Inflammatory Bowel Disease Controls Research Articles

Comparative Outcomes of Endoscopic Mucosal Resection for Laterally Spreading Lesions in Inflammatory Bowel Disease.

The role of endoscopic mucosal resection (EMR) for laterally spreading lesions (LSLs) in inflammatory bowel disease (IBD) remains controversial despite its effectiveness in the general population. We aim to characterize outcomes of EMR for IBD-associated LSLs compared to controls without IBD. We performed a retrospective observational cohort study of patients with IBD who underwent EMR and endoscopic follow-up for LSLs, compared to a control group without IBD. The primary outcome was histologic recurrence; secondary outcomes included en bloc resection and adverse events. Factors associated with recurrence were identified using multivariate mixed effects logistic regression. A total of 210 pre-malignant lesions in 155 patients were included. By histology, 91% were adenoma/low-grade dysplasia or sessile serrated lesions. Average lesion size was 22.9 mm (SD 11.3 mm) in the IBD group, and 21.5 mm (SD 12.4 mm) in the control group. Recurrence occurred in 30.4% of IBD-associated lesions (7/23) compared to 20.9% of controls (39/187; OR=2.51, CI .59-10.71). En bloc resection was less common in the IBD group (2/23, 8.7%, 95% CI 1.1-28.0) versus controls (106/187, 57.9%, 95% CI 50.4-65.2). After adjusting for lesion size and histology, recurrence appeared more common in patients with IBD compared to controls (OR=3.08, 95% CI 1.04-9.13). Recurrence of LSLs after EMR appears more frequent in patients with IBD. Given the added complexity, EMR in patients with IBD should be performed in expert centers with close endoscopic surveillance.

HIV infection is associated with a less aggressive phenotype of inflammatory bowel disease. A multicenter study of the ENEIDA registry.

The coexistence of human immunodeficiency virus (HIV) infection and inflammatory bowel disease (IBD) is uncommon. Data on the impact of HIV on IBD course and its management is scarce. To describe the IBD phenotype, therapeutic requirements and prevalence of opportunistic infections (OI) in IBD patients with a coexistent HIV infection. Case-control, retrospective study including all HIV positive patients diagnosed with IBD in the ENEIDA registry. Patients with positive HIV serology (HIV-IBD) were compared to controls (HIV seronegative), matched 1:3 by year of IBD diagnosis, age, gender and type of IBD. A total of 364 patients (91 HIV-IBD and 273 IBD controls) were included. In the whole cohort, 58% had ulcerative colitis (UC), 35% had Crohn's disease (CD) and 7% were IBD unclassified. The HIV-IBD group presented a significantly higher proportion of proctitis in UC and colonic location in CD but fewer extraintestinal manifestations than controls. Regarding treatments, non-biological therapies (37.4% vs. 57.9%; P=0.001) and biologicals (26.4% vs. 42.1%; P=0.007), were used less frequently among patients in the HIV-IBD group. Conversely, HIV-IBD patients developed more OI than controls regardless of non-biological therapies use. In the multivariate analysis, HIV infection (OR 4.765, 95%CI 2.48-9.14; P<0.001) and having ≥1 comorbidity (OR 2.445, 95%CI 1.23-4.85; P=0.010) were risk factors for developing OI, while CD was protective (OR 0.372, 95%CI 0.18-0.78;P=0.009). HIV infection appears to be associated with a less aggressive phenotype of IBD and a lesser use of non-biological therapies and biologicals but entails a greater risk of developing OI.

Immunohistochemical Analysis of IL-19 and IL-24 Expression in Inflammatory Bowel Disease (IBD) Patients: Results From a Single Center Retrospective Study.

