non-IBD Patients Research Articles

Pregnancy and stomas: a 9-year retrospective series at a major metropolitan hospital in Brisbane Queensland.

Over 42 000 Australians live with a stoma, and this number increases annually. Pregnancy in stoma patients is a rare but complex condition and there is limited published literature regarding surgical and obstetric complications in pregnant stoma patients. The aim of this paper was to review stoma outcomes, perinatal morbidity and mortality, and early postpartum period in pregnant stoma patients. Data was retrospectively obtained on women of childbearing age, with a stoma, who had been pregnant and birthed in the last nine years at the Royal Brisbane and Women's Hospital between January 2014 to December 2022. Data recorded included patient demographics, type of stoma, indication for stoma, need for additional abdominal surgeries, method of conception, pregnancy complications, length of stay, neonatal outcomes and post pregnancy stomal complications. In total, there were 16 births from 13 mothers with stomas. Of 10 births to IBD patients, 40% experienced a serious stomal complication. Caesarean section (CS) rate was 90% for IBD and 83% for non-IBD. In-vitro fertilisation rates were 40% in IBD patients and 0% in non-IBD patients. The average gestational age at delivery was 36 weeks in IBD and 35 weeks in non-IBD patients. Neonates delivered to IBD mothers had a birth weight under 2500g in 40% of cases and in non IBD mothers at 33.3% (p = 0.62). Of the sixteen births there was five complications (31.25%) associated with the stoma either during pregnancy or during the sixty-day postpartum period. Pregnancy in stoma patients is a rare occurrence and appears to be associated with high rates of CS, preterm delivery, low birth weight and stomal complication.

Co-prevalence of chronic rhinosinusitis and inflammatory bowel disease: A large aggregated electronic health record study.

IBD patients have a 4.04-fold elevated likelihood of having CRS compared to non-IBD patients. CRS patients have a 4.23-fold elevated likelihood of having IBD compared to non-CRS patients. The risk of CRS development after IBD is five times higher than IBD development after CRS.

Risk of Hematologic Malignancies in Patients with Inflammatory Bowel Disease: A Meta-Analysis of Cohort Studies.

Inflammatory bowel disease (IBD) may contribute to the development of hematologic malignancies. In this study, the potential relationship between IBD and hematologic malignancies was investigated. We searched the PubMed, Web of Science, Embase, and Cochrane Library databases for all cohort studies comparing the incidence of hematologic malignancies in non-IBD populations with that in IBD patients, and we extracted relevant data from January 2000 to June 2023 for meta-analysis. Twenty cohort studies involving 756,377 participants were included in this study. The results showed that compared with the non-IBD cohort, the incidence of hematologic malignancies in the IBD cohort was higher (standardized incidence ratio [SIR]=3.05, p<0.001). According to the specific types of IBD, compared with the non-IBD patients, the incidences of hematologic malignancies in ulcerative colitis patients (SIR=2.29, p=0.05) and Crohn's disease patients (SIR=3.56, p=0.005) were all higher. In the subgroup analysis of hematologic malignancy types, compared with the control group, the incidences of non-Hodgkin's lymphoma (SIR=1.70, p=0.01), Hodgkin's lymphoma (SIR=3.47, p=0.002), and leukemia (SIR=3.69, p<0.001) were all higher in the IBD cohort. The incidence of hematologic malignancies, including non-Hodgkin's lymphoma, Hodgkin's lymphoma, and leukemia is higher in patients with IBD (ulcerative colitis or Crohn's disease) than in non-IBD patients.

Helicobacter Pylori infection in children with inflammatory bowel disease: a prospective multicenter study

BackgroundThe relationship between Helicobacter-pylori(Hp)infection and inflammatory-bowel-disease(IBD) in pediatric-patients remains controversial. We aimed to assess the Hp-infection occurrence in newly-diagnosed pediatric-patients with IBD compared to no-IBD patients. Additionally, we aimed to examine differences in clinical-activity-index(CAI) and endoscopic-severity-score(ESS)between IBD-patients with and without Hp-infection, at baseline and at 1-year-follow-up(FU), after eradication-therapy(ET).MethodsIBD diagnosis was based on Porto-criteria, and all patients underwent gastroscopy at baseline and 1-year FU. For Crohn's-disease(CD) and ulcerative colitis(UC), IBD-CAI and -ESS were classified using PCDAI/SES-CD and PUCAI/UCEIS, respectively.Results76 IBD-patients were included in the study[35 F(46.1%),median-age 12(range 2–17)]. CD and UC were diagnosed in 29(38.2%) and 45(59.2%)patients, respectively, and unclassified-IBD in two(2.6%)patients. Non-IBD patients were 148[71 F(48.0%),median-age 12(range 1–17)]. Hp-infection at baseline was reported in 7(9.2%) and 18(12.2%)IBD and non-IBD patients, respectively(p = 0.5065).The 7 IBD patients with Hp infection were compared to 69 IBD patients without Hp-infection at baseline evaluation, and no significant differences were reported considering CAI and ESS in these two groups.At 1-year FU, after ET, IBD patients with Hp infection improved, both for CAI and ESS, but statistical significance was not reached.ConclusionThe occurrence of Hp-infection did not differ between IBD and no-IBD patients. No differences in CAI or ESS were observed at the diagnosis, and after ET no worsening of CAI or ESS was noted at one-year FU, between Hp-positive and -negative IBD patients.

