non-IBD Patients Research Articles

DOP29 Single cell analysis of Crohn’s disease fistula; comparison of different locations

Abstract Background A common complication of Crohn’s disease(CD) are perianal fistulae, highly impacting the quality of life in these patients. The pathogenesis of these fistulas is incompletely understood. Treatment is often given based on knowledge of disease processes in the inflamed intestine itself, but whether the immune activity in the fistula tract is similar remains unknown. Full characterization of the intestinal mucosa versus the fistula tract itself may reveal immunological differences between the two, and generate leads for both development of new interventional options as well as allow better stratification of patients. Methods Matched biopsies were obtained from the rectal mucosa, the internal opening of the fistula and the tract itself. A total of 30 patients were included (20 CD; 10 non-IBD patients). Tissues were processed to cell suspensions and selected for live CD66b- cells. Single cell RNASeq analysis was performed using 10x Chromium. In total, 111.955 immune cells were annotated and used for analysis. Results T cells comprised the largest cluster of immune cells, which was subclustered into 19 clusters. Both the internal opening and the fistula tracts contained elevated proportions of effector memory and cycling T cells. Conversely, the rectum contained more central and tissue resident memory cells. T cells expressing IL-22, which were previously described in fistula were detected in considerable number in the rectum and internal opening, but were scarce in the fistula tract itself. These cells were clearly distinct from the IL17A producing subset, and IL17F expressing cells and mainly found in the fistula tracts. Only the tract contained a clear subset of CXCL13 expressing T cells, suggesting follicular helper T cells. Presence of these cells was strongly correlated to the presence of lymphoid inducer cells as well as IgG producing B cells rather than the IgA subset found in the rectum. Clusters of myeloid cells were largely derived from the fistula tracts. Subclustering into 10 clusters indicated a shift from anti-inflammatory to pro-inflammatory macrophages in the tracts compared to the rectal mucosa. Finally, a striking difference in NK cells subsets was observed, with significantly more CD56bright NK cells present in the rectal samples while the internal opening and the tracts were comparable. Conclusion Cellular composition and activity of the immune cell compartment differs considerably between the rectum, the internal opening of the fistula and the tract. Subsequently, therapy targeted at processes involved in mucosal inflammation may not actually target the fistula itself, which may explain the low success rate in fistula resolution. Careful analysis of the fistula may help to identify targets useful in the treatment.

P350 Endoscopic sedation in IBD patients: a propensity score-matched retrospective study

Abstract Background Colonoscopy plays an essential role in the prevention of colorectal cancer screening and the management of inflammatory bowel disease (IBD). For patients with IBD, colonoscopy is advocated for detection of complications, guiding clinical decisions, and cancer surveillance. In most cases, sedation is a fundamental constituent of the procedure, reducing peri-procedural discomfort and improving examination quality. We aimed to compare the dosing of sedative medications and the duration of procedure for IBD patients compared to non-IBD controls in a large-volume endoscopic center. Methods This was a propensity score–matched retrospective study that took place at a high-volume gastroenterology department between June 2020 and September 2021. Colonoscopy data of patients with established IBD including medications and duration of procedure was collected, compared to a 1:2 propensity-scored matched cohort of non-IBD patients. Patients with polyposis, past abdominal surgery, known or suspected malignancy, suspected IBD, incomplete colonoscopies and colonoscopies with inadequate preparation were excluded. The sedation protocol in our institution includes an induction of Midazolam 1-2 mg and Fentanyl of 0.025-0.05 mg administered five minutes prior to procedure. An initial dose of 10-30 mg Propofol is initiated as well, with subsequent increments of 10-20 mg every 1-2 minutes, depending on sedation depth. Results During the study period, 14502 patients including 996 patients with IBD underwent colonoscopy and 4933 patients were excluded in accordance with the exclusion criteria. Propensity score matching was conducted using four characteristics - patient age, gender, American Society of anaesthesiologists score determined by the endoscopist, and endoscopists’ experience. A total of 2289 patients were included in the final analysis (763 IBD patients, 1526 control patients). The groups were similar in administered Propofol sedation doses [IBD- median dose of 100 mg, interquartile ratio (IQR) 70-150 vs control, 100 mg, IQR 80-150, p=0.2). In addition, total procedure time (considered the time from procedure start and end as recorded by the endoscopy nurse) was significantly longer in the IBD group (23 median minutes, IQR 18-30 vs 20 median minutes, IQR 16-27, p<0.0001). There were no differences in terminal ileum intubation rates between the groups (51% in IBD vs 49.5% in control, p=0.5). Conclusion In a retrospective analysis from a large-scale tertiary center cohort, colonoscopies of patients with IBD were significantly longer despite comparable terminal intubation rates; IBD patients did not require more intensive sedation than controls.

