BACKGROUND:Surveillance colonoscopies are predominantly normal, identifying patients for potential polypectomy is advantageous. AIM:To assess colon capsule endoscopy (CCE) and/or faecal immunochemical test (FIT) as filters in surveillance. METHODS:Patients aged ≥ 18 due for polyp surveillance were invited for CCE and FIT. Identifying polyps or colorectal cancer resulted in a positive CCE. Significant lesions (≥ 3 polyps or ≥ 6 mm polyps), incomplete studies and positive FITs (≥ 225 ng/mL) were referred for endoscopy. CCE and endoscopy results, FIT accuracy and patient preference were assessed. RESULTS:From a total of 126 CCEs [mean age 64 (31-80), 67 (53.2%) males), 70.6% (89/126) were excreted, 86.5% (109/126) had adequate image quality. CCE positivity was 70.6% (89/126), 42.9% (54/126) having significant polyps with 63.5% (80/126) referred for endoscopy (19 sigmoidoscopies, 61 colonoscopies). CCE reduced endoscopy need by 36.5% (46/126) and 51.6% (65/126) were spared a colonoscopy. CCE positive predictive value was 88.2% (45/51). Significant extracolonic findings were reported in 3.2% (4/126). Patients with positive CCEs were older > 65 [odds ratio (OR) = 2.5, 95% confidence interval (CI): 1.1517-5.5787, P = 0.0159], with personal history of polyps (OR = 2.3, 95%CI: 0.9734-5.4066, P = 0.045), with high/intermediate polyp surveillance risk (OR = 5.4, 95%CI: 1.1979-24.3824, P = 0.0156). Overall, 5/114 (4.4%) FITs were positive (range: 0-1394 ng/mL, mean: 54 ng/mL). Sensitivity (9.6%) and negative predictive values (20.3%) were inadequate. Receiver operating curve analysis gave a sensitivity and specificity of 26.9% and 91.7%, for FIT of 43 ng/mL. Patients preferred CCE 63.3% (76/120), with less impact on daily activities (21.7% vs 93.2%) and time off work (average days 0.9 vs 1.2, P = 0.0201). CONCLUSION:CCE appears effective in low-risk polyp surveillance. FIT does not appear to be of benefit in surveillance.

Abstract Background Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) characterised by chronic mucosal inflammation of the colon. Patients with IBD may have higher fatigue scores compared to non-IBD controls [1] with up to 41% reporting fatigue as a debilitating symptom [2]. Previous clinical trials have demonstrated anti-inflammatory properties of Bifidobacterium longum 35624® in people with UC [3], and increased energy/vitality with Bifidobacterium longum 1714® in a healthy population [4]. However, studies of this dual combination of strains have not been conducted in people with IBD. Methods This single-centre, randomised, double-blind, placebo-controlled trial investigated the safety, tolerance and effect on fatigue of 12-weeks’ intervention with a dual-strain probiotic containing B. longum strains 35624 and 1714 (probiotic) versus an identical placebo. Fatigue (IBD Fatigue Self-Assessment Scale Section II; IBD-F-II), fecal calprotectin and plasma C-reactive protein (CRP) values were measured at baseline and 12 weeks. Safety and tolerance were measured with by monitoring of adverse events throughout the study period. Results 59 participants completed the study (probiotic n=30; placebo n=29)(Table 1). There was a statistically significant reduction in IBD-F-II scores at 12 weeks compared to baseline in both the probiotic (p=0.0003) and placebo (p<0.0001) groups, with no significant difference between groups (p=0.398)(Table 2). There were no significant changes in calprotectin or CRP from baseline to week 12 in the probiotic (p=0.80 and p=0.27) or placebo (p=0.76 and p=0.47) groups. No adverse events were thought to be related to the intervention. Conclusion The findings of this study showed statistically significant improvements in fatigue scores in individuals with UC following 12 weeks of probiotic and placebo intervention respectively, which may be suggestive of a high placebo response in the UC population. Contrary to previous clinical findings showing improvements to plasma CRP with B. longum 35624 in people with UC [3], significant changes in inflammatory markers were not observed in the present study. This study also provides evidence to show that a combination of B. longum 35624 and 1714 was safe and well-tolerated by UC patients. Additional analysis investigating the effect of the probiotic intervention on the gut microbiome is warranted. Further studies conducted in a larger sample are required to better understand the placebo response in the UC population. References 1.Gibble TH, Minyang S, Xhou X, Naegeli AN, Dubey S, Lewis JD. Association of Fatigue with disease activity and clinical manifestations in patients with Crohn’s Disease and Ulcerative Colitis: An Observational Cross-Sectional Study in the United States. Current Medical Research and Opinion. 2024;9:1537-1544. 2.Römkens TEH, van Vugt-van Pinxteren MWJ, Nagengast FM, van Oijen MGH, de Jong DJ. High prevalence of fatigue in inflammatory bowel disease: A case control study. Journal of Crohn’s and Colitis. 2011;5(4):332-7. 3.Groeger D, O’Mahony L, Murphy EF, Bourke JF, Dinan T, Kiely B, Shanahan F, Quigley EM. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes. 2013;4(4):325-339. 4.Wang H, Braun C, Murphy EM, Enck P. Bifidobacterium longum 1714™ Strain Modules Brain Activity of Healthy Volunteers During Social Stress. American Journal of Gastroenterology. 2019;144(7):1152-1162.

