bluuebunny/crossref_metadata_2025 huggingface dataset:
P1116 Risk of fractures in children and adults with inflammatory bowel disease: A report from the epi-IIRN
Authors: Orlanski Meyer E , Buchuk R , Ben Tov A , Ledderman N , Loewenberg Weisband Y , Matz E , Dotan I , Turner D , Assa A
Published: January 2024

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.
P1120 New-onset Inflammatory Bowel Disease is uncommon in patients with psoriasis, psoriatic arthritis and spondylarthritis treated with secukinumab: a retrospective cohort study in a tertiary centre
Authors: Masic N , Anjie S I , Sungur R , D'Haens G R A M , van de Sande M G H , van der Laken C J , de Boer N K
Published: January 2024

Background

Secukinumab (SEC) is an IL-17A inhibitor prescribed in patients with immune mediated inflammatory diseases like psoriasis (PsO), psoriatic arthritis (PsA) and spondylarthritis (SpA). Conflicting data are available on the onset of inflammatory bowel disease (IBD) among patients after the start of SEC. We aimed to provide data evaluating pre-existing and newly diagnosed IBD in patients being treated with SEC.

Methods

All patients receiving SEC at a single tertiary centre in The Netherlands between 2012-2022 were identified through the pharmacy registry. Data from electronic medical records were retrospectively collected: baseline (i.e. at initiation of SEC) characteristics, medical history (including pre-existing IBD), use of (disease modifying) concurrent medication, clinical symptoms, biochemistry (C-reactive protein, faecal calprotectin), endoscopy with pathology and cross-sectional imaging (CT, MRI, intestinal ultrasound). Patients were excluded if they received ≤3 doses of SEC.

Results

A total of 351 patients were included with one or more of the following indications for SEC treatment: PsO in 166/351 (47%), PsA in 130/351 (37%), axial SpA in 130/351 (37%), peripheral SpA in 31/351 (9%) and juvenile idiopathic arthritis in 1/351 (0.3%). Frequently used co-medication were NSAIDs (44%), topical corticosteroids (37%) and methotrexate (16%). Median follow-up time was 48 months (IQR 22,74). In total, ten patients with IBD were identified: 5/351 (1.4%) patients had pre-existing IBD (2/5 Crohn’s disease, 3/5 ulcerative colitis) and 5/351 (1.4%) patients developed IBD after SEC initiation (3/5 Crohn’s disease, 1/5 ulcerative colitis, 1/5 IBD-unclassified) (Table 1). All new-onset IBD cases were confirmed with endoscopy and pathology. Predominant clinical symptoms were diarrhoea, abdominal pain and haematochezia. In patients with new-onset IBD median time from initiation of SEC to development of clinical symptoms was 1.3 months (range 0-12) and median time to diagnosis was 7.5 months (range 3-16). Out of patients with pre-existing IBD in remission 2/5 developed clinical symptoms after start of SEC with a median time to development of 9 months (range 6-12); 3/5 patients sustained remission. After starting SEC 25% of patients reported gastrointestinal symptoms, however diagnostic work-up took place in only 52% of these patients revealing no signs of IBD.

Conclusion

In our cohort new-onset IBD after SEC initiation was uncommon (<2%) with a short median time to onset. IBD seemed equally distributed among indications. Caution and monitoring of gastrointestinal symptoms during SEC treatment is warranted in patients with pre-existing IBD, considering the possibility of an exacerbation.
P1133 Relative survival and cause-specific mortality of a Chilean Inflammatory Bowel Disease cohort
Authors: Hernandez-Rocha C , Chahuan J , Uslar T , Salas R , Sepúlveda I , Pavez C , Perez T , Cofre C , De la Cruz R , Quintana C , Álvarez-Lobos M
Published: January 2024

Background

In the past two decades, multiple studies have shown an improvement in outcomes of inflammatory bowel disease (IBD) patients including a decreasing mortality associated with new treatments, surveillance, and healthcare support. There are no large studies in Latin-American countries addressing survival and death causes in IBD patients. We aimed to assess relative survival (RS) and causes of death in Chilean IBD patients.

Methods

IBD patients treated in a tertiary reference centre (Pontificia Universidad Católica of Chile, Santiago, Chile) since January 1990 were included in a local database. Death certificates were analysed to obtain the date and specific cause of death. The recorded time started on the date of definitive diagnosis and lasted until death or censoring on December 31st, 2020. The survival of IBD patients was compared with the life expectancy of the Chilean general population based on official life tables collected in the Human Mortality Database (www.mortality.org). The RS was computed using the Ederer II method implemented in the RELSURV package of the R software. A RS greater than 1.0 indicates that the analysed cohort has a higher survival than the expected survival of the reference population for the same age, sex and date at which age was coded. Inclusion of 1.0 within 95% CI indicates no difference between observed and expected survival. Data were also expressed graphically as the observed cumulative survival curves over time and the 95% confidence interval (CI) and compared to the reference population.