Comparative Efficacy of Fecal Microbiota Transplantation in Treating Refractory or Recurrent Clostridioides difficile Infection among Patients with and without Inflammatory Bowel Disease: A Retrospective Cohort Study.

Clostridioides difficile infection (CDI) worsens inflammatory bowel disease (IBD) prognosis. While fecal microbiota transplantation (FMT) is effective for refractory or recurrent CDI (rrCDI), comparative success rates between IBD and non-IBD patients are scarce. This study addresses this gap. A retrospective cohort study was conducted at Chang Gung Memorial Hospital from April 2019 to October 2023. Patients receiving FMT for rrCDI were categorized into IBD and non-IBD groups. Baseline characteristics and outcomes were compared at one month and one year, with successful FMT defined as the resolution of diarrhea without CDI recurrence. The study included 88 patients: 30 with IBD and 58 without IBD. The IBD group was younger, with fewer comorbidities. Success rates at one month were similar between groups (IBD: 80.0% vs. non-IBD: 78.9%, p = 0.908), as were negative toxin tests (IBD: 83.3% vs. non-IBD: 63.8%, p = 0.174). One-year success rates (IBD: 70.0% vs. non-IBD: 67.6%, p = 0.857) and eradication rates (IBD: 94.4% vs. non-IBD: 73.9%, p = 0.112) were also similar. Poor bowel preparation predicted FMT failure at one month (OR = 0.23, p = 0.019). No safety issues were reported. FMT is a safe, effective treatment for rrCDI, demonstrating similar success rates in patients with and without IBD.

Molecular profiling of visible polypoid and invisible conventional intestinal-type low-grade dysplasia in patients with idiopathic inflammatory bowel disease

AimsLittle is known about the molecular features of visible polyps with low-grade intestinal-type dysplasia in patients with inflammatory bowel disease (IBD). To better understand their origins and biological potential, we...

Acute pancreatitis in children with inflammatory bowel disease: Risk factors, clinical course, and prognosis.

To characterize the clinical course of acute pancreatitis (AP) in pediatric inflammatory bowel disease (IBD) patients compared to children with AP without IBD and to identify risk factors associated with AP among IBD patients. This retrospective, single-center study compared clinical characteristics of children (<19 years) with AP with and without concomitant IBD who were hospitalized 2005-2019. We also conducted a risk factor analysis of AP development in pediatric IBD. Sixty-eight (54% males) patients with 120 episodes of AP were admitted at a median age of 15.3 years. Thirteen patients (14 episodes) had a co-diagnosis of IBD, representing 4% of our IBD patient population. The AP-IBD patients presented with lower amylase levels compared to the non-IBD patients (160 [interquartile range, IQR: 83-231] vs. 418 [IQR: 176-874] U/L, p > 0.01), all had a mild pancreatitis, and none required invasive intervention. The presumed etiology for AP in all IBD patients was IBD-related: IBD flare-up in five, side effects of medications in two, and undetermined in seven. The only risk factor for AP development among IBD patients was IBD-associated arthritis (23% vs. 3% for IBD-non-AP, p = 0.04), while extracolonic Crohn's disease and induction therapy with nutrition were negative risk factors (15% vs. 51%, p = 0.05, and 8% vs. 44%, p = 0.04, respectively). Other parameters, including disease type and medications, were nonsignificant. The clinical course of AP in pediatric IBD patients is mild. Only IBD-associated arthritis emerged as a risk factor for the development of AP, while, unexpectedly, IBD medication did not.

Inflammatory Bowel Disease in Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy.

