bluuebunny/crossref_metadata_2025 huggingface dataset:
P1127 Diagnostic delay and economic burden in IBD: a multicenter italian experience in patients treated with biologics
Authors: Mocci G , Orrù G , Onidi F M , Bodini G , Picchio M , Ferronato A , Zampaletta C , Corpino M , Lorenzetti R , Usai Satta P , Elisei W , Tursi A
Published: January 2024

Background

Inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis (UC), are chronic and immune-mediated diseases with a relapsing-remitting trend. The overall incidence of these diseases is increasing. However, it is estimated that more than one third of patients experienced symptoms for more than one year before diagnosis. Delay in IBD diagnosis has several clinical, therapeutic and economic implications. Early diagnosis and proper treatment are the cornerstones for improving the standard of care for these patients.

This study aims to evaluate the diagnostic delay (DD) in patients with IBD and to analyze the clinical burden of the delay in IBD diagnosis in patients treated with biological drugs.

Methods

An observational and retrospective study was performed in IBD patients, regularly followed in four IBD Units. Data regarding delay in IBD diagnosis were assessed through a questionnaire evaluating the disease course. Moreover, data about biologics dispensation were obtained from the medical records in the period 2020-2022

Results

344 IBD patients were enrolled (UC 228, CD 116, M 198, F 146). Median age at diagnosis was 42 years (IQR 9-82); Median DD was 12 months (IQR: 6-24). No significant difference was found in median DD between UC [12 months (IQR: 4.5-12.0)] and CD patients [12 months (IQR: 12-48)]. However, the proportion of patients with a DD >24 months was significantly (p=0.007) higher in CD (41/110 = 37,3%) than in UC patients (20/220=9%).

After a median disease duration of 10 years (IQR: 4-17), overall, 164 patients (49.7%) were exposed to one biologic agent, 105 patients (31.8%) were exposed to two biologic agents, 61 (18.5%) to three or more biologic agents. 18,5% of patients (61/330) underwent surgery.

The statistical analysis showed that DD >24 months was not statistically significant associated with history of ≥ 2 biological drugs (p=0.51). Conversely, there was association with surgical treatment (p=0.004).

Conclusion

The diagnostic delay in IBD represents a challenge with clinical and, therapeutic impact. It’s crucial to cooperate with general practitioner and gastroenterologists not dedicated to IBD in order to reduce the diagnostic delay and guarantee an effective, appropriate and early treatment that will improve the patients’ quality of life and meanwhile reduce the health care system costs.
P1131 Epidemiological Characteristics of Inflammatory Bowel Diseases in The Last Decade: Multi-Center Türkiye Data
Authors: Akyuz F , Agargun B F , Atug O , Eskazan T , Yuksel I , Kochan K , Barutcu S , Asil M , Demirtas C , Bozkurt B , Cankurtaran E , Degirmenci A , Kefeli A , Ustaoglu M , Keskin M K , Sahin M , Ucer M , Erurker Ozturk T , Dervis Hakim G , Uyanikoglu A , Poturoglu S , Kalkan I H , Gulten M , Arhan M , Kav T , Toruner M , Akpinar H , Issever H , Celik A F
Published: January 2024

Background

This study aims to assess the past decade's epidemiology of inflammatory bowel disease (IBD) patients in Türkiye and identify year-to-year variations.

Methods

A total of 3463 patients diagnosed between 2010 and 2022 were included. The patients' demographic and phenotypic characteristics, smoking habits, and family histories were assessed. Differences between geographic regions and age groups were analyzed.

Results

Among patients, 1523 (44%) had Crohn's disease (CD), 1768 (51.1%) had ulcerative colitis (UC), and 23 (0.7%) had indeterminate colitis (Table). Male proportions were higher in both CD and UC patients, with the most common age range for diagnosis being 21-30 years (Figure). Over time, newly diagnosed cases and rates per population increased according to Turkish Statistical Institute data (Figure). Patients were divided into two groups based on diagnosis years (2010-2016 and 2016-2022), CD initially dominated, but UC prevalence grew in the last 6 years (p<=0.001). Recently diagnosed CD patients showed higher inflammatory involvement (78.0% vs. 63.4%; p<=0.001), and the inflammatory phenotype rose post-2016 (75.2% vs. 60.4%; p<=0.001). CD patients had more smokers (24.2% vs. 10.9%; p<=0.001) and family history of IBD (6.8% vs. 4.5%; p=0.004) than UC patients. Patients over 60 years old had a higher male gender ratio (64.4% vs. 55.9%; p<=0.001) and UC frequency (62.2% vs. 52%; p<=0.001) compared to those under 60 years old. The inflammatory phenotype in CD patients was lower in those under 60 years old compared to those over 60 years old (70.4% vs. 85.4%; p<=0.001). The frequency of pancolitis in UC patients was lower in those over 60 years old (31.3% vs. 41.4%; p<=0.001).

Conclusion

In Türkiye, IBD is more prevalent in males and is frequently diagnosed between ages 20 to 30. In CD, inflammatory and ileocolonic involvement is most common, while in UC, pancolitis is observed. The earlier diagnosis peak and increased pancolitis in UC patients might relate to tertiary centers' inclusion with transition clinics and focus on severe cases. Recently, newly diagnosed UC cases have notably surpassed CD cases.
P1137 Long-term trend of cumulative incidence of venous thromboembolism in Korean patients with inflammatory bowel disease: A nationwide population-based cohort study
Authors: Kim Y E , Kim S P , Park Y , Kim S H , Choi S , Choi H J , Jeong I S , Kim S H , Kim D Y , Oh S H , Yoon H J , Kim K M
Published: January 2024

Background

Venous thromboembolism (VTE) is a serious extraintestinal manifestation of inflammatory bowel disease (IBD). However, limited research has been conducted on the cumulative incidence of VTE in patients with IBD. Therefore, this study aimed to observe the trend of cumulative incidence of VTE after IBD diagnosis.