Background IL-19 and IL-24 induce proinflammatory cytokine production through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. The primary objective of this study was to investigate any changes in IL-19 and IL-24 expression between inflammatory bowel disease (IBD) patients and healthy controls, as well asbefore and after the initiation of biologics. The secondary objective was to investigate any relation betweentheir expression anddisease phenotype and activity. Methods IL-19 and IL-24 expression was measured in intestinal tissue samples from 121 patients with moderate to severe IBD versus healthy controls using immunohistochemistry. Their expression was then measured 12 months after treatmenton the patient group treated with biologics. The disease activity was measured before and after treatment using the Harvey Bradshaw Index (HBI) for Crohn's disease (CD) patients and the Mayo Score (MS) for ulcerative colitis (UC) patients. Data were analyzed using SPSS (IBM Inc., Armonk, New York). Results IL-19 expression was raisedin the IBD group versus healthy controls. In the CD group, the IL-19 expression was related with the disease activity scorepost-biologic treatment. IL-24 was also highly expressed in patients with active UC and CD and was increased post-treatment. Itsexpression in UC was statistically related with the MS. Conclusions IL-24 and IL-19 are key factors in IBD-related intestinal inflammation and this is one of the few human studies to suggest that. An immunosuppressive role of IL-24 was demonstrated in the UC group. A future use as biomarkers of disease activity and response to treatment might be feasible.

Oncostatin M Induces a Pro-inflammatory Phenotype in Intestinal Subepithelial Myofibroblasts.

Oncostatin-M (OSM) is associated with antitumor necrosis factor (anti-TNF)-α resistance in inflammatory bowel disease (IBD) and fibrosis in inflammatory diseases. We studied the expression of OSM and its receptors (OSMR, gp130) on intestinal subepithelial myofibroblasts (SEMFs) and the effect of OSM stimulation on SEMFs. The mRNA and protein expression of OSM, OSMR, gp130, and several fibrotic and chemotactic factors were studied in mucosal biopsies and isolated human intestinal SEMFs of patients with IBD and healthy controls (HCs) and in a model of human intestinal organoids (HIOs). Subepithelial myofibroblasts and HIOs were stimulated with OSM and interleukin (IL)-1α/TNF-α. RNAseq data of mucosal biopsies were also analyzed. Oncostatin-M receptors and gp130 were overexpressed in mucosal biopsies of patients with IBD (P < .05), especially in inflamed segments (P < .05). The expression of OSM, OSMR, and gp130 in SEMFs from HCs was increased after stimulation with IL-1α/TNF-α (P < .001; P < .01; P < .01). The expression of CCL2, CXCL9, CXCL10, and CXCL11 was increased in SEMFs from patients with IBD and HCs after stimulation with OSM in a dose-dependent manner (P < .001; P < .05; P < .001; P < .001) and was further increased after prestimulation with IL-1α/TNF-α (P < .01 vs OSM-alone). Similar results were yielded after stimulation of HIOs (P < .01). Oncostatin-M did not induce the expression of collagen I, III, and fibronectin. Oncostatin-M receptor expression was positively correlated with CCL2, CXCL9, CXCL10, and CXCL11 expression in mucosal biopsies (P < .001; P < .001; P = .045; P = .033). Human SEMFs overexpress OSMR in an inflammatory microenvironment. Oncostatin-M may promote inflammation in IBD via its stimulatory effects on SEMFs, which primarily involve chemoattraction of immune cells to the intestinal mucosa.

Faecal Volatile Organic Compound Analysis in De Novo Paediatric Inflammatory Bowel Disease by Gas Chromatography-Ion Mobility Spectrometry: A Case-Control Study.

The gut microbiota and its related metabolites differ between inflammatory bowel disease (IBD) patients and healthy controls. In this study, we compared faecal volatile organic compound (VOC) patterns of paediatric IBD patients and controls with gastrointestinal symptoms (CGIs). Additionally, we aimed to assess if baseline VOC profiles could predict treatment response in paediatric IBD patients. We collected faecal samples from a cohort of de novo therapy-naïve paediatric IBD patients and CGIs. VOCs were analysed using gas chromatography-ion mobility spectrometry (GC-IMS). Response was defined as a combination of clinical response based on disease activity scores, without requiring treatment escalation. We included 109 paediatric IBD patients and 75 CGIs, aged 4 to 17 years. Faecal VOC profiles of paediatric IBD patients were distinguishable from those of CGIs (AUC ± 95% CI, p-values: 0.71 (0.64-0.79), <0.001). This discrimination was observed in both Crohn's disease (CD) (0.75 (0.67-0.84), <0.001) and ulcerative colitis (UC) (0.67 (0.56-0.78), 0.01) patients. VOC profiles between CD and UC patients were not distinguishable (0.57 (0.45-0.69), 0.87). Baseline VOC profiles of responders did not differ from non-responders (0.70 (0.58-0.83), 0.1). In conclusion, faecal VOC profiles of paediatric IBD patients differ significantly from those of CGIs.

