bluuebunny/crossref_metadata_2025 huggingface dataset:
P076 The endocannabinoid system in the intestinal biopsies of children with Inflammatory Bowel Disease
Authors: Creoli M , Strisciuglio C , Vitale A , Oglio F , Paino S , Luongo L , Tortora C , Argenziano M , Di Paola A , Maione S , Rossi F
Published: May 2021

Background

The endocannabinoid (EC) system has been recently indicated as a possible therapeutic target in inflammatory bowel disease patients (IBD). G-protein-coupled cannabinoid receptors type 1 and 2 (CB1 and CB2) are the two most important components of the EC system. In our previous study, we demonstrated that a specific CB2 variant contributes to the risk for pediatric IBD, especially UC, and that this variant is associated with a more severe phenotype in both UC and CD. The aim of this study was to directly evaluate on intestinal biopsies of pediatric IBD patients the expression of EC system receptors and of several molecules associated with inflammatory pathway in IBD.

Methods

In this preliminary study, we analyzed the CB1 and CB2 expression in the intestinal mucosa of paediatric patients affected by Crohn’s disease (CD) or ulcerative colitis (UC), recruited at diagnosis, and of non-IBD healthy controls (HC). Three patients were enrolled for each group. In particular, we analyzed biopsies taken from the ileum and rectum, which are the tract often more inflamed in CD and UC respectively. Moreover, we evaluated Toll-like receptor 4 (TLR 4), interleukin- 6 (IL6), interleukin-1 β (IL1-β), prokineticin receptor 2 (PKR2) expression, which are known as pro-inflammatory elements. The expression of these receptors and pro- inflammatory cytokines was analyzed by western blot and immunofluorescence.

Results

We found an increased expression of CB2 and TLR4 in UC rectum biopsies compared to CD and HC children. Accordingly, there was also a significant increase of IL-6 expression in UC rectum biopsies compared to CD and HC children (p≤0.05 UC vs HC), as well as, we identified a high expression of IL-6 in CD ileum compared to UC and HC patients. Moreover, in CD ileum, we found an increase in TLR4 compared to UC and HC ileum. We did not find statistical difference for the low number of analyzed samples, but to be a preliminary work we are confident to reach statistical significance increasing the samples enrolled.

Conclusion

In according with our previous data, our results confirm that the EC system and in particular the receptor CB2 is more expressed in the intestine of IBD patients, especially in the rectum of UC patients, which is the tract with greater inflammatory involvement. We can speculate that CB2 receptor is involved in the pathogenesis of paediatric IBD, but additional functional studies are required to understand how the EC system contributes to disease development in pediatric IBD, and if these cannabinoid receptors might represent a new disease marker and could be used as a potential therapeutic target.

Expression of CB2 receptor in rectum biopsies
P077 What matters to Ulcerative Colitis patients when they make treatment decisions? A systematic review
Authors: Folan A M , Jones G , Baker D , Brown S , Lee M , Lobo A
Published: May 2021

Background

The decision for ulcerative colitis (UC) patients to opt for elective surgery or continue medical treatment is dependent on patient preferences taking into account a range of factors. In addition to choosing between medical and surgical treatment, patients undergoing elective surgery are presented with a further decision regarding which operation to choose. The aim of this systematic review is to identify and understand what matters to UC patients when they are making these decisions.

Methods

Five electronic databases (PubMed, Scopus, CINAHL, Medline, and Embase) were searched for relevant literature up to 15 October 2020. Qualitative, quantitative and mixed-methods studies were included in this review. Studies reporting on what was important to UC patients (over 16 years of age) when they make treatment decisions were included. The Mixed Methods Appraisal Tool was used to assess the quality of the papers. Thematic analysis was used to analyse the data.

Results

The searches identified 6,917 papers and a final 19 (eight quantitative, seven qualitative, four mixed methods) papers were included. All studies were published since 2007 and included a total of 3,328 participants from nine countries. Five overarching themes (and their associated 20 sub-themes) were generated to describe the factors reported as important to UC patients in making treatment decisions. These were: 1. Information provision (information content, knowledge about their illness, quality of information); 2. Impact of the treatment upon daily life (controlling physical symptoms, quality of life); 3. Levels of risk (trade-off, high risk, concern and worry); 4. Burden of treatment (the need to see benefits of medication, route and size of medication, side effects, dosing frequency, costs, effort of being the patient, adherence to medication, surgery concerns, timing of surgery); and 5. Patient-clinician relationship (shared decision-making, communication, mismatch between what clinicians and patients consider to be important).

Conclusion

Communication between patients and their IBD teams should take into account the range of factors that influence their treatment decision making. Decision support interventions that incorporate such factors may better support the patient-clinician relationship and improve knowledge of treatment options and how these impact on what matters to them. Future studies are needed to determine which factors identified in this review are dominant.
P079 Valproic acid increases MiR449a expression in intestinal mucosa from patients with inflammatory bowel disease
Authors: Felice C , Lewis A , Armuzzi A , Lindsay J O , Silver A
Published: May 2021

Background

Histone acetylation/deacetylation and microRNAs (MiRNA) are epigenetic mechanisms involved in the pathogenesis of inflammatory bowel diseases (IBD). Histone deacetylase (HDAC) inhibitors, such as valproic acid (VPA), demonstrated anti-inflammatory and anti-tumour effects in animal models of colitis.1,2 Modulation of MiRNAs is hypothesized to be a possible mechanism of action of HDAC inhibition.3 Recently, VPA was shown to modulate histone-3 (H3) acetylation and cytokine production in the human gut.4 In this study, we analysed whether VPA influences MiRNA expression in ex-vivo biopsies from IBD patients.