Abstract Background Ulcerative colitis (UC) is a form of Inflammatory Bowel Disease (IBD) characterised by chronic mucosal inflammation of the colon. It has been shown that fatigue in patients with ulcerative colitis is a particularly burdensome symptom[1]. Studies have shown that patients with IBD have higher fatigue scores than non-IBD control groups[1]. In UC, alterations in the microbiome is understood to be a contributing factor to the pathophysiology of the disease and have been found to be reduced compared with healthy controls[2-4]. The aim of this study therefore is to evaluate the effects of a dual-strain probiotic versus placebo and assess its effects on the microbiome. Methods This is a single centre double-blind randomised placebo-controlled trial in Tallaght University Hospital, Dublin. Participants are between the ages of 18 to 65 and have a confirmed diagnosis of ulcerative colitis. After randomisation, participants were enrolled on either a 3 month probiotic or placebo arm. Participants had blood tests and a faecal calprotectin at baseline and at conclusion of the study. The probiotic is a dual strain Bifidobacterium longum 35624® combined with B. longum 1714®. Results 10 controls and 59 participants meeting eligibility criteria were successfully recruited. After double-blind randomisation, 30 participants were on the active dual-probiotic arm with 29 participants on the placebo arm (table 1). In our microbiome analysis the taxonomic composition was as expected of a faecal microbiome, with high abundances of Faecalibacterium, Bacteroides, and Phocaeicola. The measured alpha diversity, the measure of the diversity, richness and relative abundance of taxa within a sample, were within expected ranges across the probiotic and placebo group and across timelines. Shannon alpha diversity was significantly higher in the placebo treatment group, both when considering both baseline analysis and post-intervention analysis and when considering only the post-intervention timepoint (table 2). Conclusion This was an exploratory endpoint and further studies need to be done with non-UC healthy controls to further elucidate any clinically significant changes on the diversity of the microbiome when exposed to probiotics. Targeted probiotics with strains of specific taxa based on individual microbiome profiling may be more beneficial than generic probiotics in UC. References 1.Römkens TEH, van Vugt-van Pinxteren MWJ, Nagengast FM, van Oijen MGH, de Jong DJ. High prevalence of fatigue in inflammatory bowel disease: A case control study. Journal of Crohn’s and Colitis. 2011;5(4):332-7. 2.Sokol H, Seksik P, Rigottier-Gois L, Lay C, Lepage P, Podglajen I, et al. Specificities of the fecal microbiota in inflammatory bowel disease. Inflammatory bowel diseases. 2006;12(2):106-11. 3.Du L, Ha C. Epidemiology and Pathogenesis of Ulcerative Colitis. Gastroenterology Clinics of North America. 2020 2020/12/01/;49(4):643-54. 4.Frank DN, St. Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proceedings of the National Academy of Sciences. 2007;104(34):13780-5.

