non-IBD Patients Research Articles

P1045 Comparative Efficacy of Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with and without Inflammatory Bowel Disease: A Retrospective Cohort Study

Abstract Background Clostridioides difficile infection (CDI) significantly exacerbates and worsens the prognosis of inflammatory bowel disease (IBD). While fecal microbiota transplantation (FMT) is recognized as a safe and efficacious therapy for patients battling recurrent or refractory CDI, but comparative studies focusing on the success rates in IBD and non-IBD patients remain scarce. Our study aims to shed light on this gap in knowledge. Methods In this retrospective cohort study conducted at Chang Gung Memorial Hospital between April 2019 and February 2023, patients undergoing FMT via colonoscopy for recurrent or refractory CDI were enrolled. Participants were categorized into IBD and non-IBD groups based on their underlying conditions. We compared baseline characteristics and clinical outcomes at one-month and one-year follow-up intervals. CDI diagnosis was confirmed through positive CD toxin A/B genes and associated clinical symptoms. Donor specimens were sourced from Chang Gung Microbiota Therapy Center's fecal bank. Results Our study included 88 patients who received FMT, comprising 30 in the IBD group and 58 in the non-IBD group. The indications were recurrent CDI in 31 patients, refractory CDI in 54, and both conditions in 3 patients. Among the IBD subgroup, 20 patients had ulcerative colitis, and 10 had Crohn's disease. In the baseline comparison, the IBD group was significantly younger (mean±SD, 45.23±16.45 years vs. 61.90±24.40 years, P = 0.001) and had fewer comorbidities such as hypertension (10.0% vs. 55.2%, P < 0.001), diabetes mellitus (6.7% vs. 31.0%, P = 0.014), and cancer (3.3% vs. 31.0%, P = 0.012) than the non-IBD group. Additionally, the IBD group had less prior Fidaxomin use (6.9% vs. 26.3%, P = 0.021) and fewer HMG-CoA reductase inhibitor users (0.0% vs. 15.5%, P = 0.025). Post-FMT, IBD severity indices showed significant improvement at one month. The mean partial Mayo score in the IBD group decreased by 2.9 points, the endoscopic Mayo subscore decreased by 0.7 points, and the Crohn’s Disease Activity Index decreased by 79.98 points. At this time, the IBD group showed a similar percentage of negative CDI toxin A/B tests (83.3% vs. 63.8%, P = 0.174) but had lower clinical remission rates (79.5% vs. 96.5%, P = 0.006) compared to the non-IBD group. However, at the one-year follow-up, the eradication rate (94.4% vs. 73.9%, P = 0.112) and clinical remission rate (84.2% vs. 90.3%, P = 0.661) were comparable between both groups. No safety issues or adverse effects were reported in any of the patients. Conclusion FMT demonstrates safety and efficacy in treating recurrent or refractory CDI in both IBD and non-IBD patients, also aiding in mitigating IBD-associated inflammation.

P1116 Risk of fractures in children and adults with inflammatory bowel disease: A report from the epi-IIRN

Abstract Background Both adult and pediatric patients with inflammatory bowel disease (IBD) are at risk of osteopenia and osteoporosis, nevertheless, whether patients with IBD are subjected to a higher risk for bone fractures is debated. Thus, we aimed to assess the risk for bone fractures, osteopenia and osteoporosis in IBD vs non-IBD patients, using the epi-Israeli IBD Research Nucleus (IIRN) data. Methods Data of patients with IBD and non-IBD matched controls (approximately 3 non-IBD controls per case) were retrieved from the epi-IIRN cohort (January 2005- June 2020) that maintain data on all patients with IBD from the four Israeli HMOs. Data included demographics, osteoporosis medications, fracture data and IBD related characteristics. Patients were stratified by age group (0-17,18-49, and ≥50). Patients with known osteopenia or osteoporosis before IBD diagnosis were excluded. Results We included 32,263 patients with IBD and 89,423 non-IBD controls [48% female, 56% Crohn’s disease (CD)]. Time to first fracture was significantly shorter in female pediatric patients (p=0.01), in both female (p=0.0004) and male (p=0.003) adult and elderly patients (p<0.0001) (Figure 1). Time to diagnosis of osteopenia/osteoporosis in patients with IBD was significantly shorter in all age groups and genders. Rate of fractures was significantly higher in patients with IBD versus controls for all groups, and rate of osteopenia/osteoporosis was also higher in patients with IBD in all groups (Table 1). In a subgroup analysis, fracture rate did not significantly differ between CD and ulcerative colitis (UC) for all age groups, but osteopenia and osteoporosis were significantly higher in CD compared to UC in all age groups. The hazard ratio for fractures in the pediatric IBD population was 1.02 (0.88-1.16) for males and 1.17(0.95-1.44) for females, in adults 1.08 (0.99-1.16) for males and 1.12 (1.02-1.21) for females, and in the elderly 1.2 (1.08-1.32) for males and 1.19 (1.08-1.31) for females. Arthritis was significantly associated with fracture risk [HR: children 1.47 (1.15-1.88); adults 1.3 (1.17-1.44); elderly 1.19 (1.07-1.30)]. In adults and elderly, older age at diagnosis, chronic obstructive pulmonary disease, diabetes and long-term proton pump inhibitors usage were also associated with a significant increase in fracture risk. Conclusion In this large nationwide cohort, patients with IBD had significantly higher risk for bone fractures than matched controls in almost all age groups, with no difference between CD and UC. Additionally, the rate of osteopenia and osteoporosis was higher in patients with IBD, suggesting that further efforts need to be invested in bone health of this at-risk population.

