bluuebunny/crossref_metadata_2025 huggingface dataset:
P1078 The influence of different 5-aminosalicylic acid preparations on mercaptopurine metabolism
Authors: Anjie S , Hettinga J , Volkers A G , van Gennep S , Clasquin E , Duijvestein M , van Bodegraven A A , van der Zanden E P , Jansen J M , van Asseldonk D P , West R L , D'Haens G R A M , Löwenberg M , de Boer N K
Published: January 2024

Background

5-aminosalicylic acid (5-ASA), the cornerstone treatment for ulcerative colitis (UC), can impact thiopurine S-methyltransferase (TPMT) activity and thiopurine metabolism. We performed a post-hoc analysis of OPTIC, a randomised prospective controlled trial comparing mercaptopurine (MP) to placebo while continuing 5-ASA treatment in UC, to provide insight into the influence of different 5-ASA preparations on 6-thioguaninenucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) levels.

Methods

UC patients with active disease, despite ≥2 g/day 5-ASA treatment, received remission induction therapy with corticosteroids and conjunctively started weight-based MP therapy (1-1.5 mg/kg of bodyweight). For this analysis, the initial TDM measurement, using the Dervieux method, at week 6 was selected to exclude subsequent time points where dose adjustments were made. Different 5-ASA preparations were used, including time-dependent release (Pentasa® 4 g/day), Multi-Matrix (MMX) (Mezavant® 2.4, 3.6 or 4.8 g/day) and pH-dependent release (Salofalk® 3 or 4 g/day). Associations between 6-TGN and 6-MMP levels and 5-ASA preparations were analysed.

Results

In total, 29 patients started MP treatment, 27 patients reached the initial TDM measurement (41% female, median age 46 years [IQR 26-58], median disease duration 6 years [IQR 1-14]). Median 5-ASA dose was 4 g/day (IQR 3-4), the majority was treated with MMX 5-ASA (13/27), followed by time-dependent release 5-ASA (9/27) and pH-dependent release 5-ASA (5/27). Distribution of MP dose, body weight and age were similar across the different 5-ASA groups. At week 6, patients using an MMX 5-ASA formulation were more likely to have toxic 6-MMP concentrations (>5700 pmol/8×108 RBC), but not 6-TGN levels, compared to time-dependent release formulation users (91% vs 38%, P=0.041) as well as an unfavourable 6-MMP/6-TGN ratio (P=0.024). This effect was not dose-dependent. Median 6-MMP levels at week 6 varied statistically significantly between the different 5-ASA preparations: i.e. MMX 5-ASA showed the highest and time-dependent release 5-ASA the lowest 6-MMP level (19000 [IQR 10519-31000] vs 3950 pmol/8×108 RBC [IQR 2200-31000], resp., P=0.026, Figure 1). MP treatment persistence up to week 52 differed numerically between different 5-ASA preparations (MMX: 46%, time-dependent release: 78%, pH-dependent release: 60%), while no differences in hepatotoxicity or leukopenia were seen between 5-ASA formulations.

Conclusion

In UC patients receiving MP treatment, concomitant use of MMX 5-ASA was associated with higher toxic 6-MMP concentrations accompanied with an unfavourable 6-MMP/6-TGN ratio compared to time-dependent release 5-ASA leading to higher MP discontinuation rates.
P1087 A retrospective study on the GLIM criteria for assessing malnutrition in patients with Crohn's Disease and its correlation with clinical outcomes
Authors: Song X , Zhou X , Yang J , Guo H
Published: January 2024

Background

It is a common occurrence for patients with Crohn's disease (CD) to suffer from malnutrition. A novel approach to assessing malnutrition has been devised by the Global Leadership Initiative on Malnutrition (GLIM). Therefore, the objective of this study was to investigate the prevalence of malnutrition in CD patients using GLIM criteria and evaluate the clinical utility of GLIM in this population.

Methods

A retrospective cohort study was conducted with 386 patients with Crohn's disease. Data were extracted from the medical records, including demographic and clinical characteristics. All patients were evaluated using the nutritional screening and diagnosis criteria of the NRS 2002 and the GLM criteria. The prevalence of malnutrition was reported and the relationship between malnutrition and clinical outcome was analyzed.

Results

The prevalence of malnutrition among CD patients was 73.6% and 35.1% in mild malnutrition, 35.4% in moderate malnutrition, and 35.4% in severe malnutrition. The majority (143, 50.4%) of malnourished patients were categorized as B2 or B3 phenotype, with a significant difference (P= 0.001). The malnourished group had significantly higher CDAI scores than the non-malnourished group (122.9±70.5 vs. 77.3±61.3, P<0.001). In the primary cohort, patients at risk of malnutrition with inflammatory load exhibited a significantly worse clinical outcome compared to those without inflammatory load (OR 4.07, 1.56-10.7; P=0.004).

Conclusion

Malnutrition caused by Crohn's disease is a significant issue for numerous patients. Malnutrition identified using the GLIM criteria was found to be associated with CDAI, age, and behavior, providing prognostic value for clinical outcomes.
P1088 Real-world data on the treatment with Upadacitinib in a biological-experienced Crohn's disease cohort
Authors: Kubesch A , Lande R , Farrag K , Jungheim F , Dienethal A , Sprinzl K , Zeuzem S , Blumenstein I
Published: January 2024

Background

Upadacitinib was approved for the treatment of Crohn's disease in June 2023. However, real-world data, especially in biological-experienced patients, is scarce. We aimed to determine the treatment efficacy and persistence of Upadacitinib in treatment-experienced Crohn's disease (CD) patients

Methods

All patients treated for Crohn's disease in the IBD outpatient clinic of the University Hospital Frankfurt from 06/23-11/23 were retrospectively analyzed. Data on clinical (Harvey-Bradshaw index (HBI)) and biochemical disease activity (fecal calprotectin FC), as well as patient history, were collected. Patients were followed up for at least 12 weeks.