METABOLOMICS ANALYSIS IDENTIFIED AN ORALLY ACTIVE METABOLITE FOR TREATING CROHN’S DISEASE-ASSOCIATED INTESTINAL FIBROSIS

Abstract BACKGROUND Intestinal fibrosis is a debilitating complication of Crohn’s disease (CD) patients. Surgical resection is used to treat intestinal strictures, but this approach may adversely affect the patients' quality of life. Based on the findings of our groups and others, we hypothesize that intestinal metabolites are associated with intestinal fibrosis. We aimed to discover novel anti-fibrogenic metabolites. METHODS We compared the intestinal metabolite profiles between non-IBD, stricturing CD, and non-stricturing CD patients in an inflammatory bowel disease (IBD) multi-omics database to identify CD stricture-related metabolites. We compared the fecal metabolite profiles between trinitrobenzene sulfonic acid (TNBS)-treated mice with and without anti-fibrogenic CSA13 treatment to identify mouse intestinal fibrosis-related metabolites. RESULTS Compared to non-stricturing CD patients and non-IBD patients, stricturing CD patients had reduced fecal levels of inosine. Compared to normal mice, TNBS-treated mice had reduced fecal levels of inosine. CSA13-exposed TNBS-treated mice had increased fecal inosine levels. Oral administration of inosine (10 mg/kg/day for 14 days) effectively reduced ileal fibrosis in fibrotic 40-week-old SAMP1/YitFc mice with 96-100% reduction of intestinal collagen mRNA expression and 87% reduction of overall ileal disease activity. Although inosine did not directly inhibit collagen expression in primary human ileal fibroblasts from stricturing CD patients (CD-HIF), it reduced collagen mRNA expression in fresh ileal tissues from stricturing CD patients. RNA-seq and proteomics identified that peroxiredoxin 2 (PRDX2) is negatively associated with intestinal strictures in CD patients. PRDX2 is a thiol-specific antioxidant gene that reduces peroxides to alcohols. Inosine increased the secretion of peroxiredoxin 2 (PRDX2) in primary human intestinal epithelial cells (HPEC). The inosine-mediated PRDX2 secretion was inhibited by the pretreatment of adenosine 2A receptor (A2AR) inhibitor ZM241385. PRDX2 reduced cell stress, induced cell stress-related protein (cyclooxygenase 2/COX-2), and inhibited collagen expression in the CD-HIF. Inhibition of COX2 by indomethacin reversed the anti-fibrogenic effect of PRDX2 in the CD-HIF. Inhibition of PRDX2 caused increased collagen expression in the CD-HIF. Lentiviral overexpression of Prdx2 ameliorated ileal fibrosis in the fibrotic SAMP1/YitFc mice. Fibrotic SAMP1/YitFc mice had reduced circulating free thiol, reflecting increased systemic oxidative stress. Inosine restored circulating free thiol levels in SAMP1/YitFc mice. CONCLUSIONS Inosine is an orally active anti-fibrogenic metabolite that promotes PRDX2 expression from intestinal epithelial cells. PRDX2 is a newly identified anti-fibrogenic protein, which may inhibit collagen expression by reducing cell stress.

MANAGEMENT STRATEGIES FOR OBESITY VARY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Abstract INTRODUCTION Obesity among patients with inflammatory bowel disease (IBD) is increasing with prevalence of 15-40%. Studies have shown that obesity may have poor prognostic implications on IBD treatment and outcomes. There is lack of data focused on the management of obesity in IBD patients. This study’s primary aim was to evaluate whether patients with obesity and IBD have similar rates of obesity management compared to non-IBD obese patients with and without nonalcoholic fatty liver disease (NAFLD). METHODS This is a single-center retrospective study of 400 obese (body mass index > 30 kg/m2) adult patients seen in a primary care clinic between March 2019 and August 2021. Four cohorts, each with 100 patients, were studied. The 4-level cohort analysis included patients with ulcerative colitis and obesity (UC-O), Crohn’s disease and obesity (CD-O), NAFLD and obesity (NAFLD-O), and a control group of patients with obesity only. The 3-level cohort analysis combined UC-O and CD-O and compared this cohort to the NAFLD-O and obesity-only cohorts. Obesity management data collected included: if obesity was documented (OD) in the medical record’s problem list, dietician referral, pharmacologic therapy, and bariatric surgery referral. One-way ANOVA was used to compare numeric variables and chi-squared was used for categorical variables. Logistic regression models were used for primary outcomes. RESULTS Baseline characteristics of BMI, age, gender, and race were similar among patients in the 4-level and 3-level cohort analyses (Tables 1 and 2). Across both analyses, NAFLD-O patients had the highest prevalence of OD (79% p<0.001) and 2.61 higher odds of OD than the control (p =0.003). NAFLD-O patients also had the highest prevalence of dietician referrals (69%, p=0.01). CD-O patients had the highest prevalence of pharmacologic intervention (17%, p=0.01). UC-O patients were less likely to be referred to a dietician (OR=0.55, p=0.03) while CD-O patients were more likely to have pharmacologic management (OR=3.21, p=0.02). Secondary outcomes of comparisons of IBD-specific variables between UC-O and CD-O revealed significant differences as well (Table 3). DISCUSSION This is the first study investigating differences in treatments offered for obesity in IBD. With emerging evidence that obesity likely plays a role in IBD pathogenesis, timely identification and treatment is crucial. Significant differences in management of IBD patients with obesity highlight the need for increased awareness among healthcare providers. Our findings that CD-O patients had a higher rate of corticosteroid, immunomodulator, anti-TNF, anti-interleukin use, and IBD surgery compared to UC-O patients suggests that obesity may contribute to the pathogenesis of CD more so than UC. Further studies are needed to determine which obesity therapies are most effective in the IBD population.

Risk of COVID-19 Infection After Full Immunization in Patients With Inflammatory Bowel Disease on Treatment: A Research Network Analysis.

Acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an issue in treating patients with Inflammatory Bowel Disease (IBD) due to concerns for infection risk and poor post-vaccination antibody response. We examined the potential impact of IBD treatments on SARS-CoV-2 infection rates after full immunization against COVID-19. Patients who received vaccines between January 2020 and July 2021 were identified. The post-immunization Covid-19 infection rate at 3 and 6 months was assessed in IBD patients receiving treatment. The infection rates were compared to patients without IBD. Results: The total number of IBD patients was 143,248; of those (n=9405), 6.6% were fully vaccinated. In IBD patients taking biologic agents/small molecules, no difference in Covid-19 infection rate was found at 3 (1.3% vs. 0.97%, p=0.30) and 6 months (2.2% vs. 1.7%, p=0.19) when compared to non-IBD patients. No significant difference in Covid-19 infection rate was found among patients receiving systemic steroids at 3 (1.6% vs. 1.6%, p=1) and 6 months (2.6% vs. 2.9%, p=0.50) between the IBD and non-IBD cohorts. Conclusions: The COVID-19 immunization rate is suboptimal among IBD patients (6.6%). Vaccination in this cohort is under-utilized and should be encouraged by all healthcare providers.

Comparison of Migraine Characteristics in Patients With and Without Inflammatory Bowel Disease: A Retrospective Cohort Study.