Methods

From 2005 to 2016, a population-based cohort study was conducted using health administration claims data from South Korea. IBD and VTE were defined by ICD-10 codes. Incidence density and cumulative incidence rate were analysed. The risk of variables including age, sex, and IBD subtype was comparatively analysed.

Results

A total of 35,508 newly diagnosed patients with IBD between 2005 and 2015 were followed up until 2016. Among them, 634 (1.8%) experienced VTE (619 adults and 15 children). The incidence densities of VTE per 10,000 person-year were 28.90 (range, 27.75–32.54) for overall IBD, 30.07 (range, 27.75–32.54) for adult IBD, and 11.08 (range, 6.20–18.27) for PIBD, respectively. The cumulative incidences of VTE at 0, 1-, 3-, 5-, and 10 years post-diagnosis were 0.01%, 0.30%, 0.80%, 1.30%, and 3.0%, respectively (Figure 1-A). Adulthood, female sex, and ulcerative colitis were associated with an increased risk of VTE (Figure 1-B, C, D).

Conclusion

The study showed a steady and gradual increase in the cumulative incidence of VTE in patients with IBD over a follow-up period of up to 11 years, with a slightly more rapid increase after 8 or 9 years. This trend was even more pronounced in children. This suggests that vigilant monitoring of VTE is necessary in the management of patients with IBD.
P1138 Long-term Epidemiological Trends in Emergency Hospital Admissions and Hospitalizations of Patients with Inflammatory Bowel Diseases in one of the biggest metropolises in western Poland in years 2010 to 2021
Authors: Mahadea D , Kotecki P , Miechowicz I , Dobrowolska A , Eder P
Published: January 2024

Background

A worldwide significant dynamic shift in the incidence and clinical course of Inflammatory Bowel Diseases (IBD) has been observed in the past years. One key indicator that embodies this variability is the necessity for urgent hospitalisation due to exacerbations of Crohn's Disease (CD) and Ulcerative Colitis (UC). The objective of this study was to assess this phenomenon in the Poznan Metropolis, one of the biggest metropolises in western Poland, over a 12-year timeframe.

Methods

Using the National Health Fund's database, urgent hospitalisations of patients with CD or UC from 2010-2021 were identified, and defined as unplanned admissions to emergency departments and inpatient units in Poznan Metropolis hospitals, which required hospitalisation. The ratio of emergency to planned hospitalisations were compared in two identical timeframes: 2010-2015 vs. 2016-2021 and, additionally, during the COVID-19 pandemic years 2020-2021 vs. 2018-2019. The data were analysed and compared according to diagnosis, age, gender and length of hospitalisation.

Results

The numbers of urgent and planned hospitalisations in regard to predefined time periods are shown in Table 1. The rate of acute to planned hospitalisations from 2010-2015 vs. 2016-2021 was 27% (809/3006) vs. 44.5% (1131/2540) (p <0.0001). It increased significantly in all defined categories, except for patients over 60 years of age, where an insignificant decrease from 79% to 71% (p=0.4) was noted. Lower hospitalisation rates were observed among men compared to women (2010-2015: 28% vs. 46%; 2016-2021: 25% vs. 43%). The COVID-19 pandemic posed a paramount challenge to global healthcare systems. However, a statistically significant decrease in the rate of urgent to planned hospitalisations was only found in CD patients (47% vs. 34%; p=0.02; Figure 1). No impact on hospitalisation duration was observed during the COVID-19 pandemic as compared to 2018-2019.

Conclusion

Despite ongoing therapeutic advances, IBD remains a substantial challenge to healthcare systems, as evidenced by the increasing trend in urgent hospitalisations over time, regardless of the diagnosis, particularly among women. The COVID-19 pandemic significantly triggered global economic and healthcare crisis. However, the repercussions on the treatment of IBD patients in our Metropolis were inconsequential.
P1150 The sulfur microbial diet and prognosis of individuals with Inflammatory Bowel Disease in a prospective cohort study
Authors: Chen J , Dan L , Sun Y , Fu T , Wang X
Published: January 2024

Background

Intestinal sulfur-metabolizing microbes and its products like hydrogen sulfide can impact gut health and involves course of multiple gastro intestinal diseases. Recent studies demonstrated a specific diet pattern, sulfur microbial diet, can significantly influence these microbes. The sulfur microbial diet was delineated as a specific dietary pattern linked with the augmentation of sulfur-metabolizing microorganisms in humans, wherein an enhanced prevalence of these bacteria potentially escalates microbial hydrogen sulfide synthesis. This offered an opportunity to improve and modify disease course of chronic gastrointestinal diseases like inflammatory bowel disease (IBD) via the diet pattern that needed evidence. We aimed to prospectively examine the associations between sulfur microbial diet and the prognosis of individuals with IBD.