Inflammatory bowel diseases (IBDs) pose an increased risk of gastrointestinal cancer with especially worse prognosis. Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) improves outcomes in selected patients with colorectal peritoneal metastases. Little published data describes the outcomes of CRS/HIPEC in IBD patients. We performed a retrospective review of a prospectively maintained CRS/HIPEC database. Outcomes in patients with and without IBD were compared for short-term outcomes such as hospital/intensive care unit stay, blood loss/transfusions, complications, and reoperations. We also examined oncological outcomes including recurrence, overall (OS), and disease-free survival (DFS). We identified 232 patients that underwent CRS/HIPEC for colorectal or small bowel adenocarcinoma, of which 10 were with IBD. Patients with IBD had lower ASA (p=0.005), less hypertension (p=0.033), and 30% small bowel primary compared to none in the non-IBD cohort (p<0.001). Otherwise, demographic and perioperative characteristics were similar between the groups. The median peritoneal cancer index (PCI) was 7 and similar between the cohorts (p=0.422). Extent of organ resections and peritonectomies performed were similar. Complications occurred in 60.3% of patients (21.2% major), similar between the groups (p=0.744 and p=0.444, respectively). Reoperation rate of 27% was similar between groups (p=0.097). The median OS in the IBD cohort was 19.6 vs 53.2 months in the non-IBD cohort (p = 0.056). The median DFS in the IBD cohort was 4.9 vs 9.4 months in the non-IBD cohort (p=0.174). Cytoreductive surgery and heated intraperitoneal chemotherapy in patients with IBD has similar complication profile and trended towards poorer oncological outcomes as CRS/HIPEC in non-IBD patients.

Bariatric surgery in inflammatory bowel disease: a comparative analysis of 450,000 patients

BackgroundStudies were conducted to investigate the outcomes of bariatric surgery (BS) among inflammatory bowel disease (IBD) patients. ObjectivesWe aimed to analyze previous literature, comparing the outcomes of BS between IBD and non-IBD patients. SettingNot applicable. MethodsPubMed, Scopus, and Web of Science were searched on 25/9/2023 for comparative studies on outcomes of BS in IBD patients. RevMan Software v5.4 was used to conduct the analysis. ResultsOur analysis revealed an insignificant difference in the change of body mass index (BMI) at 1-year post-BS between IBD and non-IBD patients. IBD patients had a higher risk of acute renal failure, hemorrhage, and readmission following BS (RR: 2.16, 95% CI: 1.55–3, RR: 1.57, 95% CI: 1.22–2.04, RR: 1.56, 95% CI: 1.17–2.08, respectively). No significant difference was observed between both groups regarding wounds, leak/intra-abdominal infection, thromboembolic complications, and bowel obstruction. A higher incidence of postoperative complications was seen among IBD patients undergoing RYGB compared with SG (RR: 2.21, 95% CI: 1.43–3.41). There was a significant decline in steroid use following BS in IBD patients (RR: .67, 95% CI: .53–.84). Comparison between UC and Crohn’s disease (CD) revealed insignificant differences in treatment escalation or de-escalation. Both IBD and non-IBD patients had similar lengths of hospitalization. ConclusionsBS is equally effective in IBD and non-IBD patients in terms of weight loss at 1-year follow-up. Nevertheless, IBD patients are at a higher risk of postoperative complications, micronutrient deficiency, and readmission. Both UC and CD reported a decline in steroid use following surgery without a preferential advantage to a particular IBD sub-type.

Crosstalk between Anxiety and Depression and Inflammatory bowel diseases: preliminary data on circulating miRNAs