P434 Incidence of chronic end-stage renal disease in patients with inflammatory bowel disease: a population-based cohort study from the French National Health Insurance Database

Abstract Background Renal disorders are among the extra-intestinal manifestations of inflammatory bowel disease (IBD), and treatments may also lead to renal failure. However, the incidence of end-stage renal disease (ESRD), defined as the need for renal replacement therapy (dialysis and/or renal transplantation(RT)), is poorly known. The primary objective of our study was to assess the incidence of ESRD in IBD patients, and to compare it with the non-IBD population. Methods We conducted a prognostic cohort study based on data from the French National Health Insurance Database(SNDS). Prevalent cases of IBD affiliated to the general health insurance scheme during the period 2011-2020 were identified on the basis of declarations long-term diseases ALD 24 or the presence of 2 hospital stays for IBD with ICD-10 codes or a single stay with reimbursement of specific treatments. Incident cases of ESRD were identified on the basis of a stay with a RT or a period with dialysis sessions for at least 45 days. Crude incidence rates of ESRD were calculated over the period for the IBD and the non-IBD population, with their 95% confidence intervals. Results A total of 280,283 IBD patients were included in the study over the period 2011-2020, 134,567 with ulcerative colitis(UC) and 145,716 with Crohn’s disease(CD). The mean age at study inclusion was 39.8 (± 17.1) years. The M/F sex ratio was 0.9. The mean age at incidence of ESRD in the non-IBD population was 65.0 (±17.0) years, the M/F sex ratio cases was 1.7. Among IBD patients, 534 patients began replacement therapy by dialysis or RT, they were younger than non-IBD patients (60.3(±16.7)years, P<0.001).The mean incidence rate of ESRD over the period was 26.4 per 100,000 person-years (IC95% 23.1-29.6), 480 (89.9%) patients entered ESRD by dialysis, and 54 (10.1%) by preemptive RT. In the non-IBD population the mean rate of ESRD was 15.9 per 100,000 person-years (IC95% 14.8- 17.1; P<0.0001 compared with IBD): 79,606 (94.5%) patients entered ESRD by dialysis, and 4,634 (5.5%) by RT (as compared with IBD,P<0.001). In subgroup analysis, the mean incidence rate of ESRD was 22.8 per 100,000 person-years (IC95% 18.9-26.7) in UC patients and 29.5 (IC95% 25.3-33.6) in CD patients. The rates of preemptive RT were 12.4% in UC patients (87.6% dialysis) and 8.6% in CD patients (91.4% dialysis). Over a median follow-up of 6.8 years, the survival rate after ESRD was 40.8% in ESRD-IBD patients VS 34.2% in ESRD non-IBD patients (P<0.001). Conclusion This study shows that the incidence of ESRD is significantly higher in IBD than in the non-IBD population, confirming the need for regular monitoring of renal function in our patients. The high incidence of RT confirms that access to transplantation is not restricted in this population.

P429 Explainable AI identified metabolome and diet interactions in the blood and faceal samples

Abstract Background Background: Inflammatory Bowel Disease (IBD) represents a multifaceted condition that can be characterised by the interplay of four primary elements: immunity, genetics, microbiome and environmental factors. Among these, the relationship between nutrition and the metabolome is pivotal and a number of machine learning based approaches have been developed in an effort to gain a better understanding of this relationship. Nevertheless, to date, these approaches suffer from interpretability, thereby restricting their practical applicability within clinical settings.Hence, in this study, we leverage two publicly available datasets, the UK Biobank (UKB) and the Human Microbiome Project Phase II IBD Multi’Omics Database (HMP2), to perform metabolomics-based IBD disease predictions. We apply explainable an AI (XAI) based framework to understand these predictions and explore the diet-metabolite relationships in IBD and non-IBD individuals. Methods 4,137 plasma samples (2,099 IBD, 2,038 non-IBD) from UKB and 546 fecal samples (411 IBD, 135 non-IBD) from HMP2 with complete dietary data were used in the analysis. Random forest classification, optimized by grid search and estimator retraining was then trained to predict disease with Shapley Additive exPlanations (SHAP) included downstream to generate further insight on the model’s predictions. Finally, diet-metabolite associations were examined using Spearman-based correlations. Results From the plasma dataset, inflammatory markers, HDL and LDL cholesterols and omega 3 fatty acids were identified in relationship with IBD diagnosis. Within the feces samples, the discriminatory metabolites identified included B vitamins, phospholipids, urobilin, and taurine, and these latter provided a better predictive power than the plasma derived biomarkers (AUC: fecal 0.90.(95% CI: 0.84-0.96), plasma 0.66 (95% CI: 0.61-0.71). Regarding diet contribution, fish, fruit, vegetables, and processed foods exhibited a strong correlation with metabolites in both datasets, with correlations in fecal samples exhibiting a stong difference between IBD and non-IBD patients. Conclusion While this study has certain limitations, these results suggest that, compared to healthy individuals, IBD patients are characterised by a distinct gut profile primarily influenced by diet. It also suggests that disease, or health, influences how the gut responds to food intake. Future studies should confirm these findings using XAI and analysing both gut and blood matrices in same individuals along with their dietary intake for personalized IBD therapy development.