Survey studies have found an increased prevalence of migraine in patients with inflammatory bowel disease (IBD). However, the clinical characteristics of migraines in this population are unknown. We conducted a retrospective medical record review study to characterize migraines in the IBD population. Six hundred seventy-five migraine patients (280 with IBD, 395 without IBD) who were evaluated at Mayo Clinic Rochester, Mayo Clinic Arizona, or Mayo Clinic Florida between July 2009 and March 2021 were included. Patients with ICD codes for migraine and either Crohn's disease (CD) or ulcerative colitis (UC) were selected. Electronic health care records were reviewed. Patients confirmed to have IBD and migraine were included. Demographic, IBD, and migraine characteristics were collected. Statistical analysis was completed using SAS. Patients with IBD were less often male (8.6% vs 21.3%, P < .001) and had a higher Charlson Comorbidity Index (>2: 24.6% vs 15.7%, P = .003); 54.6% had CD and 39.3% had UC. Patients with IBD had migraine with aura and without aura more frequently ( OR 2.20, P < .001 and OR 2.79, P < .001, respectively) than non-IBD patients. Additionally, those with IBD less commonly had chronic migraine (OR 0.23, P < .001) and less commonly had chronic migraine or treatment for migraine (ORs 0.23-0.55, P ≤ .002). Migraine with and without aura have increased prevalence in IBD patients. Further study of this topic will be helpful to clarify the prevalence of migraine, establish this population's response to treatment, and better understand the reason(s) for a low rate of treatment.

Effects of bowel cleansing on the composition of the gut microbiota in inflammatory bowel disease patients and healthy controls.

In patients with inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC), numerous cases of exacerbations could be observed after colonoscopy, raising the possible pathogenetic effect of colonic microbiota alterations in IBD flare. We aimed to investigate the changes in the fecal microbiota composition in IBD patients influenced by the bowel preparation with sodium picosulfate. We enrolled patients with IBD undergoing bowel preparation for colonoscopy in the prospective cohort study. The control group (Con) comprised non-IBD patients who underwent colonoscopy. Clinical data, blood, and stool samples were collected before colonoscopy (timepoint A), 3 days later (timepoint B), and 4 weeks later (timepoint C). Disease activity and gut microbiota changes were assessed at each timepoint. Fecal microbiota structure - at family level - was determined by sequencing the V4 region of the 16S rRNA gene. Statistical analysis included differential abundance analysis and Mann-Whitney tests. Forty-one patients (9 CD, 13 UC, and 19 Con) were included. After bowel preparation, alpha diversity was lower in the CD group than in the UC (p = 0.01) and Con (p = 0.02) groups at timepoint B. Alpha diversity was significantly higher in the UC group than in the CD and Con (p = 0.03) groups at timepoint C. Beta diversity difference differed between the IBD and Con (p = 0.001) groups. Based on the differential abundance analysis, the Clostridiales family was increased, whereas the Bifidobacteriaceae family was decreased in CD patients compared to the Con at timepoint B. Bowel preparation may change the fecal microbial composition in IBD patients, which may have a potential role in disease exacerbation after bowel cleansing.

Incidence and risk of herpes zoster in patients with ulcerative colitis and Crohn's disease in the USA.

Patients with inflammatory bowel disease (IBD) are at increased risk of herpes zoster (HZ). We evaluated the incidence of HZ in ulcerative colitis (UC) and Crohn's disease (CD) patients and compared this with HZ incidence in a non-IBD population. We conducted a retrospective cohort study (GSK study identifier: VEO-000043) of adults aged ≥18 years with UC and CD and without IBD who were identified from claims recorded in a US healthcare database between October 2015 and February 2020. Crude HZ incidence rates/1,000 person-years (PY) were calculated, and comparisons of HZ incidence rates between UC or CD and non-IBD cohorts were made using adjusted generalized linear models. The study population comprised a total of 29,928 UC, 25,959 CD, and 11,839,329 non-IBD patients. Crude overall HZ incidence rates were 13.64/1,000 PY (UC), 15.94/1,000 PY (CD), and 7.95/1,000 PY (non-IBD). UC and CD patients had increased HZ incidence rates, with adjusted incidence rate ratios of 1.35 (95% confidence interval [CI], 1.26-1.44) and 1.66 (95% CI, 1.56-1.77), respectively, compared with non-IBD patients. Stratified analysis indicated increased relative rates of HZ in progressively younger age strata in the UC and CD patients compared with non-IBD patients. HZ incidence rates were higher in UC and CD patients who had previously received thiopurines or methotrexate, TNF-inhibitors, or corticosteroids than in UC and CD patients who did not take those medicines. UC and CD patients had increased HZ incidence rates compared with patients without IBD, demonstrating the importance of HZ prevention in IBD patients.

Impact of IBD-Associated Dysbiosis on Bacterial Quorum Sensing Mediated by Acyl-Homoserine Lactone in Human Gut Microbiota

Intestinal dysbiosis is a key feature in the pathogenesis of inflammatory bowel disease (IBD). Acyl-homoserine lactones (AHL) are bacterial quorum-sensing metabolites that may play a role in the changes in host cells-gut microbiota interaction observed during IBD. The objective of our study was to investigate the presence and expression of AHL synthases and receptor genes in the human gut ecosystem during IBD. We used an in silico approach, applied to the Inflammatory Bowel Disease Multi'omics Database comprising bacterial metagenomic and metatranscriptomic data from stools of patients with Crohn's disease (CD) (n = 50), ulcerative colitis (UC) (n = 27) and non-IBD controls (n = 26). No known putative AHL synthase gene was identified; however, several putative luxR receptors were observed. Regarding the expression of these receptor genes, the luxR gene from Bacteroides dorei was under-expressed in IBD patients (p = 0.02) compared to non-IBD patients, especially in CD patients (p = 0.02). In the dysbiosis situation, one luxR receptor gene from Bacteroides fragilis appeared to be over-expressed (p = 0.04) compared to that of non-dysbiotic patients. Targeting LuxR receptors of bacterial quorum sensing might represent a new approach to modulate the gut microbiota in IBD.

