures of disease activity.

Abstract BACKGROUND Studies suggest approximately between 10-20% of patients with pediatric Ulcerative Colitis (UC) will require surgical intervention with colectomy. Although prior studies have attempted to find predictors for the need of colectomy in pediatric UC, biomarkers for surgical interventions are still lacking. We set out to identify transcript and protein signatures of medication-refractory colitis through spatial single-cell transcriptomics and multiplex protein staining to predict the need for colectomy. METHODS Patients were identified from 2019 to 2023 who required inpatient hospitalization for acute severe colitis (ASC) at diagnosis. Deidentified intestinal biopsy and intestinal resection samples were obtained through ISTAT study (Seattle Children’s IRB Study ID 00001308) from pediatric patients with ASC at diagnosis, on treatment, and at the time of colectomy. We profiled diagnostic human biopsies from the colon of treatment-naïve pediatric patients with ASC at the time of diagnosis (n = 12) in two cohorts of patients [colectomy (n = 6) and no colectomy (n = 6)] (Figure 1A and 1C). Data was obtained using 10x Xenium with 475 transcript probes on formalin fixed paraffin embedded (FFPE) samples (Figure 2Ai+ii) Patients in both groups had similar clinical presentation in age, PUCAI scores, Mayo scores, and laboratory parameters (CRP, ESR, Stool calprotectin) at time of diagnosis (Figure 1B). RESULTS Using 10x Xenium platform, we identified cell types from 5 major cell type classes (Stromal cells, Epithelial cells, T cells, B cells and Myeloid cells) via 326 million spatially-localized transcripts from 1.1 million cells. We identified shared cellular neighborhoods (termed zones 0 through 8) to define sub-anatomic regionalized networks of disease activity and to use as a basis for comparison across samples. We mapped neighborhood structure onto tissue samples (Figure 2Ai) and visualized cell-type clustering via uniform manifold approximation projection (UMAP) (Figure 2Aii). Cell types were identified using reference single-cell RNA-seq datasets available from previous single-cell studies available in the literature. Using data from naïve-to-treatment colonic biopsies at time of diagnosis, we identified an expansion of inflammatory fibroblasts in the cohort that went on to need colectomy (Figure 2Aiii). Further analysis reveals divergent transcript signatures in inflammatory fibroblasts in the two cohorts (Figure 2B), along with differences in fibroblast proximity to immune cells (T cells) and fibroblast location within the lamina propria. CONCLUSION Taken together, this suggests that there exist distinct inflammatory microenvironments driving recalcitrant disease states. Further analysis is underway to identify specific pathways and understand cell-cell network pathogenesis.

P0669 Thirty-day postoperative outcomes and predictive factors in Crohn’s disease patients undergoing intestinal resection

P1114 Histologic inflammation at resection margins predicts clinical and surgical recurrence in Crohn’s disease: a multicenter observational study

DOP029 One-Year Effectiveness and Safety of Upadacitinib in 261 Patients With Crohn’s Disease: A Multicenter Real-World Cohort Study.

P0182 Altered SCFA Metabolism Following Intestinal Resection: A Mechanistic Link Between Dysbiosis and Adverse Outcome in SBS?

P1167 Changes in the natural history of postoperative recurrence in Crohn’s disease: A meta-analysis of placebo groups from randomized controlled trials

P0688 Clinical characteristics and treatment patterns of ustekinumab in patients with Crohn’s disease: Sub-group analysis from a one-year prospective nationwide K-STAR study in Korea

Introduction and Importance: Short bowel syndrome (SBS) is a serious complication following extensive intestinal resection. It is rarely reported in Africa, probably due to the high mortality rate in the acute phase. This article reports a case of acute SBS that was successfully managed. Case Presentation: A 60-year-old female patient was admitted for an occlusive syndrome with shock that had been developing for 4 days. A CT scan revealed a right paraduodenal hernia complicated by intestinal necrosis. Surgical exploration found 450 cm of necrotic small intestine incarcerated in the hernia. After resection, 130 cm of proximal jejunum and 15 cm of terminal ileum remained. A gunshot ileostomy was performed. The postoperative period was marked by hyponatremia, weight loss, hyperproductive stoma, skin irritation, and a buttock bedsore. Treatment included parenteral nutrition (Perikabiven), transit retardants, proton pump inhibitors, enteral nutrition, oral rehydration salts, and Plumpy’nut. Digestive continuity was restored on day 26, with postoperative complications including deep venous thrombosis and an enterocutaneous fistula treated medically. The patient was discharged 12 days later, treatment was continued at home except for Perikabiven, and the fistula healed on day 37. Clinical Discussion: Strangulated internal hernias are a rare cause of SBS. Type III, jejuno-ileo-colonic anastomosis has a favorable prognostic factor in the acute phase. This phase is marked by significant fluid and electrolyte losses, causing diarrhea, dehydration, and electrolyte disturbances. This phase is characterized by the need for constant fluid resuscitation and nutritional intake. It requires early detection, rigorous monitoring, and pragmatic adaptation of nutritional strategies to available means. Conclusion: SBS is a serious complication of major intestinal resection, especially in the acute phase. It increases the burden of hospital care in settings with limited resources. It requires early detection, rigorous monitoring, and pragmatic adaptation of nutritional strategies to available means.