Results

Twenty patients with CD were included. All patients had already received at least one biological agent before starting upadacitinib. Six patients reported extraintestinal manifestations, most commonly arthralgia. Five patients had stenosis of the terminal/neoterminal ileum, and one patient underwent surgery during Upadacitinib induction. Five patients had preexisting fistulae; four reported fistulae activity at treatment initiation. The median Harvey-Bradshaw Index was 11. We report an HBI reduction after induction (8.5). The median FC level at induction was 719 ug/g. After the induction, the median FC was 216 ug/g. Nineteen of the twenty patients completed the induction period of 12 weeks at the time of this interim analysis. All patients continued with 30mg of Upadacitinib post-induction. The most common adverse event was acne. No significant changes in the patients' lipid status were observed.

Conclusion

We report preliminary real-world data on the treatment with upadacitinib. In our interim analysis, Upadacitinib is an effective and safe treatment in biological-experienced CD patients.
P1097 The effect of lockdowns during the COVID-19 pandemic on the epidemiology of inflammatory bowel diseases: a comparison of two nationwide cohorts
Authors: Atia O , Bryder N , Mendelovici A , Ledderman N , Ben-Tov A , Osooli M , Forss A , Loewenberg Weisband Y , Matz E , Dotan I , Turner D , Olén O
Published: January 2024

Background

Mechanistic evidence suggest a link between COVID-19 infections and the development of immune mediated diseases. Additionally, the lockdowns during the pandemic limited the accessibility to medical care, possibly leading to reduced number of diagnosed patients with inflammatory bowel disease (IBD). We aimed to explore these contending trends on the epidemiology of IBD during the COVID-19 pandemic in two countries with different lockdown policies.

Methods

We utilized nationwide IBD cohorts in Israel and Sweden to explore the incidence of IBD during the pandemic (2020-2021) compared to three years prior (2017- 2019). We examined temporal trends through the presence of inflection points by Joinpoint regression analysis and reported average monthly percentage changes (AMPC).

Results

A total of 155,837 patients with IBD were included (Israel, 58,640; Sweden, 97,197). The incidence of IBD was stable during the three years prior to the beginning of the COVID-19 pandemic in February 2020 (AMPC: Israel 0.0% [95%CI -0.5% to 0.4%]; Sweden 0.2% [95%CI -0.3% to 0.7]). Thereafter, the incidence rate in Israel remained stable until November 2020 (AMPC 2.3% [95% CI -13.4% to 29.9%]) and then decreased sharply (AMPC -6.4% [95%CI-20.8% to 17.0%]) until February 2021 and -20.1% [95%CI -38.9% to -4.7%]) from February 2021), while in Sweden, which had a less stringent lockdown policy, the incidence rate decreased slightly until July 2020 (AMPC -3.3% [95%CI -21.6% to 20.3%]), but increased thereafter (AMPC 13.6% [95%CI -12.6% to 27.0%]; Figure).

In Israel, the reduced incidence rate during the pandemic (February 2020 to July 2021) was notable mainly in the adult-onset disease, while in Sweden, although the overall incidence rate increased steadily across all age groups, the largest change was apparent among the elderly.

Conclusion

In this study of two nationwide cohorts we found that the initial decrease in incidence of IBD was most apparent in Israel with a more stringent lookdown policy and among elderly in Sweden, the only population there with significant social restrictions during the pandemic. Taken together, it is likely that the reduced incidence stemmed from the limited access to the healthcare system. Future studies are needed to determine the long-term effect of the pandemic on IBD incidence.
P1106 Is indoor radon associated with new diagnosis of inflammatory bowel disease patients?
Authors: Mauriz Barreiro M V , Ruano-Raviña A , Ferreiro-Iglesias R , Baston-Rey I , Calvino-Suarez C , Nieto-García L , Porto-Silva S , Martinez-Seara X , Peón-González J , Dominguez-Munoz J E , Barreiro-de Acosta M
Published: January 2024

Background

Inflammatory Bowel Diseases (IBD) are a group of pathologies of unknown etiology associated with some environmental factors, only partially identified. The role of indoor radon, a radioactive gas, has not been formally studied and it might play a role on the onset of the disease. The aim of this study is to analyze the role of individual residential radon exposure on the incidence of IBD in a radon-prone area also characterized as a high incidence IBD region.

Methods

A case-control study was developed in the health area of Santiago de Compostela (Galicia, Spain) between June 2020 and September 2023, including incident cases with IBD. Controls were selected trough a frequency matching based on sex and age and without IBD. All participants had to be living at least 5 years in the same dwelling, those with a change of address in the last 5 years prior to diagnosis were excluded. Endoscopic index, imaging techniques and analytic parameters were collected. Radon levels measured over three months in the participants’ home were compared between cases and controls, and between the different types of IBD. Each individual was provided with a residential radon meter (a RSKS trace detector), given and read by the Galician Radon Laboratory, a certified radon laboratory. Procedure is summarized in Figure 1. Radon concentrations were categorized into three groups, 0-99 Bq/m3, 100-299 Bq/m3 and >299 Bq/m3. Results are expressed as Odds Ratios with their 95%CI obtained through logistic regression.