S81 Comparison of Clinical Characteristics Between Young IBD and Non-IBD Patients With Adenomatous Colon Polyps

S81 Comparison of Clinical Characteristics Between Young IBD and Non-IBD Patients With Adenomatous Colon Polyps

S6 Serrated Epithelial Change: To Follow or Not to Follow?

Case: Dysplasia surveillance is an important aspect of management in inflammatory bowel disease (IBD). A variety of lesions can be identified on surveillance biopsies, including serrated epithelial change (SEC). In this report, we aim to raise awareness about SEC and discuss its implications in IBD patients. Case 1: A 76 -year-old female with left sided ulcerative colitis (UC) on Adalimumab underwent a colonoscopy which revealed a flat 1 cm rectal polyp. Remainder of the colon was endoscopically normal and biopsies showed quiescent colitis, however polyp returned as SEC. Case 2: A 64 -year-old male with UC on Infliximab and a history of low grade dysplasia (LGD) on 2 previous surveillance colonoscopies presented for colonoscopy with chromoendoscopy. Previous area of dysplasia was biopsied and showed SEC with LGD. Remainder of colonic biopsies showed quiescent disease. Discussion: In accordance with established guidelines, patients with IBD are recommended to have regular colonoscopies every 1 to 2 years for dysplasia surveillance. Our patient in Case 2 had LGD for several years before SEC was seen, which raised the question of the importance of SEC and its dysplastic potential. While traditional serrated adenomas (TSA) and sessile serrated polyps are commonly seen in both IBD and non-IBD patients, SEC is a distinct entity that has only been described in patients with IBD. It has also been termed hyperplastic-like change and flat serrated change. There is no standardized endoscopic appearance of SEC. Histologically, SECs have crypt distortion and loss of perpendicular orientation of crypts with no typical features of dysplasia. Review of the current literature demonstrates differing opinions on the dysplasia risk associated with SEC. Brcic et al identified mutations in KRAS and BRAF genes in several serrated lesions, that were not seen in mucosa with SEC, implying that the neoplastic potential is comparatively lower in SEC. However, a separate study of serrated lesions identified evidence of aneuploidy that was present in TSA and SEC samples suggesting that there may be an association with neoplasia on a molecular level. From a clinical perspective, in 1 study of patients with SEC, 21% developed dysplasia over the observed 8-year period, suggesting a possible association between SEC and dysplasia, albeit not a causative one. A more recent case controlled study of 196 patients showed that in UC patients with SEC, the rate of metachronous/synchronous neoplasia was 26.5% compared with 3.1% in UC patients without SEC. High grade dyplasia was also seen more commonly in patients with UC and SEC (11.2%) compared with 2% in UC patients with SEC. This study concluded that due to this association, close attention should be paid on subsequent surveillance colonoscopies to patients with SEC. Conclusion: Ultimately, further controlled studies and prospective trials are needed to assess the true impact of SEC as a risk factor for dysplasia. This is still an under-recognized entity and the associations that have been noted in the recent studies suggest that closer endoscopic follow up may be necessary when SEC is revealed on surveillance biopsies.

Patients with inflammatory bowel disease are more hesitant about Coronavirus disease 2019 vaccination.

Despite the impact of the Coronavirus Disease 2019 (COVID-19) pandemic, vaccine hesitancy remains common in the general public and patients with Inflammatory Bowel Diseases (IBD). We sought to examine the reasons for vaccine hesitancy in patients with IBD. In this case-control study, we performed a retrospective chart review of 1,349 IBD patients and 215 non-IBD patients seen at University of Maryland Medical Center, a tertiary referral medical center, between March 2020 and October 2021. Data obtained included demographics, vaccination records, disease history, number of IBD-related surgeries, and IBD medications. 813/1,349 (60.3%) IBD patients received at least one dose of either the Pfizer/BioNTech, Moderna, or Johnson & Johnson vaccines. In a multivariate logistic regression, COVID vaccination was found to be positively associated with older age (p-value = 1.65e-5), female sex (p = 0.00194), Asian and White races (p = 0.02330, 0.00169), number of clinic visits (p = 1.11e-08), and biologic use (p = 7.82e-5). There was no association between vaccination and other types of vaccination nor with the use of other IBD medications. There was a negative association between vaccination status and the total number of IBD related surgeries (p = 0.02857). In non-IBD patients, only the number of clinic visits was positively associated with COVID-19 vaccination. Although the majority of IBD patients are immunosuppressed, COVID-19 vaccination rate was only 60.3%. Younger adults, males, African Americans, and those requiring IBD-related surgeries were less likely to receive COVID-19 vaccine. Healthcare providers need to recognize these potential risk factors for COVID-19 vaccine hesitancy.

Comprehensive Phenotyping in Inflammatory Bowel Disease: Search for Biomarker Algorithms in the Transkingdom Interactions Context.

Inflammatory bowel disease (IBD) is the most common form of intestinal inflammation associated with a dysregulated immune system response to the commensal microbiota in a genetically susceptible host. IBD includes ulcerative colitis (UC) and Crohn's disease (CD), both of which are remarkably heterogeneous in their clinical presentation and response to treatment. This translates into a notable diagnostic challenge, especially in underdeveloped countries where IBD is on the rise and access to diagnosis or treatment is not always accessible for chronic diseases. The present work characterized, for the first time in our region, epigenetic biomarkers and gut microbial profiles associated with UC and CD patients in the Buenos Aires Metropolitan area and revealed differences between non-IBD controls and IBD patients. General metabolic functions associated with the gut microbiota, as well as core microorganisms within groups, were also analyzed. Additionally, the gut microbiota analysis was integrated with relevant clinical, biochemical and epigenetic markers considered in the follow-up of patients with IBD, with the aim of generating more powerful diagnostic tools to discriminate phenotypes. Overall, our study provides new insights into data analysis algorithms to promote comprehensive phenotyping tools using quantitative and qualitative analysis in a transkingdom interactions network context.

Aberrant Mucin Expression Profiles Associate With Pediatric Inflammatory Bowel Disease Presentation and Activity.