OP17 IBD ulcers are characterized by bioactive interleukin-1 and transcriptomic hallmarks of stromal cell state reprogramming

Abstract Background The programs that perpetuate the inflammation and prevent epithelial repair in Inflammatory Bowel Disease (IBD) remain unclear. Interleukin (IL)-1 plays a role in the maintenance of mucosal homeostasis but also in IBD. Expansion of IL-1 expressing myeloid cells is a hallmark of IBD tissue, including severe and anti-TNF unresponsive disease, and IL-1 expression is highly localized to ulcer beds. However, little is known about the presence of bioactive IL-1 proteins in the cell-free mucosal environment of IBD, nor whether IL-1-driven programs affect epithelial regeneration in IBD ulcers. Methods We established a highly sensitive assay (~500-fold greater than ELISA) to assess bioactive extracellular IL-1 from previously cryopreserved IBD biopsies. We assessed 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/uninflamed regions (primarily colon but also ileal). We assessed IL-1 bioactivity, including IL-1α vs IL-1β contributions, and performed RNA-seq of samples’ matched cellular compartments. An ulcer-associated gene signature was interrogated in a single-cell (sc)RNA-seq cohort (n=42) of very early onset (VEO)IBD including monogenic disorders, as well as publicly available IBD bulk RNA-seq datasets and scRNA-seq of mouse models of colitis. Results IL-1α and IL-1β bioactivity corresponded with disease and ulcer severity in CD and UC. The most extreme signals were seen in select CD patients with deep ulceration. IL-1α was the predominant contributor to total IL-1 bioactivity in most patients although several with ulcers displayed IL-1β predominance. IL-1 bioactivity correlated with IL-1 transcripts in matched RNA-seq, and weighted gene co-expression network analysis revealed a compelling ulcer-specific module. This module contained transcription factors and genes related to cell state, validated in publicly available datasets (e.g. RISK cohort of ileal CD and scRNA-seq of murine DSS colitis), that when interrogated in a scRNA-seq dataset of VEOIBD (including patients with IL-10RA mutations characterized by deep ulcers), suggests an orchestrated IL-1-driven myeloid/stromal response to epithelial ulceration involving cell state reprogramming and loss of key myofibroblast populations. 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.

P1094 Rectal cancer in patients with inflammatory bowel disease - a nationwide cohort study

Abstract Background Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. The aim of this study was to investigate surgical outcome and survival in patients with rectal cancer (RC) with and without IBD. Methods The study was performed as a national population-based cohort study based on the Colorectal Cancer Data Base (CRCBaSe). All patients ≥18 years of age with a diagnosis of stage I-III RC treated with curative intent during the period 1997-2021 were included, with preliminary data for 1997-2016 available. Overall and disease-free survival after surgery was compared between patients with and without a previous diagnosis of IBD. Adjusted flexible parametric survival models were used to estimate proportional and time-dependent hazard ratios (HRs) with 95% confidence intervals (CIs). Updated data until 2021 with addition of cause-specific survival and perioperative data will be made clear by the time of the ECCO congress. Results In all, 16,263 patients with RC were included in the study, 1997-2016, among whom 235 had IBD. Patients with IBD were significantly younger, had a higher CCI, and lower tumours at diagnosis of RC, compared with patients without IBD. Among IBD patients, 45 (19.2%) were previously operated with colectomy, and 14 of these were reconstructed with ileorectal anastomosis. Among IBD patients, pT4 tumours were more prevalent (8.9%) than in patients without IBD (5.1%). Clear resection margins were less common in patients with IBD (90.6%) versus patients without IBD (95.1%). From preliminary adjusted analyses allowing the relative mortality rate to vary over follow-up time, RC patients with IBD experienced worse progression-free survival during the second year after surgery, after which their progression-free survival was superior in comparison with IBD-free patients. Conclusion The prognosis in RC patients with and without IBD varied over time. RC patients with IBD had an inferior progression-free survival initially, followed by an improved prognosis for the majority of the follow-up time. Despite a higher rate of pT4 tumours, R1-resections and lower tumors among IBD patients, unadjusted overall survival did not differ significantly compared to non-IBD CRC patients.