Methods

Colonic biopsies from IBD patients collected during routine endoscopic procedures were cultured with VPA (5 mM) or control media for 24 hours. Total RNA was extracted and a MiRNA array was performed (miScript™ miRNA PCR Array), profiling the expression of 84 MiRNAs predicted to regulate pro- or anti-inflammatory genes. Significantly altered MiRNAs were then validated in an independent cohort of samples using quantitative (q) RT-PCR. Caco-2 (ATCC® HTB-37™) cell cultures treated with VPA (5 mM) or control media were used to confirm changes of H3 acetylation and MiRNA expression. After 24 hours, H3 acetylation was evaluated by immunofluorescence and apoptotic markers were analysed by qPCR.

Results

Colonic biopsies from inflamed mucosa of 6 IBD patients (2 with Crohn’s disease (CD) and 4 with ulcerative colitis (UC)) were cultured with VPA or control media. MiRNA analysis showed a significant increase of miR449a, miR373-3p, miR300 and miR520d-3p in treated biopsies compared to control (p=0.004, p=0.024, p=0.04 and p=0.014, respectively). Validation was performed in an independent cohort of 14 IBD patients (7 CD; 7 UC), confirming a significant increase of MiR449a (p=0.026) in VPA treated biopsies. VPA treated Caco-2 cell cultures showed a significant increase of H3 acetylation density level (p=0.02), confirming the HDAC inhibitory activity. Gene expression analysis showed increased Caspase-3 (p=0.015), a pro-apoptotic marker, and decreased BCL-3 (p<0.01), an anti-apoptotic marker. The level of MiR449a expression in VPA treated cells was significantly elevated (p<0.01).

Conclusion

VPA increases the expression of MiR449a in cultured ex-vivo biopsies and in Caco-2 cells. This MiRNA has recently demonstrated to be involved in IBD pathogenesis and in colitis-associated colon cancer. This may represent a new insight into IBD pathogenesis and colitis-associated colon cancer development. Further work is required to determine the functional significance of miR-499a in the human intestine.

References
P095 Initial disease course in a Belgian, prospective inception cohort of patients with inflammatory bowel disease: the PANTHER cohort
Authors: Verstockt S , Glorieus E , Ukunda C , Barbaraci M , Verstockt B , Sabino J , Ferrante M , Geldof J , De Vos M , Laukens D , Cleynen I , Vandermeulen L , Lobatón T , Vermeire S
Published: May 2021

Background

Successful personalized treatment in inflammatory bowel disease (IBD) is critically dependent on identifying those patients at greater risk of a complicated disease course and who therefore may benefit from early advanced therapies. To this end, prospective inception cohorts integrating medical records with multi-omics data are needed. The Belgian Prognostic biobANk of paTients witH Early cRohn’s or colitis (PANTHER) was therefore initiated in 2015. We here present the initial disease course of this cohort.

Methods

The PANTHER cohort is an inception cohort of adult IBD patients from 3 Belgian, tertiary IBD referral centres. Patients are included within 3 months after diagnosis, are naïve for immunosuppressives and biologicals, and without previous IBD-related surgery. Clinical data are prospectively collected; and DNA, serum, feces and intestinal biopsies are taken at predefined time points. Patients are treated according to routine clinical management. Log-rank tests, and univariate and multivariate analyses were performed in R 3.6.2.

Results

A total of 289 newly-diagnosed IBD patients were recruited (median [IQR] follow-up of 2.9 [1.4–4.2] years), of whom 161 (56%) had Crohn’s disease (CD), 122 (42%) had ulcerative colitis, and 6 (2%) had IBD type unclassified (Table 1). Thus far, 242 of these patients (83%) are minimally at 1-year follow-up. Twenty-two patients (9%) already needed surgery (n=5 for colectomy and n=17 for ileocecal or small bowel resection) and 124 patients (51%) received biological therapy within the 1st year after diagnosis. Time series analysis showed a clear trend for increase in biological use within the 1st year after diagnosis when comparing 2015–2017 (42%) to 2018–2020 (54%) (p=0.06) (Fig.1). Being exposed to a biological within the 1st year was associated with age (OR=0.98 [95%CI: 0.96–0.99]), CD diagnosis (OR=3.7 (95% CI: 2.2–6.3) and more recent diagnosis (2018–2020 as opposed to previous years) (OR=1.2 [95% CI: 1.2–3.4]). Within CD, perianal disease was the strongest driver for early biological use (OR=4.4 [95% CI: 1.8–12.8]). Early biological exposure led to clear trends in decreased surgery rates one year later (2/99 [2%]) as compared to non-exposed patients (8/108 [7%]) (p=0.07), while hospitalization rates significantly decreased (4% versus 12%, p=0.04).

Conclusion

In this Belgian inception cohort, an increase in early biological use is observed in recent years and is associated with reduced IBD-related surgery and -hospitalization.
P131 Serum Proteomics and Intestinal Ultrasound Differentiates Fibrostenotic and Inflammatory Crohn’s Disease
Authors: Lu C , Filyk A , Mainoli B , de Almeida L , Novak K , Panaccione R , Hirota S , Dufour A
Published: May 2021

Background

Fibrostenotic Crohn’s disease (CD) is a challenging phenotype often leading to surgical resection. Easily accessible and cost-effective diagnostic tools are needed to advance precision medicine to manage fibrostenotic CD patients. To date, there are no biomarkers that can discriminate stricturing CD from other phenotypes. Early studies suggest that protein biomarkers identified from serum proteomics may differentiate CD subtypes. Utilizing intestinal ultrasound (IUS), which readily detects strictures, the serum of patients with and without strictures was collected for proteomic characterization.