Results

We included 1,289 IBD patients with a media age at diagnosis of 35.9±14 years, 40.9% males and a follow-up of 22,525 patients-year. Ulcerative Colitis, Crohn’s disease and IBD unclassified patients comprised 50.2%, 43.1% and 6.7% of the cohort, respectively. A total of 106 patients (8.9%) died during the study period. Compared with the general population, the survival of IBD patients was higher (RS = 1.04; 95% CI: 1.02-1.07) at 20 years of follow-up (Table and Figure). This higher RS in IBD patients was observed in males and females, as well as CD patients and IBD patients older than 40-year-old (Table). The main causes of death in IBD patients were cancer (34%), infections (27.7%) and cardiovascular diseases (21.3%).

Conclusion

Compared to the general population, a higher long-term survival was observed in this large cohort of Chilean IBD patients. These findings may be due to a closer surveillance of this group of patients. Causes of death mirrored those in previously reported cohorts; therefore, a special care should be pay on their prevention in Latin-American countries as well.
P1142 Antibiotic use in the twelve months prior to ileal pouch-anal anastomosis increases the risk for pouchitis: A population-based Danish cohort study
Authors: Barnes E , Karachalia Sandri A , Herfarth H , Jess T
Published: January 2024

Background

Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), however clinical and environmental risk factors for pouchitis remain poorly understood. We explored the relationship between specific clinical factors and the incidence of pouchitis.

Methods

We established a population-based cohort of all adult persons in Denmark undergoing proctocolectomy with IPAA for UC between January 1, 1996 and May 31, 2020. We used Cox Proportional Hazard modeling and logistic regression to assess the impact of antibiotic and non-steroidal anti-inflammatory drug (NSAID) exposure and appendectomy on the primary outcome of diagnosis of acute pouchitis in the first 2 years after IPAA surgery. A 2-year time window was utilized given the clinical relevance of early pouchitis and to mirror prior studies in both administrative claims and the Danish health registers.

Results

Among 1,616 eligible patients, 738 (46%) developed pouchitis in the first 2 years after IPAA. Among all patients undergoing IPAA surgery for UC, 51% were prescribed antibiotics in the 12 months prior to the index date and 17% were prescribed NSAIDs in the 12 months prior to the index date. In Kaplan-Meier analyses, those persons who were prescribed antibiotics in the 12 months prior to the final stage of IPAA surgery were significantly more likely to develop pouchitis in the 2 years after the index date when compared to patients who were not prescribed antibiotics (p<0.001, Figure 1B). Additionally, male patients demonstrated a decreased risk for pouchitis in the first 2 years after the index date when compared to female patients (p=0.014, Figure 1A). Antibiotic exposure in the 12 months prior to IPAA was associated with an increased risk of pouchitis (adjusted Hazard Ratio [aHR] 1.40, 95% CI 1.21-1.62) after adjusting for year of surgery and sex (Table 1). In a secondary analysis, compared to persons without any antibiotic prescriptions in the 12 months prior to IPAA, the risk of pouchitis was increased in those with 1 or 2 courses of antibiotics in that period (aHR 1.29, 95% CI 1.10-1.51) and 3 or more courses (aHR 1.79, 95% CI 1.43-2.23, Figure 1C). NSAID exposure in the 12 months prior to IPAA and appendectomy were not associated with risk of acute pouchitis (p=0.201 and p=0.865 respectively).

Conclusion

In this population-based cohort study, we demonstrated that antibiotic exposure in the 12 months prior to IPAA is associated with an increased risk of acute pouchitis. Future prospective studies may isolate specific microbial changes in at-risk patients to drive earlier interventions.
P1146 Familial Coaggregation of Inflammatory Bowel Disease with Cardiovascular Disease: a Nationwide Multigenerational Cohort Study
Authors: Sun J , Yao J , Ludvigsson J
Published: January 2024

Background

Genetics contribute to the development of both inflammatory bowel disease (IBD) and cardiovascular disease (CVD). Although an increased risk of CVD has been documented in IBD patients, little is known about the risk of CVD in family members of patients with IBD.

Methods

In this Swedish nationwide multigenerational cohort, we identified patients with biopsy-confirmed IBD (≥18 years) who had at least one family member living in Sweden at their date of diagnosis from 1969 through 2017. Each patient was matched with up to five IBD-free reference individuals from the general population. We then identified 205,642 first-degree relatives (FDRs: father, mother, full-siblings, offspring) and 44,790 spouses of IBD patients as well as 1,015,010 FDRs and 222,969 spouses of their reference individuals. These family members were followed from the later date of turning 18 years or their linked IBD patients/reference individuals being diagnosed/matched (i.e., index date), until the interested CVD outcome, heart transplant, emigration, death, or 31/12/2020, whichever came first. The primary outcome was any incident CVD and CVD mortality. Secondary outcomes included incident ischemic heart disease, heart failure, cerebrovascular disease, deep vein thromboembolism, pulmonary embolism, and atrial fibrillation/flutter. Flexible parametric survival models estimated the adjusted hazard ratio (aHR) with 95% confidence interval (CI).