IntroductionNumerous studies have established a heightened prevalence of anxiety and depression (A&amp;D) in individuals diagnosed with Inflammatory Bowel Diseases (IBD) when compared to the general population. Research indicates that patients with active IBD exhibit a higher frequency of anxiety symptoms and depression symptoms compared to those with inactive disease. In patients with IBD, anxiety was linked to reduced medication adherence and an increased likelihood of undergoing surgery. Furthermore, associations were identified between depression and an elevated risk of disease relapse, as well as a poorer response to treatment in IBD patients. In both IBD and depression, there is evidence of disruptions in circulating miRNAs.ObjectivesOne facet of the ongoing project titled “The brain-gut axis linking inflammatory bowel disease with anxiety and depression: the inflammation-microbiome network” (CRP/ROU21-01) involves the exploration of circulating miRNA profiles in various patient groups.MethodsThese groups encompass IBD patients with symptoms of anxiety and/or depression (IBD+A&amp;D+), patients lacking anxiety and depression symptoms (IBD+A&amp;D-), a cohort of individuals without IBD but experiencing depressive and anxiety symptoms (IBD-A&amp;D+), and a control group (IBD-A&amp;D-). Thus far, our investigation has entailed screening a comprehensive panel of 179 miRNAs in the plasma of six IBD patients and 12 non-IBD patients (CTRL) to identify a subset of highly dysregulated miRNAs. MiRNA isolation was achieved using the miRNeasy Serum/Plasma Kit, and miRNA expression levels were assessed via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) utilizing the Human serum/plasma focus, MIRCURY LNA miRNA Focus PCR panel (Qiagen).ResultsOur statistical analysis revealed significant differential expression in 45 miRNAs (p&lt;0.05). Specifically, we identified 29 miRNAs with elevated expression and seven miRNAs with reduced expression. Among these dysregulated miRNAs, 15 (miR-223-3p, miR-143-3p, let-7f-5p, miR-30b-5p, miR-26a-5p, let-7a-5p, miR-339-5p, let-7d-5p, miR-221-3p, miR-191-5p, let-7g-5p, miR-24-3p, miR-107, miR-26b-5p, miR-320b) were associated with depression and/or anxiety and were previously identified as dysregulated in the plasma of patients in other studies. These miRNAs will soon undergo evaluation in the plasma of IBD-A&amp;D+ and IBD+A&amp;D+ patients.ConclusionsThese initial findings provide us with a panel of circulating miRNAs that warrant further investigation in the aforementioned patient groups. The miRNA profile we obtained may either be unique to IBD or linked to the intricate phenotypes of IBD occurring concurrently with anxiety and depression. A more profound comprehension of these mechanisms will aid in the development of enhanceddiagnostic tools and disease monitoring strategies, as well as the exploration of innovative therapeutic approaches.Disclosure of InterestNone Declared

DNA methylation fine-tunes pro-and anti-inflammatory signalling pathways in inactive ulcerative colitis tissue biopsies

DNA methylation has been implied to play a role in the immune dysfunction associated with inflammatory bowel disease (IBD) and the disease development of ulcerative colitis (UC). Changes of the DNA methylation and correlated gene expression in patient samples with inactive UC might reveal possible regulatory features important for further treatment options for UC. Targeted bisulfite sequencing and whole transcriptome sequencing were performed on mucosal biopsies from patients with active UC (UC, n = 14), inactive UC (RM, n = 20), and non-IBD patients which served as controls (NN, n = 11). The differentially methylated regions (DMRs) were identified by DMRseq. Correlation analysis was performed between DMRs and their nearest differentially expressed genes (DEGs). Principal component analysis (PCA) was performed based on correlated DMR regulated genes. DMR regulated genes then were functional annotated. Cell-type deconvolutions were performed based on methylation levels. The comparisons revealed a total of 38 methylation-regulated genes in inactive UC that are potentially regulated by DMRs (correlation p value < 0.1). Several methylation-regulated genes could be identified in inactive UC participating in IL-10 and cytokine signalling pathways such as IL1B and STAT3. DNA methylation events in inactive UC seem to be fine-tuned by the balancing pro- and anti- inflammatory pathways to maintain a prevailed healing process to restore dynamic epithelium homeostasis.

Contemporary Assessment of Adhesiolysis and Resection for Adhesive Small Bowel Obstruction in the State of New York.

Adhesive small bowel obstruction (aSBO) is a common surgical problem, with some advocating for a more aggressive operative approach to avoid recurrence. Contemporary outcomes in a real-world setting were examined. A retrospective cohort study was performed using the New York Statewide Planning and Research Cooperative database to identify adults admitted with aSBO, 2016-2020. Patients were stratified by the presence of inflammatory bowel disease (IBD) and cancer history. Diagnoses usually requiring resection were excluded. Patients were categorized into four groups: non-operative, adhesiolysis, resection, and 'other' procedures. In-hospital mortality, major complications, and odds of undergoing resection were compared. 58,976 patients were included. 50,000 (84.8%) underwent non-operative management. Adhesiolysis was the most common procedure performed (n = 4,990, 8.46%), followed by resection (n = 3,078, 5.22%). In-hospital mortality in the lysis and resection groups was 2.2% and 5.9% respectively. Non-IBD patients undergoing operation on the day of admission required intestinal resection 29.9% of the time. Adjusted odds of resection were highest for those with a prior aSBO episode (OR 1.29 95%CI 1.11-1.49), delay to operation ≥3 days (OR1.78 95%CI 1.58-1.99), and non-New York City (NYC) residents being treated at NYC hospitals (OR1.57 95%CI 1.19-2.07). Adhesiolysis is currently the most common surgery for aSBO, however nearly one-third of patients will undergo a more extensive procedure, with an increased risk of mortality. Innovative therapies are needed to reduce the risk of resection.