Methods

All consecutive CD patients attending outpatient appointments received IUS, and CT (computed tomography)/MR (magnetic resonance) within 6 months of study inclusion. Strictures were defined as a fixed segment of the ileum with increased bowel wall thickness (BWT) and luminal apposition with or without prestenotic dilation. Thirty two patients with ileal strictures were matched with CD patients without strictures (inflammatory behaviour). Serum of patients were collected for quantitative shotgun proteomics using liquid chromatography and tandem-mass spectrometry (LC-MS/MS).

Results

64 patients in the stricture group had a significantly greater mean ileal bowel wall thickness (7.5 mm) compared to the inflammatory group (4.5mm, p = 0.02). A distinct and statistically significant protein signature was discovered between both patient populations. In the stricture group: plexin-A2, CD5 antigen-like protein, neogenin and dystonin were found, while in the non-strictured patients, matrix metalloproteinase 16, C-reactive protein, vinculin and apolipoprotein C-III were detected. Using Metascape and STRING-db, gene ontology and reactome pathway analyses, we identified enrichment of B cell differentiation and muscle contraction in the stricture patients, whereas in the non-stricture group, an enrichment for high-density lipoprotein remodeling, innate immune system and calcium ion transport were found.

Conclusion

We identified a unique protein signature that could robustly distinguish CD strictures from inflammatory phenotypes. This innovative diagnostic preliminary protein panel will be further expanded and validated in inflammatory and fibrostenotic CD populations, potentially allowing for future clinical decision optimization.
P140 Predicting Non-Responsiveness to Iron Therapy in Anaemic Children with Inflammatory Bowel Disease
Authors: Bevers N , Aliu A , Rezazadeh Ardabili A , Winkens B , Raijkmakers M , van de Vijver E , Swinkels D , Pierik M , van Rheenen P
Published: May 2021

Background

Anaemia negatively impacts physical fitness and quality-of-life, and therapy is aimed at normalization of haemoglobin (Hb) levels. In the majority of patients with inflammatory bowel disease (IBD) anaemia has a mixed aetiology resulting from chronic inflammation and iron deficiency. A considerable proportion of patients will fail to respond to iron therapy, but it has been difficult to identify non-responders at baseline with currently used iron indicators. Hepcidin is a peptide hormone involved in iron homeostasis. Upregulation leads to decreased iron availability, whereas downregulation facilitates iron absorption and release from macrophages to allow for erythropoiesis.

We evaluated commonly used iron indicators (ferritin and transferrin saturation [TSAT]) and emerging biomarkers (soluble transferrin receptor [sTfR] and hepcidin levels) at baseline to predict non-responsiveness to iron therapy in anaemic children with IBD.

Methods

We performed a prospective multi-centre cohort study among patients with IBD and anaemia (defined as Hb > 2 standard deviations (SD) below the reference mean according to WHO cut-offs). We assessed iron indicators, sTfR, and hepcidin at baseline and again one month after the initiation of oral or intravenous iron therapy. Therapy was given according to international guidelines. Primary outcome was based on the change of Hb z-score (one month after treatment vs baseline) divided by baseline SD, where non-responsiveness was defined as a standardised change score of less than 1. Hepcidin was expressed as z-score to allow correction for age and gender. Baseline data of ferritin and TSAT were used to construct a basic logistic regression model. Hepcidin and/or sTfR were then added to the basic prediction model (models [M] 1–3). Optimal sensitivity and specificity were identified using the Youden’s J Index.

Results

Of 40 anaemic IBD patients (mean age 12.8 years; mean Hb z-score -3.1 SD), sixteen (40%) were non-responsive to iron therapy one month after initiation. The basic prediction model yielded an area under the curve (AUC) of 0.69. Figure 1 shows that adding sTfR, hepcidin or both to the model increased the AUC to 0.78 (M1), 0.82 (M2), and 0.90 (M3), respectively. For model 3, sensitivity and specificity at the optimal cut-off value were 94% and 71%, respectively.

Figure 1: Receiver operating characteristic (ROC) curves representing the accuracy of iron therapy non-responsiveness. AUC, area under the curve; CI, confidence interval

Conclusion

Based on prediction quality of the models, triaging with a strategy that involves baseline ferritin, TSAT, sTfR, and hepcidin is preferred to assess non-responsiveness to iron therapy in anaemic children with IBD.
P149 Application of revised Pediatric Inflammatory Bowel Disease (PIBD) classes criteria to the Korean PIBD patients
Authors: Shin M , Lim J G , Kim M S , Moon S Y , Hahn J W , Kim D H , Moon J S , Ko J S
Published: May 2021

Background

In 2017, Porto group of ESPGHAN published the PIBD classes criteria, a diagnostic classification criteria for PIBD by conducting multi-center study, and the revised PIBD classes criteria were released in 2020 after multi-center verification. Consisting of 19 items classified into a total of 3 classes, this criteria classifies PIBD into UC, atypical UC, CD, and IBD-U through an algorithm. The purpose of this study is to examine the appropriateness of diagnosis and criteria by applying the revised PIBD classes-criteria for PIBD patients diagnosed in a certified tertiary hospital.