Association between hepcidin levels and inflammatory bowel disease: A systematic review and meta-analysis of observational studies.

Hepcidin has a crucial role in iron homeostasis upon inflammatory conditions such as inflammatory bowel disease (IBD). Thus, we conducted a systematic review and meta-analysis to determine the overall association between serum hepcidin concentrations and IBD. Based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols, an electronic literature search was conducted on PubMed/MEDLINE, Scopus, and Web of Science until June 2020. Studies were deemed eligible for inclusion if they met the following criteria: (1) diagnosis of IBD, (2) observational design, and (3) measured serum hepcidin and prohepcidin concentrations in IBD patients and control group. Overall, 10 studies including 1184 participants were evaluated. Random-effects meta-analysis revealed that subjects with IBD had 7.22 ng/mL (95% CI: 2.10, 12.34; p = .006) higher serum hepcidin concentrations compared to control groups. A nonsignificantly lower serum prohepcidin concentration (0.522 ng/mL, 95% CI: -1.983 to 0.939; p = .484) was found for IBD patients compared to healthy subjects. However, there was significant heterogeneity among the studies regarding both hepcidin (I 2 = 98%, p < .001) and prohepcidin levels (I 2 = 96%, p < .001), respectively. In an age-based subgroup analysis, patients aged ≥18 years with IBD displayed higher serum hepcidin levels when compared to healthy individuals (22.36 ng/mL, 95% CI, 2.12-42.61; p = .030). Hepcidin concentrations are elevated in subjects with IBD; however, the clinical relevance of this finding requires further evaluation in future investigations as the increase is relatively small compared to the wide range of normal hepcidin values.

Microbial Disruptions in Inflammatory Bowel Disease: A Comparative Analysis.

The fecal microbiota was studied in patients with inflammatory bowel disease (IBD), and the characteristics of gut microbiota were compared among patients with different subtypes and stages of IBD, aiming to identify the gut microbiota associated with IBD. Fecal samples were collected from 41 IBD patients (18 patients with ulcerative colitis [UC] and 23 patients with Crohn's disease [CD]) in the Department of Gastroenterology of East China Hospital, Fudan University between January 2021 and January 2022. In addition, fecal samples were collected from 20 healthy volunteers. The fecal microbiota was subjected to 16S rRNA gene sequencing, followed by bioinformatics analysis. There was significant difference in the fecal microbiota between IBD patients and controls. The abundance and diversity of fecal microbiota in the IBD patients were significantly lower than in controls. The relative abundance of Subdoligranulum, Ruminococcus, Anaerostipes and Lachnospira was reduced markedly in the IBD patients. As compared to controls, the relative abundance of Streptococcus increased dramatically in the UC patients. The relative abundance of Lachnoclostridium, Fusobacterium, Cloacibacillus and Erysipelatoclostridium significantly increased in the CD patients. As compared to CD patients, the relative abundance of Alistipes was reduced markedly in the UC patients; the relative abundance of Faecalibacterium, Roseburia and Haemophilus was reduced dramatically in the CD patients. In addition, significant difference was also noted in the fecal microflora between patients with active IBD and those with IBD in remission period. In active IBD patients, the relative abundance of Roseburia, Coprococcus and Ruminiclostridium was reduced significantly. There is intestinal microbiota imbalance in IBD patients, and the abundance of Roseburia, Coprococcus and Ruminiclostridium is reduced significantly in the active period of IBD, which may be related to the active IBD.

The intestinal microbiome of inflammatory bowel disease across the pediatric age range

ABSTRACT Dysbiosis is associated with pediatric and adult-onset inflammatory bowel disease (IBD), but the role of dysbiosis and the microbiome in very early onset IBD (VEO-IBD) has not yet been described. Here, we aimed to demonstrate the impact of age and inflammation on microbial community structure using shotgun metagenomic sequencing in children with VEO-IBD, pediatric-onset IBD, and age-matched pediatric healthy controls (HC) observed longitudinally over the course of 8 weeks. We found disease-related differences in alpha and beta diversity between HC and children with IBD or VEO-IBD. Using a healthy microbial maturity index modeled from HC across the age range to characterize their gut microbiota, we found that children with pediatric-onset IBD and VEO-IBD had lower maturity than their age-matched HC groups, suggesting a disease effect on the microbial community. In addition, patients with pediatric IBD had significantly lower maturity than those with VEO-IBD, who had more heterogeneity at the youngest ages, highlighting differences in these two cohorts that were not captured in standard comparisons of alpha and beta diversity. These results demonstrate that young age and inflammation independently impact microbial community structure. However, the effect is not additive in the youngest patients, likely because of the heterogeneous and dynamic stool microbiome in this population.