Abstract Background Ulcerative colitis (UC) is a form of Inflammatory Bowel Disease (IBD) characterised by chronic mucosal inflammation of the colon. It has been shown that fatigue in patients with ulcerative colitis is a particularly burdensome symptom[1]. Studies have shown that patients with IBD have higher fatigue scores than non-IBD control groups[1]. In UC, activation and dysregulation of the adaptive immune response at the epithelial level results in the abnormal response to antigens leading to an inflammatory cascade resulting in a production of multiple different pro-inflammatory cytokines including IL10, IL23 and TNF-α amongst others[2]. The aim of this study therefore is to evaluate the effects of a dual-strain probiotic versus placebo on cytokines in relation to UC and fatigue. Methods This is a single centre double-blind randomised placebo-controlled trial in Tallaght University Hospital, Dublin. Participants are between the ages of 18 to 65 and have a confirmed diagnosis of ulcerative colitis. After randomisation, participants were enrolled on either a 3 month probiotic or placebo arm. Participants had blood tests and a faecal calprotectin at baseline and at conclusion of the study. The probiotic is a dual strain Bifidobacterium longum 35624® combined with B. longum 1714®. Results 10 controls and 59 participants meeting eligibility criteria were successfully recruited. After double-blind randomisation, 30 participants were on the active dual-probiotic arm with 29 participants on the placebo arm (table 1). In our cytokine analysis the mean concentrations for IFN-α, IFN-γ, IL-10, IL-12p70, IL-6, IL-8, IP-10 and MCP-1 increased post the probiotic. SAA and IL-17A remained relatively unchanged post the probiotic, and an improvement was seen in IL-1β and TNF-α. Contrasted with the placebo arm of the study where mean concentrations in IFN-γ, IL-17A, IL-6, IP-10 and MCP-1 increased post the placebo. SAA and IL-8 remained relatively unchanged post the placebo. There was an improvement seen in IFN-α, IL-10, IL-12p70, IL-1β and TNF-α (table 2). Results could be due to low detection rates. Conclusion This study found probiotics may not always be beneficial for patients with UC and may worsen some pro-inflammatory cytokine levels. References 1.Römkens TEH, van Vugt-van Pinxteren MWJ, Nagengast FM, van Oijen MGH, de Jong DJ. High prevalence of fatigue in inflammatory bowel disease: A case control study. Journal of Crohn's and Colitis. 2011;5(4):332-7. 2.Ordás I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet. 2012 Nov 3;380(9853):1606-19.

Abstract Background Vedolizumab (VDZ) is an anti α4β7-integrin inflammatory bowel disease (IBD) therapy postulated to reduce immune cell trafficking to the intestine. A significant proportion of patients fail to respond to VDZ. We aimed to assess the effect of VDZ on a panel serum inflammatory proteins (IPs) during induction therapy for IBD with the aim of identifying a serum biomarker of VDZ therapy response. We also aimed to gain further insights in VDZ mechanism of action by evaluating changes in serum IP concentrations during induction. Methods Patients commencing VDZ for IBD were prospectively recruited. All received standard VDZ induction. Baseline and week 6 serum concentrations of 54 IPs were measured by ELISA (Meso Scale Discovery, USA). Clinical outcomes were evaluated at weeks 14 and 30 of VDZ therapy. Corticosteroid-free remission (SFR) was defined as persistence of VDZ therapy, absence of corticosteroid therapy, a partial Mayo score ≤1 Ulcerative Colitis (UC) or HBI <5 Crohn’s Disease (CD). The associations between baseline serum IP concentrations and VDZ therapy outcome at weeks 14 and 30 were evaluated. Changes in IP concentrations from week 0 to week 6 of VDZ therapy were assessed. P values <0.05 following multiple test correction were considered significant in all analyses. Results Thirty-nine patients were included: 51% male, 51% UC, median [range]: age 52 [18.2-75.8] years; disease duration 13.4 [0.4–40.8] years; clinical Mayo subscore 4 [0–9]; and HBI 7 [1–20]. 28(72%) had received prior anti-TNF therapy. In univariate analysis, at higher baseline serum TNF-β concentration and lower IL-22, VEGF-C, and IL-7 concentrations were associated with week 14 SFR, p values p=0.003, 0.034, 0.042, and 0.045 respectively. Higher baseline serum IL-4, MDC and MCP-4 concentrations and lower baseline IL-10 concentration were associated with week 30 SFR, p=0.011, 0.026, 0.028 and 0.03 respectively. Significance was not maintained after correction for multiple testing. From baseline to week 6 post VDZ initiation, significant increases were observed in the concentration of six IPs: bFGF, eotaxin, eotaxin-3, MIP-1β, TARC and TNF-β, p=0.034, 0.0012, 0.0013, 0.043, 0.015 and 0.0077 respectively; and a significant decrease in one IP, IL-15, p=0.0004. The significant changes observed in IL-15, eotaxin, and eotaxin-3 concentrations from baseline to week 6 following VDZ initiation remained significant after multiple test correction. Conclusion No serum inflammatory protein was identified as a biomarker of SFR in patients receiving VDZ therapy for IBD. VDZ was observed to significantly affect serum IPs known to be involved in chemotaxis. Further study is required to identify biomarkers of VDZ therapy response.