Methods

Among 156 new patients aged 1–18 years old diagnosed with PIBD at Seoul National University Children’s Hospital from January 1, 2014 to August 18, 2020, 102 patients who had no underlying disease, did not administer drugs that affect the immune system, whose key items of PIBD class criteria (upper and lower gastrointestinal endoscopy, gastrointestinal imaging, pathology, etc.) and basic demographic characteristics were verified were analyzed retrospectively through electronic medical records.

Results

Of the 102 PIBD patients, 85 (83%) were initially diagnosed with CD, 15 (15%) with UC, and 2 (2%) with IBD-U by clinicians. Of the 102 patients, 69 (68%) were male, and the age of first diagnosis was 11.5±3.7 years. After applying the revised PIBD classes criteria, the diagnosis was changed to CD for 2 IBD-U patients, IBD-U for 7 UC patients, and CD for 1 UC patient. Finally, the diagnosis was changed to 86 (84%) CD, 8 (8%) UC and 7 (7%) IBD-U. The two patients whose diagnosis was changed from IBD-U to CD satisfied the items of Class 1, so the diagnosis was changed. All 7 patients whose diagnosis changed from UC to IBD-U did not satisfy all the items of Class 1, but most of the items ‘Focal active colitis on histology in more than one biopsy’ (6/7) and ‘Focal enhanced gastritis on histology’ (7/7) of class 3 criteria were satisfied, and the diagnosis has changed.

Conclusion

As a result of applying the PIBD class criteria, there was no significant change in the diagnosis of CD, but the diagnosis of UC decreased by 73% and the diagnosis of IBD-U increased by 5 times. In this study group, the positive rates of items ‘Fistulising disease’, ‘‘Thickened jejunal or ileal bowel loops on radiology or other evidence of significant small bowel inflammation on capsule endoscopy’, ‘Focal active colitis on histology in more than one biopsy’ and ‘Focal enhanced gastritis on histology’ tended to be significantly higher than those of the previous study. So, Further validation and confirmation are needed.
P157 Microbiome Analysis Reveals That Ralstonia is Responsible for Decreased Renal Function in Patients with Ulcerative Colitis
Authors: Kim J M , Rim J H , Kim D H , Kim H Y , Choi S K , Kim D Y , Choi Y J , Yu S , Gee H Y , Cheon J H
Published: May 2021

Background

Inflammatory bowel diseases (IBDs), such as ulcerative colitis (UC), are characterized by a disturbance of the normal gut microbiota and contribute to the development of chronic kidney disease (CKD). The incidence of CKD is higher in individuals with UC, but the causal link is unknown. Therefore, we investigated the role of gut microbiota in decreasing renal function in patients with UC

Methods

We performed 16S ribosomal DNA sequencing using ileocecal mucosal samples from nine individuals with UC and CKD (UC+CKD), 29 individuals with UC only, and 12 healthy controls. We also analyzed the operational taxonomic units, microbial diversity, and correlation with renal function. Co-culture assay using kidney organoids and Caco-2 cells was performed.

Figure 1. The taxonomic composition of the gut microbiota of the study population and comparison of the 10 most abundant genera and species in the UC + CKD, UC, and control groups.

Results

Bacterial species diversity was significantly decreased in the UC+CKD group compared to that in the other groups based on Shannon and inverse Simpson indexes. At the genus level, Ralstonia had significantly greater abundance in the UC+CKD and UC groups compared to the control group. At the species level, unclassified Ralstonia species and Citrobacter portucalensis showed higher abundance in the UC+CKD group compared to the other groups. The relative abundance of Ralstonia showed a negative correlation with the estimated glomerular filtration rate (eGFR), but a positive correlation with the serum uric acid level. Ralstonia pickettii represented a negative correlation with eGFR, and induced damaging changes to kidney organoids in co-culture assay.

Figure 2. The correlation between the relative abundance of Ralstonia with renal function (indicated by eGFR) and serum uric acid level. Effects of Ralstonia pickettii on Caco-2 cells and kidney organoids. (A) mRNA expression of pro-inflammatory cytokine genes in Caco-2 cells treated with and without Ralstonia pickettii, reflecting the inflammation seen in ulcerative colitis.

Conclusion

Gut microbial community profiles of the UC+CKD group are different from those of the UC group. Furthermore, Ralstonia pickettii contributes in decreasing renal function in patients with UC.
P206 Paediatric Genital Crohn’s Disease: Presentation and Treatment, a combined case series
Authors: Sethuraman A , Kontaki E , Gaynor E , Jones K , Cherian A , Zamvar V , Kiparissi F
Published: May 2021

Background

Metastatic Crohn’s Disease (MCD) affecting the genitalia is a rare condition, characterised by granulomatous inflammation of the genital tract. Only few paediatric cases have been described in the literature with a female preponderance. Paucity of literature is noted with regards to treatment and outcome.

Methods: Aim

To describe the clinical presentation, associated features, and response to treatment in a cohort of paediatric patients diagnosed as genital metastatic Crohn’s disease (MCD).

Methods

All cases of paediatric genital MCD were retrospectively collected from two centres at Great Ormond Street Hospital for Children and Leeds Children’s Hospital for the past 20 years (January 2001 to January 2021). Medical history, symptoms at presentation, histological characteristics, results of investigations and response to treatment were reviewed.