P407 Validation of a newly developed patient-reported experience measure for people with Inflammatory Bowel Disease

Abstract Background Patient-Reported Experience Measures (PREMs) assess a patient’s healthcare experiences and are important to improve the quality of healthcare. A PREM specific to inflammatory bowel disease (IBD) was co-produced with service users. This study aimed to validate the PREM. Methods The IBD PREM contains 38-items and comprises three domains: ‘the care team’, ‘what matters to me’, and ‘living with Crohn’s or Colitis’. Scores can be calculated for each domain and summated to give a total score. Validation was completed on data collected from participants who completed the PREM every 3 months alongside the IBD-Control measure of disease activity at a single UK tertiary IBD service. The PREM was assessed for acceptability; reliability (internal consistency and repeatability); known groups validity; criterion validity and responsiveness. Face and content validity were completed before finalisation using ‘Think Aloud’ interviews. Results The dataset used for validation was extracted in September 2023 and contained responses from 287 participants (63% female, 89% White British, median age: 52) comprising 1,699 PREM responses between November 2021 and August 2023. Acceptability was demonstrated with very low rates of missing data (four items with &amp;gt;5% missing) and median submission duration of 4.8 minutes (IQR: 3.6 – 6.6). High Cronbach’s alpha scores (0.85, 0.97, 0.88 and 0.97 for each of the domains and total PREM score respectively) show internal consistency of the measure. However, the particularly high value on one domain and the total score suggest some overlapping items may remain. An intraclass corelation coefficient of 0.88 (95% CI: 0.85 to 0.91) suggests good repeat reliability over a two-week timeframe. Good comprehension of the measure by service users satisfied face and content validity. Known groups validity was supported with lower score on ‘living with Crohn’s or Colitis’ domain the for those with an IBD Control score of less than 13 by 0.38 (95% CI: 0.23 to 0.54), p&amp;lt;0.001). A low to moderate correlation of 0.37 (95% CI: 0.32 to 0.42) was found between the total PREM score and the IBD Control score, as expected. Ceiling and floor effects had a maximum of 6% demonstrating potential responsiveness of the PREM. The change over a year detected by those that stated that had experienced a change was 0.53 (95% CI: 0.41 to 0.66, n=38) on a five-point scale.Conclusion The co-produced PREM is an acceptable, valid, reliable, and responsive tool to measure experience of IBD care for quality improvement. Further work should assess the potential for item reduction as well as correlation to other related measures.

P1056 T cell responses to repeated SARS-CoV-2 vaccination and breakthrough infections in patients with inflammatory bowel disease on TNF inhibitor treatment, a prospective cohort study