Methods

We included 1528 participants with IBD (477 Crohn’s disease [CD] and 1051 ulcerative colitis [UC]) from the UK Biobank. Sulfur microbial diet was a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism. We assessed adherence to this dietary pattern using validated 24-hour dietary recalls that were collected in 2009-2012 for five rounds. Two outcomes, bowel resection surgery and colorectal cancer (CRC), were obtained based on the national health databases. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

After a mean (SD) follow-up of 9.9 (2.3) years, we documented 117 bowel resection surgeries events and 28 incident CRC. Compared to participants in the lowest tertile of sulfur microbial diet scores, those in the highest scores were associated with 76% higher risk of bowel resection surgeries (HR 1.76, 95% CI 1.12-2.77, P=0.014; P-trend=0.037) and 268% higher risk of CRC (HR 3,68, 95% CI 1.19-11.35, P=0.023; P-trend=0.019) in IBD (Table 1).

Conclusion

A higher sulfur microbial diet score was associated with an elevated risk of bowel resection surgery and CRC in individuals with IBD. More research is needed to explore whether this association differs across disease subtypes and locations.
P1154 Mediterranean dietary approaches to stop hypertension intervention for neurodegenerative delay (MIND) diet can reduce Inflammatory Bowel Disease risk: a prospective cohort study
Authors: Ye S , Sun Y , Chen X , Fu T , Ruan X , Dan L , Chen J , Du Z , Wang X
Published: January 2024

Background

The global increasing prevalence of Inflammatory Bowel Diseases (IBD) places a substantial burden on families and society at large. The lack of a definitive cure for this chronic condition underscores the critical need for effective preventive measures. Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, emphasizing natural plant-based foods while limiting animal products and high-saturated fats, emerges as a promising dietary approach. This study aims to bridge the gap in understanding the impact of the MIND diet on IBD risk.

Methods

We utilized data from 187,549 participants in the UK Biobank who provided dietary information and were free of IBD at baseline. Dietary information including the consumption of over 200 common foods and 30 beverages was collected for five rounds by a validated web-based 24-hour dietary recall questionnaire. A MIND diet score was evaluated based on the intake of ten beneficial and five unhealthy food groups and was further grouped by tertiles. The outcome of interest was Crohn’s disease (CD) and ulcerative colitis (UC), ascertained via inpatient data and primary care data. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

After a mean follow-up of 10.7 years, we documented 335 and 655 incident CD and UC. The average age of the participants was 56.2 years, of which 55.0% were females. We found that greater adherence to the MIND diet, represented by higher diet score, was associated with a lower risk of CD (HR comparing extreme tertiles 0.66, 95% CI 0.50-0.89, P=0.006; P-trend=0.005) and UC (HR 0.80, 95% CI 0.65-0.98, P=0.030; P-trend=0.029) (Table 1). In the secondary analysis, we investigated the impact of fifteen individual food components in the MIND diet and found that consumption of olive oil was inversely associated with CD, and consumption of wine was inversely associated with UC.

Conclusion

We found higher adherence to the MIND diet was associated with lower risk of CD and UC. Our findings call for further research on the potential of the MIND diet to prevent IBD.
P1158 Comparison of comorbidities, and lifestyle habits between IBD patients, IBD patients with suspected SpA, and controls
Authors: Karling P , Pettersson N , Forsblad-d´Elia H
Published: January 2024

Background

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a complex condition with systemic implications. Recent research emphasizes the connection between IBD and spondyloarthritis (SpA), sharing genetic and clinical traits. This cross-sectional case-control study investigates comorbidities and lifestyle habits in three groups: IBD patients, IBD patients with suspected SpA, and control group from the general population.

Methods

We obtained data from the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG) for 1,032 IBD patients (592 UC and 440 CD) and selected a control group of 16,756 individuals from the 2018 Swedish National Public Health Survey. Questionnaires covered comorbidities, self-perceived health, smoking, alcohol, and physical activity. Modified criteria for ASAS and AMOR was used to define SpA. Risk factors in patients with IBD for SpA were explored by logistic regression.

Results

IBD patients have higher rates of comorbidities such as hypertension (34.4%), asthma (15.6%), and diabetes (8.3%) compared to the control group.(Table 1). Notably, those with suspected concurrent SpA had even higher rates: hypertension (41.3% in axial SpA, 43.6% in peripheral SpA), asthma (22.4% in axial SpA, 21.5% in peripheral SpA), and diabetes (10.2% in axial SpA, 10.5% in peripheral SpA). Smoking habits differ, with a greater proportion of former smokers in the IBD group (38.3%) and a higher percentage of individuals who had never smoked in the control group (64.6%). Encouragingly, IBD patients demonstrated increased physical activity, with 70.3% engaging in 150 minutes of activity per week. Logistic regression analyses revealed associations between specific factors and the presence of SpA in IBD patients, including female gender (1.815, SD 1.325–2.488), BMI (1.073, SD 1.034–1.113), asthma (1.628, SD 1.038–2.553), gastritis (1.694, SD 1.070–2.683), and current/former smoking (1.359, SD1.004–1.840).

Conclusion

The prevalence of hypertension, asthma and diabetes were higher in patients with IBD compared to the general population. A higher proportion among the controls had never smoked but patients with IBD had lower alcohol consumption and were more physically active. This study sheds light on the IBD-SpA relationship and its impact on comorbidities and lifestyle. The findings aid clinicians in holistic patient management, emphasizing tailored care for specific comorbidities and lifestyle factors.
P1159 Gene and environment interactions in inflammatory bowel disease: a systematic review of human epidemiologic studies
Authors: Bai J , Bouwknegt D , Weersma R , Dijkstra G , van der Sloot K , Festen E
Published: January 2024

Background

Complex gene-environment interaction for Inflammatory Bowel Disease (IBD) remains elusive. This systematic review aims to summarize the current evidence of gene and environment interactions in IBD.