Inpatient outcomes of inflammatory bowel disease in hospitalized patients with COVID-19: analysis of a nationally representative sample

Purpose To compare the risks of adverse outcomes, including mortality, gastrointestinal bleeding, and venous thromboembolism, between COVID-19 patients with inflammatory bowel disease (IBD) and those without IBD. Methods We analyzed data from the National Inpatient Sample between January and December 2020. The study included adult patients with Crohn’s disease (CD) and ulcerative colitis (UC) who contracted COVID-19. Inpatient outcomes were compared between the IBD and non-IBD COVID-19 cohorts. Results Out of 1,050,045 COVID-19 hospitalizations, 0.28% had CD (2954 patients) and 0.26% had UC (2794 patients). After adjusting for confounding factors, UC patients had a significantly higher risk of deep vein thrombosis compared to non-IBD patients, with an adjusted odds ratio (aOR) of 2.55 (P < 0.001). However, CD patients did not show a significant association with deep vein thrombosis (aOR 1.29, P = 0.329). There were no significant associations between IBD patients (both UC and CD) and pulmonary embolism, nonvariceal gastrointestinal bleeding, or in-hospital mortality. UC patients had a longer average hospital stay (8.25 days) compared to non-IBD patients (adjusted mean difference 0.89, P = 0.007). Healthcare resource utilization was similar among the three groups. Conclusion Our national study on COVID-19 hospitalizations indicates that patients with IBD have comparable rates of gastrointestinal bleeding, pulmonary embolism, and mortality as those without IBD. However, patients with UC hospitalized with COVID-19 have a higher risk of deep vein thrombosis than COVID-19 patients hospitalized without UC. Further research is needed to better understand the relationship between COVID-19 and IBD.

Occurrence of Colorectal Cancer After a Negative Colonoscopy in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Despite the application of colorectal cancer (CRC) surveillance guidelines, the detection of early neoplastic lesions might be difficult in patients with inflammatory bowel disease (IBD). To explore the risk of post-colonoscopy CRC (PCCRC) in patients with IBD we performed a systematic review and meta-analysis. A systematic literature search was performed (PROSPERO; no. CRD42023453049). We included studies reporting the 3-year PCCRC (PCCRC-3y) prevalence, according to World Endoscopy Organization (WEO)-endorsed definition, in IBD and non-IBD patients. As primary outcome we evaluated the PCCRC-3y prevalence, according to WEO definitions, in IBD- and non-IBD patients and calculated the odds ratio (OR). The secondary outcome was to assess risk factors for PCCRC development in IBD patients. Three retrospective observational cohort studies were included. The pooled PCCRC-3y rate in patients with IBD was 30.8% [95% confidence interval (CI)=24.4-37.5%] and in non-IBD patients was 6.8% (95%CI=6.2-7.4%). The PCCRC-3y occurrence in IBD patients was significantly higher than that in non-IBD patients (OR=6.04; 95%CI=4.04-9.4; I2=95%), but a high heterogeneity among studies was noted. Furthermore, patients with ulcerative colitis (UC) had a significantly higher prevalence of PCCRC than patients with Crohn's Disease (CD): 30.9% (95%CI=27.8-34.2%) vs. 22.3% (95%CI=18-27%), respectively (OR=1.6, 95%CI=1.2-2.2; I2=0%). One-third of CRC in IBD patients were PCCRC, and these numbers were significantly higher when compared with those in non-IBD patients. Furthermore, the prevalence of PCCRC in patients with UC was higher compared to those with CD. However, prospective studies are required to better characterize risk factors for PCCRC development in patients with IBD.

Utility of four machine learning approaches for identifying ulcerative colitis and Crohn's disease

ObjectivePeripheral blood routine parameters (PBRPs) are simple and easily acquired markers to identify ulcerative colitis (UC) and Crohn's disease (CD) and reveal the severity, whereas the diagnostic performance of individual PBRP is limited. We, therefore used four machine learning (ML) models to evaluate the diagnostic and predictive values of PBRPs for UC and CD. MethodsA retrospective study was conducted by collecting the PBRPs of 414 inflammatory bowel disease (IBD) patients, 423 healthy controls (HCs), and 344 non-IBD intestinal diseases (non-IBD) patients. We used approximately 70 % of the PBRPs data from both patients and HCs for training, 30 % for testing, and another group for external verification. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnosis and prediction performance of these four ML models. ResultsMulti-layer perceptron artificial neural network model (MLP-ANN) yielded the highest diagnostic performance than the other three models in six subgroups in the training set, which is helpful for discriminating IBD and HCs, UC and CD, active CD and remissive CD, active UC and remissive UC, non-IBD and HCs, and IBD and non-IBD with the AUC of 1.00, 0.988, 0.942, 1.00, 0.986, and 0.97 in the testing set, as well as the AUC of 1.00, 1.00, 0.773, 0.904, 1.00 and 0.992 in the external validation set. ConclusionPBRPs-based MLP-ANN model exhibited good performance in discriminating between UC and CD and revealing the disease activity; however, a larger sample size and more models need to be considered for further research.