Abstract Background Understanding T cell responses to SARS-CoV-2 immunisation in patients on immunosuppressive treatment is important for future vaccine recommendations. Our aim was to investigate the magnitude and quality of T cell responses following repeated SARS-CoV-2 vaccine doses and COVID-19 (breakthrough infections). Methods In this prospective, observational study of responses to SARS-CoV-2 vaccines (Nor-vaC)1, patients with inflammatory bowel disease (IBD) on TNF inhibitor (TNFi) therapy receiving up to four SARS-CoV-2 vaccine doses, and healthy controls receiving three vaccine doses were included. CD4 and CD8 T cell responses to SARS-CoV-2 peptides were measured by flow cytometry before and 2-4 weeks following vaccination and breakthrough infection. Antibodies to the receptor binding domain (RBD) of the Wuhan-Hu-1 and BA.1 (omicron) strains were measured. Results Between March 2, 2021, and December 20, 2022, 118 IBD patients, and 21 healthy controls were included in the study (Table). Following three vaccine doses, the humoral immune response was attenuated in IBD patients compared to healthy controls (median 3954 BAU/ml vs. 6280 BAU/ml, p=0.008). However, both the percentage of spike-specific T cells (CD4 median 0.11% vs. 0.10%, p=0.259, CD8 0.030% vs. 0.046%, p=0,333) and T cell polyfunctionality scores (a measure of quality of vaccine response) (CD4 median 0.403 vs. 0.371, p=0.386, CD8 0.105 vs. 0.101, p=0.871), showed comparable quality in IBD patients and controls following three doses. CD4 T cell responses increased rapidly and plateaued after two vaccine doses whereas CD8 T cell responses continued to improve up to four vaccine doses (Figure). Breakthrough infection in patients following the third or fourth vaccine dose increased CD8 polyfunctionality and generated broad CD4 and CD8 T cell responses against non-spike peptides. There was no difference in T cell responses between patients using TNFi mono- and combo therapy after primary vaccination (three vaccine doses) (p=0.648). Conclusion Despite attenuated antibody responses, IBD patients on TNFi treatment demonstrated T cell responses comparable to healthy controls following three SARS-CoV-2 vaccine doses. Repeated vaccination and breakthrough infection increased the quality and breadth of T cell responses, reaching a plateau. Distinguishing between CD4 and CD8 immune compartments and dynamics of activation after SARS-CoV-2 immunisation may provide nuanced understanding of protective cellular responses The study results indicate that IBD patients on TNFi treatment may in future follow the same recommendations for further SARS-CoV-2 vaccines as the general population. 1Clinialtrials.gov NCT04798625

P071 Neonatal levels of inflammatory markers in individuals who later develop early onset Inflammatory Bowel Disease

Abstract Background The early life period is suggested to be important in development of Inflammatory Bowel Disease (IBD). Studies in babies from mothers with IBD observed increased faecal calprotectin and changes in the microbial compartments compared to babies from healthy mothers1,2, which suggests that changes in early life might be associated with later disease development. Prospective studies of IBD risk following early life changes at the molecular level are sparse. We aimed to investigate if individuals with early onset (EO) IBD had changes in systemic inflammatory markers shortly after birth. Methods We measured the concentration of 9 cytokines in a cohort of 464 neonatal dried blood spot samples stored at the Danish National Biobank from individuals who later developed EO IBD (median age of diagnosis 11 years), as well as matched controls. Individuals who developed IBD were identified through the use of the Danish National Patient Registry. Uni- and multivariate logistic regression with adjustment for birth year, sex, and gestational age was conducted to assess the association between 6 of the inflammatory markers with later disease development (INF-γ, TNF-α, IL-1β, IL-4, IL-6 and IL-17a). Further exploratory analyses were performed investigating risk of very early onset (VEO) IBD (onset from 0-5 years) in 88 cases and their matched controls. Results No significant association with EO IBD was observed for any of the cytokines in uni- and multivariate models when adjusting for multiple testing. In the exploratory analysis of VEO IBD, increased IL-4 was associated with significantly reduced risk of IBD (OR=0.992, p-value=0.023) and increased IL-17a was borderline-significantly associated with increased risk of IBD (OR=1.002, p-value=0.063) in a multivariate logistic model including all 6 cytokines. This association did not remain significant when adjusting for multiple testing, which may reflect limited power. Conclusion In our unique study of 464 dried blood spots from later IBD patients and controls, we could not find an association between measured cytokines and EO IBD. In contrast, patients with VEO IBD had decreased levels of IL-4 and increased levels of IL-17a. This sub-cohort was small, and significance disappeared after adjusting for multiple testing. Still, we find it important to report these findings, as they are novel and may inspire future studies into the aetiology of VEO IBD. 1. Kim, E. S. et al. Longitudinal Changes in Fecal Calprotectin Levels Among Pregnant Women With and Without Inflammatory Bowel Disease and Their Babies. Gastroenterology (2021) 2. Torres, J. et al. Infants born to mothers with IBD present with altered gut microbiome that transfers abnormalities of the adaptive immune system to germ-free mice. Gut (2020)

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&amp;lt;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.