Type 1 and type 2 diabetes mellitus (DM) are often accompanied by mild forms of pancreatic exocrine insufficiency (PEI). The prevalence rates of PEI in diabetic patients are unclear and variable depending on the testing modality and the studies published. The clinical consequences of PEI in diabetics are also not well defined. We aimed to determine the prevalence of PEI in a diabetic cohort using the faecal elastase-1 (FE-1) assay as a screening test and to validate a patient-reported symptom-based scoring system, the (PEI-S) for diagnosing PEI within this patient population. Two hundred and three diabetic patients attending diabetic and gastroenterology outpatients of a university hospital without previously known PEI were recruited for the study. Demographic parameters, PEI score (PEI-S), and glycated hemoglobin (HBA1c) were documented in standardized data sheets, and a stool sample was obtained. A FE-1 value < 200 μg/g and or a PEIS of > 0.6 was used as the screening cut-off for PEI. One hundred sixty-six patients returned faecal samples. The prevalence of PEI, as measured by low FE-1, was 12

Abstract Background Ustekinumab (UST) is a monoclonal antibody that binds to the p40 subunit shared by pro-inflammatory interleukins 12 and 23. UST has demonstrated efficacy for the induction and maintenance of remission in patients with Crohn’s disease (CD). A proportion of patients with CD do not respond to UST at the standard dose of 90 mg every 8 weeks. Methods A multi-centre retrospective study of CD patient who commenced UST therapy at two specialist tertiary referral centres between October 2012 and March 2021 was performed. Patient demographics, baseline characteristics, medication history and disease behaviour were characterised. Duration of UST therapy and UST dose escalation were documented. UST therapy persistence, was considered a proxy for treatment response, and was expressed as time to discontinuation of UST therapy. The study evaluated whether UST dose optimisation was associated with increased UST therapy persistence; and clinical factors associated with UST therapy persistence. Optimised dosing was defined as a dosing regimen of UST 90mg at less than an 8-weekly interval. Statistical analysis was performed using survival analysis and multivariate cox logistic regression with effect of covariates on outcome expressed as odds ratios (OR). Results 133 patients commenced UST during the study period (age [mean, range] 39 years, 16-79; 59% female; disease duration [mean, range] 12.4 years, 1-35). 99% of patients had failed at least 1 biologic and 72 patients (54%) required dose escalation during the study period. The mean duration of UST therapy was 74 weeks (range 2-427). 75 (56%) patients were still receiving UST at end of study period. Survival analysis demonstrated that there was no significant difference in UST persistence between patients receiving standard and optimised UST dosing regimens, p=0.58. Patients with early UST dose optimisation (within 6 months of therapy initiation) had increased UST therapy persistence, p=0.003. A multivariate regression analysis demonstrated that early UST dose optimisation (within 6 months of therapy initiation) was independently associated with a longer time to UST therapy discontinuation (OR 0.31 (95%CI 0.15-0.68), p=0.003). Neither disease duration (OR 1.11, p=0.66), male sex (OR 0.91, p=0.83), concomitant immunomodulator use (OR 1.03, p=0.95), perianal disease (OR 1.09, p=0.85), smoking status (OR 1.16, p=0.68) nor previous surgery (OR 1.47, p=0.33) were independently associated with time to UST therapy discontinuation. Conclusion UST is an effective treatment for CD patients with prior biologic therapy exposure. Optimised UST dosing regimens are frequently utilised in routine clinical practice. There appears to be an increased likelihood of treatment success with early UST dose optimisation.

Abstract Background Sleep disturbances affect 40-50% of patients with IBD and are associated with disease flares. Symptoms, treatment side effects and pro-inflammatory status have been shown to have an effect on sleep quality and duration. Anxiety and Depression disorders are also common with both conditions affecting approximately 20% of IBD patients. These disorders may also be associated with sleep disturbance Aim Our primary aim was to assess for a correlation between sleep quality and mood disorders in people with IBD. Our secondary aim was to assess the impact of these factors on quality of life. Methods 87 patients with IBD were invited to complete an online survey. This survey included general demographic information, inflammatory bowel disease information, Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), disease activity scores (Harvey Bradshaw Index and partial MAYO score), and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). One-way ANOVA tests, Fisher’s test and unpaired t-tests were used to calculate the statistical significance. Results Mean age 43years. 46% male (n=40) and 54% female (n=47). Ulcerative Colitis 35.6% (n=31), Crohn’s Disease 62.1% (n=54), and indeterminate 2.3% (n=2). The mean global PSQI score was 7.66, with 62% (n=54) of participants having a global PSQI score >5, indicating poor sleep quality. Poor sleep quality was not associated with age or disease duration. However unsurprisingly, it was associated with increased disease activity; Remission 5.89, mild activity 7.53, and moderate activity 10.61 (p<0.001). See FIGURE 1 Participants with poor quality of sleep had significantly higher rates of anxiety (HADSA >8) with a mean HADS anxiety score of 10.78 with 79% (n=39/49) reporting anxiety, compared to those with good reported sleep with mean scores of 4.97 and 21% (n=7/33).reporting anxiety p<0.001. They also had higher rates of depression, 42%(n=21/49) versus 6%(n=2/33), p<0.001. Conclusion Poor sleep quality increases levels of anxiety and depression, which in turn impacts quality of life in patients with IBD. Physicians should enquire about sleep & mood when treating patients with IBD to improve sleep quality.