Results

178 incident cases and 178 controls (102 ulcerative colitis, 70 Crohn’s disease and 6 unclassified colitis) were included, with a median age of 51 years old (IQR 40 – 59.5). 51.7% were females. Median radon levels of IBD patients´ homes were 144.5 (IQR 83 – 260) and median radon levels of controls´ homes were 189.5 (IQR 112 – 292.5) (figure 1). Adjusting by age and sex, high radon levels showed a negative association for the development of IBD (taking levels of 0-99 Bq/m3 as reference, OR 100-299 Bq/m3 is 0.5 (95%CI 0.3-0.8), and OR >299 Bq/m3 is 0.5 (95%CI 0.3-0.9). Results are shown in table 1. Analyzing women and men separately, there are no statistically significant differences (p>0.05 in each group). Taking into account the different types of IBD, radon levels show the same negative association but without statistical association.

Conclusion

High radon levels might be a protective factor for developing IBD overall and its most common types, Crohn’s disease and ulcerative colitis. Further studies in other areas with lower radon concentrations will be necessary to corroborate whether it influences the incidence of IBD.
P1113 Depressive symptoms in ulcerative colitis and Crohn's disease – differences in improvement at 1 year follow-up
Authors: Selin K A , Repsilber D , Strid H , Lindqvist C M , Kruse R , Magnusson M K , Öhman L , Carlson M , Keita Å V , Söderholm J D , Halfvarson J , Hedin C R H
Published: January 2024

Background

Mental health (MH) has been reported to be poorer among patients with inflammatory bowel disease (IBD) than general population. However, it is not known whether MH is more driven by inflammation itself or related to gastrointestinal (GI) symptoms. Also, the dynamics of MH following IBD diagnosis is not well understood.

Methods

In the Swedish Inception Cohort of IBD (SIC-IBD), patients with Crohn’s disease (CD), ulcerative colitis (UC) and unclassified IBD (IBD-U) as well as symptomatic controls (SC) and healthy controls (HC) filled in Patient Health Questionnaire-9 (PHQ-9), a validated screening tool for depression. Patients completed PHQ-9 at diagnosis and at one year follow-up while the controls completed it once. Disease outcome was defined at one year based on requirement of advanced treatments/ surgery.

Results

In total, 286 individuals (16 HC, 89 SC, 62 CD, 104 UC, 15 IBD-U) completed the questionnaire at baseline. HC had significantly lower PHQ-9 score, (fewer depressive symptoms), at baseline compared to all the other groups (p<0.01). The baseline PHQ-9 score was not significantly different between SC and CD, UC and IBD-U patients (p=0.06).

At one year follow-up, 38 CD and 53 UC patients completed the PHQ-9. Between baseline and follow-up, UC patients had a significant drop in their PHQ-9 score (p<0.0000001), whereas CD patients did not have any significant change in their PHQ-9 score (p=0.06). Furthermore, UC patients had significantly lower PHQ-9 score compared with CD patients at follow-up (p=0.04, Figure 1).

Baseline PHQ-9 score was not correlated with calprotectin at baseline neither in UC nor CD patients (p=0.7 and 0.5 respectively). Also, there was no positive correlation between PHQ-9 score change and calprotectin change in either UC or CD patients, and neither baseline nor follow-up PHQ-9 scores were significantly different in patients with poor or good outcome (p>0.05). When analysed separately by sex, there was still no correlation between baseline PHQ-9 score and outcome in neither CD nor UC patients (p>0.05)

Conclusion

IBD patients have at the time of diagnosis more depressive symptoms than HC, but not different from SC. Depressive symptoms are more related to GI symptoms than IBD specific inflammation or disease outcome. UC patients show more of an improvement in their depressive symptoms one year after diagnosis than CD patients.
P1135 Increased prevalence of migraine in women with inflammatory bowel disease: a cross-sectional study
Authors: Pascual M , de Prado Tejerina C , Gárate G , Serrano M S , García M J , Castro B , González-Quintanilla V , Madera J , Crespo J , Pascual J , Rivero Tirado M
Published: January 2024

Background

Data on a possible comorbidity between migraine and inflammatory bowel disease (IBD) are controversial. Our aim was to determine the prevalence of migraine in a cohort of IBD patients.

Methods

We performed a cross-sectional study in a cohort of IBD patients at our IBD Unit. After informed consent, consecutive IBD patients aged 18-64 years were interviewed. Those who admitted a history of headache in the last year were asked to answer the three questions of the id-Migraine validated questionnaire. Those who answered "yes" to the three of them were classified as "definite" migraine and those who answered "yes" to two were classified as "probable" migraine. For all patients we collected demographic data, IBD subtype, disease duration, hospitalizations or surgeries and medical treatments. Migraine prevalence data of IBD patients were compared with reported local migraine prevalence data at 18-65 years of age (Cephalalgia 2011; 31: 463-70). Statistical analysis was done with SPSS®.

Results

We interviewed 283 consecutive IBD patients aged 20-65 years. Main characteristics of this population are described in table 1.

Headache was present in 176 (62.2%) patients. Of those, 59 (20.8%; 95% CI 16.1-25.5%) met migraine criteria either definite (n= 33; 11.7%; 95% CI 8-15.4%) or probable (n=26; 9.2%; 95% CI 5.8-12.5). When divided by gender, 12 men (9.6%; 95% CI 4.4-14.) and 47 women (29.8%; 95% CI 22.7-36.9%) met migraine criteria.