Results

FDRs of IBD patients were at higher risks of incident CVD (aHR=1.04, 95%CI: 1.03 to 1.05) and CVD mortality (aHR=1.03 [1.00 to 1.06]) than FDRs of reference individuals (Figure 1). The increased risks were significant for almost all secondary outcomes, with point estimates hovering around a two to eight percent increased risk. Similar patterns were observed by IBD subtypes, sex, age and calendar period at index date, and family relationship of FDRs. In contrast, spouses demonstrated no increased risks of incident CVD or CVD mortality.

Conclusion

Relative risks of incident CVD and CVD mortality were only slightly increased in FDRs of patients with IBD, but not at all in spouses, suggesting no need for extra vigilance for CVD among family members of IBD patients.
P1153 Hospital surgical volumes and outcomes in ileocaecal resection for Crohn’s disease in Sweden 2000-2019: A national cohort study
Authors: Soop M , Zuk D , Bryder M , Myrelid P , Thorell A , Ludvigsson J F , Olén O , Nordenvall C
Published: January 2024

Background

Intestinal resection for Crohn’s disease (CD) is often complex and remains associated with significant postoperative morbidity. In several other types of complex surgery, increased case volumes have been associated with better outcomes. In surgery for CD, such an association has not yet been demonstrated.

Methods

In this nationwide cohort study, we used the National Patient Register to identify all CD patients who underwent their first (primary) ileocaecal resection in Sweden 2000-2019 at age 15 years or above. Hospitals were grouped into low, middle, and high-volume centres based on the number of intestinal resections for CD the previous calendar year (1-24, 25-36 and ≥37 resections, respectively). Length of hospital stay, severe postoperative complications and deaths during the first 100 days after the date of index surgical admission were compared between groups, and adjusted for sex, age, duration of disease, preoperative corticosteroid therapy, and year of surgery. Rates of surgical reintervention were used as a measure of severe postoperative morbidity.

Results

In the 20-year study period, 3396 patients underwent primary ileocaecal resection for CD in Sweden; 2371 (69.8%), 527 (15.5%) and 498 (14.7%) in low, middle, and high-volume hospitals, respectively. Median age at surgery was 41, 39 and 34 years, respectively, and the proportion of patients with a diagnostic record of perianal disease was 9, 10 and 16%. Sex, extraintestinal manifestations and preoperative medical therapies and hospital admissions did not differ between hospital types. Laparoscopic surgery was performed in 351 (15%), 126 (24%) and 122 (24%) patients, respectively. Surgical reintervention within 100 days was performed in 117 (4.9%), 19 (3.6%) and 13 (2.6%) patients in the three groups (adjusted odds ratios 0.72 (95% confidence interval 0.43-1.15) for middle-volume and 0.52 (0.28-0.89) for high-volume hospitals, compared to low-volume hospitals, Figure). There were no differences in the length of index admission hospital stay or mortality.

Conclusion

In primary ileocaecal resection for CD, high-volume hospitals had lower odds of early surgical reintervention, compared to low-volume hospitals. This finding may inform considerations of subspecialisation and centralisation in surgery for Crohn’s disease.
P1162 Upadacitinib in Crohn’s Disease Patients: for what type of patients in real world setting ?
Authors: Juillerat P , Martinho-Grueber M , Ruetsch R , Moubayed H , Vullièmoz- M , Michetti. P
Published: January 2024

Background

The oral selective JAK kinase inhibitor, Upadacitinib (UPA; Rinvoq®) has been shown to induce and maintain clinical response and remission in Crohn’s disease (CD), but also in rheumatic and skin diseases. We report here on the largest Swiss experience in "off label" use of this drug.

Methods

A chart review of the Crohn’s and Colitis Center Beaulieu Lausanne and Gastroenterology Center Bulle of CD patients was conducted.

Results

Eighty-nine IBD patients were exposed to UPA treatment. After exclusion of 22 patients (UC and unknown consent status) we analyzed patients’ characteristics of 67 CD patients (72% women) treated between April 2019 and Nov. 2023. All patients had previously failed or were intolerant to, at least, one anti-TNF agent, 75% had been exposed to 4 or more biologics/ small molecules and two-third had received all classes of biologics. Disease location and behavior were mostly ileo-colonic and inflammatory (L3B1) or ileal only and stricturing (L1B2). Half of the patients had co-existing extraintestinal manifestations (mostly spondylarthritis and arthralgias). Advanced combination therapy was used in 27% of cases with anti-TNF agents (n=10), vedolizumab (n=6) and ustekinumab (n=2). UPA was prescribed after a median disease duration of 14 years (range 1-68) for a mean treatment duration of 14 months (mo) (+/- 9.1 SD; range 1-37). Forty-four CD patients (66%) were still on UPA at the time of study completion. A partial or complete response was observed in 51/67 patients (76%) with a mean decrease of CRP of 10.4 mg/l (+/- 17.6 SD) and calprotectin of 610 mcg/g (+/- 1165 SD). Adverse events were mostly viral infections, acnea, hypercholesterolemia, fatigue and headaches.