P1145 Assessing disease control in inflammatory bowel disease (IBD) – a real world cross-sectional study in the UK

Abstract Background There is a paucity of data on disease control in patients with inflammatory bowel disease (IBD) in clinical practice. The Proportion Of suboptimal Disease Control And Strategy of Treatment in IBD (PODCAST-IBD) multicentre, non-interventional study aimed to quantify real-world rates of disease control using the STRIDE-II recommendations, explore contributors to, and the economic burden of, suboptimal disease control. Methods Cross sectional assessment of patients with IBD attending routine clinic appointments was carried out in four UK centres between Oct 2022 and Jan 2023. Clinician-reported outcomes, patient-reported outcomes and retrospective data from medical chart review were used to assess IBD control against red flags aligned to the STRIDE-II recommendations (Table). Health care resource utilisation (HCRU) was calculated using NHS reference costs. Results Data was available from 198 patients (Crohn's disease [CD]: 103, ulcerative colitis [UC]: 95) and most were currently receiving long-term IBD-specific treatment (CD: 85%, UC: 78%). IBD was suboptimally controlled in 52.4% (54/103) of patients with CD and 45.3% (49/95) with UC. Impaired quality of life (QOL), defined as Short inflammatory bowel disease questionnaire (SIBDQ) score &amp;lt;50, was the most frequent contributor to suboptimal disease control for both UC and CD. Other frequent contributors were systemic steroid overuse, extraintestinal manifestations (EIM), failure to achieve clinical improvement and perianal disease (Figure). Suboptimal disease control has a detrimental impact on fatigue and disability, demonstrated by lower (indicating more fatigue) mean total FACIT-F score in suboptimally controlled disease (CD: 81.5 vs 125, UC: 87.4 vs 122.8) and IBD Disk, a 10-item self-questionnaire used to assess IBD-related disability. HCRU more than doubled in patients with suboptimal vs optimal control (CD: £4,746 vs £1,924; UC: £2,428 vs £1,121), driven by more hospital admissions and emergency room visits in patients with suboptimal disease control. Patients with suboptimal disease control had higher rates of work productivity loss than those with optimal control (CD: 41.7% vs 11.9%, UC: 38.0% vs 22.6%). Conclusion This UK cross-sectional study found that IBD was suboptimally controlled in around one-half of patients based on STRIDE-II recommendations. Of those with suboptimally controlled disease one-third had impaired QOL making it the most common contributor. Suboptimal control of IBD had a considerable economic impact; HCRU more than doubled and productivity fell. Physicians could consider regular QOL assessments to prompt timely disease monitoring to enable identification of early active disease and ensure appropriate treatment.

P359 Persistence of severe fatigue in adults with Crohn's disease in remission

Abstract Background Fatigue is a frequent manifestation in patients with Inflammatory Bowel Disease (IBD), including those in remission. The persistence of fatigue over time in inactive disease is not well known. We aimed to determine the prevalence and continuation of severe fatigue at baseline and at 12 months follow-up in a cohort of patients with Crohn’s disease (CD) in remission. Methods Adult patients with CD in remission, defined by age ≥18 years, HBI &amp;lt;5 and faecal calprotectin &amp;lt;250mcg/g, were recruited to the INTICO2 observational study. Baseline assessment included SF36, FACIT-F and IBD Control patient-reported outcome measures. After 12 months in routine care, participants were invited to repeat FACIT-F. Severe fatigue was defined as scoring FACIT-F &amp;lt;30. Baseline data was analysed for factors associated with the persistence of severe fatigue at 12 months. Results A total of 198 patients were studied at baseline, of which 141 completed both baseline and 12-month assessments. The correlation between FACIT-F scores at baseline and 12 months was r = 0.79 (p &amp;lt; 0.001). Twenty-five (17.7%) patients were severely fatigued at both baseline and 12-month follow-up, and 99 (72.1%) were not severely fatigued at either time. Of the 34 patients severely fatigued at baseline, 9 (26.5%) were not severely fatigued at 12 months. From the 107 patients who were not severely fatigued at baseline, 12 (7.5%) became severely fatigued at 12 months. Participants with ongoing severe fatigue at baseline and 12 months had significantly worse SF36 Mental Health scores, 64 v 80 (p &amp;lt;0.001), and more night waking due to IBD, 32.0% v 7.1% (p = 0.011), at baseline assessment than those not severely fatigued at either assessment, see Table 1. Eight patients had a clinical disease flare during the 12-month follow-up period. Conclusion Most patients in this cohort in remission continued to have similar fatigue severity at 12-month follow-up. A higher proportion of severely fatigued patients at baseline improved at 12 months than non-severely fatigued patients at baseline developing severe fatigue at 12 months. Factors at baseline associated with persistent severe fatigue were worse mental health and poor sleep secondary to IBD. These may represent areas where intervention could improve reported fatigue levels in remission.

