Inflammatory Bowel Disease Database Research Articles

Identifying Common Genetic Etiologies Between Inflammatory Bowel Disease and Related Immune-Mediated Diseases.

Patients with inflammatory bowel disease (IBD) have an increased risk of developing immune-mediated diseases. However, the genetic basis of IBD is complex, and an integrated approach should be used to elucidate the complex genetic relationship between IBD and immune-mediated diseases. The genetic relationship between IBD and 16 immune-mediated diseases was examined using linkage disequilibrium score regression. GWAS data were synthesized from two IBD databases using the METAL, and multi-trait analysis of genome-wide association studies was performed to enhance statistical robustness and identify novel genetic associations. Independent risk loci were meticulously examined using conditional and joint genome-wide multi-trait analysis, multi-marker analysis of genomic annotation, and functional mapping and annotation of significant genetic loci, integrating the information of quantitative trait loci and different methodologies to identify risk-related genes and proteins. The results revealed four immune-mediated diseases (AS, psoriasis, iridocyclitis, and PsA) with a significant relationship with IBD. The multi-trait analysis revealed 909 gene loci of statistical significance. Of these loci, 28 genetic variants were closely related to IBD, and 7 single-nucleotide polymorphisms represented novel independent risk loci. In addition, 14 genes and 514 proteins were found to be associated with susceptibility to immune-mediated diseases. Notably, IL1RL1 emerged as a key player, present within pleiotropic genes across multiple protein databases, highlighting its potential as a therapeutic target. This study suggests that the common polygenic determinants between IBD and immune-mediated diseases are widely distributed across the genome. The findings not only support a shared genetic relationship between IBD and immune-mediated diseases but also provide novel therapeutic targets for these diseases.

Expression Analysis of Long Noncoding RNA-MALAT1 and Interleukin-6 in Inflammatory Bowel Disease Patients.

Inflammatory bowel disease (IBD) manifests as chronic inflammation within the gastrointestinal tract. The study focuses on a long noncoding RNA (lncRNA) known as Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1's misregulation has been linked with various autoimmune diseases and regulates proinflammatory cytokines. The role of IL6 in immune-triggered conditions, including IBD, is another focal point. In this research, the expression of MALAT1 and IL6 in IBD patients was meticulously analyzed to uncover potential interactions. The study involved 33 IBD patients (13 with Crohn's disease and 20 with ulcerative colitis) and 20 healthy counterparts. Quantitative real-time polymerase chain reaction determined the MALAT1 and IL6 gene expression levels. The competitive endogenous RNA (ceRNA) regulatory network was constructed using several tools, including LncRRIsearch and Cytoscape. A deep dive into the Inflammatory Bowel Disease database was undertaken to understand IL6's role in IBD. Drugs potentially targeting these genes were also pinpointed using DGIdb. Results indicated a notable elevation in the expression levels of MALAT1 and IL6 in IBD patients versus healthy controls. MALAT1 and IL6 did not show a direct linear correlation, but IL6could serve as MALAT1's target. Analyses unveiled interactions between MALAT1 and IL6, regulated by hsa-miR-202-3p, hsa-miR-1-3p, and has-miR-9-5p. IL6's pivotal role in IBD-associated inflammation, likely interacting with other cytokines, was accentuated. Moreover, potential drugs like CILOBRADINE for MALAT1 and SILTUXIMAB for IL6 were identified. This research underscored MALAT1 and IL6's potential value as targets in diagnosis and treatment for IBD patients.

A quality assessment of inflammatory bowel disease nursing care in Finland: a nationwide cross-sectional descriptive study

Objectives of the article Inflammatory bowel disease (IBD) nursing has been identified as a crucial component in the IBD service delivery. This article aims to provide a comprehensive overview of the state of IBD nursing care in Finland, and to identify areas that would benefit from further research. Materials and methods Tertiary IBD outpatient clinics nationwide were invited to participate in a cross-sectional descriptive study conducted using an electronic survey. The quality of IBD nursing services was assessed using the Nursing Care Quality in IBD (NCQ-IBD) evaluation tool. Results Of the 34 identified clinics, 27 participated (79.4%) in the study. The NCQ-IBD tool classifies the clinics in four categories, where A indicates the highest level of quality, and D the lowest. In this study, 26 clinics (96.3%) were classified at level C, and one clinic (3.7%) at level D. Nursing responsibilities in IBD management and informing the patients were at a high level of quality, whereas nursing research in IBD was at a low level. An IBD database (i.e. clinical IBD registry) was in use only in 10 clinics. Although training in the clinical aspects of IBD was readily available, there was a lack of training plans for IBD, and clinics seldom held an annual review of the IBD nursing activities and outcomes. There were very few clinics using structured indices and questionnaires, and only 16 clinics (59.3%) applied a written IBD protocol. Conclusion In the Finnish IBD nursing service, as measured with the NCQ-IBD tool, several areas for future improvement were identified.