The prevalence of migraine was significantly increased in IBD patients (20.8%) versus that reported for our general population (12.6%; p= 0.0001). By sex, these differences remained significant in women (29.8% in IBD versus 17.2% in our general population; p=0.0001), but not in men (9.6% in IBD vs 8.0%; p=0.45) (Figure 1).

By IBD subtypes, there were no significant differences between CD and UC in migraine prevalence (20.7% vs 19.6% respectively; p=0.58). Regarding IBD characteristics, men with total migraine had higher biologic treatment (66.7% vs 44% p=0.032), and immune mediated inflammatory diseases or extraintestinal manifestations of IBD (33.3% vs 9.6% p=0.0016), but the number of men with migraine was low (12). These associations were not significant for women, nor overall population (p>0.05). Additionally, we did not find any significant association in total migraine patients in the use of mesalazine, disease duration, immunomodulators, surgeries or hospitalizations, neither in total number of patients nor stratified by sex.

Conclusion

Migraine prevalence is higher in patients with IBD than general population, which is a further example of the bidirectional gut-brain interaction. The fact that this association was stronger for women suggests an influence of sex-related factors.

ISCIII PI20/01358 and FEDER.
P1161 Prevalence of undernutrition in patients with inflammatory bowel disease and improvement after nutritional advice
Authors: Kutar M , Dharap V , Dhoble P , Trinidade S , Gupta T , Abraham P , Desai D
Published: January 2024

Background

The prevalence of undernutrition ranges from 25% to 70% and severe undernutrition from 1% to 30% among individuals with active inflammatory bowel disease (IBD). The aetiology of malnutrition is multifactorial. There are not many studies that have assessed nutrition after therapy modification and dietary advice.

Aim

To study the prevalence of undernutrition in IBD and the change after nutritional advice.

Methods

In this single-centre prospective cohort study, 218 consecutive patients with IBD were screened. Patients with associated diseases that could lead to undernutrition were excluded (N=18). Nutritional assessment was done as per the European Society for Clinical Nutrition and Metabolism (ESPEN) definition: BMI <18.5 kg/m2 or unintentional weight loss >10% were defined as undernutrition and the Malnutrition Inflammation Risk Tool (MIRT) score was calculated. Obesity was defined as per the WHO Asian BMI classification: grade 1 (BMI 25-29.9 Kg/m2) and obesity grade 2 (BMI >30 Kg/m2)1. Patients were given nutritional advice and therapy was optimized as per disease activity. BMI and MIRT were calculated on subsequent visits to assess response to nutritional advice.

Results

Of 200 patients (median age 39 [IQR 28-53] years; 96 females), 105 had ulcerative colitis (UC), 93 Crohn’s disease (CD), and 2 IBD-unclassified. Fifty-four (27%) patients had undernutrition (28 UC, 25 CD, and 1 IBD-U). Sixty-one (30.5%) patients were obese. At follow up (median duration 24 months), of 37/54 patients with BMI <18.5 Kg/m2, BMI increased in 24 (64.8%) and decreased in 13 (35.1%); of 17 patients with >10% unintentional weight loss, 5 (29.4%) had increased weight on follow-up. MIRT score decreased in 24/54 patients (44.4%), remained same in 14 (25.9%), and increased in 16 patients (29.6%). Of the 24 patients with decrease in MIRT score, 7/24 (29.1%) received only dietary advice, 10 (41.6%) received dietary advice and optimization of IBD treatment, and 7 (29.1%) received only optimization of IBD treatment.

Conclusion

The prevalence of undernutrition and obesity in patients with IBD was 27% and 30.5%, respectively. After dietary advice and therapy optimization, nutrition improved in 53.7% while MIRT score decreased in 43.3% of patients.

References:

1. Girdhar S, Sharma S, Chaudhary A, et al. An epidemiological study of overweight and obesity among women in an urban area of north India. Indian J Community Med. 2016; 41:154-7.
P1181 Prevalence and trend of anemia in a large cohort of children with inflammatory bowel disease
Authors: D'Arcangelo G , Brecciaroli M , Gagliostro G , Auletta D , Pellegrino S , Arrigo S , Graziano F , Miele E , Illiceto M T , Alvisi P , Dilillo D , De Giacomo C , Lionetti P , Pastore M , Cananzi M , Bramuzzo M , Panceri R , Norsa L , Aloi M , Scarallo L
Published: January 2024

Background

Anemia is a common extraintestinal manifestation in inflammatory bowel disease (IBD) with an impact on patients’ quality of life. Our aim was to determine the prevalence of anemia and its characteristics at the diagnosis in children with inflammatory bowel disease (IBD) and to investigate its trend during follow-up.

Methods

We conducted an observational, multicenter cohort study including data of IBD children with anemia at the diagnosis enrolled in the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) IBD registry. Demographic, clinical, laboratory and endoscopic data were collected at the diagnosis and anemia trend was evaluated at 1-year follow-up. Anemia was diagnosed based on the WHO criteria and classified as mild, moderate, and severe accordingly.

Results

Five hundred eighty-nine [295 CD (50%) and 294 UC/IBDU (50%)] out of 1634 with IBD presented with anemia, resulting in a prevalence of 36%. Anemia rate was higher in CD than in UC (39% vs 33%, p = 0.009). Most patients presented at the diagnosis with moderate anemia (55%). The most common forms of anemia were iron deficiency anemia (IDA) and combined inflammatory and IDA anemia (InflIDA), both present in 42% of children. Only 15% of children had anemia of inflammation. Children with CD had higher rates of mild anemia than UC (38% vs 33%, p<0.0001), while severe anemia was more common in UC (13% vs 6%, p= 0.001) as well as IDA (53% vs 31%, p<0.0001). Younger age and lower albumin levels significantly correlated with the severity of the anemia in CD. In UC, females were more likely to experience severe anemia (69% vs 47%, p=0.02) and an extensive disease was more prevalent in children with moderate and severe anemia then in those with mild anemia (p=0.01 and p=0.03, respectively). At 1 year, 99 children (17%) were still anemic. At multivariable logistic regression analysis, baseline wPCDAI and SES-CD significantly correlated with the persistence of anemia at 1 year in CD. No variables correlated with the persistence of anemia in UC.