Conclusion

Upadacitinib is a good treatment option in difficult to treat CD patients with aggressive disease behavior, alone or in combination in case of concomitant rheumatic and gastrointestinal indications.
P1166 Thiopurines and Risk of Cancer in Patients with Inflammatory Bowel Disease -A Danish Nationwide Cohort study 1996-2018
Authors: Wewer M D , Letnar G , Andersen K K , Malham M , Wewer V , Seidelin J B , Bendtsen F , Burisch J
Published: January 2024

Background

Thiopurines are frequently used in patients with inflammatory bowel disease (IBD). The aim of this study was to assess the cancer risk of thiopurine monotherapy and thiopurine in combination with biologics compared to unexposed IBD patients.

Methods

Incident Danish IBD patients from 1996 to 2018 were identified in the national registers. Time at risk started at the date of IBD diagnosis and exposure status was time-dependent. Exposure was defined as registration of thiopurine and/or biologics. A lag period of 6 months was introduced at the first thiopurine registration as it was unlikely to have caused an effect on any immediate cancer case. If no new registration of thiopurines occurred 6 months from the last registration, the patient was assigned to the discontinued group. Non-melanoma skin cancer was analysed separately to avoid masking severe cancer forms and excluded from the overall cancer analyses. Cox regressions were performed to assess the risk of first cancer and risk estimates were presented as hazard ratios (HR) with 95% confidence intervals (CI). Only the incidence bar plot included non-IBD controls, matched on age, sex and municipality. Controls were unexposed to thiopurines.

Results

In total, 43,404 IBD patients were followed for a median of 8.2 years (IQR:3.7-14.2) from diagnosis. During follow-up, 7,736 Crohn’s disease (CD) (50.6%) and 6,632 ulcerative colitis (UC) patients (23.6%) were exposed to thiopurines. Cancer occurred in 1,292 (8.4%) CD and 1,840 (6.5%) UC patients. Both monotherapy and combination therapy were associated with developing any cancer (HR: 1.61 (95%CI:1.42-1.84) and (HR: 3.15 (95%CI:2.10-4.73), respectively) compared to unexposed IBD patients. In the elderly (>65 years), this was particularly apparent (Figure 1). The association between cancer and thiopurines was observed in non-melanoma skin-, melanoma-, urinary tract-, female genital organ-, lymphoid tissue-, colorectal- and digestive organ cancers. In patients who discontinued thiopurines, the HR returned to the level of unexposed HR: 1.01 (95%CI:0.91-1.13). The association with different cancer forms were higher in patients with >4 years and 1-4 years of thiopurine exposure, HR 1.58 (95%CI:1.37-1.82) and HR 1.24 (95%CI:1.07-1.44), compared to unexposed.

Conclusion

Thiopurines were associated with an increased risk of cancer in both mono- and combination therapy, especially in the elderly. This was noticeable in patients with 1-4 and >4 years of exposure, with 24% and 58% increased risk compared to unexposed. Reassuringly, discontinuation of thiopurines returned the risk to baseline and the absolute number of cancers was low. This warrants closer monitoring of all IBD patients, especially the elderly in combination therapy.
P1173 Higher total antioxidant capacity of diet is associated with reduced surgery risk in individuals with Inflammatory Bowel Disease in a prospective cohort study
Authors: Dan L , Wang S , Chen X , Fu T , Chen J , Wang X
Published: January 2024

Background

Oxidative stress exacerbates inflammatory Bowel Disease (IBD), and dietary antioxidants are proposed as a promising manner to counteract this imbalance. However, the role of individual antioxidants in the complex milieu of the human body may exhibit synergistic or interactive effects. The research has yet to comprehensively examine the impact of dietary total antioxidant capacity (TAC) on IBD prognosis. To fill this knowledge gap, this study aimed to investigate the assocaitions between dietary TAC and risk of related surgery among individuals with IBD in a prospectively recruited cohort.

Methods

We included 2439 individuals with IBD at baseline from UK Biobank. All participants have completed a web-based validated 24-h dietary recall up to five rounds in 2009-2012, reporting their consumption of more than 200 foods and beverages. We calculated the TAC of the diet using the oxygen radical absorbance capacity method and were grouped by quintiles. The outcomes of interest were IBD-related surgery (bowel resection, perianal-related surgery, Strictureplasty, and ileoanal pouch formation), ascertained via linkage to national inpatient data. Cox proportional hazard models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

During a mean follow-up of 10.4 years, we identified 261 incident surgical cases related to IBD. The mean age of the participants was 56.9 years, and 51% were females. When comparing extreme quintiles of dietary TAC, individuals with higher dietary TAC were associated with a lower risk of related surgery (HR 0.57, 95% CI 0.38-0.86, P=0.007). The inverse associations between dietary TAC and related surgery were consistent among individuals with ulcerative colitis (HR comparing extreme quintiles 0.59, 95% CI 0.36-0.96, P=0.036). For individuals with Crohn’s disease, the associations were not significant when comparing extreme quintiles of dietary TAC (HR 0.51, 95% CI 0.25-1.03, P=0.060), while we observed a significant 9% risk reduction (HR 0.81, 95% CI 0.65-1.00, P=0.048) of related surgery by per 1-SD increment in dietary TAC among individuals with Crohn’s disease.(Table 1)