Management of the Rectal Stump after Subtotal Colectomy Operations for Inflammatory Bowel Disease in the Era of Immunologic Therapy: A Two-Centre Cohort Study

Introduction: Inflammatory bowel disease (IBD) often requires surgical resection, such as subtotal colectomy operations to alleviate symptoms. However, IBD also has an inherently increased risk of colorectal dysplasia and cancer. Despite the well-accepted surveillance guidelines for IBD patients with an intact colon, contemporaneous decision-making models on rectal stump surveillance is sparse. This study looks at the fate of rectal stumps in IBD patients following subtotal colectomy. Methods: This is a two-centre retrospective observational cohort study. Patients were identified from NHS Grampian and NHS Highland surgical IBD databases. Patients that had subtotal colectomy between January 01, 2010 and December 31, 2017 were included with the follow-up end date on April 1, 2021. Socio-demographics, diagnosis, medical and surgical management data were collected from electronic records. Results: Of 250 patients who had subtotal colectomy procedures, only one developed a cancer in their rectal stump (0.4%) over a median follow-up of 80 months. A higher than expected 72% of patients had ongoing symptoms from their rectal stumps. Surveillance was varied and inconsistent. However, no surveillance, flexible sigmoidoscopy, or MRI identified dysplastic or neoplastic disease. Conclusion: Based on our results, we estimate that the prevalence of rectal cancer is lower than previously reported. Surveillance strategy of rectal stump varied as no current guidelines exist and hence is an important area for future study. Given the relatively low frequency of rectal cancer in these patients, and the low level of evidence available in this field, we would propose a registry-based approach to answering this important clinical question.

Safety of full bowel preparation and colonoscopy in elderly patients with ulcerative colitis: A real-world multicenter retrospective cohort study.

The number of elderly patients with ulcerative colitis (UC) has been increasing worldwide. Complications are common in elderly patients who undergo colonoscopy, raising doubts about whether colonoscopy should be performed in the same way in this age group as in younger patients. The aim of this study was to determine the safety of full bowel preparation and colonoscopy in elderly patients with UC. We retrospectively reviewed a cohort of patients with UC who had visited any of the 12 hospitals and were registered in our inflammatory bowel disease database. We compared complications associated with colonoscopy and bowel preparation and relapse of UC after colonoscopy in 133 patients aged ≥65 years with UC (the elderly group) and 116 randomly selected patients aged <65 years with UC (the non-elderly group). Nine elderly patients were not referred for colonoscopy by their physicians because of poor performance status or advanced age. There was no significant between-group difference in the complication rate (p = 0.57) or frequency of relapse of UC after colonoscopy (p = 0.67). The findings of this study indicate that colonoscopy can be performed as safely in elderly patients with UC as in their younger counterparts. However, our results also indicate that colonoscopy is often avoided in elderly patients, possibly because of concerns about safety.

Crohn's Disease as a Possible Risk Factor for Failed Healing in Ileocolic Anastomoses.

Anastomotic leakage (AL) after colorectal resections is a serious complication in abdominal surgery. Especially in patients with Crohn's disease (CD), devastating courses are observed. Various risk factors for the failure of anastomotic healing have been identified; however, whether CD itself is independently associated with anastomotic complications still remains to be validated. A retrospective analysis of a single-institution inflammatory bowel disease (IBD) database was conducted. Only patients with elective surgery and ileocolic anastomoses were included. Patients with emergency surgery, more than one anastomosis, or protective ileostomies were excluded. For the investigation of the effect of CD on AL 141, patients with CD-type L1, B1-3 were compared to 141 patients with ileocolic anastomoses for other indications. Univariate statistics and multivariate analysis with logistic regression and backward stepwise elimination were performed. CD patients had a non-significant higher percentage of AL compared to non-IBD patients (12% vs. 5%, p = 0.053); although, the two samples differed in terms of age, body mass index (BMI), Charlson comorbidity index (CCI), and other clinical variables. However, Akaike information criterion (AIC)-based stepwise logistic regression identified CD as a factor for impaired anastomotic healing (final model: p = 0.027, OR: 17.043, CI: 1.703-257.992). Additionally, a CCI ≥ 2 (p = 0.010) and abscesses (p = 0.038) increased the disease risk. The alternative point estimate for CD as a risk factor for AL based on propensity score weighting also resulted in an increased risk, albeit lower (p = 0.005, OR 7.36, CI 1.82-29.71). CD might bear a disease-specific risk for the impaired healing of ileocolic anastomoses. CD patients are prone to postoperative complications, even in absence of other risk factors, and might benefit from treatment in dedicated centers.