Intestinal mucosal healing is nowadays preferred as the therapeutic endpoint in inflammatory bowel disease (IBD), but objective measurements at the molecular level are lacking. Because dysregulated mucin expression is suggested to be involved in mucosal barrier dysfunction in IBD, we investigated mucin expression in association with barrier mediators and clinical characteristics in colonic tissue of a pediatric IBD population. In this cross-sectional monocentric study, we quantified messenger RNA (mRNA) expression of mucins, intercellular junctions, and cell polarity complexes in inflamed and noninflamed colonic biopsies from pediatric IBD (n = 29) and non-IBD (n = 15) patients. We then validated mucin expression at protein level and correlated mucin mRNA expression with expression of barrier mediators and clinical data. The expression of MUC1, MUC3A, MUC4, and MUC13 was increased in the inflamed colon of pediatric IBD patients compared with the noninflamed colon of non-IBD control subjects. Especially MUC13 mRNA expression associated with the expression of barrier mediators, including CDH1, OCLN, and TJP2. MUC1 and MUC3B mRNA expression in combination with calprotectin levels most accurately discriminated IBD patients from non-IBD control subjects (90.6% area under the receiver-operating characteristic curve [AUCROC], 92.0% sensitivity, 73.7% specificity), whereas aberrant mRNA expression of MUC1, MUC3A, MUC4, and MUC13 was distinctive for ulcerative colitis and of MUC3B for Crohn's disease. Furthermore, expression of MUC3A, MUC3B, and MUC4 correlated with clinical disease activity (ie, Pediatric Ulcerative Colitis Activity Index and Pediatric Crohn's Disease Activity Index), and of MUC1, MUC2, MUC4, and MUC13 with endoscopic colitis severity in ulcerative colitis patients. Colonic mucin expression is disturbed in pediatric IBD patients and associates with disease activity and presentation, suggesting its use as molecular marker to aid in disease diagnosis and management.

Inflammatory bowel disease-associated adherent-invasive Escherichia coli have elevated host-defense peptide resistance.

Adherent-invasive Escherichia coli (AIEC) are isolated from inflammatory bowel disease (IBD) patients at a higher rate than from control patients. Using a collection of E. coli strains collected from Crohn's disease (CD), ulcerative colitis (UC), or non-IBD control patients, antibiotic and resistance to the antimicrobial peptides HBD-3 and LL-37 was assessed. Carriage of bacterial-encoded omptin protease genes was assessed by PCR and omptin protease activity was measured using a whole-cell based fluorescence assay. Elevated resistance to antibiotics and host defense peptides in IBD-associated AIEC were observed. IBD-associated strains showed increased (but statistically non-significant) antibiotic resistance. CD-associated strains showed greater (but statistically non-significant) resistance to HBD3-mediated killing while UC-associated strains showed statistically greater resistance to LL-37 mediated killing. High-level resistance to LL-37 was associated with carriage of omptin protease genes and with increased omptin protease activity. Antimicrobial host defense peptide resistance may be an adaptive feature of AIEC leading to enhanced pathogenesis during the initiation or progression of IBD.

S926 Epidemiology of Interstitial Lung Disease in Patients With Inflammatory Bowel Disease – A Large Population-Based Study

Introduction: Interstitial lung disease (ILD) is a diverse spectrum of diseases resulting in scarring of lung parenchyma. Though considered rare, it is increasingly recognized in patients with inflammatory bowel disease (IBD). The pathogenesis is unclear but the changes in the lung are thought to represent the same type of inflammatory changes that occur in the bowel. The available literature on the association between IBD and ILD is largely based on case series. In this study, we sought to describe the epidemiology of ILD in patients with IBD. Methods: We queried a commercial database (Explorys Inc, Cleveland, OH), an aggregate of EHR data from 27 integrated healthcare systems in the United States between 3/2017-3/2022. We identified all patients in the database with CD or UC based on Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT). We compared the prevalence of ILD at least 30 days post-CD or post-UC diagnosis to a control cohort of patients without CD or UC. Results: Of the 31,699,800 patients in the database, 145,290 patients had CD and 123,800 patients had UC. Overall prevalence of ILD was higher in CD (1.89%) and UC (1.91%) compared to non-IBD patients (0.8%), with odds ratio (OR) for CD 2.38 [95% CI, 2.29-2.47, p< 0.001], and UC 2.41 [95% CI, 2.31-2.51, p< 0.001]. Odds of ILD in IBD patients tended to be higher in the cohort aged 18-65 versus age > 65, in African Americans compared to Caucasians, and was otherwise similar across gender. Among autoimmune conditions associated with ILD, IBD patients with RA and SLE had a significantly lower prevalence of ILD compared to non-IBD patients with RA or SLE. IBD patients on treatment with sulfasalazine, azathioprine, infliximab, or adalimumab tended to have lower odds of developing ILD compared to non-IBD patients on the same medications. (Table) Conclusion: In this large population-based study, we found a significantly higher prevalence of ILD in patients with CD and UC compared to patients without IBD. Interestingly, IBD patients on treatment with any of the various anti-inflammatory agents, most of which are independently associated with ILD, had lower odds of developing ILD compared to non-IBD patients on the same drugs. This data suggests that anti-inflammatory medications and IBD may be independent risk factors for development of ILD. Thus, the mechanism of lung injury in IBD patients may be unique, in which case treatment with anti-inflammatory medications may serve as a protective factor. Table 1. - Prevalence of ILD after at least 30 days post-IBD diagnosis - Above is for Crohn's Disease (CD) and below is for Ulcerative Colitis (UC) X CD Prevalence per 100,000 No CD Prevalence per 100,000 Odds Ratio 95% CI P-Value TOTAL 2750 1892 253640 804 2.38 2.29-2.47 <0.001 Adult (18-65) 1250 1225 92020 497 2.48 2.35-2.63 <0.001 Senior (65+) 1480 3583 142000 1873 1.95 1.85-2.05 <0.001 Female 1610 1827 129250 746 2.48 2.36-2.6 <0.001 Male 1140 2014 124580 888 2.29 2.16-2.43 <0.001 Caucasian 2290 2098 181110 1085 1.95 1.88-2.04 <0.001 African American 310 2391 37420 1040 2.33 2.08-2.61 <0.001 Asian 30 1685 3430 690 2.47 1.72-3.55 <0.001 Amyloidosis 20 8696 1110 6442 1.38 0.87-2.2 0.17 Systemic Sclerosis 50 16290 3850 18527 0.85 0.62-1.15 0.281 Polymyositis 30 12000 2360 13003 0.91 0.62-1.34 0.64 Rheumatoid Arthritis 510 2802 18350 4779 0.57 0.53-0.63 <0.001 Systemic Lupus Erythematosus 260 2014 6360 5332 0.37 0.32-0.41 <0.001 x x x x x x x x X UC Prevalence per 100,000 No UC Prevalence per 100,000 Odds Ratio 95% CI P-Value TOTAL 2370 1914 254000 804 2.41 2.31-2.51 <0.001 Adult (18-65) 910 1155 92360 498 2.32 2.18-2.48 <0.001 Senior (65+) 1450 3260 142010 1874 1.78 1.69-1.87 <0.001 Female 1290 1740 129570 746 2.35 2.23-2.48 <0.001 Male 1080 2191 124610 888 2.5 2.35-2.66 <0.001 Caucasian 2020 2120 181370 1086 1.97 1.89-2.06 <0.001 African American 240 2556 37500 1041 2.49 2.19-2.83 <0.001 Asian 20 1163 3440 692 1.69 1.09-2.63 <0.02 Amyloidosis 20 10526 1100 6369 1.73 1.08-2.76 0.022 Systemic Sclerosis 30 11539 3870 18590 0.57 0.39-0.84 0.004 Polymyositis 30 13636 2360 12981 1.06 0.72-1.56 0.774 Rheumatoid Arthritis 320 2362 18520 4765 0.48 0.43-0.54 <0.001 Systemic Lupus Erythematosus 110 1175 6490 5283 0.21 0.18-0.26 <0.001

