bluuebunny/crossref_metadata_2025 huggingface dataset:
P801 Treatment patterns of complex perianal fistula in Crohn’s disease in five European countries: the PREFACE study, a retrospective chart review
Authors: Ferrante M , Siproudhis L , Poggioli G , Reinshagen M , Milicevic S , Roset M , Thun B , Bent-Ennakhil N , D′Ambrosio R , Fernandez-Nistal A , Panes J
Published: January 2020

Background

Presence of fistulas in Crohn’s disease (CD) is an indicator of poor prognosis; 22.1% of CD patients suffer from fistulising disease1 with high variability in complex perianal fistula (CPF) prevalence2. There is limited information available about the management of CPF in a real-world setting. This study describes the treatment patterns of patients with CPF in CD in Europe.

Methods

Retrospective medical chart review of consecutive patients with CD receiving treatment for a new episode of CPF during the period (September 2011 to September 2014), in Belgium, France, Germany, Italy and Spain. Index date was defined as the date of treatment initiation for a new episode of CPF during the eligibility period. Data was collected from CD diagnosis to at least 3 years after index date (except for deceased or lost to follow-up patients) to describe patient characteristics and treatments used for all CPFs episodes since CD diagnosis.

Results

A total of 386 patients (51% female) were included with a mean (SD) age of 38 (13) and 10 (9) years since CD diagnosis. At CD diagnosis, 28% of patients had ileal, 29% colonic and 39% ileocolonic involvement; 24% of study patients had anal or perianal fistula. Prior to index date, 42% of patients had at least one surgery, being partial resection of small bowel the most common one. ASA-5, anti-TNFs and immunosuppressants were used for CD or complications in 47%, 48% and 42% of patients. Patients presented 584 CPFs during the study period. More than half of these CPFs were trans-sphincteric (60%). Out of the 584 CPFs, 92% were treated with at least one surgical intervention (most frequent: 56% long-term seton placement, 46% surgical drainage), and 86.6% with at least one medical treatment. Medical treatments most frequently used for CPFs or CD and complications (overlapping a CPF episode) were anti-TNFs (49%), antibiotics (44%) and immunosuppressants (26%).

Conclusion

Almost one fourth of the patients with CPF already had anal or perianal fistulas at CD diagnosis. Based on ECCO guidelines it was expected that almost all CPFs in CD patients should be treated with anti-TNF with or without surgical intervention. However, the use of anti-TNF during CPF episodes was lower than expected. Surgical drainage and seton placement were performed in a majority of patients in at least 3 years following treatment intensification, with a low rate of other types of surgery. Almost two third of CPFs were trans-sphincteric and if inadequately treated, sphincter function may be compromised.
P807 UCEIS is associated with PRO2, partial Mayo and SCCAI remission in UC: preliminary results from a prospective study
Authors: Golovics P A , Gonczi L , Reinglass J , Verdon C , Afif W , Wild G , Bitton A , Seidman E , Bessissow T , Lakatos PhD P L
Published: January 2020

Background

Optimal management of patients with ulcerative colitis (UC) requires the accurate assessment of disease activity. Endoscopic evaluation is considered the gold standard approach, but it is invasive. We aimed to determine the operating characteristics of the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), to quantify the cut off most closely correlated with clinical remission or activity and determine agreement with the Mayo endoscopic subscore (MES), Baron score, clinical scores and biomarkers.

Methods

136 patients were included prospectively (age: 48 (IQR38-61) years, duration 12 (4–19)years, 63 females, 53.7% extensive disease, 40.4% on biologicals) at the time of the colonoscopy. Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Mayo endoscopic subscore (MES), Baron scores were calculated, as well as the2 item patient reported outcome (PRO), partial MAYO, Simple Clinical Colitis Activity Index (SCCAI). CRP and faecal calprotectin (FCAL) was available in 58.1 and 33.8% of patients. 20.7% had clinical flare, treatment was escalated in 17.8% of patients. ROC analysis and K-statistics were performed and Spearman’s correlation was calculated.