Conclusion

More than one-third of pediatric patients present with anemia at the diagnosis of IBD, most commonly moderate. A severe anemia is most common in UC compared to CD. Iron deficiency anemia (alone or in its form of InflIDA) is the most common cause of anemia in children with IBD. One out of five is still anemic after 1 year from the diagnosis.
P1192 Deciphering the colonic immune landscape of UC from cellular senescence by integrated bioinformatics analysis and machine learning
Authors: Zhang Y , Wang J , Zhang Y , Ke Z , Fang X , Xu J , Liu Y
Published: January 2024

Background

Nowadays, there has been extensive interest in cellular senescence in gastrointestinal diseases. However, the pathological mechanism of cellular senescence in UC and its involvement in colonic immune characteristics remain enigmatic. Therefore, we aimed to investigate the contribution of cellular senescence-related signatures to the colonic immune landscape in UC based on bioinformatics combined machine learning strategy.

Methods

Three gene sets of UC were selected from the Gene Expression Omnibus database, including two training sets and one testing set. We identified cellular senescence-associated differentially expressed genes (DEGs) in UC and performed functional enrichment analysis. Afterwards, signature genes were determined by machine learning algorithms including least absolute shrinkage and selection operator (LASSO) regression, support vector machine recursive feature elimination (SVM-RFE), and artificial neural network (ANN). Furthermore, distinct immune microenvironment abnormalities in UC were comprehensively explored, and the correlation between the signature genes and the colonic immune landscape of UC was also evaluated. Based on the signature genes, we clustered UC samples into distinct subtypes by consensus clustering analysis. Finally, we performed validation of the signature genes in dextran sulfate sodium salt (DSS)-induced colitis.

Results

41 cellular senescence-associated DEGs in UC were identified by intersecting DEGs with the cellular senescence-associated genes from the CellAge database, which were associated with cellular senescence and immune pathways. Following that, seven signature genes were determined by the machine learning method of LASSO regression, SVM-RFE, and ANN, comprising CXCL1, MMP9, CYR61, BAG3, PEX19, RPS6KA6, and ETS2, which were also validated in the testing set. Furthermore, we obtained the most correlated pairs of UC signature genes-immunocytes and found these signature genes were highly corelated with neutrophils and activated CD4+ memory T cells. Additionally, the expression profiling of human leukocyte antigen genes and immune checkpoints were also analyzed. Subsequently, two molecular subtypes related to senescence that exhibit significantly different immune characteristics were identified. Finally, the mRNA levels of the signature genes were confirmed in DSS-induced colitis, which were congruent with results gained from the datasets.

Conclusion

In summary, the result has emphasized the essential function of cellular senescence-associated genes in controlling the immune microenvironment for UC. The exploration of the etiopathogenesis of UC through cellular senescence is anticipated to lead to novel advancements in disease diagnosis and potential treatments.
P1197 ERAP2 genetic variant rs2248374 is linked to paradoxical skin reactions induced by TNF-alpha inhibitors in Romanian patients with Inflammatory Bowel Diseases
Authors: Musa A M , Tieranu C G , Bota A , Musa M , Popa L O , Dutescu M I , Popa O M
Published: January 2024

Background

The endoplasmic reticulum aminopeptidases (ERAPs) are responsible for trimming protein residues to optimal length for major histocompatibility complex class-1 mediated antigen presentation process. Genome-wide association studies have shown the influence of ERAP1 and ERAP2 genetic variants in disease susceptibility for autoimmune disorders. Their role in inflammatory bowel diseases (IBD) however remains obscure due to literature data paucity. The aim of this study was to evaluate the role of a single nucleotide polymorphism (SNP) rs2248374 (G/A) of ERAP2 gene in disease susceptibility and response to treatment in Romanian population with IBD. This SNP is of particular importance because the G allele produces a truncated ERAP2 transcript undergoing nonsense-mediated decay and therefore individuals with GG genotype have no functional ERAP2 enzyme.

Methods

The study involved 186 IBD patients (87/99 UC/CD, 91M/69F) and 150 healthy controls (77M/73F) all unrelated and of Romanian ethnicity. Extraintestinal manifestations (EIM) were documented in 43 IBD patients (19UC/24BC). Among patients with biological treatment against TNF-alpha (N=113) there were 31 (27.4%) primary non-responders and 13 (11.5%) with paradoxical skin reactions. All subjects were genotyped for ERAP2 rs2248374 (G/A) using TaqMan Allelic Discrimination Assay (C_25649529_10 Real-Time PCR System, Applied Biosystems by Thermo Fisher Scientific, USA). Association tests were performed with OpenEpi online software using Two by Two Table statistics. P-values (2-tail from Mid-P exact test) were considered significant if <0.05.