P0639 Real-World Effectiveness, Safety, and Dose Modifications of Upadacitinib in Patients with Crohn’s Disease: A Canadian Multicenter Study

P0037 Role of Enhancer of Zeste Homolog 2 (EZH2) in Intestinal Fibrosis Associated with Inflammatory Bowel Diseases

P1278 Characterization of the ‘Difficult to Treat’ Phenotype in Inflammatory Bowel Disease: Experience from a Mexican Cohort

P0808 Complementary medicine use in Inflammatory Bowel Disease patients is an independent predictor for unplanned hospitalisations and emergency presentations

DOP020 Serum micro- and nano-plastic burden as a risk marker for Crohn’s disease progression: a multi-omics discovery of gut microbiome–metabolite perturbations

OP03 Early kinetics of transmural healing in patients with Crohn’s Disease treated with risankizumab: Results of the multicenter prospective SKYNETICS study

Kohlmeier-Degos disease is a potentially severe multiorgan thrombotic vascular injury syndrome with characteristic cutaneous lesions characterized by depressed porcelain white plaques with telangiectatic rims. This occlusive vasculopathy involves the microvasculature but also extends to affect arterioles and small arteries where a peculiar intravascular and intimal fibrosing reaction occurs. We discovered in earlier studies that complement pathway activation and enhanced type I interferon signaling are held to be a critical impetus for the endothelial cell injury. Significant upregulation of type I interferon signaling is also responsible for the neointimal expansion and fibrosis. We had the opportunity of examining before and after treatment biopsies in a pediatric patient receiving the 3-drug protocol for the treatment of Kohlmeier-Degos disease. The patient was a 13-year-old girl who presented with a few months history of depressed white macular skin lesions and abdominal pain. A laparotomy revealed multiple serosal porcelain plaques and evidence of acute severe intestinal ischemia. The patient's pretreatment skin and intestinal resection samples showed a striking pauci-inflammatory microangiopathy associated with endothelial cell necrosis and microvascular thrombosis and arteriolar and arterial neointimal hyperplasia with intimal fibrosis, extensive vascular C5b-9 deposition and enhanced type I interferon signaling in the skin and intestine. Extravascular fibrosis with a loss in the expression of CD34 amid fibroblasts was observed. A diagnosis was made of Kohlmeier-Degos disease. The post-treatment biopsies of the skin and intestine demonstrated complete abrogation of both endothelial cell injury and intravascular fibrin thrombi. There was no evidence of neointimal fibrosis. The CD34 negative procollagen scleroderma phenotype was not observed in fibroblasts. A discernible but less intense type I interferon signal was present while the C5b-9 studies were negative in the post-treatment skin biopsy. The intestinal resection specimen obtained several months later had a negative interferon signature. Fibrous intravascular occlusion was limited to rare vessels in the intestinal resection specimen. The cutaneous and extracutaneous lesions of Kohlmeier-Degos disease are potentially reversible. The combination of therapeutic complement inhibition, downregulation of type I interferon expression, and the promotion of vascular patency and reduced platelet activation through prostacyclin administration define the cornerstone of treatment.

Background: In emergency as well as in elective situations, gastrointestinal anastomosis is an essential step to maintain the continuity of gastrointestinal tract following intestinal resection. Anastomotic complications, primarily, anastomotic leaks is one of the most widely feared and extensively studied problems in GI surgery. That’s why this study was conducted to identify the risk factors for early complications in gastrointestinal anastomosis Methods: This was a cross sectional observational Study which took place in the department of Surgery, Rangpur Medical College Hospital and private hospitals in Rangpur, Bangladesh from 1st October 2018 to 31st March 2019 over a period of 6 months. All statistical analysis was performed using the SPPS software program version 26.0 (SPSS, Inc., Chicago, IL, United States of America). A p value<0.05 was considered statistically significant. Results: A total number of 200 patients were included in the study by purposive sampling method. Mean age of the study population was 46±13.6 years with a male female ratio of 2:1. Among them 44% patients had gastro-jejunal anastomosis and 66% patients had anastomosis involving small and large gut. Anastomotic leaks (AL), (4.5%) and hemorrhage (2.2%) were the main post-operative complications. Re-operation was required in 3.5% patients. Operative mortality rate was 5.5%, with 06 deaths (54%) secondary to anastomotic complications. Univariate analysis of the overall population male patient, age, malnutrition, malignancy, sepsis and uses of steroids were independent predictors of postoperative complication following gastrointestinal anastomosis. Conclusions: Anastomotic complications, particularly anastomotic leaks, remain a major unsolved problem in GI surgery.

ABSTRACTBackgroundLimited data are available on the management and outcomes of postoperative Crohn's disease (CD) in older patients. We aimed to describe the management of CD in the postoperative setting and assess surgical postoperative recurrence (POR) in this population.MethodsThis was a case‐control study including all adult patients with CD from the ENEIDA registry who had undergone a first intestinal resection with ileo‐colonic anastomosis. Patients were grouped according to their age at the time of the first surgery in older (over 60 years) subjects and controls (between 18 and 60 years of age).ResultsA total of 3982 (535 older subjects and 3454 controls) underwent a first intestinal resection for CD with an ileo‐colonic anastomosis. Time from CD diagnosis to surgery was significantly longer in older patients (114 ± 128 vs. 93 ± 97 months; p < 0.001). Older patients also had a lower proportion of penetrating CD (25% vs. 39%; p < 0.0001) and perianal disease (14% vs. 25%; p < 0.0001). A significantly lower proportion of older patients started preventive therapies for POR (32% vs. 51%; p < 0.0001). The cumulative risk of surgical POR was 3.2%, 5.3% and 10.1% in the older group and 3.6%, 6.6% and 14.2% in the control group at three, five and 10 years, respectively (p = 0.093). In the multivariate logistic regression analysis, only prevention with thiopurines was associated with a lower risk of surgical POR.ConclusionsAlthough postoperative preventive therapy with immunomodulators or biologicals is prescribed less often in older patients after a first intestinal resection, they develop surgical POR as often as younger adult patients.

Clinical features and outcomes of perianal disease in pediatric onset Crohn's disease.