Results

A total of 12 patients (7 male and 5 female) were diagnosed with genital MCD. The mean age at presentation of genital MCD symptoms was 8.9 years of age (1.5–14 years). Generalised swelling of the genital region was the most common presentation. 5/12 (42%) children had luminal Crohn’s disease (CD) before development of Genital MCD whereas 4/12 (33%) children developed luminal CD after Genital MCD presentation. 3/12 (25%) children after evaluation were found to have only Genital MCD with no luminal pathology of CD. Genital MCD was the first presentation of Crohn’s disease in 7/12 children (58.3%) in our cohort. 6/12(50%) children were seen to have perianal disease. All children were extensively investigated endoscopically and radiologically. Genital biopsy was done in 6/12(50%) patients showing non caseating granulomatous inflammation. 11/12 patients received dual therapy at some point in their treatment with azathioprine and infliximab. Switch of infliximab to adalimumab was seen in 7/12 (58.3%) patients mostly in view of escalating treatment to control luminal CD. Initiation of treatment since first symptoms of genital MCD appeared to be prolonged, perhaps due to delay in diagnosis via referral pathways from local paediatrician via urologist to paediatric gastroenterologist. Improvement of genital MCD was seen in most children with dual therapy of azathioprine and infliximab.

Conclusion

Genital MCD can be the first presentation of Crohn’s disease and may not be associated with GI symptoms or luminal CD. All children with MCD do benefit from histological as well as radiological and endoscopic evaluation. Formal MDT discussions with the urologist, radiologist and gastroenterologist may help in early diagnosis and treatment. A retrospective multi-centre case reviews will help to identify the prevalence of genital MCD in children and also help develop a national pathway.
P237 Prevalence of dysplasia and colorectal cancer in Ulcerative Colitis patients from a referral center in Latin America
Authors: Junior R S F , Carvalho M F , Silva J C , Barros L L , Azevedo M F C , Carlos A D S , Oba J , Hashimoto C L , Cançado E L R , Damiao A O M C , Sipahi A M
Published: May 2021

Background

Ulcerative colitis (UC) is a chronic inflammatory disease characterized by relapsing and remitting course of bloody diarrhea. UC patients are at higher risk of dysplasia and colorectal cancer (CRC) when compared to the general population, especially those with primary sclerosing cholangitis (PSC), long-standing disease and active inflammation. The aim of this study was to determine the prevalence of dysplasia and CRC in a large cohort of UC patients in Latin America.

Methods

This study was a retrospective analysis of all UC patients registered and followed-up in our outpatient clinic between January 2010 and September 2020. The diagnosis was confirmed by clinical, endoscopic, histopathological, and radiologic findings according to current guidelines. CRC was confirmed by one or more experienced pathologists. Medical records were abstracted for the data: demographic characteristics; duration, extent, and treatment of UC; dysplasia and cancer.

Results

In total, 560 patients with UC were identified. Of all cases, 364 (64.8%) had pancolitis, 115 (20.5%) had left side colitis and 81 (14.4%) were diagnosed with proctitis. There was a slight predominance of female, 331 (59.1%). The mean age at inclusion was 48 years. Among these patients 11.2% had concomitant PSC. Aminosalicylates were the most common treatment in 70% of our cohort, whereas 40% were treated with immunobiologics at any time during UC course. The length of the disease was between 10 to 20 years in 42% of cases and from 20 to 30 years in 17% of them. In our analysis the prevalence of dysplasia was 21%. Five of them were of high grade, which occurred in whom the length of the disease was between 10 to 20 years. In the majority of cases dysplasia was related to the inflammatory burden of UC (75.2%) and 37 patients were diagnosed with sporadic dysplasia. Seven cases (1.25%) of colorectal cancer were found (median time from UC diagnosis to CRC = 18 years), which two of these patients had concomitant PSC. All UC-CRC patients had extensive colitis.

Conclusion

Recent studies have suggested that the risk of CRC in UC population has decreased during the last decades due to tight control treatment and adequate endoscopic surveillance. In Latin America data on the prevalence and prognosis of UC-CRC patients are scarce. Herein we report the frequency of UC-related dysplasia and UC-CRC in Brazil over a period of 10 years. Our results revealed higher prevalence rates when compared to underdeveloped countries, such as India and China. Longer disease duration and extensive colitis were identified as important risk factors for developing CRC in accordance with the literature. Further research is warranted to better identify ethnical and environmental risk factors in this population.
P247 Carotid Plaque Assessment reclassifies patients with Inflammatory Bowel Disease into Very-High Cardiovascular Risk
Authors: Hernandez Camba A , Carrillo-Palau M , Ramos L , Hernández Alvarez-Buylla N , Alonso-Abreu I , Hernández A , Vela M , Arranz L , Hernández-Guerra M , González-Gay M A , Ferraz- Amaro I
Published: May 2021

Background

The addition of carotid ultrasound into cardiovascular (CV) risk scores has been found to be effective in identifying patients with chronic inflammatory diseases at high-CV risk. We aimed to determine if its use would facilitate the reclassification of patients with inflammatory bowel disease (IBD) into the very high-CV-risk category and whether this may be related to disease features.

Methods

Multicenter cross-sectional study encompassing 186 IBD patients and 175 controls. Systematic Coronary Risk Evaluation (SCORE), disease activity measurements, and the presence of carotid plaques by ultrasonography were assessed. Reclassification was compared between patients and controls. A multivariable regression analysis was performed to evaluate if the risk of reclassification could be explained by disease-related features and to assess the influence of traditional CV risk factors on this reclassification.