Methods

PubMed, EMBASE, Web of Science and Scopus were systematically searched from inception through July 20, 2022 to identify publications examining the interaction effect of genetic variants and environmental factors in IBD. Two investigators independently screened the title/abstract and full text according to the predefined criteria. All eligible studies were graded using STREGA guideline. The protocol was registered on PROSPERO (CRD42023443071).

Results

4,305 publications were identified and screened, resulting in 36 eligible studies. 17 studies reported statistically significant interactions.

The interaction effect of NOD2 and smoking was most frequently investigated and showed variant-specific interaction at rs2066847 regrading risk of Crohn’s disease (CD). Gene-smoking interactions were further identified in 1) other IBD risk genes (ATG16L1, IL23R, CALM3), as well as the IBD-genetic risk score (GRS), 2) detoxification genes (GSTP1 and ΗΜΟΧ1), 3) smoking-associated genes (CHRNA3, CHRNA5, PPP1R3C, BDNF), as well as the general smoking-GRS, and 4) the inflammation cytokine gene (IL-1β) using the candidate gene approach. Using the Illumina immune-focused Chip, another 64 smoking interacting variants were identified.

Gene-diet interactions were reported across different nutritional measures, including the intake of fatty acids with CYP4F3 and FADS2, serum level of selenium with SEPHS1and SEPSECS, dietary intake of potassium with IL21, alcohol consumption with IL12B, dietary heme iron intake with FcgRIIA and serum level of 25-hydroxyvitamin D with VDR. No genome wide environment interaction studies (GWEIS) of IBD have been conducted to date, while this strategy holds great potential to unravel the missing heritability influenced by environment factors for IBD.

Conclusion

While past studies have increased insights into potential gene-environmental interactions in the pathophysiology of IBD, current evidence is limited and inconclusive due to lack of replication of presented results, and limited study power. Further research, including GWEIS and clinical trials, is needed for future recommendations on lifestyle and dietary modification, based on individual genetic backgrounds.
P1165 Epidemiology and distinct features of inflammatory bowel disease in South Asia: a systematic review
Authors: Shenoy S , Jena A , Levinson C , Sharma V , Deepak P , Aswani-Omprakash T , Sebastian S , Colombel J F , Agrawal M
Published: January 2024

Background

Inflammatory bowel disease (IBD) is rising at an alarming rate in South Asia (SA, Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka). However, studies detailing the epidemiology and clinical features of IBD in this region are limited. The purpose of this review is to comprehensively synthesise data on IBD in South Asia.

Methods

We developed and performed a systematic search in four biomedical electronic databases (Ovid Medline, Embase (Ovid), Global Health, Web of Science) and in relevant scientific meeting abstracts to identify all observational and interventional studies on the epidemiology, natural history, phenotype, therapeutics, and psychosocial features of IBD in SA from inception to November 15, 2021. The titles and abstracts of all the publications were screened and reviewed by two independent reviewers (SS, AJ). A descriptive review of the relevant data extracted from the selected publications was analysed.

Results

Of 11,673 eligible studies, 4416 were duplicates, 800 were reviewed in full text, and 413 were eligible for inclusion in one or more categories.

The following are the main findings of the systematic review: IBD incidence is higher in SA compared to other Asian countries. Similarly, IBD incidence and period prevalence are higher among SA immigrants compared to other immigrants. Ulcerative colitis (UC) is more prevalent than Crohn’s disease (CD) in SA across all age groups. Family history of IBD is important risk factor for IBD in SA. The mean delay in IBD diagnosis in SA is 2 years, and it is associated with increased risk of strictures and surgery. Male sex, small intestinal disease, perianal involvement, and penetrating and stricturing disease behaviour are predictors of surgery in CD. Disease duration and extent of colitis are risk factors for colorectal cancer. Colonic distribution and inflammatory behaviour is common in CD, whereas left sided colitis is common in UC. Steroids and azathioprine are mainstays of treatment, biologic use is less than 2%. Depression, anxiety, and post-traumatic stress are common among SA patients with IBD.

Conclusion

This comprehensive review highlights the current epidemiological trends and features of IBD in SA. Contrary to previous viewpoints, IBD in SA is similar in severity, complications, and burden as that in developed countries, and warrants urgent clinical interventions and allocation of resources.
P1167 Inflammatory Bowel Disease: a phenome-wide pre- and post-diagnostic association study
Authors: Ebert A , Elmahdi R , Poulsen G , Bøgsted M , Verstockt B , Lees C , Jess T
Published: January 2024

Background

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is known to be associated with various extra-intestinal manifestations, impacting organ systems beyond the gastrointestinal tract. Identifying comorbidities in IBD and the timing of their development can provide valuable insight into the mechanisms underlying IBD development.

Methods

We conducted the first population- and disease-wide phenomic association study in IBD, using >6 million ICD-10 coded healthcare contacts from 10 years before and up to 17 years after IBD diagnosis to investigate associations with 1583 diseases. To explore co-morbidities with potential aetiological significance with IBD, we additionally assessed the strength of association with all diseases in the pre-diagnostic compared with the post-diagnostic period. To correct for multiple testing, we adjust our significance threshold (p<0.05) with the Bonferroni correction, resulting in an adjusted p-value of 7.90×10, which we refer to as disease-wide statistical significance.