Results

Controls and patients were in Hardy-Weinberg equilibrium for the investigated SNP. No significant differences were observed in relation with the risk of disease or with the therapy response. The minor allele A frequency was significantly lower in IBD patients with paradoxical skin reactions (27%) versus patients without these manifestations (50%, p=0.02, OR 0.36). The genotype AA, responsible for full ERAP2 expression, had 0% frequency in the group with adverse skin reactions compared with 23.2% in patients without (p=0.04, OR 0.0). The GG genotype which is related with no ERAP2 protein expression was more frequent in the subgroup of patients with EIM (41.8%) than in patients without EIM (26.7%), showing a marginal association (p=0.06, OR 1.97).

Conclusion

Our results point to the fact that ERAP2 rs2248374 AA genotype exerts a protective effect over paradoxical skin reaction induced by TNF antagonist agents, and GG genotype shows marginal association with the presence of EIM in Romanian patients with IBD. We consider these results worthy of replication in larger cohorts of patients.
P1219 Changes in gut microbiota of patients with inflammatory bowel disease receiving biologic therapy
Authors: Tai W C , Yao C C , Tsai Y -C
Published: January 2024

Background

Inflammatory bowel disease (IBD), comprising the predominant forms Crohn’s disease (CD) and ulcerative colitis (UC), is associated with compositional and metabolic changes in the intestinal dysbiosis. The aim of this study is to evaluate the composition in the microbiota of IBD patients who received biologic therapy

Methods

This is a prospective study recruited 14 patients with IBD received biologic therapy and 13 IBD controls who received conventional treatment . The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The stool samples at baseline, weeks 6 and 48 after biologic therapy initiation were assessed. We also evaluated the level of inflammation and treatment response of biologics by BD activity score (CD patient by Crohn’s disease activity index [CDAI] and in UC patient by Mayo score).

Results

In CD group, we recruited 7 CD patients receiving biologic therapy (Anti-tumor Necrosis Factor for 4 and anti-integrin for 3) and 6 controls.In UC group, we recruited 7 UC patient receiving biological therapy (Anti-tumor Necrosis Factor for 2 and anti-integrin for 5) and 7 controls.

Community α-diversity was lower in patients at baseline of biologics group compare to controls significantly but increase abundance and richness after achieving remission in trend at week 6 and week 48, respectively. In Top 10 taxon bacterial distribution, the Firmicutes were increase its abundances gradually ( relative abundance in biologics W0,W6,W48 and controls were 46.3%, 51.7%,62.0%, and 66.4%, respectively). Conversely, the Bacteroidetes were decrease its abundances ( relative abundance in biologics W0,W6,W48 and controls were18.3%, 18.8%, 10.2% and 6.4%, respectively). Increased F/B ratio significantly after biologics therapy also found in our study. (F/B ratio were 9.4, 12.5,64.0,and 84.3,respectively).

Patients in control group had higher abundance of Firmicutes of the phylum.By contrast, Enterobacteriaceae and Bacteroidaceae were significantly more abundant in patients of biologics group at W0 .

Conclusion

Treatment with biologic therapy induced improvement of community diversity and increased F/B ratio in IBD patients which seemed correlate the level of clinical inflammation. The dysbiosis-representative bacteria, such as Enterobacteriaceae, could induce colonic inflammation,were more abundant in patients who had higher activity of IBD. Further larger prospective studies are needed to determine whether the biologic therapy could induce long-term changes of intestinal microbiome.
P1221 Analysis Of Oral And Intestinal Microbiome Of Korean Patients With Crohn's Disease
Authors: Yoon J , Jeen Y T
Published: January 2024

Background

We aimed to conduct a study comparing the fecal and oral microbiomes of Korean Crohn's disease patients with those of healthy individuals. Since most of microbial study of inflammatory bowel disease patients are conducted overseas, this study would reveal if the microbiome of Korean patients and patients of other countries are the same or not. Also, since the process of fecal sample collection is inconvenient, saliva sample analysis was performed to find a relevance of disease activity.

Methods

This single center study recruited patients with CD between September 2022 and January 2023. At first visitation, stool collecting tube and saliva collecting tube were given to CD patient. Collected stools samples and saliva samples were sent to the environmental bioengineering laboratory in Korea University and assessed by 16S rRNA sequencing.

Results

26 CD patients and 6 healthy individuals were enrolled to this study. In the comparison of helathy individual’s fecal microbiome, the flora of fecal sample of CD patients were slightly different. The diversity of microbiome was decreased in CD patients compared to healthy individuals. There were 17 species existed only in CD patient’s feces. The most frequently detected one was Ruminococcus gnavus, and the the highest abundance was Unclassified Fusobacterium. In the phylum level of bacteria, Bacteroidota, Firmicutes, and Proteobacteria were predominant. Saliva samples showed no significant difference between CD patient and control.

Conclusion

Fecal sampling can be usefully used as a diagnostic test technique that can reflect CD patients’ microbiota. Similar to patient in overseas, dysbiosis of fecal microbiome and abundant species were detected.
P1225 The interplay of donor-derived gut microbiota correlates with the efficacy of combination therapy of fecal microbiota transplantation with antibiotics for ulcerative colitis
Authors: Ishikawa D , Nomura K , Zhang X , Kouma M , Maruyama T , Shibuya T , Watanabe H , Yamada T , Nagahara A
Published: January 2024

Background

Our previous reports suggest fecal microbiota transplantation (FMT) following bowel cleansing with amoxicillin, fosfomycin, and metronidazole (Antibiotic FMT: A-FMT) improved its efficacy and the recovery of the Bacteroidota species composition, which is associated with ulcerative colitis (UC) severity. Building upon these previous findings, we considered that manipulating the intestinal microbiome to improve the intestinal immune system seems to be a feasible therapeutic regimen for patients with UC. In this study, we explored the gut microbiota signatures through elucidating donor-derived microbe that colonized the recipients and examined the contributions of these microbe to the efficacy of A-FMT.