Conclusion

In this large large-scale population-based cohort study, we observed that higher dietary TAC was associated with reduced risk of related surgery in individuals with IBD. Our findings provide insights that could inform dietary recommendations and potentially improve IBD management strategies.
P1176 The Influence of positive family history on the phenotype and clinical course of inflammatory bowel disease: A Systematic review and meta-Analysis
Authors: Kim Y , Oh D J , Han S J , Park J J
Published: January 2024

Background

The phenotypes and clinical course of familial and sporadic inflammatory bowel disease (IBD) are not yet well-established. We sought to perform a systematic review and meta-analysis to assess the pooled influences of positive family history on disease characteristics and clinical outcomes in IBD.

Methods

We searched MEDLINE, EMBASE, and the COCHRANE library to identify full text articles analyzing disease phenotypes and clinical courses in IBD based on the presence or absence of a family history of IBD. A meta-analysis was performed using a random-effects model to pool estimates and report odds ratios [ORs].

Results

A total of 14 studies were identified as eligible for the meta-analysis. A positive family history (of any degree) of IBD was associated with a lower prevalence of extensive colitis in ulcerative colitis (OR 0.83, 95% confidence interval [CI] 0.72-0.94) but was not associated with most phenotype features including male gender (OR 0.89, 95% CI 0.74-1.07), small intestine involvement (OR 1.11, 95% CI 0.81-1.52), and stricturing or penetrating disease behavior (OR 0.99, 95% CI 0.76-1.29) in Crohn's disease, extraintestinal manifestations (OR 1.26, 95% CI 0.89-1.78), or perianal fistula (OR 1.02, 95% CI 0.84-1.23). Additionally, various clinical outcomes of IBD including IBD-related hospitalization (OR 1.52, 95% CI 0.93-2.47), corticosteroid use (OR 0.91, 95% CI 0.58-1.44), immunomodulator use (OR 1.07, 95% CI 0.98-1.17), biologics use (OR 1.13, 95% CI 0.91-1.42), and intestinal resection surgery (OR 1.01, 95% CI 0.83-1.23) were not associated with family history. In the subgroup analysis of studies analyzing first-degree family history alone, family history was also not associated with small intestine involvement, stricturing or penetrating behavior, perianal fistula, corticosteroid use, immunomodulator use, biologics use, or intestinal resection surgery.

Conclusion

Familial cases with IBD exhibited a lower prevalence of extensive colitis compared to sporadic cases, but the overall disease phenotype and clinical course were similar in both types of IBD.
P1177 Perceptions of patients with Inflammatory Bowel Disease and first degree relatives on prediction and prevention of disease
Authors: Bravo A , Christensen S G , Julsgaard M , Lago I R , Ginard D , Sørensen H G , Fiorino G , Buisson A , Stemmer N , Queiroz N , Ribas A , Izquierdo V P , Siegel C , Croitoiru K , Spencer E A , Peter I , Colombel J F , Agrawal M , Ungaro R , Fidalgo C , Morão B , Torres J
Published: January 2024

Background

Significant advances have been made in understanding the preclinical stages of IBD, and in identifying risk factors and biomarkers to predict IBD onset. With the use of predictive testing to identify patients at risk of developing the disease, it would be possible to intervene and try to mitigate that risk. However, the feasibility of such strategy, would depend on whether individuals at risk of developing IBD would be willing to undergo predictive testing and preventive interventions.

Methods

A Redcap® electronic survey, available in five languages, was disseminated by clinicians and patient’s associations to patients with IBD, first-degree relatives (FDRs) of those with IBD, parents with IBD and healthy children at risk (based on family history), and healthy couples with multiple children including one with IBD. Participants were asked to express their concerns regarding their own or offspring’s risk of developing IBD and acceptable predictive testing and preventive interventions.

Results

817 individuals (75% women, mean age of 41±12 years) living in 28 different countries participated. The majority were parents with IBD of healthy at-risk children (59%). Among individuals with IBD, 50% had Crohn's disease, 55% were on biologic treatment, 25% had undergone surgery, and 62% reported a significant impact on their quality of life. Overall 85% expressed willingness for predictive testing, favoring minimally-invasive methods. Half of participants would agree to cross-sectional imaging and 38% would accept a colonoscopy. The main benefits recognized with predictive testing were the possibility of starting preventive interventions to minimize the risk of developing IBD (74%) and obtaining an earlier diagnosis (63%). Anxiety from a positive result was a concern (57%). A total of 98% would accept preventive interventions. The most accepted were quitting smoking (64%), physical exercise (81%), dietary modification/supplementation (86%/71%) and probiotics (79%); with the optimal duration of the intervention to last up to one year (33%). Participants deemed a risk of minor adverse events up to 10% acceptable, with 33% tolerating a higher risk if disease risk was reduced by 75%. Half agreed that costs should be supported entirely or shared (39%) with the government.