P617 Dual biologic therapy in pediatric Inflammatory Bowel Disease

Abstract Background There is paucity of data on the effectiveness of combination biologic agents as an option for children with refractory inflammatory bowel disease (IBD) that is inadequately controlled by biologic monotherapy. The aims of this study were to determine the effectiveness and safety of combination biologic use in pediatrics IBD. Methods A retrospective cohort study of children with IBD seen at Sidra Medicine and who received combination biologic therapy from October 2018 to April 2022. The diagnosis of IBD was established according to the revised Porto criteria. Children with IBD on two or more biologics were identified from our IBD database and their electronic medical records were reviewed. Patients included in the study must have been on combination biologic therapy for at least two months. Relevant clinical and demographic data were collected. Results Out of the 211 patients in our IBD database, we identified a total of 14 patients who had received dual biologic therapy within the study period. 3 patients were excluded because they had received dual biologic therapy for less than 2 months. 11 patients with IBD met our inclusion criteria and were included in this study. All 11 patients had Crohn’s disease. Overall, 7 patients (63%) were male, the median age at the start of starting combination therapy was 15.1 years (IQR 13.9 to 17.4), and the median disease duration was 2.3 years (IQR 1.4 to 3.2). Patients had been on the first biologic for a median of 20.3 months (IQR 13.0 to 32.3) before the addition of the second biologic. The reasons for dual biologic therapy included active disease, failure of single biological therapy, and development of complications. The patients had failed therapy with a median of two (range 1-3) prior biological medications. Concomitant dermatological disease (psoriasis) was present in one patient (9.1%). After a median follow-up of 5.2 months (IQR 2.9-5.5), median PCDAI significantly reduced from 22.5(IQR 16.75-30) to 5(1.25-13.75) {P&amp;lt;0.001}…Figure 1. Median fecal calprotectin reduced from 1534 (1361-1612) to 489 (379-658) {P&amp;lt;0.001}. No adverse events were noted. Conclusion Dual biologic therapy was associated with clinical and biomarker improvements in patients with Crohn’s disease who previously failed at least one single biologic. Dual biologic treatment was not associated with adverse events during the study period. Dual biologic therapy may be an attractive strategy but the lack of randomized controlled trials as well as long-term safety concerns means that there is a need for further trials on this subject. Future studies should assess risk: benefit ratios, safety, and efficacy of specific combinations of biologic use in IBD.

P247 Oncostatin M and its receptor are markers of endoscopic and histological disease activity in Inflammatory Bowel Disease

Abstract Background Oncostatin M (OSM) and its receptor (OSMR) have been associated with active disease in patients with inflammatory bowel disease (IBD). This study compared the expression of OSM and OSMR in intestinal tissue according to clinical, endoscopic, and histological disease activity. Methods A multi-centre IBD database containing RNA-sequencing datasets, was used to analyse OSM and OSMR expression in ileal and/or colonic tissue, expressed as transcripts per million (TPM). Clinical scoring systems included the Harvey Bradshaw Index for Crohn’s disease (CD) and partial Mayo score for ulcerative colitis (UC). Endoscopic scoring systems included the simple endoscopic score for CD (SES-CD) and UC endoscopic index of severity (UCEIS). Histological scoring included the modified Naini and Cortina, and Riley scores. Graphs were presented in log transformed TPM+1 values. Results 155 patients (108 CD, 47 UC) and 38 controls were included. For IBD patients, 49% were men, median age was 35 years and intestinal tissue was collected at endoscopy (73%) and surgery (27%). Compared to controls, patients with CD and UC had significantly elevated median expression of OSM (0.08, 0.29 and 0.34 TPM respectively) and OSMR (1.21, 1.69 and 3.53 TPM respectively). OSMR expression was higher in UC patients than CD (p&amp;lt;0.001). There was no difference in OSM or OSMR between Harvey Bradshaw Index categories (0-4 vs 5-7 vs 8-16) or partial Mayo scores (0 vs 1-3 vs 4-7). Endoscopically, OSM was higher for SES-CD scores of 16-51 (1.11 TPM), compared to SES-CD scores of 0-3 (0.14 TPM, p=0.003) and controls (0.08 TPM, p&amp;lt;0.0001). Median OSMR increased non-significantly with increasing SES-CD scores (score 0-3: 1.59 TPM; score 4-15: 1.90 TPM; score 16-51: 2.04 TPM). There was no difference in OSM and OSMR expression between UCEIS scores, but the most severe disease (UCEIS score 5-8) had higher expression than controls for both OSM (3.92 vs 0.08 TPM, p&amp;lt;0.001) and OSMR (6.10 vs 1.21 TPM, p&amp;lt;0.0001). Increasing expression of OSM and OSMR was found with increasing histological scores, see Figure. Using the modified Naini and Cortina score for CD, OSM and OSMR were most expressed in the highest scores compared to the lowest scores (OSM: 1.48 vs 0.09 TPM, p&amp;lt;0.001; OSMR: 5.50 vs 1.27 TPM, p=0.003). For the modified Riley score for UC, both OSM and OSMR were also able to differentiate between the highest and lowest score groups (OSM: 3.14 vs 0.12 TPM, p=0.0001; OSMR: 6.61 vs 1.58 TPM, p&amp;lt;0.0001). Conclusion This study showed that OSM and OSMR expression in intestinal tissue is associated with inflammation both histologically and endoscopically. Further investigations are needed to confirm our observations and explore the OSM pathway’s relevance in intestinal inflammation.