Methods

In this study, 97 patients with active UC were enrolled between March 2014 and October 2019, of whom 49 patients were individually assigned a different donor on a one patient-to-one donor basis. FMT was performed via colonoscopy after a two-weeks oral administration of three antibacterial agents. The Lichtiger’s clinical activity index (CAI) at 4 weeks after A-FMT treatment was defined as "response" if the CAI was ≤9 points and improved by ≥3 points. Each case contributed three fecal samples (pre A-FMT, post A-FMT, and Donor). 16S rRNA gene sequence analysis was performed on 147 collected fecal samples, and 6,501 Amplicon Sequence Variants (ASV) were identified and characterized.

Results

In responders, the relative abundance of 6 taxonomies including Alistipes were significantly abundant in both post A-FMT treatment samples and their donors’ samples, while 6 other taxonomies were significantly low. In non-responder, significantly low proportion of donor-derived and significantly high proportions of patients-origin and/or new ASV were observed compared with responders. The similarity of gut microbiota composition between donor and post A-FMT treatment was predominantly higher in responders compared to non-responders (Figure 1).

Conclusion

This study revealed that the engraftment of specific donor-derived microbes is a major factor in A-FMT outcomes, which may be the foundation for precision FMT. Rational identification of patient and donor characteristics can further advance the development of A-FMT therapy for UC.
P1230 Integrated analysis of microbiome and metabolome reveals disease-specific profiles in inflammatory bowel disease and intestinal Behcet’s disease
Authors: Park Y , Ahn J B , Kim S W , Kim W H , Cheon J H
Published: January 2024

Background

Gut microbial and metabolic characteristics in intestinal Behcet’s disease (BD), a condition sharing many clinical similarites with ulcerative colitis (UC) and Crohn’s disease (CD), are largely unexplored. This study aimed to investigate the gut microbial and metabolic characteristics, as well as potential biomarkers in intestinal BD, comparing them with UC and CD, along with healthy controls.

Methods

Patients with UC, CD, and intestinal BD, along with healthy volunteers undergoing diagnostic endoscopies, were enrolled. Colon tissue and stool samples were analyzed using 16S ribosomal RNA sequencing, assessing microbial diversity, taxonomic composition, and functional profiling by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). Plasma metabolomic analysis was performed using gas chromatography and ultra-performance liquid chromatography-time-of-flight mass spectrometry, and quantitative enrichment analysis (QEA) was performed.

Results

In total, 100 patients (35 UC, 30 CD, and 35 BD) and 41 healthy volunteers were enrolled. While CD exhibited reduced microbial diversity in colon tissue, BD showed no significant decrease. The taxonomic profile of intestinal BD resembled healthy controls more than UC or CD but exhibited specific distinct features. Common changes across all conditions included a decrease in five beneficial bacteria producing short-chain fatty acids (Fusicatenibacter saccharivorans, Coprococcus comes, Blautia obeum, Dorea formicigenerans, and Roseburai ceciola). Additional changes in intestinal BD included a decreased abundance of Subdoligranulum variable and Blautia wexlerae, which were shared features with either UC or CD. Intestinal BD-specific alterations involved decreased abundance of certain bacteria, including Bacteroides fragilis. Metabolomic profiles of intestinal BD by QEA showed similarity to CD and distinction from UC and controls, with pronounced functional changes in energy metabolism and genetic information processing, correlating with microbial functional analysis by PICRUSt.

Conclusion

This integrative analysis unveiled both common and distinctive profiles in intestinal BD when compared to UC, CD, and controls. The study identified potential biomarkers, contributing to a deeper comprehension of the unique features in these diseases, which could serve as key elements for elucidating their pathogenesis.
N03 Flexibility & Accessibility, e-Literacy, Resourcing and The Human Factor: Early Lessons from EIBD, a UK Qualitative Interview Study
Authors: Avery P , Kemp K , Dibley L , Green S
Published: January 2024

Background

Since the COVID-19 pandemic, the use of health tools (video/phone consultations, patient portals, and digital applications) has increased in the clinical management of patients with Inflammatory Bowel Disease (PIBD). We aimed to evidence the acceptability of eHealth tools by investigating the shared experience of PIBD and healthcare professionals (HCPs) in using eHealth to carry out follow-up appointments and support self-management.

Methods

An exploratory qualitative method was used. Participants were recruited via professional networks, social media platforms, Crohn's and Colitis UK website and newsletters. Semi-structured interviews were conducted remotely in April/May 2023 using MS Teams or Zoom. Transcripts were analysed using a thematic analysis.

Results

Fifteen HCPs (13 female) participated: IBD specialist nurses (n=9); gastroenterologists (n=2), pharmacists (n=2) and Dieticians (n=2). The 16 PIBD (10 female) participants were living with Crohn’s Disease (n=9), Ulcerative Colitis (n=6), and Inflammatory Bowel Disease Unclassified (n=1); age was reported in ranges 18 -24 (n=3), 24-34 (n=1), 35-54 (n=8), and 55-65 (n=2) and 75-85 (n=1). Time since IBD diagnosis ranged from < 6 months - 43 years (mean time 18.7 years). Some participants had pre-diagnosis symptoms for at least one year (81%) to over five years (25%). Four themes emerged:

• Flexibility and Accessibility: PIBD appreciated the ease of virtual appointments and access to test results and information but wanted flexibility and a personal approach to their care; eHealth connected them to their IBD team more easily.