Conclusion

In this international survey of patients with IBD or parents of children at-risk of developing IBD, minimally-invasive predictive testing would be well accepted as well as non-pharmacological and highly effective preventive interventions.
P1202 Genome wide association study result for inflammatory bowel disease: A single institute experience in Taiwan
Authors: Huang P J , Sun T H , Hsu K C , Wang C P , Wu Y H , Chou J W , Cheng K S
Published: January 2024

Background

Inflammatory bowel disease (IBD) have two major subtype disease, including Crohn’s disease(CD) and Ulcerative colitis(UC). These two diseases of IBD in which abnormal reactions of the immune system induced inflammation and ulcers in any part of gastrointestinal tract from oral cavity to rectum, especially in colon and small intestine. Now, IBD still not have an identifiable cause and many articles that discussion about risk loci of IBD was published in recent years. Hence, we try to identify the risky locus related with IBD.

Methods

From January 1992 to December 2023, we retrospectively reviewed the medical records of patients diagnosed as inflammatory bowel disease at our hospital. We also use Phecode Map with ICD9 codes for finding out more pateints. Then, we used the our hospital’s genetic data warehouse to assay these patient’s genome for identifying the specific loci associated with inflammatory bowel disease.

Results

A total of 286 patients with inflammatory bowel disease from January 1992 to December 2023 was in medical record. The number of Crohn's disease and ulcerative colitis were 102 and 184 respectively. However, only 85 patient with CD and 145 patient with UC were in our hospital’s genetic data warehouse. In addition, we seek cooperation with our hospital’s artificial Intelligence Center for using Phecode Map with ICD9 codes for finding out more patients. Finally, 660 case was in genetic data warehouse.The our result of Genome-wide association study (GWAS) for inflammatory bowel disease that identified 15 potential SNPs, such as RTN4, EML6, CLHC1, MYO10, EFEMP1, ADCY2, TPD52 etc.. Two of 15 potential SNPs, NPAS3, DSCAM has been found to be a risky SNPs of IBD in past study and our result of GWAS for IBD. Another 13 SNPs was potential association with IBD in our result, but not well-known risky gene in past research. Only one genetic locus: CRY2 had statistically significant difference and vaule of -log10(p) is more than 6. But, no similar thesis was reported after we review other published papers about loci associated with inflammatory bowel disease. The relationship between CRY2 and inflammatory bowel disease is still pending investigation.

Conclusion

Although, around 200 genomic loci was considered to be associated with inflammatory bowel disease. But, the precise mechanism by which these loci contribute to IBD were still being investigated. However, more genetic loci associated with IBD was identified can lead us to approach the understanding of the underlying biology of the disease.
P1212 Effects of Enterococcus faecalis-derived Gelatinase E on HCT116 colorectal cancer cells
Authors: Henstra C , Fadavizad K , Van Praagh J , Olinga P , Nagelkerke A
Published: January 2024

Background

The leading cause of death in colorectal cancer (CRC) patients is metastasis to crucial organs, such as the lung, brain and liver. The tumour microenvironment (TME) influences metastasis heavily. One important component in the TME of CRC is the microbiota. Microbiota can affect several pathways related to the origin of metastasis and reorganization of the extracellular matrix. One of the possible contributors to early CRC metastasis is Enterococcus faecalis. E. faecalis produces Gelatinase E (GelE), a quorum-sensing protein with collagenolytic properties. The primary goal of our study was to determine the effect of GelE on CRC behaviour, and especially on migration and invasion in HCT-116 human CRC cells. Moreover, we aimed to uncover the underlying pathways by which GelE influences CRC cells.

Methods

Extracellular GelE was purified from E. faecalis strain V583 from the culture medium. HCT-116 cells were cultured and exposed to different concentrations of GelE. We performed a viability assay using CCK-8 to assess potential toxicity of GelE. To test effects of GelE on collagen structure, we measured stiffness of collagen-I. A transwell assay was used to assess the influence of GelE on invasive capacity of cells through a collagen-I matrix. GelE exposed cells were assessed for shape and motility markers using immunofluorescent staining for β-catenin (cell shape) and loss of E-cadherin (cell motility marker). For mechanistic insight of GelE exposure on HCT116, we performed proteomics analysis on the cells.

Results

GelE treatment did not affect relative cell viability of HCT116 cells up to a concentration of 100 μg/ml. Exposure to GelE caused a concentration-dependent increase in HCT-116 cell invasion through collagen-I. The immunostainings showed a downregulation of E-cadherin, indicating an induction of cell motility. Immunostaining for β-catenin showed a statistically significant effect on cell shape, becoming more elongated, an additional indication of cell motility. Proteomics showed possible mechanistic pathways that explain the increased motility including activation of the SMAD pathway, RhoGTPAse activation and activation the urokinase-plasminogen system. Reactome database analysis on the proteomics data also revealed an increase in cell-cycle related pathways.