DOP10 Early intestinal resection in Crohn’s Disease is not associated with severe long-term disease course

Abstract Background Crohn’s Disease patients (CD) with early complicated behaviour (stenosis and/or fistula) are thought to have a more severe long-term disease course. To address this question, we focused on ileal CD that requires early intestinal resection after diagnosis. We aimed to assess the impact of the time to surgery from diagnosis on the risk of severe disease course in patients with ileal CD undergoing a primary ileocecal resection (ICR) or ileal resection (IR). Methods All CD patients who underwent ICR or IR between January 2001 and December 2015 and followed in two Inflammatory Bowel Disease (IBD) tertiary centres in France were included. Data were retrieved using dedicated IBD database and patients’ medical records. Early resection was defined as a surgery performed within 6 months after diagnosis. Two control groups with patients who underwent the first surgery between 6 months and 2 years and between 2 and 5 years after diagnosis were enrolled. The primary outcome was second intestinal resection. Secondary outcomes included the need for biologic treatments after initial intestinal surgery. Patients were followed from the date of first surgery until September 2022. Kaplan Meier survival analysis and log-rank test were used to estimate the survival without second intestinal resection and biologic initiation according to the time of first intestinal resection to diagnosis. Results Among 404 patients who underwent ICR or IR within 5 years after diagnosis, 130 (32.2%) patients had undergone surgery within 6 months after diagnosis (Group A), 138 (34.2%) patients between 6 months and 2 years (Group B) and 136 (33.7%) patients between 2 and 5 years (Group C). Clinical data are shown in Table 1. The cumulative risk of a second ICR or IR ten years after the first surgery was 25.2% (95% CI 12.5 - 40.2) in group A, 16.6% (5.1 - 33.9) in group B and 22.8% (9.8 – 39.1) in group C, without statistically significant difference (p = 0.25) (Figure 1). The risk of biological exposure after the first surgery was not significantly different in the three groups (p = 0.12) (Figure 2). The cumulative risk to start a biologic therapy at ten years was 46.2% (35.0 – 56.6) in group A, 39.0% (26.2 – 51.5) in group B and 48.0% (36.3 – 58.8) in group C. Conclusion In a bicentric cohort with long-term follow-up, intestinal resection within 6 months of CD diagnosis was not associated with an increased risk of second surgery as compared to patients with primary ICR/IR later after diagnosis. Furthermore, patients with early intestinal resection did not need more biological therapies after the first surgery. These data suggest that early intestinal resection in CD is not a predictor of poor long-term prognosis compared to late resection.

Growth After Menarche in Pediatric Inflammatory Bowel Disease.

Growth impairment in pediatric patients with pediatric onset inflammatory bowel disease (IBD) is multifactorial. Reports on the effect of age at menarche on adult stature in this population are limited. This study investigated the impact of age at menarche, disease-associated factors, and mid-parental height on growth from menarche to final height (FHt) in pediatric patients with Crohn disease (CD) and ulcerative colitis (UC) and IBD unclassified (IBD-U). Subjects were enrolled from a prospectively maintained pediatric IBD database when IBD preceded menarche and dates of menarche and FHt measurements were recorded. One hundred forty-six patients: CD 112 and UC 30/IBD-U 4. Mean age (years) at diagnosis (10.9 vs 10.1), menarche (14.4 vs 14.0), and FHt (19.6 vs 19.7). CD and UC/IBD-U patients showed significant association between Chronological age (CA) at menarche and FHt (cm, P < 0.001) but not FHt z score (FHt-Z) < -1.0 (P = 0.42). FHt-Z < -2.0 occurred in only 5 patients. Growth impairment (FHt-Z < -1.0) was associated with surgery before menarche (P = 0.03), jejunal disease (P = 0.003), low mid-parental height z score (MPH-Z) (P < 0.001), hospitalization for CD (P = 0.03) but not UC, recurrent corticosteroid, or anti-tumor necrosis factor alpha (anti-TNFα) therapy. Early age of menarche was associated with greater potential for linear growth to FHt but not FHt-Z (P < 0.05). Surgery before menarche, jejunal disease, hospitalization for CD, low MPH, and weight z score were associated with FHt-Z < -1.0.

Validity of Inflammatory Bowel Disease Diagnoses in the Danish National Patient Registry: A Population-Based Study from the North Denmark Region

PurposeThe Danish National Patient Registry (DNPR) is recognized for providing high-quality data. However, only a few minor studies have validated inflammatory bowel disease (IBD) diagnoses in the DNPR, reporting various degrees of validity. To pave the way for large-scale studies of IBD in Denmark, we aimed to investigate the validity of IBD among >8000 patients registered in the DNPR between 2002 and 2020 in the North Denmark Region.Patients and MethodsTo evaluate the reliability of the diagnoses in the DNPR, we initially compared all patients registered with one IBD diagnosis during 2002–2020 to a list of already verified patients in the regional IBD database GASTROBIO. Medical records on all DNPR registered patients not on the list were manually reviewed by a gastroenterologist to verify or dismiss the IBD diagnosis. Positive predictive values (PPV) were calculated.ResultsOf 8040 patients with at least one IBD diagnosis in DNPR, 5263 were already confirmed cases, leaving 2777 for medical record evaluation, of whom 849 had IBD. In total, 6112 were correctly registered with IBD based on one diagnosis, and 1343 were incorrectly registered, resulting in a PPV of 0.82 (95% CI, 0.81–0.83). For patients registered with at least two diagnoses, the PPV was 0.95 (95% CI, 0.95–0.96), and with at least three diagnoses, the PPV was 0.98 (95% CI, 0.98–0.99). Results were similar for UC and CD separately. Of note, the completeness of valid cases went from 6112 to 4606 (75%; 95% CI, 74%-76%) when demanding at least two registered diagnoses and to 3320 (54%; 95% CI, 53%-56%) when demanding at least three registered diagnoses.ConclusionReassuringly, the validity of IBD diagnoses in DNPR is high, especially for patients registered more than once. However, the reduced completeness when applying a true case definition of at least two registered diagnoses should be considered.