S978 Impact of Inflammatory Bowel Disease on Outcomes of Patients Admitted With Pulmonary Embolism: A Nationwide Perspective

Introduction: Inflammatory Bowel Disease (IBD) patients have an established higher risk of Venous Thromboembolism, including Pulmonary Embolism (PE), secondary to chronic inflammatory state. However, Impact of IBD on the prognosis of admitted PE patients remains unstudied. Therefore, authors aim to investigate outcomes of hospitalized PE patients in the setting of IBD. Methods: Using International Classification of Diseases Tenth Revision (ICD-10) codes, the National Inpatient Sample database of the years 2016 to 2019 was searched for patients admitted with a primary diagnosis of PE, with and without a past medical history of IBD listed as secondary diagnosis. Univariate and Multivariate logistic regression analysis was performed to determine the risk of mortality and in-hospital complications in PE/IBD group compared to PE/non-IBD group. Baseline patients and facilities characteristics were incorporated into the analysis. Data was considered statistically significant if p-value was < 0.05. Results: Among 750,654 adults’ patients who were hospitalized in US with a primary diagnosis of PE from 2016 - 2019, 6,995 (1%) had a secondary diagnosis of IBD. Patients baseline characteristics are listed in Table. After running multivariate regression analysis, history of IBD was not associated with mortality difference in PE patients (aOR 0.80, p=0.245). In term of in-hospital outcomes (Figure), IBD/PE patients had an increased risk of cardiac arrythmias (aOR 1.18, p= 0.035) and sepsis (aOR 1.37, p=0.048), with no significant difference in risk of acute kidney injury (aOR 1.01, p=0.882), septic shock (aOR 1.28, p=0.516), acute coronary syndrome (aOR 0.83, p=0.337), acute respiratory failure (aOR 0.92, p=0.244) and in-hospital cardiac arrest (aOR 2.24, p=0.319). IBD/PE group had a prolonged length of stay (aMD 0.56 days, p=< 0.001) and increased cost of care (aMD 4093$, p=0.023) when compared to admitted PE patients who are IBD-free. Conclusion: Our study demonstrates that patients with PE have a slightly worse in-hospital outcomes in the setting of IBD, represented by increased risk of sepsis and cardiac arrythmias, and prolonged length of stay and healthcare resources utilizations. Further studies are needed to validate our findings, to prompt proper risk satisfaction and for IBD patients who are admitted with PE in a goal to reduce the incidence of the before mentioned outcomes and to reduce healthcare resources utilization in this group of patients.Figure 1.: Forest plot of outcomes in patient hospitalized for PE with history of IBD, compared to non-IBD Patients. Table 1. - Baseline characteristics of PE patients stratified based on diagnosis status of IBD VARIABLE OVERALL, PE %, No. WITHOUT IBD %, No. WITH IBD %, No. P value 100.0 (750,654) 99.0 (743659) 1.00 (6995) PATIENT’S CHARACTERISTICS AGE, MEAN YEARS 62.8 62.9 58.8 () < 0.001 FEMALE 51.9 (389589) 51.9 (385959) 55.1 (3854) < 0.001 RACIAL DISTRIBUTION < 0.001 WHITE 71.6 (537468) 71.5 (531716) 83.3 (5827) BLACK 18.9 (141874) 19.0 (141295) 11.2 (783) HISPANIC 5.83 (43763) 5.87 (43653) 2.73 (191) OTHERS 2.10 (15764) 2.10 (15617) 1.92 (134) INSURANCE TYPE < 0.001 MEDICAID 53.6 (402351) 53.7 (399345) 47.6 (3330) MEDICARE 12.3 (92330) 12.4 (92214) 10.8 (755) PRIVATE 29.8 (223695) 29.7 (220867) 39.2 (2742) UNINSURED 4.06 (30477) 4.09 (30416) 2.27 (159) CHARLSON COMORBIDITY INDEX SCORE < 0.001 1 23.3 (174902) 23.3 (173273) 24.1 (1686) 2 16.5 (123858) 16.5 (122704) 16.7 (1168) ≥3 29.3 (219942) 29.4 (218636) 22.5 (1574) MEDIAN ANNUAL INCOME, US$ < 0.001 1–43,999 28.5 (213936) 28.5 (211943) 22.0 (1539) 44,000–55,999 26.5 (198923) 26.5 (197070) 25.8 (1805) 56,000–73,999 24.8 (186162) 24.8 (184427) 26.8 (1875) ≥74,000 20.0 (150131) 20.0 (148732) 25.3 (1770) HOSPITAL CHARACTERISTICS HOSPITAL REGION < 0.001 NORTHEAST 18.0 (135118) 18.5 (137577) 20.8 (1455) MIDWEST 25.2 (189165) 25.1 (186658) 27.0 (1889) SOUTH 38.8 (291254) 38.8 (288540) 34.6 (2420) WEST 17.8 (133616) 17.8 (132371) 17.5 (1224) HOSPITAL BED SIZE 0.8425 SMALL 21.0 (157637) 21.0 (156168) 21.5 (1504) MEDIUM 29.6 (222194) 29.6 (220123) 29.8 (2085) LARGE 49.3 (370072) 49.3 (366624) 48.6 (3400) HOSPITAL LOCATION RURAL LOCATION 9.55 (71687) 9.57 (71168) 7.72 (540) < 0.001 URBAN LOCATION 22.7 (170398) 22.8 (169554) 18.6 (1301) TEACHING HOSPITAL 67.6 (507442) 6.76 (50271) 73.6 (5148) COMORBIDITIES HYPERTENSION 42.3 (317527) 42.3 (314568) 35.6 (2490) < 0.001 DIABETES MELLITUS 23.2 (174152) 23.3 (173273) 16.3 (1140) < 0.001 SMOKING HISTORY 38.7 (290503) 38.7 (287796) 39.6 (2770) 0.8226 HYPERLIPIDEMIA 35.9 (269485) 36.0 (267717) 27.8 (1945) < 0.001 OBESITY 25.4 (190666) 25.5 (189633) 19.8 (1385) < 0.001 CHRONIC KIDNEY DISEASE 12.7 (95333) 12.7 (94445) 10.2 (713) < 0.001 CORONARY ARTERY DISEASE 21 (157637) 17.5 (130140) 14.3 (1000) < 0.001 PERIPHERAL VASCULAR DISEASE 21.5 (161391) 2.16 (16063) 1.86 (130) 0.2200 CONGESTIVE HEART FAILURE 16.5 (123858) 16.5 (122704) 972 < 0.001 CHRONIC OBSTRUCTIVE LUNG DISEASE 18.3 (137370) 18.3 (136090) 17.1 (1196) 0.0053 CHRONIC LIVER DISEASE 4.68 (35131) 4.67 (34729) 6.65 (465) < 0.001 CORTICOSTEROID USE 4.13 (31002) 4.07 (30267) 11.8 (825) < 0.001 PE=Pulmonary Embolism, IBD=Inflammatory Bowel Disease.