Results

After evaluation of carotid ultrasound, a significantly higher frequency of reclassification was found in patients with IBD compared to controls (35% vs. 24%, p=0.030). When this analysis was performed only on subjects included in the SCORE low-CV-risk category, 21% IBD patients compared to 11% controls (p = 0.034) were reclassified into the very high-CV-risk category. Disease related data, including disease activity, were not associated with reclassification after fully multivariable regression analysis. Traditional CV risk factors showed a similar influence over reclassification in patients and controls. However, LDL-cholesterol disclosed a higher effect in controls compared to patients (beta coef. 1.03[95%CI 1.02–1.04] vs. 1.01[95%CI 1.00–1.02], interaction p=0.035) after adjustment for confounders.

Conclusion

Carotid plaque assessment is useful to identify high-CV risk IBD patients.
P380 Comparison of mucosal healing through segments of ileocolonic Crohn’s disease treated with biologics
Authors: Temido M J , Portela F , Lopes S , Mendes S , Ferreira M , Ferreira M , Figueiredo P
Published: May 2021

Background

Although major advances in Inflammatory bowel disease’s treatment have been observed, the response to the pharmacologic therapies is still unpredictable and highly variable. Mucosal healing (MH) is an important endpoint in Crohn’s disease patients undergoing biologic therapies as it improves outcomes. Nevertheless, endoscopic response is usually evaluated as a whole entity and not by intestinal segments. Moreover, to the best of our knowledge, it has never been assessed whether different plasmatic drug levels (PDL) of biologics result in different response rates by segments of disease. Taking all these considerations into account, this work aimed at assessing putative differences in MH between ileal and colonic disease.

Methods

Retrospective, single centre, cohort study of 131 consecutive patients undergoing biological therapies for Crohn’s disease. Patients included had at least six months of follow-up and an endoscopic evaluation before and after the initiation of biologic therapy. Clinical and endoscopic data were obtained at baseline and at the time of assessment of response. Potential prognostic factors included were: age at diagnosis, time from diagnosis at beginning of biologic agents, location and behaviour of disease, biologic agent taken, PDL and smoking. MH was defined as absence of ulcers in the previously affected segment.

Results

Mean age at diagnosis was 28±12.9 years (range 10-67years). 26.7% of patients had ileal disease and 34.5% only had colonic lesions. 61.83% of patients initiated infliximab and 29.8% started treatment with adalimumab. MH was present in 48.85% of patients. Rates of response were significantly different between ileal (48.9%) and colonic lesions (69.8%) both in the whole cohort and in patients with ileocolonic disease (54.9% and 74.5% respectively) (p<0.05). PDL were higher in the patients achieving response comparing subgroups of patients (responders versus non-responders) with ileal and colonic lesions (p<0.05). There were no significant differences in the PDL between ileal and colonic lesions achieving response. In the multivariate analysis, factors independently associated with higher rates of MH were PDL, location (ileum versus colon) of the affected areas and type of disease (ileal versus colonic versus ileocolonic) (p<0.05).

Conclusion

Rates of MH of ileal lesions are significantly different from colonic segments in Crohn’s Disease. This discrepancy appears not to be related to higher plasmatic concentrations of biologic agents.
P386 Two year follow up of children with Inflammatory Bowel Disease (IBD) treated with vedolizumab and ustekinumab
Authors: Mardare R , Burgess N , Studart D , Deb P , Gasparetto M , Croft N , Naik S , Kadir A
Published: May 2021

Background

In 2018, our Trust approved the use of vedolizumab in children with Ulcerative Colitis (UC) and ustekinumab in children with Crohn’s Disease (CD). At the time, access to these drugs for children was only possible through research studies.

Our aim was to assess the efficacy and safety of these novel treatments in our cohort.

Methods

We conducted an observational single centre cohort study. Data was obtained from our electronic system, Cerner Millennium, and Infoflex database. Analysis was performed using SPSS.

Results

27 children were treated with vedolizumab or ustekinumab with 1 receiving both. All patients had failed anti-TNF medication, except 1 research patient who commenced on vedolizumab at diagnosis.

Conclusion

In children with refractory IBD failing anti-TNF treatment, vedolizumab and ustekinumab are effective and safe alternatives for inducing and maintaining remission, avoiding major invasive surgery.
P392 A mobile application to monitor Inflammatory Bowel Disease patients during intravenous biologic treatment: Results of a feasibility study
Authors: Van Erp L W , Groenen M J M , Heida W , Wisse J , Roosenboom B , Wahab P J
Published: May 2021

Background

Active monitoring of IBD patients during intravenous (iv) biologic treatment is recommended but time-consuming and inconvenient for both patients and nurses. We developed a mobile application to promote self-management and monitor IBD patients cost-effectively during iv biologic treatment. We aimed to study the feasibility of the mobile application.

Methods

A prospective cohort study was performed in a secondary care centre with adult IBD patients treated with infliximab (iv) or vedolizumab (iv) for at least three months. The mobile application was used during four rounds of iv biologic treatment (figure 1). The application includes information modules and a personal interactive timeline with messages one week prior to iv biologic treatment (figure 1). Patients are asked to fill in a health check prior to each treatment to screen for contra-indications, such as respiratory infections or severe side-effects. Patients can also note any particularities or request contact with the IBD nurse. Blood tests are performed before every other infusion. Previously, patients were contacted by telephone prior to each biologic treatment by the IBD nurse. Using the application, patients are only personally contacted in case of abnormalities or upon request.