Incidence and Prevalence of Paediatric Inflammatory Bowel Disease Continues to Increase in the South of England.

The incidence of paediatric inflammatory bowel disease (IBD) has been increasing over 25 years; however, contemporary trends are not established and the impact of COVID-19 on case rates is unclear. Data from Southampton Children's hospital prospective IBD database were retrieved for 2002-2021. Incidence rates were calculated based on referral area populations and temporal trends analysed. Disease prevalence for those aged <18 years was calculated for 2017-2021. Monoclonal prescriptions were reported. In total, 1150 patients were included (mean age at diagnosis 12.63 years, 40.5% female). An estimated 704 patients had Crohn's disease (61.2%), 385 had ulcerative colitis (33.5%), and 61 had IBD unclassified (5.3%). Overall IBD incidence increased, β = 0.843, P = 3 × 10 -6 , driven by Crohn's disease, β = 0.732, P = 0.00024 and ulcerative colitis, β = 0.816, P = 0.000011. There was no change in IBDU incidence, β = 0.230, P = 0.33. From 2002-2021, 51 patients were diagnosed <6 years of age, 160 patients aged 6 to <10 years and 939 patients aged 10 to <18 years of age. Increased incidence was observed in patients aged 10 to <18 years of age (β = 0.888, P = 1.8 × 10 -7 ). There was no significant change in incidence of IBD in <6 years (β = 0.124, P = 0.57), or 6 to <10 years (β = 0.146, P = 0.54). IBD prevalence increased by an average of 1.71%/year from 2017 to 2021, β = 0.979, P = 0.004. The number of new monoclonal prescriptions increased from 6 in 2007 to 111 in 2021. IBD incidence continues to increase in Southern England. Compounding prevalence and increased monoclonal usage has implications for service provision.

Viral Enteric Infections in Acute Severe Ulcerative Colitis.

Excluding superimposed enteric infection is critical in the management of acute severe ulcerative colitis [ASUC]. Whilst infection with Clostridium difficile and cytomegalovirus have been shown to increase colectomy and mortality rates, no data exist regarding the impact of common viral enteropathogens in ASUC. Our aim was to determine if viral enteric infection in ASUC alters the severity or outcomes of these episodes. This was a retrospective review of cases presenting to a large tertiary centre. Data were obtained from an in-house, prospectively maintained inflammatory bowel disease database. We identified all ASUC cases treated between October 2015 and January 2021 and compared those testing positive for adenovirus 40/41, human rotavirus or norovirus GI by faecal multiplex polymerase chain reaction [PCR] to those testing negative. We identified 147 patients with ASUC and faecal multiplex PCR testing for viral pathogens. In total, 22/147 patients [14.9%] tested positive, two of whom tested positive for two viruses. The infected and non-infected cohorts did not differ significantly with regard to admission C-reactive protein [81.7 vs 76.6, p = 0.77], Mayo endoscopic subscore [2.4 vs 2.3, p = 0.43], length of hospital admission [7.9 vs 7.9 p = 0.99], requirement for rescue therapy [59% vs 56%, p = 0.75] or colectomy rate [4.5% vs 4.1%, p = 0.69]. Infection with viral enteropathogens was common in our ASUC cohort, but did not appear to affect disease severity at presentation, the need for rescue therapy or the success rate of rescue therapy.

COVID-19 INFECTIONS IN VACCINATED PATIENTS WITH INFLAMMATORY BOWEL DISEASE: OUTCOMES AND RISK FACTORS FOR SEVERE DISEASE

BACKGROUNDThere are limited data on coronavirus disease 2019 (COVID-19) in vaccinated patients with inflammatory bowel disease (IBD). We aimed to describe outcomes and identify risk factors for hospitalization, severe COVID-19, and death in this population.METHODSData from the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database were analyzed. Patients with IBD who received at least one vaccine dose prior to diagnosis of COVID-19 were included. Patients received mRNA (Pfizer and Moderna), adenovirus vector (CanSino, AstraZeneca, Sputnik, and Janssen), or inactivated SARS-CoV-2 (Sinovac) vaccines. Partial vaccination was defined as having not received the full complement of doses for the vaccine received. Outcomes were hospitalization, death, and severe COVID-19, a composite of intensive care unit admission, mechanical ventilation, and/or death.RESULTSAmong 141 cases, 12 (8.5%) were hospitalized, 4 (2.8%) had severe COVID-19, and 1 (0.7%) died. During the same period, proportions in the unvaccinated were 9.3%, 1.9%, and 1.2%, respectively. Nearly three-quarters of patients with COVID-19 after vaccination were on biologics and one-third were taking immunomodulators. Fewer hospitalizations occurred in those with completed vaccine series than partially complete series (5.7% vs 13.2%, p = 0.13), and in those receiving mRNA vaccines than adenovirus vector (4.7% vs 22.7%, p = 0.01) or inactivated SARS-CoV-2 (4.7% vs 16.7%, p=0.15) vaccines. Only 2.9% of those with completed mRNA series were hospitalized. Patients on biologic monotherapy were less frequently hospitalized than patients on immunomodulator monotherapy (4.2% vs 27.3%, p=0.03) or combination therapy (4.2% vs 10.0%, p = 0.36). Overall, hospitalized patients were older (mean age 50 years vs 40 years, p = 0.03). Severe COVID-19 was less common in those receiving mRNA vaccines than adenovirus vector (0.9% vs 4.6%; p = 0.31) or inactivated SARS-CoV-2 (0.9% vs 16.7%; p = 0.02) vaccines. Of the four patients with severe COVID-19, two were taking tumor necrosis factor antagonists, three were taking azathioprine, and one had chronic lung disease. The only death was in a patient on triple immunosuppression with adalimumab, azathioprine, and systemic steroids.CONCLUSIONIn patients with IBD, incomplete vaccination, non-mRNA vaccines, and immunomodulator use are associated with increased risk of adverse events during COVID-19 infections.