Conclusion

Our results indicate that E. faecalis-derived GelE drives HCT-116 invasion with an elongated motility. Therefore, drugs inhibiting the activity of GelE could decrease the risk of metastasis in patients with a high E. faecalis V583 abundance in the TME.
P1216 Oral Health status in Inflammatory Bowel Disease patients
Authors: Rodrigues C , Gomes A , Mendes K , Correia M J , Rosa N , Pereira P , Lopes P C , Martins R , Veiga N , Soares C , Ministro P
Published: January 2024

Background

Inflammatory bowel diseases (IBD) affect de gastrointestinal tract primarily as it occurs in oral Crohn´s disease (CD) or as an extraintestinal manifestation (EIM) as aphthous stomatitis either in CD or ulcerative colitis (UC). Moreover, data suggest that IBD patients have a higher prevalence of caries and periodontal disease. The aim of our study was the characterization of oral heath in a cohort of IBD patients compared with a control group without IBD and determine the need of oral health intervention in IBD population.

Methods

This was a collaborative transversal cohort study between an IBD medical appointment in a tertiary hospital and a faculty of dental medicine. Patients from IBD appointment were invited to participate and gave their informed consent. The only exclusion criteria were the incapacity to open the mouth or give a written informed consent. Data was collected regarding demographics, disease characterization, activity, previous IBD related surgeries and current and previous IBD treatments. The control group were heathy controls matched by age and sex. Oral health assessment was achieved by an intraoral clinical examination with the aid of artificial light, oral mirror and WHO periodontal probe. Periodontal diagnosis was achieved through an online periodontal chart (https://www.periodontalchart-online.com), and classified according to periodontal health, periodontitis (stage and grade) and gingivitis. Oral examination provided the Decayed, Missing due to caries, and Filled Teeth Score (DMFT Score) and need for dental treatment and/or prosthetic rehabilitation.

Results

Oral health status of IBD patients confirm the high incidence of PD, with a prevalence of 55.3% and 69.4% for CD and UC patients, respectively. It is important to refer most of the patients diagnosed with PD suffer from the most severe stage of the disease (III and IV), which is not observed for the control group. Poor oral health status is also evident due to the need for dental treatment, since 88.1% of IBD patients need dental treatment and 38.1% need prosthetic rehabilitation (table 1).

Conclusion

IBD affects mainly the digestive system, however there is growing evidence that it also has implications for oral health, namely in periodontitis development, as shown in this study. Thus, good oral hygiene practices, including regular dental check-ups and personalized protocol of periodontal therapy are essential for these patients. Moreover, the collaboration between gastroenterologists and dental professionals is crucial to providing comprehensive care for patients with IBD, addressing both their gastrointestinal and oral health needs.
P1217 The gut microbiota as a determinant in the development of post-surgical recurrence in Crohn`s disease
Authors: Ortiz Sánchez A , Martinez Tirado M P , Rodriguez Nogales A , Moron Romero R , Rodriguez Cabezas M E , Martin Rodriguez M D M
Published: January 2024

Background

Crohn's disease (CD), is a chronic condition with a growing incidence in recent decades. Despite the development of new biologic therapies it is estimated that up to 70% of CD patients will require surgical intervention during their lifetime. However, surgery is not considered curative even in cases where a resection of all macroscopic involvement is performed, and the management of post-surgical recurrence remains a therapeutic challenge.

Bacterial dysbiosis has been postulated as a precipitating factor in CD and may play a significant role in the development of post-surgical recurrence (PSR) of this condition.

We prospectively studied the characteristics of bacterial diversity in patients with CD following ileocecal resection to identify the predictive value of intestinal microbiota in the onset of PSR.

Methods

We collected fecal and healthy and affected intestinal mucosal samples from 12 patients with CD who underwent surgery during the course of their disease. PSR was defined using a Rutgeerts index ≥i2b. The microbiota was assessed using 16S rRNA sequencing, and a correlation analysis was conducted between the intestinal microbiota and clinical variables of the patients.

The study was conducted in accordance with the Helsinki Declaration, and all patients were recruited from among those undergoing scheduled colonoscopy for clinical indications at the Gastroenterology Unit of the University Clinical Hospital San Cecilio in Granada, Spain.

Results

In patients with CD and severe recurrence, mucosa-associated microbiota was characterized by a significant reduction in alpha and beta diversity compared to subjects in clinical remission.

An enrichment of bacteria belonging to the phyla Bacillota and Pseudomonadota was observed, along with a reduction in Bacteroidota in subjects with PSR.

We observed a negative correlation between the presence of E. coli and Shigella in patients in clinical remission and those actively undergoing treatment with biological therapy.

Conclusion

The recolonization of microbiota after ileocecal resection differs between patients with and without recurrence, with Fusobacteria and butyrate-producing bacteria being the most prominent contributors to driving PSR. The reduction in the abundance of short-chain fatty acid-producing bacteria and stimulators of anti-inflammatory cytokines like IL-10 could create a proinflammatory environment conducive to the development of PSR.