Results

We identified 312 disease-wide statistically significant associations with 125 of these diseases appearing up to 10 years before diagnosis. The risk of immune-mediated diseases and extra-intestinal manifestations are among those diseases increased up to 10 years prior to IBD diagnosis (psoriasis: CD-RR: 2.57, 95% CI: 2.00-3.29; UC-RR: 1.54, 95% CI: 1.25-1.87; enteropathic arthropathies: CD-RR: 3.57, 95% CI: 2.65-4.78; UC-RR: 1.8, 95% CI: 1.38-2.32). This was also the case for gastroenterological and liver disorders (gall stones: CD-RR: 1.82, 95% CI: 1.62-2.04; UC-RR: 1.26, 95% CI: 1.15-1.37; acute pancreatitis: CD-RR: 1.83, 95% CI: 1.30- 2.53; UC-RR: 2.27, 95% CI: 1.84-2.79). The risk of cardiometabolic diseases and neuropsychological disorders had increased disease-wide statistical significance both pre- and post-diagnostically, whereas potential sequelae of treatment, such as osteoporosis (CD-HR: 2.56, 95% CI: 2.30-2.86; UC-HR: 1.92, 95% CI: 1.79-2.07) or herpes simplex infections (CD-HR: 4.04, 95% CI: 2.76-5.91; UC-HR: 1.69, 95% CI: 1.2-2.38) were primarily seen post-diagnostically. Of potential aetiological importance to CD, diagnosis with infectious mononucleosis (RR: 1.87, 95% CI: 1.37-2.52) was significantly associated with the pre- compared to the post-diagnostic period.

Conclusion

Our results demonstrate IBD as an essentially multisystemic disease, particularly manifesting as gastrointestinal, metabolic, immune, and neuropsychological disorders, present up to 10 years prior to IBD diagnosis. Infectious diseases of aetiological interest identified warrant further investigation.
P1168 Anthropometric trajectories prior to the development of inflammatory bowel disease in Danish school-aged children and adolescents from 1997 to 2017
Authors: Brusco De Freitas M , Juul Poulsen G , Jess T
Published: January 2024

Background

Compromised nutritional status during the disease course can be a major clinical challenge in children diagnosed with inflammatory bowel disease (IBD). However, a key question is knowing how long these changes precede the disease; to this end, the impact of childhood-onset IBD on mean Z-scores for length/height (HAZ), weight (WAZ) and body mass index (BAZ) before and after IBD diagnosis will be evaluated.

Methods

The study used a nationwide children's database that collects health information from health visitors and school nurses and linked these data to anthropometric measurements at birth, diagnosis and family history obtained from national registries. Individuals with birth weight and length/height measurements and at least two weight and length/height measurements (at least one at school age) within +/- 4 SD at ages 1-16.5 years were included. Within this population, individuals with IBD diagnosed by two hospital contact at age 5-17 years were identified. Age- and sex-specific Z-scores were computed using generalized additive models for location scale and shape models on the study population and applied to the IBD population. Linear mixed models were used to estimate mean Z-scores in years before and after IBD diagnosis.

Results

In the period 1997-2017, data from 1,305,852 schoolchildren were recorded, and the final sample, after applying the inclusion and exclusion criteria, was 707,918 individuals with a median of 3 pairs of height and weight (IIQ: 2, 5) measurements collected. There were 1,424 cases of IBD [Crohn disease (CD), n= 784; ulcerative colitis (UC), n= 640] with a mean age at diagnosis of 14.16 years old. Preliminary data (results presented in the figure) show that the decline of WAZ, HAZ and BAZ markers in schoolchildren was observed years before IBD diagnosis, remaining for a later period, with a different pattern among individuals diagnosed with CD or UC. Individuals with a later diagnosis of CD, compared to UC, became progressively less healthy, showing a clear decline in anthropometric markers approximately 3 years earlier (UC individuals approximately 1 year earlier) and with a slower recovery after diagnosis.

Conclusion

Preliminary findings show that impaired linear growth and lower weight and body mass index can be observed at least 3 years before diagnosis in schoolchildren with CD and that they are more prominent in this population compared to UC cases. These results emphasize the importance of frequent nutritional screening and monitoring, with the aim of identifying the need for early intervention and providing a healthy transition to adulthood.
P1169 Multimorbidity and Disease Trajectories in Patients with INFLAMMATORY BOWEL DISEASES: Insights from Observational and Genetic Analyses
Authors: Jiang F , Zhao J , Chen J , Wang L , Yuan S , Kalla R , Wellens J , Nowak J , Larrson S , Ludvigsson J , Satsangi J , Theodoratou E , Li X
Published: January 2024

Background

The multi-morbidity pattern of inflammatory bowel disease (IBD) remains under-explored. We integrated both observational and genetic data to elucidate multisystem comorbidities and health consequences of IBD.

Methods

Phenome-wide association study (PheWAS) based on the international classification of disease (ICD)-diagnosed IBD was conducted to explore its associations with 1,053 unique clinical outcomes in the UK Biobank. Disease trajectory analyses were implemented to illustrate sequential patterns of IBD-related comorbidities. The associations of genetic liability to IBD proxied by a polygenic score with identified clinical outcomes were examined to strengthen causality (N=385,917). To investigate potential shared genetic bases and causality, we performed a cross-trait linkage disequilibrium score regression (LDSC) and two-sample Mendelian randomization (TSMR) analysis using the FinnGen biobank (N=377,277). The impact of IBD subtypes and the age at diagnosis were also evaluated in sensitivity analyses.