Abstract Background Sleep disturbances affect 40-50% of patients with Crohn’s Disease and are associated with disease flares. Symptoms, treatment side effects and pro-inflammatory status have been shown to have an effect on sleep quality and duration. Vitamin D deficiency affects between 18% and 70% of inflammatory bowel disease (IBD) patients and is independently associated with lower Health Related Quality of Life and greater disease activity. Our primary aim was to assess for a correlation between sleep quality and Vitamin D deficiency in people with IBD. Our secondary aim was to assess the impact of these factors on quality of life. Methods 54 patients with Crohn’s Disease were invited to attend for Vitamin D testing and complete a survey. Vitamin D deficiency was defined as a serum Vitamin D less than 30 nmol/L. The survey included general demographic information, inflammatory bowel disease information, Pittsburgh Sleep Quality Index (PSQI), disease activity score (Harvey Bradshaw Index), and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). One-way ANOVA tests and unpaired t-tests were used to calculate the statistical significance. Results · Median age 42.5 years. 50% female (n=27) and 50% male (n=27). · Mean duration of IBD was 17 years · 46% of patients were in clinical remission per HBI, 13% had mild activity, 37% moderate activity and 4% severe disease. · The mean global PSQI score was 7.7, with 61% (n=33) of participants having a global PSQI score >5, indicating poor sleep quality. · 24% of patients (n=15) had Vitamin D deficiency · Mean PSQI of patients with Vitamin D deficiency was 10.5 compared to 6.7 in those without (P= 0.008). Conclusion Vitamin D deficiency is associated with poorer sleep quality in IBD, which in turn impacts quality of life in patients with IBD. IBD patients presenting with fatigue and sleep difficulties should be assessed for Vitamin D levels and treated where deficient.

Abstract Background Globally rising rates of obesity and consequent metabolic diseases have been reflected in the inflammatory bowel disease (IBD) population. Non-alcohol fatty liver disease (NAFLD) is a common liver disorder associated with obesity, that occurs more frequently in people with IBD. Methods A prospective single-centre cohort study. In total, we recruited 203 patients from our IBD service in a tertiary academic hospital. 7 participants were excluded due to later diagnosed non-NAFLD liver disease. Following informed consent, participants underwent a fibroscan for liver stiffness (LSM) and controlled attenuation parameter (CAP) measurement, and blood tests for HbA1c and fasting lipids. Basic demographics, past medical history, exercise measured on the Godin-Shepard Leisure Time Physical Activity Questionnaire, physical functioning on SF-36 Questionnaire, blood pressure, CAP and LSM were recorded. T-test and Fishers exact test were used to test for statistical significance as appropriate. Results Of the 196 IBD patients included, 34.7% (n=68/196) had a healthy BMI, 34.7% (n=68/196) were overweight (BMI≥25-29.9), and 30.6% (n=60/196) were obese (BMI≥30). Overall, 16.3% (n=32) had a CAP score >294dB/m consistent with NAFLD, and 2.55% (n=5) had a LSM >8.1kPa consistent with fibrosis. When compared to those without NAFLD, those with NAFLD had higher BMIs, 26.9 vs 32.3 p<0.05. They also had a much higher incidence of diabetes 28.1% vs 0% p=0.0001, higher overall rates of abnormal HbA1C (≥6%), 21.9% (n=7/32) vs 6.4% (n=10/156) p=0.0121, and higher rates of abnormal HbA1c without a diagnosis of diabetes 13% (n=3/23) vs 6.45% (n=10/155) p=0.4043. Additionally, they had non-significant higher mean systolic blood pressure and higher rates of diagnosed hypertension. Compared to those without NAFLD, the NAFLD cohort had higher rates of diagnosed hypercholesterolaemia 34.4% (n=11/32) vs 15.3% (n25/163) p=0.022 and there were higher rates of elevated total cholesterol (>5mmol/L) in those not previously diagnosed with hypercholesterolaemia, 42.9% (n=9/21) vs 31.8% (n=47/148) p=0.3292. Participants with NAFLD also had lower exercise scores 17 vs 24.9 p=0.03543, and lower scores for physical functioning 71.9 vs 83.2 p=0.00676. Of particular note, they had more than double the 10-year risk of myocardial infarction or death determined by the Framingham risk scores for hard coronary heart disease, 2.48% vs 5.75%, p=0.00012. Conclusion Our study shows that people with concurrent NAFLD and IBD have a significant cardiovascular risk profile. With increased awareness of this, metabolic syndrome conditions should be screened for and treatment initiated where appropriate, to decrease cardiovascular related mortality in this cohort.