Results

UCEIS was strongly associated to PRO2 SF (AUC:0.866), RBS (AUC:0.921), PRO2 combined remission (AUC:0.905), partial MAYO (AUC:0.956) and SCCAI (AUC:0.907) remission in a ROC analysis. A UCEIS of ≤3 was identified as the best cut-off to identify RBS subscore of 0, or total PRO2 remission (RBS 0 and SF ≤1), partial MAYO (≤2) and SCCAI (≤2.5) remission, while a UCEIS≥4 identified active disease frequently needing change in medical therapy. A moderate agreement was found between UCEIS and MES (K=0.451) or Baron (K=0.499) scores. Correlation between FCAL and UCEIS (coeff:0.743, p < 0.0001) was strong, while modest only with CRP (coeff:0.333, p = 0.01).

Conclusion

A UCEIS was strongly associated with clinical remission defined as PRO2, SF, RBS, partial Mayo or SCCAI with best agreement with RBS and partial Mayo remission. A UCEIS of ≤3 was identified as a cut-off for quiescent disease, while a UCEIS≥4 identified active disease, which can support clinical decision-making based on endoscopic findings. Agreement between UCEIS and FCAL was strong, while agreement with UCEIS and MES/Baron scores was moderate.
P814 Incidence and significance of fatigue in patients with IBD
Authors: Kokkotis G , Bekiari D , Bletsa M , Gizis M , Perlepe N , Athanasiou V , Kounadis G , Koutsounas I , Kolios G , Bamias G
Published: January 2020

Background

Fatigue is common in IBD patients, even in clinical remission and adversely affects the quality of life. For this reason, it has been suggested to use fatigue questionnaires as PROS (patient reported outcomes). We aimed to study the degree of fatigue in IBD patients and identify factors that are positively or negatively related to its presence.

Methods

Patients with IBD (men: 51.6%, Crohn’s Disease: 65.2%, age: 36.7 years median, 18.1–72 yrs range), with a regular f-up in our Department completed the Fatigue Severity Scale, IBD Fatigue self assessment 1 & 2, short IBDQ and Short Health Scale upon consensus. Two groups of patients were studied: Group A, patients attended the IBD outpatient clinic (121 patients / 144 questionnaires) and Group B, patients attended the infusion centre for biological therapy (55 patients / 414 questionnaires). The SPSS-23 statistical programme was used to identify correlations between fatigue and various clinical-laboratory parameters of patients.

Results

Problematic fatigue (FSS> 36) was reported by 46.5% of patients. No difference was observed between Crohn’s disease and Ulcerative Colitis or between the two groups of patients. There were statistically significant correlations between fatigue and disease activity (R = 0.428, P <0.001) and HGB (R = −0.177, p < 0.001). Fatigue was significantly associated with quality of life based on the short IBDQ and SHS questionnaires (R = −0.655, p < 0.001 and R = 0.485, p < 0.001 respectively). There was also a statistically significant relationship of both fatigue and quality of life with parameters such as female sex (p < 0.01), arthralgia (p < 0.05) and biological agent treatment (p < 0.05), while quality of life was statistically significant related with the disease type (P =0.01) too. Sequential measurements showed that the quality of life and fatigue rate were consistently maintained in patients with remission under biological therapy.

Conclusion

In the group of IBD patients we studied, a significant correlation with various clinical characteristics was observed. The presence of fatigue is a factor associated with poor quality of life for patients.
P816 Association of autoimmune rheumatic disease with inflammatory bowel disease: a nationwide population-based study
Authors: Baek D , Lee H S , Park S B , Song H K , Jang B I , Bae J H , Goong H J , Kang H S , Jung S H , Kim T O , Song G A , Park E Y
Published: January 2020

Background

Increasing evidence demonstrated that inflammatory bowel disease (IBD) has a shared genetic background with autoimmune rheumatic diseases (ARDs). However, the association between these two disease entities is not vigorously elucidated. The aim of this study is to investigate the prevalence and association between IBD and ARDs.