Results

Of 55 included patients, 52 patients completed the study. Mean age was 42 years (min 19 – max 68), 71% had Crohn’s disease, 76% had clinically quiescent disease, 85% used infliximab and 15% vedolizumab. Most patients used internet for over three years (98%) and their smartphone or tablet every day (98%). Compliance to health checks and blood tests was 67% during the 1st round of biologic treatment and 70%, 87% and 80% during the 2nd, 3rd and 4th round respectively. Patients used the application between median 6 (IQR 5 – 9) and 8 (IQR 5 – 11) times per round of biologic treatment. Patient satisfaction with the application was median 8 (VAS score, IQR 7 – 9). Prior to the 1st round of biologic treatment, all patients (100%) were contacted by telephone as in previous standard care. Using the application the number of patients requiring telephone contact decreased to 47%, 35% and 49% before the 2nd, 3rd and 4th round respectively. Patients remained equally satisfied with IBD care: median VAS score 8 (IQR 8 – 9) before and after implementation of the mobile application. The majority of patients (92%) wanted to continue using the application after the study ended.

Figure 1: Study procedures

Conclusion

Monitoring of IBD patients treated with biologics using a mobile application is feasible. We saw a high compliance and satisfaction of patients, and reduction of health-care utilization. Almost all patients preferred using the application over previous standard care.
P405 Development and validation of a rapid immunoassay for monitoring of ustekinumab concentrations in Inflammatory Bowel Disease patients
Authors: Thomas D , Compernolle G , Guedelha Sabino J P , Ferrante M , Vermeire S , Declerck P
Published: May 2021

Background

Several studies have reported an association between ustekinumab serum concentrations and clinical outcomes, suggesting a potential role of therapeutic drug monitoring (TDM) for guiding clinical decision-making and treatment optimisation in ustekinumab-treated patients with inflammatory bowel diseases. Usually, ustekinumab concentrations are measured with an enzyme-linked immunosorbent assay (ELISA). Disadvantages of using ELISA for TDM are the rather long time-to-result and the necessity of collecting multiple samples in order to reduce the price per determination. The performance of TDM could be further enhanced by using a rapid point-of-care assay, which would allow immediate and individualised dose optimisation based on real-time pharmacokinetic information instead of awaiting dose adjustments at the subsequent administration.

Methods

A fiber-optic surface plasmon resonance (FO-SPR) assay was developed on a White FOx 1.0 device (FOx Biosystems), using a monoclonal antibody (MA)/MA sandwich approach. MA-UST56A2D11 was covalently immobilised to a gold-sputtered fiber surface to capture ustekinumab. After incubation with the serum sample, biotinylated MA-UST56C1H12 was used for detection of bound ustekinumab, and the signal was amplified using a polyclonal anti-biotin antibody conjugated to gold nanoparticles. A calibration curve was constructed by spiking ustekinumab in 1/1000 diluted human serum. Recovery and imprecision were assessed, and the performance of the FO-SPR assay was compared with that of our previously developed in-house ELISA using twelve serum samples of ustekinumab-treated patients.

Results

A dose-response curve ranging from 1.25 – 40 ng/mL was obtained, allowing quantification of ustekinumab concentrations from 0.31 µg/mL (using a 1/250 dilution) up to 80 µg/mL (using a 1/2000 dilution) in serum samples. Measurement of ustekinumab-spiked samples (1 – 25 µg/mL) showed an average intra-assay recovery of 111% (range: 95-124%) and imprecision of 10% (range: 8-15%), and an average inter-assay recovery of 109% (range: 100-122%) and imprecision of 5% (range: 1-8%). Comparison of measurements between FO-SPR and ELISA revealed a very good correlation (Pearson r coefficient of 0.980, 95% CI 0.928-0.995, p<0.001; Figure 1). Using a pre-functionalised fiber, the FO-SPR assay requires 55 min for measuring a single ustekinumab serum sample.

Conclusion

A rapid FO-SPR assay for quantification of ustekinumab concentrations in serum samples was established and showed a very good correlation with ELISA. The reduced assay time and the possibility of measuring a single sample are advantages compared to ELISA, and may allow implementation of FO-SPR as a point-of-care diagnostic tool.
P471 Predictors of bowel damage in long term progression of Crohn’s disease
Authors: Fernandez Clotet A , Panes J , Ricart E , Castro Poceiro J , Masamunt M C , Rodríguez S , Caballol B , Ordas I , Rimola J
Published: May 2021

Background

Crohn’s disease is a chronic inflammatory bowel disorder that progresses to bowel damage over time. An image-based index, the Lémann Index, has been developed to measure the cumulative bowel damage.

AIMS

To characterize the long-term progression of bowel damage in Crohn’s disease based on changes in the Lémann Index and to determine risk factors for long term progression.

Methods

This was a single-center longitudinal cohort study. Patients who had participated in prospective studies on the accuracy of magnetic resonance imaging using endoscopy as gold standard and had a follow-up of at least 5 years were reevaluated after 5–12 years.

Results

Seventy-two patients were included. Lémann Index increased in 38 patients (52.8%), remained unchanged in 9 patients (12.5%) and decreased in 25 patients (34.7%). Small bowel score and surgery subscale significantly increased (p=0.002 and p=0.0001), whereas fistulizing subscale significantly decreased (p=0.001). Baseline parameters associated with bowel damage progression were ileum location (p=0.026), phenotype (stricturing, fistulizing or both with p=0.007, p=0.006 and p=0.035), disease duration >10 years (p=0.019) and baseline Lémann Index stricturing score (p=0.049). No correlation was observed between bowel damage progression and baseline clinical activity, biological markers or endoscopic lesions. Need of surgery during follow-up was a major determinant of bowel damage progression (p=0.0001). Baseline stricturing Lémann Index score was associated with the risk of future surgery (p=0.02).