S967 Inflammatory Bowel Diseases Results in Worse Hospital Outcomes in Patients Admitted for Acute Diverticulitis: A Study of the National Inpatient Sample

Introduction: The association between Acute Diverticulitis (AD) and Inflammatory Bowel Diseases (IBD) is extremely rare in literature and not well studied as a result of the scarcity of reports and overlapping clinical and radiological features. In this study, we aim to investigate the clinical impact of IBD on the outcomes of patients admitted for AD. Methods: The National Inpatient Sample Database of the years 2016 to 2019 was analyzed, and patients who were hospitalized for AD, with or without a secondary diagnosis of IBD (Crohn’s Disease and ulcerative colitis) were identified using the 10th Revision of International Classification of Diseases codes. Univariates and Multivariate logistic regression analysis was performed to determine risk difference in mortality and AD-related complications. Data was considered statistically significant with p-value < 0.05. Results: A total of 313,054 adults AD hospitalizations were identified, among which 3090 (1%) had a history of IBD. AD patients baseline characteristics and comorbidities are listed in Table stratified by IBD diagnosis. IBD patients found to have 27% increase in risk of AD than IBD-free patients (adjusted odds ratio (aOR) 1.27, p< 0.001) with no difference in risk of mortality between the two groups (aOR 1.37, p=0.437). AD/IBD patients had significant increased risk of bowel perforation (aOR 3.41, p=0.04), sepsis (aOR 1.69, p=0.002), septic shock (aOR 3.16, p< 0.001), acute kidney injury (aOR 1.35, p=0.036) and undergoing colonic resection (aOR 1.28, p=0.018) than AD/non-IBD group. In term of healthcare resources utilization, IBD patients had a prolonged length of stay (adjusted mean difference (aMD) 1.39 days, p< 0.001) and increased cost of care (aMD 16993$, p< 0.001) when hospitalized for AD when compared to non-IBD patients. (Figure) Conclusion: This is the first descriptive analysis to demonstrate the effect of IBD on outcomes of patients with AD. IBD patients are at higher risk of developing AD, and IBD patients admitted for AD were found to have had higher risk of bowel perforation, sepsis, septic shock, acute kidney injury and undergoing colonic resection with significant increase in healthcare resources utilization. As such association is unique in clinical practice, misdiagnosis can occur and therefore physicians should keep high index of suspicion in this challenging scenario to primarily avoid catastrophic outcomes and decrease resources utilization.Figure 1.: Forest plot of outcomes in patient hospitalized for AD with history of IBD, compared to non-IBD patients. (AD=Acute Diverticulitis, IBD=Inflammatory Bowel Diseases) Table 1. - Baseline characteristics of AD patients stratified based on diagnosis status of IBD VARIABLE ALL AD %, NO. WITHOUT IBD %, NO. WITH IBD %, NO. P value (100.0) 313054 99.0 (309964) 1.00 (3090) Patient’s characteristics Age, mean years 58.4 58.4 60.3 0.001 Female 49.8 (155901) 49.8 (154362) 54.3 (1678) 0.028 Racial distribution < 0.001 White 76.3 (238860) 76.3 (236503) 83.4 (2577) Black 8.62 (26985) 8.65 (26812) 6.46 (200) Hispanic 11.0 (34436) 11.1 (34406) 6.29 (194) Others 2.29 (7169) 2.29 (7098) 2.65 (82) Insurance type 0.002 Medicaid 36.5 (114265) 36.5 (113137) 43.4 (1341) Medicare 11.2 (35062) 11.2 (34716) 9.43 (291) Private 45.7 (143066) 45.7 (141654) 42.7 (1319) Uninsured 6.49 (20317) 6.52 (20210) 4.38 (135) Charlson comorbidity index score 0.082 1 22.1 (69185) 22.1 (68502) 21.5 (664) 2 9.20 (28801) 9.18 (28455) 11.6 (358) ≥3 9.86 (30867) 9.85 (30531) 11.3 (349) Median annual income, us$ 0.281 1–43,999 23.9 (74820) 23.9 (74081) 23.1 (714) 44,000–55,999 26.1(81707) 26.2 (81211) 23.4 (723) 56,000–73,999 26.3 (82333) 26.3 (81521) 27.0 (834) ≥74,000 23.5 (73568) 23.4 (72532) 26.2 (810) Hospital characteristics Hospital region 0.079 Northeast 20.8 (65115) 20.8 (64473) 24.7 (763) Midwest 22.6 (70750) 22.6 (70052) 23.4 (723) South 38.0 (118961) 38.0 (117786) 35.2 (1088) West 18.4 (57602) 18.4 (57033) 16.5 (510) Hospital bed size 0.338 Small 23.3 (72942) 23.3 (72222) 22.6 (698) Medium 31.0 (97047) 31.0 (96089) 28.8 (890) Large 45.6 (142753) 45.6 (141344) 48.5 (1499) Hospital location Rural location 9.76 (30554) 9.78 (30314) 8.09 (250) 0.023 Urban location 25.0 (78264) 25.0 (77491) 21.3 (658) Teaching hospital 65.2 (204111) 65.1 (201787) 70.5 (2178) Comorbidities Hypertension 41.8 (130857) 41.8 (129565) 40.6 (1255) 0.534 Diabetes mellitus 13.9 (43515) 14.0 (43395) 11.3 (349) 0.055 Smoking history 40.0 (125222) 39.9 (123676) 42.7 (1319) 0.171 Hyperlipidemia 29.5 (92351) 29.5 (91439) 30.4 (939) 0.617 Obesity 19.5 (61046) 19.5 (60443) 16.0 (494) 0.030 Chronic kidney disease 6.45 (20192) 6.44 (19962) 8.41 (260) 0.045 Coronary artery disease 10.2 (31932) 10.2 (31616) 11.4 (352) 0.284 Peripheral vascular disease 1.07 (3350) 1.06 (3286) 2.27 (70) 0.003 Congestive heart failure 5.01 (15684) 4.99 (15467) 7.44 (230) 0.005 Chronic obstructive lung disease 8.68 (27173) 8.66 (26843) 11.0 (340) 0.039 Chronic liver disease 4.97 (15559) 4.97 (15405) 5.02 (155) 0.961 Constipation 8.46 (26484) 8.46 (26223) 8.74 (270) 0.800 AD=Acute Diverticulitis, IBD=Inflammatory Bowel Disease.

Efficacy of Paxlovid and Lagevrio for COVID-19 Infection in Patients With Inflammatory Bowel Disease: A Propensity-Matched Study

The world has been faced with the coronavirus disease 2019 (COVID-19) pandemic. Several antiviral medications have been granted emergency use authorization for treatment of patients with COVID-19 including Paxlovid (nirmatrelvir and ritonavir) and Lagevrio (molnupiravir).1 There are no data on the use of these medications in patients with inflammatory bowel disease (IBD) who develop a COVID-19 infection. This report compares the outcomes of patients with IBD who received antiviral medications for COVID-19 with those who did not and with non-IBD patients who received antiviral medications.

Humoral Immunogenicity After Vaccination Against SARS-CoV-2 Infection in Inflammatory Bowel Disease Patients Under Immunosuppressive Therapy: Should We Prioritize an Additional Booster Injection?

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to the development of the novel coronavirus disease (coronavirus disease 2019 [COVID-19]). Scarce data are available regarding safety and efficacy of SARS-CoV-2 vaccination in inflammatory bowel disease (IBD) patients, which may present differences between subgroups. Lower humoral immunological response could require additional booster injections.MethodsThis is a prospective study including adult patients with IBD after complete vaccination against SARS-CoV-2 infection with BioNTech vaccine. Patients with previous SARS-CoV-2 infection were excluded. A control group with healthy individuals matched for age and sex was also analyzed. Blood samples were collected 30 days after complete vaccination to quantify immunoglobulin G (IgG) antibody titers against SARS-CoV-2 in both groups.ResultsThe final sample included 81 IBD and 32 non-IBD patients, 55 (48.7%) of them women, with a mean age of 40.2 ± 13.0 years. From IBD patients, 58 (71.6%) had Crohn’s disease and 23 (28.4%) had ulcerative colitis. IBD patients had significantly lower median anti-SARS-CoV-2 IgG levels when compared with the control group (6479 [interquartile range (IQR) 1830-11883, 10 053] AU/mL vs 13 061 [IQR 2826-21427, 15 539] AU/mL; P = .003). Regarding IBD medication, significant lower levels of SARS-CoV-2 IgG antibodies when compared with control subjects were observed in patients treated with thiopurines (5423 [IQR 3109-13369, 10 260] AU/mL; P = .011), methotrexate (834 [IQR 507-3467, 4155] AU/mL; P = .002), anti-tumor necrosis factor α agents (5065 [IQR 1033-11669, 10 636] AU/mL; P = .001), and corticosteroids (548 AU/mL; P = .001). The incidence of SARS-CoV-2 infection after vaccination was also significantly higher in patients treated with these agents.ConclusionsIBD patients treated with immunomodulators, anti-tumor necrosis factor α agents and corticosteroids presented significantly lower anti-SARS-CoV-2 IgG levels following complete vaccination when compared with healthy control subjects. These findings support the benefit of additional booster injections in this population.