Results

A total of 5,782 cases with IBD (3,940 cases with UC and 1,800 cases with CD) were diagnosed at baseline in the UK Biobank. Observational PheWAS revealed elevated risks of all-cause mortality with HRs of 1.34 (95%CI=1.24-1.45, P<0.001), 1.61 (95%CI=1.41-1.83, P<0.001) and 1.22 (95%CI=1.10-1.34, P<0.001) for patients with IBD, CD or UC respectively. Increased mortality risk was noted across pediatric, early-onset, and later-onset IBD patients. Sequential patterns of IBD-related comorbidities were primarily found in cardiometabolic, respiratory, digestive and autoimmune diseases. The polygenic PheWAS, LDSC and TSMR analyses supported both strong genetic correlations and causal associations of IBD with immune-mediated (notably psoriatic arthropathies, psoriasis, dermatitis, asthma) as well as non-autoimmune diseases ( pneumonia, anemias, and renal failure).

Conclusion

Our observational and genetic analyses suggest multisystem comorbidities and consequences of IBD, highlighting the need for multidisciplinary clinical management and investigation of shared biologically or genetically regulated mechanisms in the pathogenesis of IBD.
P1174 The disease course of elderly patients with Inflammatory Bowel Disease two years prior to their death
Authors: Majchrzak K , Lo B , Bendtsen F , Burisch J
Published: January 2024

Background

The number of elderly patients with inflammatory bowel disease (IBD) is increasing. Hence, more patients will be dying with their IBD. Limited research has examined the disease course of IBD in the aging body, particularly in the period preceding their death. The purpose of this study was to investigate the disease course of elderly IBD patients leading up to the end of their lives.

Methods

This was a nationwide population-based study using the national Danish registries. We used a validated algorithm to identify patients that were diagnosed with Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) in a period between 1976-2018 from the Danish National Patient Registry. This information was linked with other national Danish registers which provided data on dates of death, cancer, hospitalisations, and corticosteroid usage. We included 6,183 IBD patients aged 65 and above at death, with no cancer or palliative treatment at the time of death. We analysed IBD-related hospitalisations, corticosteroid usage, and disease relapses (defined as a combined endpoint of corticosteroid prescription and/or hospitalisation, or both), in the two-year period before death.

Results

We analysed CD, UC and IBDU patients separately, and observed a noticeable spike in hospitalisations, prescription rates of corticosteroids and disease relapses in the last two months before the IBD patients’ death. Out of 6,183 IBD patients, 954 (15.43%) were hospitalised in the last two years before their death (see Table 1 for key characteristics). In the last two months, hospitalisation rates were 139 (28.66%) for CD patients, 155 (23.96%) for UC patients and 83 (34.87%) for IBDU patients. Corticosteroids were prescribed to 1,054 (17.05%) out of 6,183 IBD patients, and in the last two months 90 (20.45%) CD patients, 149 (20.13%) UC patients, and 67 (19.36%) IBDU patients received a corticosteroid treatment. Overall, 1,652 (26.72%) IBD patients experienced a disease relapse two years preceding their death, and during the last two months, 553 (22.45%) CD patients, 194 (24.01%) UC patients and 228 (20.25%) IBDU patients experienced relapses.

Conclusion

During the two-year period prior to death, we observed that hospitalisation, prescription, and relapse rates were highest during the final two months of life. For better understanding of the disease course of elderly IBD patients, further research should investigate the cause of death and differences between early- and late disease-onset patients as well as establish a cohort for comparison.
P1191 Genetic determinants for smoking behaviour improve our understanding of sporadic versus familial Inflammatory Bowel Disease
Authors: Jans D , Abakkouy Y , Becelaere S , Verstockt S , Vermeire S , Cleynen I
Published: January 2024

Background

Inflammatory bowel disease (IBD) is influenced by genetic and environmental factors. The latter are often difficult to quantify and may vary over time, unlike genetics. Here, instead of looking at actual smoking behaviour, we explored the impact of genetic determinants of smoking behaviour on IBD risk in sporadic and familial IBD.

Methods

We calculated polygenic scores (PRS) for smoking initiation, smoking cessation, age of smoking initiation, and cigarettes per day in 2784 sporadic cases (1700 CD, 1084 UC), 682 non-IBD controls, and 60 multiplex IBD families with ≥3 affected first-degree relatives (FDR) (142 CD, 31 UC and 100 unaffected FDR). PRS were calculated for different p-value thresholds (5e-8, 1e-5, 0.01, 0.05, 0.1, 0.5 and 1), and based on effect estimates of Saunders et al (Nature 2022, table 1). Groups were compared using logistic regression. P<1.43e-3 was the significance threshold for Bonferroni correction.

Results

Sporadic IBD cases had a higher PRS for smoking initiation than controls (p=4.49e-3), which was driven by the CD cases (p=7.17e-4, fig 1A). CD cases also showed a trend for a higher PRS for cigarettes per day (p=0.026). In familial cases compared to unaffected FDR, we observed some differences in PRS for smoking, but none survived multiple testing (fig 1B). Comparing familial and sporadic cases, we found that the PRS for age at smoking initiation was higher in familial than in sporadic UC (p=9.09e-4, fig 1C). Familial CD showed a trend towards a lower PRS for age at smoking initiation (p=0.023) and smoking cessation (p=0.013) than sporadic CD. Familial CD cases are thus more at risk than sporadic CD cases as they genetically tend to start smoking younger, while the opposite is seen for UC. Also, unaffected FDR of UC families showed a lower PRS for age at smoking initiation (p=5.47e-5, fig 1D) than controls, giving them additional protection. The PRS for smoking cessation (p=3.88e-5) and cigarettes per day (p=4.47e-3) was greater in unaffected FDR of mixed families than in controls, while familial mixed cases had a lower cigarettes per day PRS than sporadic cases (p=1.59e-4).