P654 Clinical outcomes in familial versus sporadic inflammatory bowel disease diagnosed in the era of biological therapies. Prospective data from the ENEIDA registry

Abstract Background It has been reported that familial aggregation occurs in 10–20% of inflammatory bowel disease (IBD) patients1. Familial IBD has been associated with disease anticipation2 and with an increased need for immunosuppressants3 and surgery4. However, most studies were performed before the widespread use of biological agents and this may impact on the need for surgery. We aimed to compare the clinical outcomes of IBD (by means of the need for biological therapy and abdominal surgery) between familial and sporadic forms of IBD in the era of biological therapies. Methods Data were extracted from the ENEIDA registry by GETECCU, a Spanish, prospectively-maintained, IBD database in which more than 80 centers are participating. Only adult patients diagnosed with IBD since 2005 and prospectively followed in the registry since diagnosis were included. Familial IBD was defined as those cases with at least one first-degree relative diagnosed with IBD. Sporadic IBD was defined as those cases with no familial relative (of any degree) with IBD. Kaplan-Meier survival curves were performed to evaluate the cumulative probabilities of remaining biologic-free and surgery-free. Log-rank test was performed to compare them between familial and sporadic IBD forms. Chi-square test was performed for the rest of variables. Results A total of 5,263 patients (2,627 Crohn’s disease [CD]; 2,636 ulcerative colitis [UC]) were included. Of them, 507 (10%) were familial cases (274 CD, 233 UC; P=0.05). The median follow-up was 38,4 and 35.5 months, respectively (P=0.086). Familial cases were younger (P=0.022) and had a higher proportion of females among UC cases (P=0.048). No differences were observed in the need for biological therapy in both CD and UC between familial and sporadic IBD. Regarding surgery, no differences were observed in the cumulative probabilities of a first intestinal resection for CD and colectomy for UC. Similar results were obtained when all the analyses were restricted to those subgroups at high-risk for surgery (i.e. CD with ileal involvement and extensive UC). Conclusion In patients diagnosed with IBD in the era of biological therapies, familial forms have the same requirements for biological agents and resectional surgery as sporadic forms. Therefore, familial aggregation does not seem to be a factor for a more aggressive disease.

DOP23 Long-term health consequences of COVID-19 in patients with Inflammatory Bowel Diseases – A Danish prospective population-based cohort study

BackgroundThe vast majority of patients with ulcerative colitis (UC) and Crohn’s disease (CD) who acquire coronavirus disease 2019 (COVID-19) survive the infection. Still, the long-term health consequences of COVID-19 are not well described in patients with underlying inflammatory bowel disease (IBD).MethodsWe conducted a population-based study investigating the outcomes of COVID-19 among patients with UC and CD in Denmark. The Danish COVID-19 IBD Database is an extensive population-based database which prospectively monitors the disease course of laboratory-confirmed COVID-19 among patients with UC and CD. Severe COVID-19 was defined as COVID-19 necessitating intensive care unit admission, ventilator use, or death, while adverse COVID-19 was defined as requirement of COVID-19 related hospitalization. Sequelae following COVID-19 were defined as symptoms that developed during or after an infection consistent with COVID-19, were present for more than 12 weeks, and were not attributable to alternative diagnoses.ResultsThe study included 319 patients with UC and 197 patients with CD from January 28th, 2020, to April 1st, 2021. Of these, a total of 137 (42.9%) and 85 (43.1%), respectively, participated in a subsequent investigation of post-COVID-19 sequelae after a median of 5.1 months (IQR 4.5–7.9) after infection (Table 1). An equal proportion of patients with UC (58 (42.3%)) and CD (39 (45.9%), p=0.60) reported persisting symptoms of COVID-19 for at least 12 weeks, consistent with the development of post-COVID-19 syndrome. The most common persisting patient-reported symptoms included fatigue (UC: 49 (35.8%), CD: 31 (36.5%), p=0.92), anosmia (UC: 37 (27.0%), CD: 25 (29.4%), p=0.70), ageusia (UC: 26 (19.0%), CD: 24 (28.2%), p=0.11), headache (UC: 19 (13.9%), CD: 16 (18.8%), p=0.32), dyspnea (UC: 19 (13.9%), CD: 16 (18.8%), p=0.32), and arthralgia (UC: 17 (12.4%), CD: 14 (16.5%), p=0.40) (Figure 1). Only discontinuation of immunosuppressive therapies for UC during COVID-19 (OR=1.50 (95% CI 1.07–10.22), p=0.01) and the severity of COVID-19 among patients with CD were independently associated with the long-term effects of COVID-19 (OR=2.76 (95% CI 1.05–3.90), p=0.04) (Tables 2–3). ConclusionThis Danish population-based study found a high occurrence of patient-reported persisting symptoms following the acute phase of COVID-19 infection, which were associated with the discontinuation of immunosuppressive therapies for UC during COVID-19 and the severity of COVID-19 among patients with CD. These findings might have implications for planning the healthcare of patients with inflammatory bowel diseases in the post-COVID-19 era.