The Role of Dietary Habits in the Pathogenesis and Development of Inflammatory Bowel Disease: A Narrative Review.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated disease. The incidence of IBD is influenced by various genetic and environmental factors, with dietary habits gaining significant scientific interest. While the role of diet in the pathogenesis and development of IBD is still debated, recent studies have demonstrated its potential impact. However, conflicting findings exist regarding the efficacy of dietary interventions in the treatment and control of IBD. This review aimed to summarize the current understanding of the relationship between diet and IBD, highlighting the different perspectives and reasonings observed in recent studies. Overall, it has been shown that dietary habits play a role in the incidence of IBD, and adopting a controlled dietary approach may help manage the disease. Consequently, diet can be considered a predictive and prognostic factor in IBD.

Exploring changes in brain function in IBD patients using SPCCA: a study of simultaneous EEG-fMRI.

Research on functional changes in the brain of inflammatory bowel disease (IBD) patients is emerging around the world, which brings new perspectives to medical research. In this paper, the methods of canonical correlation analysis (CCA), kernel canonical correlation analysis (KCCA), and sparsity preserving canonical correlation analysis (SPCCA) were applied to the fusion of simultaneous EEG-fMRI data from 25 IBD patients and 15 healthy individuals. The CCA, KCCA and SPCCA fusion methods were used for data processing to compare the results obtained by the three methods. The results clearly show that there is a significant difference in the activation intensity between IBD and healthy control (HC), not only in the frontal lobe (p < 0.01) and temporal lobe (p < 0.01) regions, but also in the posterior cingulate gyrus (p < 0.01), gyrus rectus (p < 0.01), and amygdala (p < 0.01) regions, which are usually neglected. The mean difference in the SPCCA activation intensity was 60.1. However, the mean difference in activation intensity was only 36.9 and 49.8 by using CCA and KCCA. In addition, the correlation of the relevant components selected during the SPCCA calculation was high, with correlation components of up to 0.955; alternatively, the correlations obtained from CCA and KCCA calculations were only 0.917 and 0.926, respectively. It can be seen that SPCCA is indeed superior to CCA and KCCA in processing high-dimensional multimodal data. This work reveals the process of analyzing the brain activation state in IBD disease, provides a further perspective for the study of brain function, and opens up a new avenue for studying the SPCCA method and the change in the intensity of brain activation in IBD disease.

Fyzická aktivita detských pacientov s nešpecifickými črevnými zápalovými ochoreniami – výhody a limitácie

Summary: Introduction: Inflammatory bowel diseases (IBDs) are a group of diseases including Crohn’s disease, ulcerative colitis and unclassified IBD. They are chronic, immune-mediated inflammatory diseases of the gastrointestinal tract. Due to their extraintestinal manifestation, they are considered to be systemic diseases. IBD has a negative impact on health-related quality of life. The treatment is life-long and may be accompanied by side effects. Low-intensity activity of moderate duration is sufficient to elicit improvements in fitness, decrease stress, and improve symptoms. In this study, the relationship between physical activity and IBD development and course is described. Aims: To assess the relationship between physical activity and exercise capacity and the severity and course of IBD. Methods: Probands with IBD and healthy controls underwent pulmonary function testing (PFT) and cardiopulmonary exercise testing (CPET). The results were compared between these two groups; in the IBD group, the results were correlated with disease activity parameters as well. In the IBD group, the probands were encouraged to perform regular physical activity. After 0.5–1 year, they underwent another CPET. Their exercise capacity development was objectively assessed and it was correlated with their IBD development. Results: Forty-one children were included in the study. Twenty of them were healthy controls, while 21 comprised the IBD patient group. These probands underwent the PFT and CPET. When comparing healthy controls and IBD patients, significant differences were found in peak oxygen uptake and peak work rate. In the IBD group, a negative correlation was found between peak work rate and C-reactive protein concentration. In faecal calprotectin, a significant correlation was found only in the subgroup with ulcerative colitis – the negative correlation with peak oxygen uptake and partial pressure of CO2 in exhaled air in the peak of the exercise. PCDAI correlated positively with ventilatory index, peak dead space and tidal volume ratio but negatively with peak work rate, work rate at the time of anaerobic threshold, peak oxygen uptake and oxygen uptake efficacy slope. In PUCAI, we found a positive correlation with CO2 ventilatory uptake at the time of anaerobic threshold and negative correlations with peak oxygen uptake and oxygen uptake efficacy slope. In further CPET in the IBD group, a significant decrease was found in faecal calprotectin and PCDAI or PUCAI; there were also positive correlations between PCDAI/PUCAI changes and resting heart rate changes. The negative correlation was found in the correlation with the changes in peak oxygen uptake, metabolic index and ventilatory equivalent for CO2 at the time of anaerobic threshold. Conclusion: These results suggest that regular recreational physical exercise positively impacts IBD. When adhering to treatment recommendations, doing sport professionally is also possible. Key words: inflammatory bowel diseases – physical activity