Conclusion

We found that genetic determinants of smoking behaviour are associated with disease risk in familial and sporadic IBD. While CD risk overall is associated with a greater genetic propensity for smoking initiation, the higher risk in families is linked to genetic age at start of smoking. Meanwhile, unaffected FDR of these families are protected through a higher genetic propensity to stop smoking in mixed families, or to start smoking sooner in UC families, compared to population controls. This study improves our understanding of familial vs sporadic IBD, and could help stratify individuals at risk of IBD.
P1193 NOD2 and Beyond: Unmasking Tobacco-Induced Epigenetic Changes in Crohn's Disease
Authors: Vañó I , Monfort Ferré D , Boronat Toscano A , Menacho M , Valldosera G , Caro A , Clua Ferré L , Suau R , Manyé J , Serena C
Published: January 2024

Background

Smoking has been shown to have a very negative impact on Crohn's disease (CD). Indeed, this harmful habit induces the early onset of the disease and doubles the risk of postoperative recurrence. This research project involves a thorough analysis of omics data, with a primary focus on DNA methylation, one of the most prevalent epigenetic modifications. Our hypothesis is that tobacco-induced alterations in gene methylation pattern of subcutaneous adipose tissue (SAT), particularly within key pathways, contribute to a more adverse disease profile in smokers.

Methods

A comprehensive epigenome-wide analysis was conducted using the Illumina EPIC/450k array to investigate subcutaneous adipose tissue in patients with CD, encompassing both smokers and non-smokers. Utilizing tools such as dmpfinder and Bumphunter (minfi), differentially methylated positions (DMPs) and regions (DMRs) were identified. Additionally, gene expression analysis for key genes was performed to establish correlations between methylation and subsequent gene expression, not only in SAT but also in other fat depots such as visceral adipose tissue (VAT) or peripheral blood mononuclear cells (PBMCs).

Results

A distinctive DNA methylation pattern in the SAT of smokers compared to non-smoker CD patients was identified (Fig. 1A). Over 27,270 DMPs associated with significant biological processes related to DNA damage, inflammation, or immunity were uncovered (Fig. 1B-C). Additionally, more than 13,000 DMRs located in the promoter region were identified (Fig. 1C). The relationship between methylation levels in the promoter regions and subsequent gene expression on SAT was validated for selected genes. Specifically, NOD2 exhibited higher DNA methylation in the promoter region among smokers compared to non-smokers CD patients (p value=0.04), resulting in reduced NOD2 gene expression on SAT (p value=0.04) (Fig.1D). Consistent results were observed in other tissues such as VAT and PBMCs (Fig. 1E). Finally, we observe the implication of NOD2 in pathways related to immune response, inflammation or apoptosis and a trend indicating that lower NOD2 expression is associated with higher levels of C-reactive protein (CRP)(Fig. 1F).

Conclusion

Our study reveals that smoking produces DNA methylation changes on SAT of CD patients and affects the expression of several key genes involved in the pathogeny of CD. Particularly, our results unveil a new link between tobacco-smoking and lower NOD2 expression and associate this to an elevated levels of PCR, paving the way for a fresh perspective in exploring disease prognosis.
P1196 Genomic structural variation and polygenic risk score for Inflammatory Bowel Disease
Authors: Jun Y K , Jeong J , Kim B M , Kim J , Choi Y , Shin C M , Park Y S , Kim N , Lee D H , Lee S , Yoon H
Published: January 2024

Background

Genome-wide association studies (GWAS) of patients with inflammatory bowel disease (IBD) have identified multiple single-nucleotide polymorphisms (SNPs) and genetic variants involving structural changes in the DNA sequence. SNPs and structural variants (SVs) can play a crucial role in IBD pathogenesis. In this study, we evaluated large deletions induced by SVs in patients with IBD. Additionally, we evaluated the ethnic contribution to a polygenic risk score (PRS) for IBD.

Methods

Seventy-five Patients with IBD of Korean ancestry from Seoul National University Bundang Hospital (SNUBH) were subjected to whole-genome sequencing (49 patients with UC and 26 patients with CD). SVs involving large deletions were detected and analyzed by using the Genome Aggregation Database (gnomAD) and AnnotSV. The SVs were prioritized based on a list of 241 IBD-associated SNPs identified in the previous GWAS. The prediction performance of European- and Korean-derived PRSs for IBD was also evaluated. For calculating PRS, we applied previously published models derived from the European and Korean populations, respectively, and used Korean Genome and Epidemiology Study (KoGES) database as the Korean controls.

Results

We found a total of 146 SVs involving large deletions in the IBD cohort. Among them, 10 SVs were annotated as likely pathogenic, according to AnnotSV and American College of Medical Genetics and Genomics guidelines; 24 SVs had the probability of being loss-of-function intolerant (pLI ≥ 0.9). We found that the frequency of large deletions that overlapped with the regions coding NOTCH1, HGF, PTPN2, and SENP7 were rare in the IBD cohort compared to the gnomAD population (Table). The large deletions that overlapped with the regions coding IL2RA, ITGA4, BANK1, and STAT3 were identified in the IBD cohort but not in the gnomAD population. The PRS for IBD in the IBD cohort was significantly higher than that in the Korean controls under the Korean- or European-derived model (Figure A). However, the PRSs for CD or UC were not able to distinguish patients with CD and UC in the IBD cohort (Figure B and C).