COVID-19 INFECTIONS IN VACCINATED PATIENTS WITH INFLAMMATORY BOWEL DISEASE: OUTCOMES AND RISK FACTORS FOR SEVERE DISEASE

There are limited data on coronavirus disease 2019 (COVID-19) in vaccinated patients with inflammatory bowel disease (IBD). We aimed to describe outcomes and identify risk factors for hospitalization, severe COVID-19, and death in this population. Data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database were analyzed. Patients with IBD who received at least one vaccine dose prior to diagnosis of COVID-19 were included. Patients received mRNA (Pfizer and Moderna), adenovirus vector (CanSino, AstraZeneca, Sputnik, and Janssen), or inactivated SARS-CoV-2 (Sinovac) vaccines. Partial vaccination was defined as having not received the full complement of doses for the vaccine received. Outcomes were hospitalization, death, and severe COVID-19, a composite of intensive care unit admission, mechanical ventilation, and/or death. Among 141 cases, 12 (8.5%) were hospitalized, 4 (2.8%) had severe COVID-19, and 1 (0.7%) died. During the same period, proportions in the unvaccinated were 9.3%, 1.9%, and 1.2%, respectively. Nearly three-quarters of patients with COVID-19 after vaccination were on biologics and one-third were taking immunomodulators. Fewer hospitalizations occurred in those with completed vaccine series than partially complete series (5.7% vs 13.2%, p = 0.13), and in those receiving mRNA vaccines than adenovirus vector (4.7% vs 22.7%, p = 0.01) or inactivated SARS-CoV-2 (4.7% vs 16.7%, p=0.15) vaccines. Only 2.9% of those with completed mRNA series were hospitalized. Patients on biologic monotherapy were less frequently hospitalized than patients on immunomodulator monotherapy (4.2% vs 27.3%, p=0.03) or combination therapy (4.2% vs 10.0%, p = 0.36). Overall, hospitalized patients were older (mean age 50 years vs 40 years, p = 0.03). Severe COVID-19 was less common in those receiving mRNA vaccines than adenovirus vector (0.9% vs 4.6%; p = 0.31) or inactivated SARS-CoV-2 (0.9% vs 16.7%; p = 0.02) vaccines. Of the four patients with severe COVID-19, two were taking tumor necrosis factor antagonists, three were taking azathioprine, and one had chronic lung disease. The only death was in a patient on triple immunosuppression with adalimumab, azathioprine, and systemic steroids. In patients with IBD, incomplete vaccination, non-mRNA vaccines, and immunomodulator use are associated with increased risk of adverse events during COVID-19 infections.

Early versus delayed ileocolic resection for complicated Crohn's disease: is "cooling off" necessary?

BackgroundIleal Crohn’s disease (CD) complicated by intraabdominal abscess, phlegmon, fistula, and/or microperforation is commonly treated with antibiotics, bowel rest, and percutaneous drainage followed by interval ileocolic resection (ICR). This “cool off” strategy is intended to facilitate the safe completion of a one-stage resection using a minimally invasive approach and minimize perioperative complications. There is limited data evaluating the benefits of delayed versus early resection.MethodsA retrospective review of a prospectively maintained inflammatory bowel disease (IBD) database at a tertiary center was queried from 2013–2020 to identify patients who underwent ICR for complicated ileal CD confirmed on preoperative imaging. ICR cohorts were classified as early (≤ 7 days) vs delayed (> 7 days) based on the interval from diagnostic imaging to surgery. Operative approach and 30-day postoperative morbidity were analyzed.ResultsOut of 474 patients who underwent ICR over the 7-year period, 112 patients had complicated ileal CD including 99 patients (88%) with intraabdominal abscess. Early ICR was performed in 52 patients (46%) at a median of 3 days (IQR 2, 5) from diagnostic imaging. Delayed ICR was performed in 60 patients (54%) following a median “cool off” period of 23 days of non-operative treatment (IQR 14, 44), including preoperative percutaneous abscess drainage in 17 patients (28%). A higher proportion of patients with intraabdominal abscess underwent delayed vs early ICR (57% vs 43%, p = 0.19). Overall, there were no significant differences in the rate of laparoscopy (96% vs 90%), conversion to open surgery (12% vs 17%), rates of extended bowel resection (8% vs 13%), additional concurrent procedures (44% vs 52%), or fecal diversion (10% vs 2%) in the early vs delayed ICR groups. The median postoperative length of stay was 5 days in both groups with an overall 25% vs 17% (p = 0.39) 30-day postoperative complication rate and a 6% vs 5% 30-day readmission rate in early vs delayed ICR groups, respectively. Overall median follow-up time was 14.3 months (IQR 1.2, 24.1) with no difference in the rate of subsequent CD-related intestinal resection (4% vs 5%) between the two groups.ConclusionsIn this contemporary series, at a high-volume tertiary referral center, a “cool off” delayed resectional approach was not found to reduce perioperative complications in patients undergoing ICR for complicated ileal Crohn’s disease. Laparoscopic ICR can be performed within one week of diagnosis with low rates of conversion and postoperative complications.