Association between inflammatory bowel disease and subsequent depression or anxiety disorders - A retrospective cohort study of 31,728 outpatients

BackgroundCrohn's disease (CD) and ulcerative colitis (UC) are characterized by chronic intestinal and systemic inflammation. The extraintestinal sequelae of inflammatory bowel disease (IBD) are major contributors to disease morbidity and significantly affect patients' quality of life. Here, we evaluated the association between IBD and subsequent depression or anxiety disorder in a large outpatient collective from Germany. Methods15,864 individual IBD patients (CD: n = 6,791, UC: n = 9073) and 15,864 nearest neighbor propensity score matched patients without IBD were included from the Disease Analyzer database (IQVIA). Diagnoses of depression and anxiety disorders were compared between IBD and non-IBD patients during a five-year follow-up period using Kaplan-Meier estimators and Cox-regression models. ResultsAfter 5 years of follow-up, depression was diagnosed in 14.4% of CD patients versus 10.2% of matched pairs (p < 0.001) and in 13.1% of UC patients versus 10.1% of matched pairs (p < 0.001). In line, the incidence of anxiety order was significantly higher among CD (4.7% vs. 4.4%, p = 0.009) and UC patients (4.3% vs. 3.5%, p = 0.005). Regression analysis confirmed a significant association between IBD and both mental conditions (Hazard Ratio (HR)CD/depression: 1.40, HRUC/depression: 1.32, HRCD/anxiety disorder: 1.21, HRUC/anxiety disorder: 1.28). Subgroup analyses revealed a stronger association for CD and depression (HR: 1.51) and UC and depression (HR:1.49) among male patients as well as UC and anxiety disorders (HR: 1.51) among female patients. ConclusionOur data argue for a significant association between IBD and mental diseases including depression and anxiety disorders. Although further pathophysiological research is warranted, we hypothesize that specific psychological screening measures in IBD patients could improve quality of life and outcome.

Resistance to apoptosis in complicated Crohn's disease: Relevance in ileal fibrosis

Background and aimsThe stiffening of the extracellular matrix, and changes in its cellular and molecular composition, have been reported in the pathogenesis of fibrosis. We analyze the mechanisms that perpetuate ileal fibrosis in surgical resections of complicated Crohn's disease patients. MethodsIleal resections were obtained from affected and non-affected tissue of stenotic or penetrating Crohn's disease behavior. Ilea from non-IBD patients were used as control tissue. All samples underwent RNA sequencing. Human small intestinal fibroblasts were treated for 48 h with IL-1β, TFGβ1, PDGFB or TNF-α. Resistance to apoptosis was analysed by RT-PCR, western blot and immunohistochemistry in ileal tissue and by RT-PCR and FACS in cultured cells. ResultsGrowth factor-driven signaling pathways and increased RAS GTPase activity were up-regulated in affected ilea in which we found expression of both the antiapoptotic molecule MCL1 and the transcription factor ETS1 in submucosal fibroblasts, and a senescence-associated secretory phenotype. In cultured intestinal fibroblasts, PDGFB induced an ETS1-mediated resistance to apoptosis that was associated with the induction of both of TGFB1 and IL1B, a cytokine that replicated the expression of SASP detected in ileal tissue. ETS1 drove fibroblast polarization between inflammatory and fibrogenic phenotypes in IL1β-treated cells. ConclusionsOur data show resistance to apoptosis in complicated ileal CD, and demonstrate that PDGFB induce an ETS1-mediated resistance to apoptosis associated with an inflammatory and fibrogenic pattern of expression in intestinal fibroblasts. Results point to PDGFRB, IL1R1 or MCL1 as potential targets against ileal fibrosis.

Abstract 18883: Inflammatory Bowel Disease is Not Significantly Associated With Cardiac Arrest in STEMI Patients