A235 INFLAMMATORY BOWEL DISEASE AND PREECLAMPSIA: A PHYSICIAN SURVEY

Abstract Background Preeclampsia is a disorder of pregnancy recognized as the second cause of maternal mortality worldwide. The association between IBD and preeclampsia remains unclear, but the significant comorbid profile, and lack of treatment aside from urgent delivery, make primary prevention a priority. Aspirin was shown to halve preeclampsia rates and is recommended for primary prevention for women at risk. Despite high-quality evidence supporting Aspirin use and its well tolerated side effect profile, studies in non-IBD patients have demonstrated a knowledge-to-practice gap. Aims While there are no studies reported in women with IBD, prescribing rates may be even lower in this population, given that it may be incorrectly perceived to increase the risk of an IBD flare. Understanding physician perceptions could allow for a targeted educational approach to increase patient and physician awareness of the indications for Aspirin prophylaxis and its safety profile. Methods This is a cross-sectional survey study assessing physician perceptions and Aspirin prescribing patterns for preeclampsia prevention conducted from Mount Sinai Hospital. Demographic information, information on perceptions of preeclampsia risk in pregnant women with IBD, and on the perceived clinical benefit and risk of Aspirin prescribing were collected. Results A total of 38 Canadian healthcare professionals (HCPs) (15 Gastroenterologists, 14 Obstetricians, 5 General Practitioners, 2 General Internists, 1 nurse practitioner, and 1 midwife) were surveyed. Most HCPs were practicing for over 10 years (71%). In total, 68% of HCPs were comfortable with pregnancy-specific management of IBD. Most HCPs correctly identified all comorbidities associated with a high risk of preeclampsia including a history of preeclampsia (95%), renal disease (87%), and autoimmune disease (68%). A total of 55% of HCPs believed that pregnant patients with IBD were at increased risk of placental related diseases, and 56% agreed that these patients were at increased risk of preeclampsia specifically. Thirty-five percent of HCPs believed that IBD in remission, in the absence of other risk factors, was an indication for Aspirin prophylaxis. More so, 45% believed that IBD, with poor disease control, was an indication. Only 8% of HCPs believed that Aspirin, when used for preeclampsia prevention, was associated with an IBD flare. In patients whom Aspirin prophylaxis was indicated, 77% agreed with its use, even in patients in whom disease control was poor. Finally, 63% agreed that the Aspirin dose should be 162 mg daily, and more than half (58%) agreed that the prescriber should be the patient’s obstetrician. Conclusions Most HCPs agreed that IBD was a risk factor for preeclampsia and that Aspirin prophylaxis was effective and safe for primary prevention. High quality studies are needed to evaluate risk of preeclampsia in IBD, especially in patients with active disease. Funding Agencies CAG

Mucin Expression Profiles in Ulcerative Colitis: New Insights on the Histological Mucosal Healing.

A structural weakness of the mucus barrier (MB) is thought to be a cause of ulcerative colitis (UC). This study aims to investigate the mucin (MUC) composition of MB in normal mucosa and UC. Ileocolonic biopsies were taken at disease onset and after treatment in 40 patients, including 20 with relapsing and 20 with remitting UC. Ileocolonic biopsies from 10 non-IBD patients were included as controls. Gut-specific MUC1, MUC2, MUC4, MUC5B, MUC12, MUC13, MUC15, and MUC17 were evaluated immunohistochemically. The promoters of mucin genes were also examined. Normal mucosa showed MUC2, MUC5B, and MUC13 in terminal ileum and colon, MUC17 in ileum, and MUC1, MUC4, MUC12, and MUC15 in colon. Membranous, cytoplasmic and vacuolar expressions were highlighted. Overall, the mucin expression was abnormal in UC. Derangements in MUC1, MUC4, and MUC5B were detected both at onset and after treatment. MUC2 and MUC13 were unaffected. Sequence analysis revealed glucocorticoid-responsive elements in the MUC1 promoter, retinoic-acid-responsive elements in the MUC4 promoter, and butyrate-responsive elements in the MUC5B promoter. In conclusion, MUCs exhibited distinct expression patterns in the gut. Their expression was disrupted in UC, regardless of the treatment protocols. Abnormal MUC1, MUC4, and MUC5B expression marked the barrier dysfunction in UC.

Application of SWATH Mass Spectrometry and Machine Learning in the Diagnosis of Inflammatory Bowel Disease Based on the Stool Proteome.