These findings may provide valuable insights into the disease prognosis, allowing for the identification of patients at higher risk of recurrence and laying the groundwork for more targeted therapeutic approaches after surgery
P1220 Dysbiosis of the gut microbiota and decreased fecal levels of short-chain fatty acid in patients with Ulcerative Colitis: a hospital-based case-control study
Authors: Yamamura R , Katsurada T
Published: January 2024

Background

Ulcerative Colitis (UC) is a typical intractable disease whose number of patients is increasing worldwide, and studies have suggested that the gut microbiota and its metabolites are closely involved in its pathogenesis and severity. However, to date, no study has comprehensively compared the microbiomes or metabolomes of UC patients and healthy controls after considering important confounding factors such as age, gender, race, and other lifestyle factors. Therefore, we conducted this clinical study to compare the compositions and diversity of the gut microbiota and the fecal metabolites between age-, sex-, and race-matched patients with Ulcerative Colitis (UC) and those without.

Methods

In total, 90 outpatients with UC (UC group) and 90 without a history of gastrointestinal diseases and their family members (without UC group) were recruited.

Results

The UC group had a significantly lower abundance of the genus Bifidobacterium, Faecalibacterium, and Lactobacillus than the without UC group. Furthermore, the UC group had a significantly lower alpha-diversity of the gut microbiota than the without UC group. The UC group had a significantly lower level of fecal SCFAs than the without UC group. These results remained significant after adjusting for sex, age, and smoking status. Furthermore, the expression of a group of genes encoded by the gut bacteria that are involved in the biosynthesis of tetrapyrrole was significantly lower in the UC group than in the without UC group.

Conclusion

Gut microbiota dysbiosis and low SCFA levels, as well as reduced tetrapyrrole biosynthetic capacity by the gut bacteria, may contribute to the development of UC. Moreover, regardless of the severity, duration, and type of UC, the gut microbiota and its metabolites were in a stable state of dysbiosis in patients with UC.
P1224 Predicting response to nutritional therapy in newly diagnosed children with Crohn’s Disease (CD) using multi-omics approach
Authors: Azulay A , Aharoni Frutkoff Y , Shimhlash Y , Borenstein E , Reshef L , Plotkin L , Focht G , Maslov T , Orlanski-Meyer E , Lev-Tzion R , Ledder O , Yogev D , Assa A , Turner D
Published: January 2024

Background

Background. One third of children with Crohn's disease (CD) will fail treatment with exclusive enteral nutrition (EEN) but predictors of response have been hitherto lacking. In this prospective cohort study, we aimed to use multiomic data to predict EEN response in treatment-naïve children with CD.

Methods

Methods. Children commenced on EEN at CD onset were followed through 8 weeks. Stool was collected for microbiome and metabolomics, and serum for metabolomics. Disease indices and clinical data were recorded. Targeted quantitative metabolomics approach was applied to analyze fecal and serum samples using a combination of direct injection mass spectrometry with a reverse-phase LC-MS/MS custom assay. DNA extracted from stool was sequenced and 16S rRNA gene was amplified. Feature selection was first utilized, using Recursive Feature Elimination with Cross-Validation (RFECV). For each omic analysis and the multiomic integration, selected components were fitted into a machine learning random forest (RF) model.

Results

Results. Included were 51 children (aged 14.8±2.7 yrs) treated with EEN, of whom 34 (66%) were responders; 36 (70%) had serum metabolomics, 20 (39%) fecal metabolomics and 31 (61%) microbiome data while 17 (33%) had all components. Clinical data and standard labs did not predict response (Table). The individual omic models ranked several key metabolites and microbes (Figure) and were able to predict EEN response with an accuracy ranging at 0.806-0.850 (Table). Serum 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), fecal phenylethylamine and fecal alpha-aminobutyric acid were higher in non-responders while serum malic acid and fecal 3-methyladipic acid were higher in responders (Fig. A-B). Moreover, levels of Veillonela and Bifidobacterium species alongside Blautia genus were higher in responders while Lachnospiraceae and Fusicatenibacter genus were higher in non-responders (Fig. C). The final multiomic model which included also clinical data, retained components from serum and fecal metabolomics but none from the microbiome; it predicted EEN response with high accuracy of 0.882 (Table). Higher level of serum 2-hydroxyglutraic acid, 2-hydroxy-2-methylbutyric acid and fecal 3-methyladipic acid were detected in responders. In non-responders there were higher level of serum alpha-aminobutyric acid, valeric acid, isovaleric acid, alpha-aminobutyric acid and kynrenine and alongside with increased fecal kynrenine/tryptophan ratio, both part of the tryptophan metabolism and kynrenine pathway (Fig. D).

Conclusion

Conclusion. In this multi-omic analysis, we generated a,metabolomics-based multiomic model to predict response to EEN, unravelling related biological insights.