Introduction: Systemic inflammatory diseases, such as psoriasis, lupus, and rheumatoid arthritis, have exhibited a strong association with an increased incidence of cardiovascular events over a patient’s lifetime. However, there is limited information regarding outcomes, particularly cardiac arrest, in STEMI patients with concurrent IBD. Thus, our study aims to assess potential outcomes, including cardiac arrest, in STEMI patients with IBD, utilizing a nationally representative sample of adult individuals in the United States, with a specific focus on MACE and associated risk factors. Our study provides valuable insights into the cardiovascular implications and associated risk factors in this unique patient population. Methods: The US-based National Inpatient Sample was queried between 2015 and 2020 using ICD-10 codes for adults ≥ 18 years with STEMI with and without IBD. The adjusted odds ratio of index hospitalization outcomes was calculated using a multivariate logistic regression analysis. Results: Overall, 3,960 out of 898,525 (0.44%) STEMI patients reported a history of IBD. Patients with IBD were predominantly middle aged, white, and female compared to non-IBD patients. STEMI patients with IBD had similar CVD risk factors (specifically hypertension and obesity) than non-IBD patients (P &gt; 0.05), however the prevalence of smoking and diabetes were lower in IBD patients (P &lt; 0.001). Notably, STEMI patients with IBD had a lower prevalence of cardiac arrest compared to their non-IBD counterparts (P &lt; 0.001). However on adjustment for baseline CVD risk factors and hospital characteristics, no significant difference was appreciated (P = 0.25) (Table 1). Conclusions: In a nationally representative adult US population IBD was not shown to confer an increased risk of cardiac arrest in patients with a history of STEMI. These findings underscore the need for further investigation to elucidate the complex relationship between IBD and cardiovascular outcomes.

Dysregulated Immunity to Clostridioides difficile in IBD Patients Without a History of Recognized Infection.

Clostridioides difficile is a toxin-secreting bacteria that is an urgent antimicrobial resistance threat, with approximately 25% of patients developing recurrent infections. Inflammatory bowel disease (IBD) patients are at increased risk of severe, recurrent C. difficile infection. To investigate a role for C. difficile infection in IBD pathogenesis, we collected peripheral blood and stool from 20 each of ulcerative colitis patients, Crohn's disease patients, and healthy control subjects. We used a flow cytometric activation induced marker assay to quantify C. difficile toxin-specific CD4+ T cells and 16S ribosomal RNA sequencing to study microbiome diversity. We found IBD patients had significantly increased levels of C. difficile toxin B-specific CD4+ T cells, but not immunoglobulin G or immunoglobulin A, compared with healthy control subjects. Within antigen-specific CD4+ T cells, T helper type 17 cells and cells expressing the gut homing receptor integrin β7 were reduced compared with healthy control subjects, similar to our previous study of non-IBD patients with recurrent C. difficile infection. Stool microbiome analysis revealed that gut homing, toxin-specific CD4+ T cells negatively associated with microbial diversity and, along with T helper type 17 cells, positively associated with bacteria enriched in healthy control subjects. These data suggest that IBD patients, potentially due to underlying intestinal dysbiosis, experience undiagnosed C. difficile infections that result in impaired toxin-specific immunity. This may contribute to the development of inflammatory T cell responses toward commensal bacteria and provide a rationale for C. difficile testing in IBD patients.

Longitudinal Trends in Pregnancy Outcomes Among Women With Inflammatory Bowel Disease in the Era of Biologics: A 20-Year Nationwide Analysis.

Many women with inflammatory bowel disease (IBD) are diagnosed by their reproductive years. Prior literature suggests that women with IBD may be at increased risk of adverse pregnancy outcomes. Biologics have revolutionized IBD treatment, and current evidence favors continuation during pregnancy. We sought to examine trends in pregnancy outcomes over 20 years with the evolution of IBD treatment. Using the National Inpatient Sample, IBD and non-IBD obstetric hospitalizations were identified between 1998 and 2018 using International Classification of Diseases 9 and 10 codes. Outcomes of interest included cesarean delivery, gestational diabetes, preeclampsia/eclampsia, premature rupture of membranes (PROM), preterm delivery, fetal growth restriction (FGR), fetal distress, and stillbirth. Stratified by Crohn's disease (CD), ulcerative colitis (UC), and non-IBD deliveries, temporal trends and multivariable logistic regression were analyzed. There were 48 986 CD patients, 30 998 UC patients, and 69 963,805 non-IBD patients. Between 1998 and 2018, CD deliveries increased from 3.3 to 12.9 per 10 000 deliveries (P < 0.001) and UC deliveries increased from 2.3 to 8.6 per 10 000 deliveries (P < 0.001). Cesarean deliveries, gestational diabetes, preeclampsia/eclampsia, PROM, FGR, and fetal distress increased over time for IBD and non-IBD women, while preterm deliveries decreased (P < 0.001). Multivariable analyses demonstrated that IBD patients had higher risk of cesarean delivery, preeclampsia/eclampsia, PROM, and preterm delivery compared with non-IBD patients. Over a 20-year period, live deliveries amongst women with IBD have increased. Trends in pregnancy outcomes have followed a similar trajectory in patients with and without IBD. However, there is still demonstrable risk of adverse pregnancy outcomes in patients with IBD.

Prevalence of Clostridium Difficile Infection (CDI) among Inflammatory Bowel Disease (IBD) Patients in Comparison to Non-IBD Patients in King Abdulaziz Medical City in Jeddah.