Inflammatory bowel disease (IBD) flare-ups exhibit symptoms that are similar to other diseases and conditions, making diagnosis and treatment complicated. Currently, the gold standard for diagnosing and monitoring IBD is colonoscopy and biopsy, which are invasive and uncomfortable procedures, and the fecal calprotectin test, which is not sufficiently accurate. Therefore, it is necessary to develop an alternative method. In this study, our aim was to provide proof of concept for the application of Sequential Window Acquisition of All Theoretical Mass Spectra-Mass spectrometry (SWATH-MS) and machine learning to develop a non-invasive and accurate predictive model using the stool proteome to distinguish between active IBD patients and symptomatic non-IBD patients. Proteome profiles of 123 samples were obtained and data processing procedures were optimized to select an appropriate pipeline. The differentially abundant analysis identified 48 proteins. Utilizing correlation-based feature selection (Cfs), 7 proteins were selected for proceeding steps. To identify the most appropriate predictive machine learning model, five of the most popular methods, including support vector machines (SVMs), random forests, logistic regression, naive Bayes, and k-nearest neighbors (KNN), were assessed. The generated model was validated by implementing the algorithm on 45 prospective unseen datasets; the results showed a sensitivity of 96% and a specificity of 76%, indicating its performance. In conclusion, this study illustrates the effectiveness of utilizing the stool proteome obtained through SWATH-MS in accurately diagnosing active IBD via a machine learning model.

ASSOCIATION OF INFLAMMATORY BOWEL DISEASE AND AUTOIMMUNE PRIMARY ADRENAL INSUFFICIENCY

Abstract AIMS To assess the prevalence and association of inflammatory bowel disease (IBD) with autoimmune primary adrenal insufficiency (APAI). BACKGROUND Patients with inflammatory bowel disease are at risk for developing other immune mediated diseases (IMD). There is a paucity of data on the association of IBD with autoimmune primary adrenal insufficiency/ autoimmune adrenalitis. To date, only small series have been published in the literature and well-designed population-based studies have not yet examined this association. METHODS We identified patients from the Healthcare Cost and Utilization Project - National Inpatient Sample between the years 2016 to 2020. Our cohort included IBD patients of all ages, and our control group consisted of non-IBD patients. The study's primary outcome was to evaluate the association of APAI in the study group compared to the control group. Secondary outcomes included demographics of IBD patients with APAI. ICD-10 diagnostic codes were used to identify patients. RESULTS During the study period, a total of 1,652,070 IBD patients were identified. Of these, 3,699 had a concurrent diagnosis of APAI, yielding an overall prevalence rate of 0.22%. In the non-IBD cohort, the total number of patients were 173,000,000 and the prevalence of APAI was 0.06%. Patients with IBD who had APAI were 70% females, and 90% were of white ethnic background. Among IBD patients, Crohn’s disease had a higher prevalence of APAI than Ulcerative Colitis, 0.27% vs. 0.14 %, respectively (p&amp;lt;0.001). Patients with IBD-APAI also had other coexisting IMDs, with asthma having the highest prevalence (13.11%), followed by rheumatoid arthritis (10.41%) and type-1 diabetes mellitus (2.57%). On multivariable logistic regression analysis, patients with IBD had 3.04 times higher odds of having a concurrent APAI diagnosis than patients without IBD (OR 3.046, CI: 2.796- 3.318, P&amp;lt;0.001). Women were 1.59 times more likely to have APAI than men (OR 1.590, CI: 1.539 - 1.643, p&amp;lt;0.001). On subgroup analysis, patients with CD had 1.9 times higher odds of having APAI than UC (OR: 1.901 CI: 1.579 - 2.290, p&amp;lt;0.001). CONCLUSIONS Patients with IBD, especially women of white ethnic background, have a higher association of APAI than non-IBD patients. CD patients are more likely to develop APAI than UC. Further studies are needed to understand the association and overlapping pathologic mechanisms between IMDs which may help further understand IBD-related comorbidities. Figure Table