Abstract Background Non-alcohol fatty liver disease (NAFLD) is one of the most common liver disorders, and occurs more frequently in people with inflammatory bowel disease (IBD). Previous research suggests that increased age, BMI, and IBD duration, previous bowel resection, and co-morbid diabetes are risk factors for the development of NAFLD with IBD. Our aim was to investigate possible risk factors for the progression of NAFLD in people with IBD. Methods A prospective single centre cohort study. In total, we recruited 203 patients from the IBD service of our tertiary, academic centre. 7 participants were excluded due to later diagnosed non-NAFLD liver disease. Following informed consent, participants underwent a fibroscan and blood tests for liver function tests and a FIB-4 and score were taken. Basic demographics, information about IBD, exercise measured on the Godin-Shepard Leisure Time Physical Activity Questionnaire, LFTs, FIB4 score, controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were recorded. T-test, Fishers exact, and Pearson’s correlation coefficient were used to test for statistical significance as appropriate. Results Of the 196 IBD patients included, 16.3% (n=32) had a CAP score >294dB/m consistent with NAFLD, and 2.6% (n=5) had a LSM >8.1kPa consistent with fibrosis. Only 40.6% of those with NAFLD (n=13/32), had abnormal liver enzymes. In regards to FIB 4 score, 8.1% (n=8/91) of those without NAFLD had a FIB4 score >1.3, none with NAFLD alone, and 50% (n=2/4) of those with fibrosis. We found a positive correlation between BMI and waist circumference with CAP score, Pearson’s r= 0.514 and 0.536 respectively. In those with NAFLD, the fibrosis group had higher BMIs and waist circumferences, 37.44 vs 31.44 (p=0.0265) and 108.6cm vs 107.6cm (p=0.0781) respectively, than the NAFLD without fibrosis cohort. They also had a higher alcohol intake in units/week (21 vs 4.1 p=0.0204), smoking pack year history (31.66 vs 23.63 p=0.482), and HbA1c (6.36% vs 5.76% p=0.108) and had lower exercise scores (0.6 vs 20.1 p=0.0186). Longer IBD disease duration, biologic therapy, anti-TNF therapy, azathioprine, previous surgery, or extra-intestinal IBD did not seem to affect those who developed fibrosis. Conclusion The development of fibrosis secondary to NAFLD in people with IBD seems to be driven by metabolic risk factors rather than related to IBD. A high index of suspicion for IBD patients with a high BMI even without deranged LFTs, should lead to consideration for fibroscan. Further research is needed on whether FIB-4 scoring has utility in the IBD population.

Abstract Background Tofacitinib is an oral small molecule directed against the JAK/STAT pathway. It is the first JAK inhibitor approved for the treatment of ulcerative colitis (UC) and is licenced for use in moderate to severely active disease. This study aims to evaluate tofacitinib effectiveness and safety in real-world clinical practice for moderate-to-severely active UC. Methods Consecutive patients receiving Tofacitinib for UC in four Irish tertiary referral centres were identified. Baseline clinical data and information on therapy outcomes were collected by retrospective review of electronic patient records. Patients included in the study cohort were older than 18 years of age, had a confirmed diagnosis of UC, had received at least one induction dose of tofacitinib, and had available clinical follow-up. The primary study endpoint was 6-month corticosteroid-free remission rate. Secondary endpoints included 3-month clinical response, inflammatory biomarkers responses to tofacitinib therapy, rates of tofacitinib discontinuation, and side effects. Continuous variables are presented as median [range]. P values < 0.05 were considered significant in all analyses. Results Fifty-three UC patients were included; age 40.4 [33.3 – 53.9] years, 66% male, disease duration 5.7 [2.6–10.9] years; follow-up 8.7 [6.4–14.1] months. 43%, 40% and 17% of patients had extensive, left-sided disease and proctitis respectively. At baseline, clinical Mayo subscore was 7 [5–8], CRP 4.0 [1.0–16.7] mg/L and faecal calprotectin 914 [444.0–1000] mcg/g. The 3-month clinical response and 6-month corticosteroid-free remission rates were 69% and 43%, respectively. Following tofacitinib therapy, compared with baseline values, a significant reduction in 3-month clinical Mayo score, 3-month CRP, and post-induction faecal calprotectin was observed, p <0.03 for all comparisons. 36% of patients (n=19) discontinued tofacitinib during study follow-up (time to Tofacitinib discontinuation 1.9 [0.5–18.9] months). Side effects occurred in 26% percent of patients with the majority minor and self-limiting. No cardiovascular or venous thromboembolic events were observed and no hospitalisations occurred due to therapy-related side effects Conclusion These data are in concordance with prior studies of tofacitinib effectiveness and safety in real world practice. They demonstrate that, in a cohort of UC patients with significant prior therapy exposure, tofacitinib is an effective therapy with an acceptable safety profile.