The prevalence of Clostridium difficile infection (CDI) as a common complication among inflammatory bowel disease (IBD) has been reported to increase worldwide and has been associated with a poor IBD outcome. In this study, our aim was to report on the prevalence of CDI among IBD vs. non-IBD patients in King Abdulaziz Medical City (KAMC). This retrospective descriptive study was carried out between 2016 and 2020. Data of 89 patients reported with CDI in KAMC were analyzed for demographics and correlations between various characteristics such as BMI, personal/family history of IBD, infection with CDI, diagnosis, method of diagnosis, and treatment modalities. Of the total 89 CDI patients, 59 (66.3%) were adults and 30 (33.7%) were pediatric, of which 36 (40.4%) were females and 53 (59.6%) were males. PCR was the main method of choice for the diagnosis of CDI (89.9%) followed by a positive-culture result (10.0%). Seventy-eight (87.6%) CDI patients were found to be immunocompromised, with two patients diagnosed with IBDs, one with UC, and one with CD. The recurrence rate was 38.4 (30 patients) among the immunocompromised group in comparison to 27.2 (3 patients) in the immunocompetent group (p=0.584). In this study, we found that adults were more prone to CDI infection, especially within hospital settings, and most of the CDI infections occurred in immunocompromised individuals, with cancer as the most common cause of it.

Characteristics and outcomes of rectal cancer in patients with inflammatory bowel disease: a single-center experience.

The increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) has been well documented in the literature. The present study aimed to assess the characteristics and outcomes of rectal cancer in patients with IBD. This study was a retrospective review of a prospectively maintained IRB-approved database at Cleveland Clinic Florida. Rectal cancer patients with or without IBD treated with curative surgery between 2016 and 2020 were compared for demographics, disease characteristics, and pathologic and oncologic outcomes. The primary outcomes were 3-year overall survival (OS) and disease-free survival (DFS). Secondary outcomes were clinicopathologic outcomes including disease stage, tumor histology and histologic features, and treatments received. 238 patients with rectal cancer were included, 15 (6.3%) of whom had IBD. IBD patients were significantly younger (52.9 vs 60.3years, p = 0.033), presented more often with cT1-2 tumors (64.3% vs 30.4%, p = 0.008), and signet-ring cell pathology (14.3% vs 2%, p = 0.02). IBD patients received neoadjuvant chemoradiation less often (40% vs 72.6%, p = 0.029) and had shorter time between diagnosis and surgery (7.5 vs 25weeks, p = 0.013) than did non-IBD patients. Both groups had similar OS (36 vs 34.7months, p = 0.431) and DFS (36 vs 32.9months, p = 0.121). IBD patients with rectal cancer tend to present at a younger age, with a less invasive disease, and signet-ring carcinomas, and receive neoadjuvant treatment less often than non-IBD patients. Based on low level of evidence, IBD and non-IBD rectal cancer patients might have similar survival.

Plasminogen Activator Inhibitor 1 Is a Novel Faecal Biomarker for Monitoring Disease Activity and Therapeutic Response in Inflammatory Bowel Diseases.

Crohn's disease [CD] and ulcerative colitis [UC] require lifelong treatment and patient monitoring. Current biomarkers have several limitations; therefore, there is an unmet need to identify novel biomarkers in inflammatory bowel disease [IBD]. Previously, the role of plasminogen activator inhibitor 1 [PAI-1] was established in the pathogenesis of IBD and suggested as a potential biomarker. Therefore, we aimed to comprehensively analyse the selectivity of PAI-1 in IBD, its correlation with disease activity, and its potential to predict therapeutic response. Blood, colon biopsy, organoid cultures [OC], and faecal samples were used from active and inactive IBD patients and control subjects. Serpin E1 gene expressions and PAI-1 protein levels and localisation in serum, biopsy, and faecal samples were evaluated by qRT-PCR, ELISA, and immunostaining, respectively. The study population comprised 132 IBD patients [56 CD and 76 UC] and 40 non-IBD patients. We demonstrated that the serum, mucosal, and faecal PAI-1 concentrations are elevated in IBD patients, showing clinical and endoscopic activity. In responders [decrease of eMayo ≥3 in UC; or SES-CD 50% in CD], the initial PAI-1 level decreased significantly upon successful therapy. OCs derived from active IBD patients produced higher concentrations of PAI-1 than the controls, suggesting that epithelial cells could be a source of PAI-1. Moreover, faecal PAI-1 selectively increases in active IBD but not in other organic gastrointestinal diseases. The serum, mucosal, and faecal PAI-1 concentration correlates with disease activity and therapeutic response in IBD, suggesting that PAI-1 could be used as a novel, non-invasive, disease-specific, faecal biomarker in patient follow-up.

Emerging Aeromonas enteric infections: their association with inflammatory bowel disease and novel pathogenic mechanisms.