• Resource: HCPs wanted better digital training since remote assessment skills differ from in-person assessment skills. They also identified the need for admin support when planning to implement eHealth tools. HCPs and PIBD wondered whether eHealth was primarily a cost-savings exercise, whilst the need for resource efficiencies across the health service was recognised.

• e-Literacy: HCPs were concerned that some older PIBD might be excluded from accessing eHealth due to e-literacy and capability issues, perceiving that eHealth is for the younger generation.

• The Human Factor: PIBD and HCPs wanted to have already met in person anyone they engaged with later virtually. For PIBD, in-person consultations meant they felt seen or understood, and they described the importance of hands-on abdominal examinations in reassuring them about their health status.

Conclusion

There is an acceptability of eHealth to support the care of PIBD, but HCPs and PIBD still value the Human factor. Concerns over Resourcing, Flexibility and Accessibility and e-Literacy may need addressing to avoid these becoming barriers to the benefits of virtual healthcare in supporting PIBD.
N08 Awareness of Inflammatory Bowel Disease-associated Colorectal Cancer risk and its management in patients with Inflammatory Bowel Disease: a systematic review
Authors: Khan F , Norton C , Czuber-Dochan W
Published: January 2024

Background

Inflammatory bowel disease (IBD) increases the risk of colorectal cancer (CRC). Although literature exists on patients’ general IBD knowledge, little is known about IBD patients’ awareness of CRC risk. This systematic review aimed to explore the literature on IBD patients’ knowledge, attitudes, and awareness of CRC risk and its management.

Methods

Medline, EMBASE, and PubMed databases were searched from inception to November 2023. All study designs and publication types were included. Non-English articles and those assessing general IBD knowledge were excluded. Cochrane’s ‘checklist of items to consider in data extraction’ was adapted for data extraction and the appraisal tool for cross-sectional studies (AXIS) was used to appraise the quality of included studies. All data relevant to the review question were extracted from the included studies and were thematically analysed for main themes.

Results

Twenty-three studies (17 full papers and 6 conference abstracts), including 4674 participants (2481 Ulcerative Colitis, 53.5% females) were included (PRISMA diagram Figure 1). The quality of included studies ranged from moderate to low. Overall, 18 studies reported CRC risk knowledge, 3 studies reported patients’ knowledge of CRC symptoms and risk factors, 7 reported attitudes towards cancer screening and 8 reported patient knowledge or attitude towards colectomy for dysplasia. The review found that IBD patients were moderately aware of the CRC risk, poorly aware of the symptoms and risk factors for CRC, and moderately feared this complication of IBD. Most overestimated their own risk of CRC and wanted more discussion with health professionals. Although the role of colonoscopy in cancer screening and diagnosis was well known, patients expressed mixed attitudes towards it due to the unpleasantness of bowel preparation, discomfort, or fear of colonoscopy complications. Low awareness of screening initiation time and varied willingness to undergo colectomy for dysplasia, irrespective of the extent of risk, was reported. Surgery was reported to be a last resort.

Conclusion

Limited literature exists on IBD patients’ awareness of CRC risk and its management to confidently infer the level of awareness and extent of educational needs of IBD patients. More research is needed to establish patients’ understanding of CRC risk and to optimise management.
N09 Transition Success Score as a valid quantitative measure to evaluate the effect of transitional care in IBD patients
Authors: van Gaalen M , van Pieterson M , de Ridder L , Derikx L , Escher J
Published: January 2024

Background

Transition programs are designed to prepare adolescent patients with inflammatory bowel disease (IBD) for their new role in adult care. The outcome of these programs is often assessed in a qualitative way (patient satisfaction, quality of life, disease burden). However, there is no quantitative measure to evaluate the effect of a transition program. The aim of this study was to develop and validate a Transition Success Score (TSS) by the identified key components of successful transition.

Methods

The TSS was developed through an international Delphi consensus study, with the expert panel of pediatric and adult healthcare providers and patients. The top 10 key outcome items associated with success of transition were collated into one questionnaire. In every round, the minimum response rate required was 80%, and a consensus of more than 80% was necessary for each item. After four rounds of discussion, a consensus was reached on the initial version of the TSS. This score included seven items for adult healthcare providers to evaluate the patient's disease management behavior, including shared decision making, therapy adherence, and appointment attendance. Additionally, two items concern patient and parent experience concerning the transition period. The TSS was subsequently employed and validated in a prospective multicenter cohort of young adult IBD patients, who made the transfer 9-15 months ago, in the Netherlands.

Results

In seven hospitals, 160 IBD patients (median age 19.05, male 48.8%, Crohn's disease 56%, median age at diagnose 13.97) completed the TSS, at 9-15 months after transfer to adult care. Hypothesis testing for construct validation revealed significant association of characteristics related to transition care such as knowledge (RTT), independence (TRAQ), and quality of life (IBDQ) (p=<0.005). In addition, Rasch analysis for structural validation showed that the TSS was discriminating at lower levels of transition success (Figure 1). Internal consistency, as measured by Cronbach alpha, was acceptable at 0.64. TSS was significantly lower in patients with high disease burden, exacerbation within the first year after transfer and parental dependency. Also, TSS was lower in certain patient profile types, characterized as either "laid back, nonchalant" or "worried and uncertain".

Conclusion

The Transition Success Score (TSS) can serve as a quantitative measure to help identify IBD patients who did not have successful transition to adult care. TSS can be utilized for identifying factors that impact successful transition and for measuring the effect of various transition programs in IBD.