Conclusion

Bowel damage, assessed by the Lémann Index, progresses in half of the patients with Crohn’s disease over a period of 5–12 years. The main determinants of bowel damage progression are ileum location, stricturing/fistulizing phenotype and disease duration.
P483 Infliximab but not adalimumab drug levels predict faecal calprotectin response in Inflammatory Bowel Disease patients on dose-intensified anti-TNF therapy
Authors: Noack S , Little R , Vaz K , Ward M , Sparrow M
Published: May 2021

Background

Secondary loss of response (SLOR) to infliximab (IFX) and adalimumab (ADA) is common and dose intensification is effective in a proportion of patients. Drug level targets associated with response as measured by faecal calprotectin (FCP) after anti-TNF intensification have not been well established.

Methods

Retrospective observational study of consecutive adult patients with Crohn’s disease (CD) or ulcerative colitis (UC) with SLOR commenced on dose-intensified IFX (5mg/kg 6 weekly) or ADA (40mg weekly) between May 2013-August 2020. Patients were managed via a protocolised virtual clinic. Trough anti-TNF drug levels and FCP were measured at baseline, and at 6 and 12 months post dose intensification. FCP response was defined as ≤150μg/g. Inter-group and longitudinal comparisons used Mann-Whitney U and Wilcoxon signed-rank tests, respectively. ROC curves evaluated anti-TNF drug levels predictive of FCP response.

Results

Of 78 patients (56% male, median age 40 years), 60 had CD (58% on IFX) and 18 had UC (100% on IFX). There were no significant differences in patient or disease demographics between FCP responders and non-responders at 6 or 12 months. At 6 months, median IFX level and increment in level from baseline were higher in FCP responders than non-responders in both CD and UC (Table 1). At 6 months, achieving an IFX level ≥5.7μg/mL in CD (AUC 0.82, sensitivity 88%, specificity 65%, p=0.012; Figure 1A) and an IFX level ≥5.2μg/mL in UC (AUC 0.89, sensitivity 100%, specificity 73%, p=0.015; Figure 1B) best predicted FCP response. ADA levels at 6 months and both IFX and ADA levels at 12 months were not predictive of FCP response in any cohort.

Conclusion

After dose-intensified IFX, CD and UC patients achieving FCP response had greater absolute and increment in drug levels than those with elevated FCP. IFX levels ≥5.7μg/mL and ≥5.2μg/mL at 6 months are predictive of FCP response in CD and UC, respectively. ADA levels were not predictive of FCP response.
P488 The COVID19 pandemic impact on Inflammatory Bowel Disease Patients Management in a Romanian Tertiary Gastroenterology Centre
Authors: Costache R , Iacob R , Vadan R , Stroie T , Gheorghe L , Diculescu M , Gheorghe C
Published: May 2021

Background

The IBD patients management has been challenging during the ongoing COVID-19 pandemic, due to lockdowns, limitation of access to medical facilities and new recommendations regarding patient management. The implications of the COVID-19 pandemic on IBD patient’s management were assessed in our Tertiary Gastroenterology Centre in Bucharest, Romania.

Methods

Using the hospital’s medical system, records of IBD patients admitted between 15th of March and 15th of August 2020 have been retrospectively reviewed and compared to a control cohort of consecutive IBD patients admitted to our unit during the corresponding period of 2019, registering the epidemiological features, patient management and the incidence of COVID-19 infection.

Results

410 individual IBD cases were managed in our unit in 2020 compared to 532 in 2019, with a significant shift towards one-day hospitalization: 1059 admissions (9% ward hospitalizations, 91% one-day hospitalizations) compared to 1327 cases in the corresponding period of 2019 (17.8% ward hospitalizations, 82.2% one day hospitalizations). There was no statistically significant difference between the distribution of patient’s gender, IBD phenotype or newly diagnosed IBD cases between the two periods. A significantly lower proportion of admitted patients received 5-aminosalicylic acid (29% vs. 41.2%, p=0.0001), whereas a substantially higher number pf patients were prescribed biological therapy in 2020 in comparison to the corresponding 2019-time frame (79.5% vs 57.9%, p<0.0001). The distribution of the biological agent used was significantly different, mainly due to the increase of vedolizumab prescription in 2020 (p<0.0001). Among the newly diagnosed cases 50.0% had a severe disease requiring a biological agent (vs 30.2% in 2019, p>0.05). Moreover, from our previously diagnosed patients, 7.1% needed the initiation of biological therapy due to disease flare-up (vs. 4.3% in 2019, p=0.003). During the study period in 2020, seven IBD patients (1.7%) were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) infection, all of them with mild symptoms without impact on the IBD course.

Conclusion

The COVID-19 pandemic led to reorganizing medical care, restricting the hospital admissions in favour of severe IBD cases, favouring telemedicine for mild disease and optimization of treatment for moderate to severe IBD with an increased use of biologicals aimed to maximize the risk/benefit ratio. Incidence of SARS-Cov2 infection during the first wave of COVID-19 infection in our study group was 1.7% and did not adversely impact the IBD disease course.