Activation of the cGAS-cGAMP-STING pathway is essential for sensing foreign DNA from pathogens or self-DNA from dying cancer cells. This pathway is critical for the innate immune response and directs the full efficacy of cancer therapeutics, including checkpoint and PARP inhibitors, radiotherapy, and CAR T-cells. Intense efforts have focused on triggering this pathway with cGAMP analogs, which are small-molecule activators of STING. However, recent reports show that STING is downregulated by promoter methylation in various cancers. Furthermore, T-cells activated by cGAMP undergo apoptosis, which limits the efficacy of T-cells based tumor eradication. Indeed, emerging studies suggest that STING activation in myeloid cells is most critical for maximal anti-cancer efficacy of therapeutics. Oncogenic silencing of STING expression is generally considered as "undruggable". At MiNA Therapeutics, we utilized our proprietary platform of RNA activation (RNAa) to design small activating RNA (saRNA) oligos that restore the transcription of the STING gene to levels that are necessary for eliciting anti-tumor effect either alone or in combination with other drugs, including cGAMP analogs. The clinical lead, saSTING increases in vitro STING expression in the range of 4 to 11-fold in multiple cell lines, and the upregulation is sustained for at least a week. The increase in STING expression is also confirmed at the protein level and an RNAseq experiment validated the functional increase of genes downstream of the STING pathway. The clinical development candidate, MTL-STING, encapsulates saSTING in NOV340 liposomes for intratumoral administration. NOV340 liposomes have previously been clinically validated to efficiently deliver saRNA to myeloid cells, which is the critical cellular subset to benefit from STING activation from an anti-tumor perspective. In the first preclinical proof of concept study, the murine surrogate of MTL-STING combined with PD-1 antibody resulted in early inhibition of tumor growth and was the only group to regress tumor below pre-treatment sizes. MTL-STING is expected to enter phase I in 2023.

Abstract Background Anti-TNF agents are effective therapies for Inflammatory Bowel Disease (IBD), however, a significant proportion of patients lose response over time. Real world data on prescribing practices and outcome of anti-TNF therapy are of utility to practicing clinicians Methods To evaluate Anti-TNF prescribing practice and durability of Anti-TNF response in a large multicentre IBD cohort. IBD patients commencing an anti-TNF agent, as first biologic therapy, at participating academic centres were identified from institutional databases. Baseline demographic data, concomitant medication and biologic therapy history were collected. Adalimumab(ADA) and Golimumab(GOL) were consider subcutaneous(SC) anti-TNF agents. Date of commencement and discontinuation of first and second line anti-TNF therapy was documented. Kaplan-Meier survival curves were constructed for time based analyses. P values less than 0.05 were considered significant in all analyses. Results N=991 patients with IBD were included in the study. 29%, 69% and 2% had UC, CD and IBD-U respectively; median [IQR] age 27 [19–37] years; 50% female. 31%, 63% and 4% received infliximab(IFX), ADA and GOL respectively as first-line anti-TNF therapy. 35% of patients received an immunomodulator in combination with first-line anti-TNF agent. Median [95% CI] survival free of therapy discontinuation for first and second-line anti-TNF agents was 4.6 [3.7 – 5.3] years and 3.0 [2.1 – 3.9] years respectively. Survival free of anti-TNF discontinuation was significantly shorter for IFX monotherapy group compared with IFX combination therapy, SC anti-TNF monotherapy and SC anti-TNF combination therapy groups, p=0.005. Conclusion While anti-TNF therapies are effective a significant proportion of patients discontinue therapy over time. Second line anti-TNF therapy results in a less durable response with a shorter time to drug discontinuation compared with first line anti-TNF therapy. The use of a combination immunomodulator is particularly important with infliximab therapy, however, does not influence durability of response for subcutaneous anti-TNF agents.