MORTALITY IN INFLAMMATORY BOWEL DISEASE: A LONGITUDINAL POPULATION-BASED STUDY IN THE UNITED STATES

Abstract INTRODUCTION Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract. Data are limited regarding how longevity in IBD compares to the general population. The aim of this study was to compare the mean age of death and causes of mortality between patients with IBD and the general population in a nationally representative cohort. METHODS A retrospective study using 2010-2019 data from the National Readmissions Database (NRD) was performed. We identified hospitalized patients with CD and UC using International Classification of Diseases (ICD) codes. We compared the mean age of death and most common causes of mortality in CD, UC, and non-IBD patients. RESULTS The mean age of in-hospital death was significantly lower in the CD group (64.60 years) compared to the UC and non-IBD groups (67.43 and 67.07 years, respectively, p&amp;lt;0.01). Among all age groups, the highest death rates were among those ages 71 through 80 years of age (p&amp;lt;0.01). The UC group had significantly higher rates of death associated with cardiovascular causes, including myocardial infarction, congestive heart failure and cardiovascular disease, and infectious causes, including Clostridioides difficile infection and sepsis. Death rates did not significantly differ among the groups for those with diagnoses of leukemia and lymphoma (p=0.20 and p=0.19, respectively). UC patients had the highest in-hospital rate of death per year from 2010-2019, followed by the CD and non-IBD groups. Common diagnoses associated with death across all ages in the CD, UC, and non-IBD groups included fluid/electrolyte imbalance, respiratory failure, anoxic brain injury, sepsis, and renal failure. CONCLUSION While those with UC had higher in-hospital death dates, those with CD were more likely to die younger compared to the general population. UC patients were more likely to die if diagnosed with cardiovascular disorders or infections. Investigation of factors that drive premature mortality in CD patients and higher rates of mortality in UC patients is crucial to guide practice improvements and for management of co-morbid conditions. Table 1 Patient demographics and hospital characteristics. Figure 1 Death rates comparing non-IBD, CD and UC groups with specific inpatient diagnoses. * p &amp;lt; 0.05.

BIOACTIVE INTERLEUKIN-1 DETECTED IN IBD PATIENT INTESTINAL BIOPSIES IS A HALLMARK OF ULCERS AND CORRELATES WITH TRANSCRIPTOMIC ASSESSMENTS, INCLUDING AN ULCER-ASSOCIATED GENE MODULE

Abstract BACKGROUND Interleukin (IL)-1 and its post-translationally modified and released forms, IL-1α and IL-1β, have been identified as key molecules to maintain mucosal homeostasis and to drive inflammatory bowel disease (IBD). Deep cellular phenotypic, transcriptional, and in vitro data highlight the importance of IL-1-associated cytokine networks and IL-1 producing cells in severe and anti-TNF non-responsive IBD. Nevertheless, little is known about the presence of bioactive IL-1 proteins within the cell-free gastrointestinal (GI) mucosal environment and associated function in severe IBD and ulceration. METHODS We established a highly sensitive functional assay (~500-fold greater than ELISA) to assess bioactive extracellular IL-1 protein from previously cryopreserved GI biopsies. We performed an ex vivo study in a cohort of Crohn’s disease (CD, n=23), ulcerative colitis (UC, n=18) and non-IBD (n=17) patients, with biopsies from paired inflamed and uninflamed intestinal regions per patient (primarily colon but also ileal). We assessed differential IL-1 bioactivity, including IL-1α vs IL-1β contributions, and performed RNA-seq of the matched cellular compartments of the samples. An ulcer-associated gene signature derived from RNA-seq analysis was evaluated in a single-cell RNA-seq cohort (n=42) of very early onset IBD including monogenic disorders. RESULTS The extent of bioactive intestinal mucosal IL-1α and IL-1β corresponded with disease and ulcer severity in both CD and UC. The most extreme signals were seen in select CD patients with deep ulceration. Bioactive IL-1α was the predominant contributor to total IL-1 signal in most patients although several with ulcers displayed an IL-1β-predominant signal. Matched RNA-seq analysis demonstrated enhanced IL-1 transcripts, correlating with IL-1 bioactivity, and a weighted gene co-expression network analysis (WGCNA) revealed a compelling ulcer-specific module enriched in IL-1 signaling genes and wound repair. We validated our findings in several published (e.g., RISK cohort of ileal CD) as well as unpublished independent adult and pediatric datasets from our group. Deconvolution of the ulcer-specific gene module and projection onto an unpublished single-cell RNA-seq cohort of very early onset IBD patients (including IBD-causative mutations such as IL-10R deficiency characterized by deep ulceration) implicated specific stromal and myeloid populations in ulcer biology. CONCLUSION Mucosal ulceration in IBD is associated with bioactive IL-1α and IL-1β proteins, and transcriptomic evaluation of the same correlates with bioactive signal. An ulcer-associated gene module, validated in other datasets, sheds light on IL-1 biology in intestinal epithelial repair. Results strongly suggest the IL-1 signaling pathway being an attractive and precision-based therapeutic target in subsets of IBD patients.