Conclusion

Our finding suggests that SVs involving large deletion may be an important genomic variability in predicting the development of IBD. The PRS for IBD can predict IBD development without ethnic specificity.
P1198 Pediatric inflammatory bowel diseases in patients with genetic syndromes: a case-control multicentre SIGENP study
Authors: Di Sario F , Olivetti L , Felici E , Garassino C , Labriola F , Branislava C , Pensabene L , Murone P , Arrigo S , Ancona S , Zuin G , Colella G , Penagini F , Martinelli M , Miele E , Fioretti M T , Graziano F , D'Arcangelo G , Bramuzzo M , Lega S , Catassi C , Gatti S
Published: January 2024

Background

Genetic syndromes are associated with a strong susceptibility to autoimmune disorders with an increased risk of developing inflammatory bowel diseases (IBD). However, data regarding the impact of genetics in the development of IBD are limited (Gatti S. et al, Frontiers in Pediatrics 2021). Furthermore, patients with genetic syndromes are affected by multiple comorbidities which increase diagnostic and therapeutic complexity as well as the risk of developing adverse reactions to drugs.

Methods

In this retrospective, multicenter case-control study, we recruited IBD children with a genetic syndrome (cases: group 1) and 2 matched IBD patients for each case (controls: group 2) comparable for gender, age at diagnosis, type of IBD and follow-up period. IBD subjects were diagnosed at 11 Italian pediatric IBD units between 2010 and 2022. Monogenic VEO-IBD were excluded. Genetic data were collected. Clinical and disease characteristics, presence of comorbidities, use of drugs and side effects, surgical outcomes and mortality were compared at diagnosis and at the last follow-up between the 2 groups.

Results

A total of 23 IBD children with a genetic condition/syndrome (Table 1) and 46 matched controls were identified.

In all cases, except 5 the diagnosis of IBD followed the genetic diagnosis. Thirty patients had Crohn’s disease (CD) and 39 had Ulcerative Colitis (UC). The 2 groups were comparable in terms of gender, age at diagnosis (8,9±4.6 vs 9.4±4.4 years), duration of follow up (5.6±3.4 vs 4.1±2.9 years) and severity of disease at diagnosis evaluated by w-PCDAI (34,7±23,5 vs 43,1±20,4) and PUCAI (45,3±16 vs 46,2±15,5) scores. Diagnostic delay was longer in patients with genetic conditions compared to controls, without reaching statistical significance (11,1 vs 4,6 months; p= 0,06). Prevalence of comorbidities was significantly higher in group 1 compared to controls both at diagnosis (43,4 vs 11,5%; p <0,005) and at last follow-up (39,1 vs 11,6%; p <0,02). Use of immunosuppressors, steroids and biologic drugs was similar at diagnosis and at last follow-up in the 2 groups. More IBD patients in group 1 developed side effects related to immunosuppressors (26 vs 4%; p < 0,02), while no difference was observed in biologics-related side effects. The need of surgery was comparable in the 2 groups (13 vs 13,9 %), whereas mortality was slightly higher in patients with IBD and genetic syndrome (13 vs 7%).

Conclusion

In pediatric IBD patients the presence of genetic syndromes does not significantly modify the course of the disease itself, but increases complexity due to the multiple comorbidities and immunosoppressive drug toxicity.
P1199 An Inflammatory Bowel Diseases Integrated Resources Portal (IBDIRP)
Authors: Nie K
Published: January 2024

Background

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease (CD), is a chronic and debilitating gastrointestinal disorder that affects millions of people worldwide. Research on IBD has generated massive amounts of data, including literature, metagenomics, metabolism, bioresources, and databases. We aim to create an IBD Integrated Resources Portal (IBDIRP) that provides the most comprehensive resources for IBD.

Methods

An integrated platform was developed that provides information on different aspects of IBD research resources, such as single nucleotide polymorphism, genes, transcriptomics, microbiota, metabolism, single cells, and other resources. Valuable and comprehensive IBD-related data were collected from PubMed, Google, GMrepo, gutMega, gutMDisorder, Single-cell Portal, and other sources. Then, the data were systematically sorted, and these resources were manually curated.

Results

We systematically sorted and cataloged more than 312 unique risk single nucleotide polymorphism associated with IBD in the single nucleotide polymorphism section. We presented over 890 IBD-related genes based on the database collection in the gene section. We also obtained 153 manually curated IBD transcriptomics data, including 12,388 samples, on the GEO database. The sorted IBD-related microbiota data from three primary microbiome databases (GMrepo, gutMega, and gutMDisorder) were available for download. We selected 23,149 IBD-related taxonomic records from these databases. Additionally, we collected 24 IBD metabolism studies with 2,896 participants in the metabolism section. We introduced two interactive single-cell data plug-in units that provided data visualization based on cells and genes. Finally, we listed 18 significant IBD web resources, such as the official ECCO and IOIBD websites, IBD scoring tools, IBD genetic and multi-omics resources, IBD biobanks, and other useful research resources.

Conclusion

The IBDIRP website is the first integrated resource for global IBD researchers. This portal will help researchers by providing comprehensive knowledge and enabling them to reinforce the multi-dimensional impression of IBD. The IBDIRP website is accessible via www.ibdirp.com.