Growth Failure in Pediatric Inflammatory Bowel Disease: A Preliminary Analysis

Background: Inflammatory bowel disease (IBD) is a chronic relapsing disease, characterized by chronic inflammation of the gastrointestinal tract (GIT). The incidence of IBD has been increasing over the last two decades, for example, from 1999- 2008 incidence increased from 21.3 to 26.2 per 100,000. Inflammatory bowel disease is mainly classified into two types: Crohn’s disease (CD), and ulcerative colitis (UC). Both types can be identified and distinguished through laboratory tests such as ESR, CRP, and fecal calprotectin, radiographic imaging, and direct visualization via colonoscopy. The etiology of growth failure in IBD, BMI z-score of less than -2.5, is poorly understood; however, chronic inflammation, low-calorie intake, and consequential steroid treatment are the most important factors. This study aims to determine the incidence of growth failure and associated factors in pediatric patients with IBD.&#x0D; Methods: This was a retrospective cohort study of children aged 15 years and below, with the diagnosis of IBD. Data were obtained from the pediatric gastroenterology department pediatric inflammatory bowel disease database from 2007 to 2017. Our study identifies the prevalence of growth failure via a calculated BMI z-score of less than -2.5 among the pediatric inflammatory bowel disease (PIBD) population. The Chi-square test is used for categorical data and Wilcoxon rank-sum test for continuous data. A p-value &lt;0.05 was considered statistically significant. All analyses were carried out with Stata IC/15.1 (StataCorp LP, College Station, TX, USA).&#x0D; Results: A total of 36 patients were included. The mean age of children with growth failure at the time of IBD diagnosis was 8 (±4), and more than half of them (58.3%) were boys. The incidence of growth failure at the time of diagnosis was 22.2% and declined to 11.1% over 26 months. Furthermore, the mean BMI z-score gradually improved from -0.741 to -0.1 over the same period of follow-up after proper management and multidisciplinary involvement.&#x0D; Conclusion: Growth failure in IBD patients according to our data is uncommon, however, it was reduced by 50% over 26 months. This could be attributed to nutritional status improvement over the management period. We recommend following the stepwise approach according to the severity of the disease and managing IBD patients by a multidisciplinary team. However, due to the relatively small sample size and low growth failure incidence, a large-scale study is recommended to determine any causal relations.

S909 Risk Factors for Colorectal Dysplasia and Colorectal Cancer (CRC) Among Patients With Inflammatory Bowel Disease (IBD) Undergoing Surveillance Colonoscopy in a Tertiary Care Center

Introduction: Patients with IBD are more likely to develop dysplasia and CRC than the general population. We aimed to evaluate risk factors for dysplasia and CRC among patients with IBD undergoing surveillance colonoscopy. Methods: We conducted a retrospective case-control study to evaluate risk factors for colorectal dysplasia/CRC in IBD patients who underwent surveillance colonoscopy in 2010-2020. Cases were patients with dysplasia/CRC found on surveillance colonoscopy and controls were those without. Dysplasia was limited to flat lesions and did not include dysplasia associated lesions/masses. Relevant data obtained from EMR included: age, gender, ethnicity, BMI, smoking status, medication hx, IBD subtype, diagnosis age, disease duration, clinical disease activity, previous IBD related surgery, h/o polyps, dysplasia, or CRC, h/o primary sclerosing cholangitis or extra-intestinal manifestations, family history of IBD, polyps, CRC, and genetic conditions. After summary statistics, logistic regression analysis was performed to examine the association between potential risk factors and incidence of dysplasia or CRC. Rstudio 4.0.2 was used for analysis. Results: 549 subjects were identified from our IBD database with 64 cases and 485 controls. The dysplasia/CRC group had a significantly larger proportion of males (67% vs 48%), patients with UC than CD (69% vs 47%), perianal disease (53% vs 25%), and were more likely to have moderate-severe disease vs remission-mild (36% vs 23%) than the control group. No significant differences were found between groups for the remaining variables. Univariate logistic regression model for each predictor variable of interest revealed statistically significant differences with gender (OR 2.25, 95% CI 1.31-3.97 p=0.004), IBD subtype (OR 2.44, 95% CI 1.42-4.35 p=0.002), disease activity (OR 1.86, 95% CI 1.06-3.21 p=0.028), and perianal disease (OR 3.49, 95% CI 2.05-5.97 p< 0.001). When fitting various multiple logistic regression models and adjusting for the three other variables, disease activity was no longer significant. Conclusion: Our case control study assessing risk factors for colorectal dysplasia or cancer in IBD found that gender, IBD subtype, and perianal disease are perhaps the most significant risk factors for this population. While previous cohorts have noted several of these as potential risk factors, perianal disease has not previously been considered a risk factor for dysplasia/CRC in IBD.