P125 MIG (CXCL9) and IL22 are key biomarkers that discriminates between paediatric IBD patients and non-IBD patients in a novel biomarker model

Abstract Background The current gold standard for diagnosis of Inflammatory bowel disease (IBD) is based on clinical and endoscopic evaluation as well as histologic and radiologic evaluation. However, endoscopic evaluation can be uncomfortable and carry some risks, especially in the paediatric population that requires general anesthesia in order to perform the procedure. Our aim was to investigate whether serum biomarkers can differentiate between paediatric patients with and without IBD. Secondary aims were to determine whether there are biomarkers that can differentiate between Crohn's disease (CD) and Ulcerative colitis (UC), and whether we can predict progression to biologic treatment within one year from diagnosis using these biomarkers. Methods Paediatric patients undergoing a first diagnostic colonoscopy at British Columbia Children's Hospital (BCCH) between December 2019 and June 2022 were invited to participate in the study. A 2 ml blood sample was taken from each participant at the time of colonoscopy. Demographic and clinical data were collected from each patient. Blood samples were analyzed using the LegendplexTM flow cytometry kits investigating 12 different inflammatory cytokines and chemokines associated with IBD. Eleven of them were found most significant in an initial analysis performed on 100 patients using 50 biomarkers, and CCL7 was added due to significance in previous studies. A prediction model was built via a supervised learning method to determine how well we can predict the different groups. Results Two hundred and forty-six paediatric patients participated in the study. Median age was 13.03 years, 92 were females (37.4%) and 155 (63.01%) were diagnosed with IBD, with 103 (66.45%) diagnosed with Crohn's disease. The AUROC using SPLS-DA classification was 0.805. MIG and Il22 were found to be the key biomarkers to discriminate between pediatric IBD patients and non-IBD patients. In a random forest analysis MIG, Il8 and Il22 were found most important for discrimination. On a univariate analysis MIG and Il18 were found statistically significant as a predictor of CD (p=0.016 for both). CXCL1 was predictive to progression to biologic treatment within one year of diagnosis (p=0.039). However, the prediction model did not predict well the subclasses nor progression to biologic treatment. Conclusion Using serum biomarkers can predict the diagnosis of Paediatric IBD. MIG and Il22 were found to be the key biomarkers in the prediction model.

P007 Neutrophil function in lesional biopsies is a strong determinant of IBD severity and may relate to an altered functional state already present in circulating cells

Abstract Background Neutrophils clear luminal bacteria from the intestinal lamina propria and have a protective role in Inflammatory Bowel Disease (IBD). However, their production of inflammatory cytokines, matrix metalloproteases and radical oxygen species causes irreversible tissue damage. Histological assessment of infiltrating neutrophils and indirect measurement of neutrophil-derived calprotectin in feces are used to assess disease severity in patients. Since IBD is a heterogeneous disease in terms of presentation, severity and course, we hypothesize that different patients have a different composition of their neutrophil compartment that leads to a different balance between protection and damage. We aim to study the variability in neutrophil phenotype and function and relate it to patient heterogeneity. Methods We analyzed endoscopic biopsies and peripheral blood samples from children diagnosed with IBD within the PIBD-SETQ cohort. Paired biopsies obtained at diagnosis were scored by a pathologist and analyzed by IHC and RNAseq. RNAseq was also performed on purified circulatory neutrophil at diagnosis and their phenotype was analyzed by whole-blood flow cytometry. Results At diagnosis, high numbers of infiltrating neutrophils in intestinal tissue differentiated IBD patients with high clinical disease activity, more severe endoscopic and histological disease and high plasma concentrations of IL-17. RNA sequencing of lesional intestinal biopsies revealed differential expression of genes linked to neutrophil degranulation and IL-17 signaling in the colon of IBD patients with high neutrophil infiltration. Moreover, these biopsies had high mRNA expression for Oncostatin M, a neutrophil product known to associate with therapy resistance. To assess whether circulating neutrophils were altered in IBD before entering the intestinal tissue, we performed bulk RNAseq analysis of purified circulating neutrophils from non-IBD and CD patients. Neutrophils from CD patients had increased expression of genes related to granule formation and filling (MMP9, S100A8, S100A9) and pathogen sensing (TLR5, NLRC4) but not cytokine production (IL1B, OSM), relative to non-IBD patients. Expression of CD10 was decreased in circulating neutrophils from UC and CD patients while CD16 expression was lower in UC-derived neutrophils, suggesting these cells have a more immature state. Conclusion We have detected changes in the maturity of neutrophils in the circulation of some IBD patients that could have functional consequences in terms of bacterial clearance and tissue damage in the intestinal mucosa. Uncovering different functional profiles in neutrophils may help dissect patient heterogeneity and provide novel targets for therapy.