People with IBD evidence more microarousals during sleep architecture assessments

ObjectivePoor sleep is common in inflammatory bowel disease (IBD) and may be associated with overall worse disease outcomes. While the sleep/IBD literature is growing, the data are often self-reported. Further,...

Evaluation of Bacterial and Fungal Biomarkers for Differentiation and Prognosis of Patients with Inflammatory Bowel Disease.

This study aimed to evaluate bacterial and fungal biomarkers to differentiate patients with inflammatory bowel disease (IBD), predict the IBD prognosis, and determine the relationship of these biomarkers with IBD pathogenesis. The composition and function of bacteria and fungi in stool from 100 IBD patients and 97 controls were profiled using next-generation sequencing. We evaluated the cumulative risk of relapse according to bacterial and fungal enterotypes. The microbiome and mycobiome alpha diversity in IBD patients were significantly lower and higher than in the controls, respectively; the micro/mycobiome beta diversity differed significantly between IBD patients and the controls. Ruminococcus gnavus, Cyberlindnera jadinii, and Candida tropicalis increased in IBD patients. Combining functional and species analyses revealed that lower sugar import and higher modified polysaccharide production were associated with IBD pathogenesis. Tricarboxylic acid cycling consuming acetyl CoA was higher in IBD patients than the controls, leading to lower short-chain fatty acid (SCFA) fermentation. Bacterial and fungal enterotypes were not associated with IBD relapse. We found differences in bacterial and fungal species between IBD patients and controls. A working model for the role of gut bacteria in IBD pathogenesis is proposed, wherein bacterial species increase modified N-glycan production and decrease SCFA fermentation.

The Anti-Inflammatory Effects of Adipose Tissue Mesenchymal Stem Cell Exosomes in a Mouse Model of Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a group of chronic, relapsing inflammatory disorders that affect the gastrointestinal tract, with the primary subtypes being ulcerative colitis (UC) and Crohn’s disease (CD). We aimed to evaluate the therapeutic potential of extracellular vesicles released by adipose-tissue-derived mesenchymal stem cells, which we, in this manuscript, call “exosomes” (ASC-EXOs), in a mouse model of IBD. We specifically aimed to determine the effectiveness of different treatment protocols and compare the effects with that of anti-IL-12 p40 monoclonal antibody. The addition of dextran sulfate sodium (DSS) to drinking water induced multiple signs of IBD, including weight loss, soft stool, and bloody feces. ASC-EXOs given by either intraperitoneal (IP) or intravenous (IV) routes resulted in moderate improvement in these signs of IBD. IV ASC-EXOs resulted in significantly reduced body weight loss, improved histopathological scoring, and suppressed the disease activity index (DAI) compared to the IBD control group. Also, a reduction in PCR for pro-inflammatory cytokines was observed. IV ASC treatment resulted in dose-related reduction in IBD signs, including weight loss. An increasing number of injections with ASC-EXOs reduced histopathological scores as well as DAI. Co-administration of ASC-EXOs with anti-IL-12 p40 significantly decreased DAI scores in the ASC-EXO + anti-IL-12 p40 group. In conclusion, ASC-EXOs have potential as a therapeutic agent for IBD, but the route of administration, number of injections, and dosage need to be considered to optimize the effects of ASC-EXO treatment. This study also highlights the potential benefits of combination therapies of ASC-EXOs and anti-IL-12. Our findings pave the way for further studies to unravel the underlying therapeutic mechanisms of ASC-EXOs in IBD treatment.