Abstract Background Anti-TNF agents are effective treatments for Inflammatory Bowel Disease (IBD), however, a significant proportion of patients require second-line biologic therapy. Real-world data on the outcome of second line biologic therapy can inform clinical decision-making. Methods To evaluate prescribing practice and second-line biologic therapy persistence in IBD patients. IBD patients, who had received one prior anti-TNF agent and commenced a second-line biologic, at participating centres, were identified. Baseline demographic data, concomitant medication and biologic therapy history were characterised by retrospective review of patients records. Adalimumab(ADA) and golimumab(GOL) were considered subcutaneous(SC) anti-TNF agents. Date of commencement and discontinuation of therapies were documented. Kaplan-Meier survival curves were constructed for time based analyses. P values < 0.05 were considered significant in analyses. Results N=395 IBD patients were included; 30%, 68% and 2% had UC, CD and IBD-U respectively; age (median[IQR]) 26[18–35] years; 56% female; 35% receiving a concomitant immunomodulator (IMM); follow-up time (median [IQR]) 1.5[0.7–3.3] years. Second-line biologic therapy with SC anti-TNF, infliximab(IFX), vedolizumab(VDZ), and ustekinumab(USTK) was used in 36%(n=143), 38%(n=151), 10%(n=38), and 16%(n=63) of patients respectively. Follow-up time (median[IQR]) was significantly longer for SC anti-TNF and IFX compared with VDZ and USTK groups: 1.7 [0.7–3.6], 1.7 [0.7–3.5], 1.1[0.3–2.5], 1.3[0.5–2.3] years respectively, p=0.03. A greater proportion of patients receiving anti-TNF therapy versus alternate class biologic therapy received a concomitant IMM: 42%, 34%, 18% and 29% of SC anti-TNF, IFX, VDZ and USTK treated patients respectively, p=0.03. In a univariate survival analysis there was no significant difference in survival-free of drug discontinuation comparing second-line biologic agents, p=0.8. In a multivariate analysis, including second-line biologic agent type, concomitant IMM use, gender and IBD phenotype the only factor significantly associated with time to drug discontinuation was UC phenotype, Hazard ratio (95%CI): 1.5 (1.1 – 2.1), p=0.007. Conclusion While follow-up time was shorter for VDZ and USTK treated patients, the durability of response to second-line biologic therapy, assessed by drug persistence, appeared similar between agents. UC phenotype was associated with a shorter time to therapy discontinuation.

Aims Inpatient video capsule endoscopy(VCE) is a regular request to gastroenterology services. Limited data exists comparing the effect of admission status on the quality of VCE. This study aimed to compare the quality of inpatient versus outpatient CCE(colon capsule endoscopy) & PIC(pan-intestinal capsule) studies & factors affecting outcomes.

Aims To assess the adherence of Warfarin (OAC) and Direct Oral Anticoagulants (DOAC) management to guidelines before endoscopy procedures at Tallaght University Hospital.

Aims Colon capsule endoscopy (CCE) is an established diagnostic tool for colonic pathology. There is a lack of clinical data on the true capsule false negative (FN) rates. We aimed to assess the causes of missed pathology in a CCE cohort.

Aims To evaluate outcomes following endoscopic balloon dilatation (EBD) of strictures in patients with Crohn’s disease (CD).

Aims The UK JAG on GI Endoscopy's minimum standard for polyp detection rates (PDR) in colonoscopy is 15 %. TheCOVID-19 pandemic precipitated the use of restrictive personal protective equipment (PPE) which might reduce dexterityand decrease PDRs. We audited our polyp excision rates both prior to and post the COVID-19 pandemic in order to assesswhether restrictive PPE led to a diminution therein. Methods Our endoscopy database was queried for all colonoscopies performed between 01/01/2014 and 29/02/2020 (Pre-COVID-19, n = 18,231) and between 01/03/2020 and 02/09/2020 (Post-COVID-19, n = 825) and subsequently irrevocablyanonymised. A polyp excision rate (PER) was calculated for each period as a proxy for PDR. A comparative odds ratio was calculated. An ordinary least squares (OLS) regression, using number of polyps excised as the dependent variable and procedure in thepost-COVID-19 period as a primary explanatory variable, was performed. The regression was controlled for age, malegender and procedure coded as therapeutic (as opposed to diagnostic). Results 4,346 and 209 patients had at least one polyp excised in the pre-COVID-19 (PER 23.8 %) and post-COVID-19 (PER25.3 %) periods respectively. Odds ratio 1.08 (95 %CIs: 0.92, 1.27). OLS regression established positive relationships between number of polyps excised and age (0.004, 95 %CIs: 0.003,0.005), male gender (0.10, 95 %CIs: 0.07, 0.13) and procedure coded as therapeutic (1.75, 95 %CIs: 1.71, 1.78). Itdemonstrated no significant relationship between procedure in the post-COVID-19 period (-0.003, 95 %CIs:-0.07, 0.07)and number of polyps excised. Conclusions Odds ratios comparing PERs and an OLS regression analysing number of polyps excised failed to demonstrateany significant difference between the pre-COVID-19 and post-COVID-19 eras.