Aeromonas species are emerging human enteric pathogens. This study examines the isolation of Aeromonas and other enteric bacterial pathogens from patients with and without inflammatory bowel disease (IBD). This study also investigates the intestinal epithelial pathogenic mechanisms of Aeromonas veronii. The isolation rates of seven enteric bacterial pathogens from 2,279 patients with IBD and 373,276 non-IBD patients were compared. An A. veronii strain (AS1) isolated from intestinal biopsies of a patient with IBD was used for pathogenic mechanism investigation, and Escherichia coli K12 was used as a bacterial control. HT-29 cells were used as a model of human intestinal epithelium. A significantly higher isolation of Aeromonas species was found in patients with IBD as compared to non-IBD patients (P = 0.0001, odds ratio = 2.11). A. veronii upregulated 177 inflammatory genes and downregulated 52 protein-coding genes affecting chromatin assembly, multiple small nuclear RNAs, multiple nucleolar RNAs, and 55 cytoplasmic tRNAs in HT-29 cells. These downregulation effects were unique to A. veronii and not observed in HT-29 cells infected with E. coli K12. A. veronii induced intestinal epithelial apoptosis involving the intrinsic pathway. A. veronii caused epithelial microvilli shortening and damage and epithelial production of IL-8. In conclusion, this study for the first time reports the association between IBD and Aeromonas enteric infection detected by bacterial cultivation. This study also reports that A. veronii damages intestinal epithelial cells via multiple mechanisms, of which the downregulating cytoplasmic tRNA, small nuclear RNA, and small nucleolar RNA are novel bacterial pathogenic mechanisms. IMPORTANCE This study for the first time reports the association between inflammatory bowel disease (IBD) and Aeromonas enteric infection detected by bacterial pathogen cultivation, highlighting the need of clinical and public health attention. The finding that patients with IBD are more susceptible to Aeromonas enteric infection suggests that detection of Aeromonas enteric infection should be routinely performed for the diagnosis and treatment of IBD. This study also reports novel bacterial pathogenic mechanisms employed by Aeromonas veronii. Through comparative transcriptomic analysis and other techniques, this study revealed the pathogenic mechanisms by which A. veronii causes damage to intestinal epithelial cells. Among the various pathogenic mechanisms identified, the downregulating tRNA, small nuclear and nucleolar RNAs in human intestinal epithelial cells are novel bacterial pathogenic mechanisms.

Relationship Between Rectal Swab and Tissue Samples in Mucosa-associated Microbiota in Patients With Inflammatory Bowel Disease.

Gut mucosa-associated microbiota is more closely correlated with disease phenotypes than fecal microbiota; however sampling via tissue biopsy is more invasive and uncomfortable. Rectal swab may be a suitable substitute for tissue biopsy, but its effectiveness is controversial. This study aimed to evaluate differences in the microbiota at these sites in patients with inflammatory bowel disease (IBD). Inflammatory bowel disease patients and a control group were enrolled when surveillance colonoscopy was scheduled. Samples of colon biopsy tissues, rectal swabs during colonoscopy, and feces before bowel preparation were collected to analyze microbial composition. To explore the short-term effects of bowel preparation on swab microbiota, prepreparation swab samples were also collected from 27 IBD patients. A total of 33 Crohn's disease, 54 ulcerative colitis, and 21 non-IBD patients were enrolled. In beta diversity analysis, fecal microbiota clearly differed from swab and tissue microbiota in the 3 disease groups. The swab microbiota was closer to, but still different from, the tissue microbiota. Consistently, we identified that swab samples differed more in abundant genera from feces than from tissue. Beta diversity analysis did not reveal a difference in swab microbiota before and after bowel preparation, but the genus composition of most individuals varied markedly. Swab microbiota more closely resembled tissue microbiota relative to fecal microbiota, but there were still differences. Bowel preparation did not alter the overall swab microbiota in the short term but markedly changed the microbial composition in most patients.

P2X7 Receptor Regulates Collagen Expression in Human Intestinal Fibroblasts: Relevance in Intestinal Fibrosis.

Intestinal fibrosis is a common complication that affects more than 50% of Crohn´s Disease (CD) patients. There is no pharmacological treatment against this complication, with surgery being the only option. Due to the unknown role of P2X7 in intestinal fibrosis, we aim to analyze the relevance of this receptor in CD complications. Surgical resections from CD and non-Inflammatory Bowel Disease (IBD) patients were obtained. Intestinal fibrosis was induced with two different murine models: heterotopic transplant model and chronic-DSS colitis in wild-type and P2X7-/- mice. Human small intestine fibroblasts (HSIFs) were transfected with an siRNA against P2X7 and treated with TGF-β. A gene and protein expression of P2X7 receptor was significantly increased in CD compared to non-IBD patients. The lack of P2X7 in mice provoked an enhanced collagen deposition and increased expression of several profibrotic markers in both murine models of intestinal fibrosis. Furthermore, P2X7-/- mice exhibited a higher expression of proinflammatory cytokines and a lower expression of M2 macrophage markers. Moreover, the transient silencing of the P2X7 receptor in HSIFs significantly induced the expression of Col1a1 and potentiated the expression of Col4 and Col5a1 after TGF-β treatment. P2X7 regulates collagen expression in human intestinal fibroblasts, while the lack of this receptor aggravates intestinal fibrosis.