Methods

A nationwide population-based cross-sectional study was performed using the Korean National Health Insurance Claims database according to ICD-10 codes (Table 1). The prevalence of ARDs, including systemic lupus erythematosus (SLE), inflammatory myositis (polymyositis (PM) and dermatomyositis (DM)), systemic sclerosis (SSc), Sjogren’s syndrome (SjS), ankylosing spondylitis (AS), and rheumatoid arthritis (RA), was determined in patients with inflammatory bowel disease, compared with general populations.

Results

A total of 82,480 IBD patients (57,382 patients with ulcerative colitis and 25,098 with Crohn’s disease) were enrolled. The analysis revealed that patient with IBD had higher risk of being concomitantly affected by AS and RA (Table 2). Other ARDs, such as SLE, inflammatory myositis, SSc, and SjS were not associated with IBD.

Conclusion

This nationwide population-based study demonstrated that RA and AS showed higher incidence in IBD patients. This result suggests that etiopathogenesis of IBD might be shared with RA and AS.
P820 An easy and rapid targeted next generation sequencing-based genotyping assay for the validated IBD risk loci
Authors: Verstockt S , Hannes L , Deman S , Wollants W J , Souche E , Verstockt B , van der Werf I , Hoischen A , Ferrante M , Vermeire S , Cleynen I
Published: January 2020

Background

Inflammatory bowel diseases (IBD) are complex genetic diseases for which 242 susceptibility loci have been identified thus far. For translational or functional follow-up studies it can be of interest to know the genotype of specific variants. For other studies a composite genetic risk score–the polygenic risk score–is of value. There currently is a gap in technology to genotype a few hundred variants in a flexible and cost-effective way. We therefore developed a genotyping assay for the 242 validated IBD susceptibility loci.

Methods

Using MIPgen v.1.1, we designed molecular inversion probes (MIPs) covering 269 independent variants from the 242 IBD loci. MIP libraries were prepared according to Neveling et al. (Clin Chem. 2017), followed by paired-end sequencing using a MiSeq® System (Illumina). In the pilot studies, 16 IBD patients were genotyped, and results were compared with available immunochip (ichip) data. Genotypes for the covered variants were obtained using an in-house developed pipeline, and performance metrics were assessed (incl. genotyping call rate, percentage off-target reads and concordance with ichip-based genotypes). After optimisation, we genotyped 279 individuals (168 IBD patients and 111 non-IBD controls). We also calculated a weighted IBD polygenic risk score (PRSice 2.0) for these.

Results

Despite a genotyping call rate of 94.3%, the first pilot run suffered from a high rate of off-target reads (52.5%). After redesigning poorly-performing MIPs, off-target reads dropped to 9.4%, and the genotyping call rate increased to 97.5%. Concordance with genotypes previously obtained from ichip was 99.3%. When applying the optimised design on a larger scale (i.e. on the 279 individuals), we obtained similar performance metrics, with 8.0% off-target reads and a genotyping call rate of 97.3%. Moreover, upscaling resulted in a turnaround time of 2.5 working days/96 samples and a cost of €14/sample. The calculated IBD polygenic risk scores showed higher scores in patients as compared with controls (5.5E−03 vs. 4.0E−03, p = 8.80E−10; R² IBD polygenic risk score = 0.15, p = 1.28E−07), however with a large overlap between both groups. Quartile analysis showed that individuals within the highest quartile had an 8.1-fold (95% CI: 3.7–17.5) increase in risk towards IBD compared with individuals in the first quartile.

Conclusion

We developed a cost-effective genotyping assay for currently known IBD risk loci, with an integrated bioinformatics pipeline from raw sequencing data to individual genotypes and calculation of a polygenic risk score. Furthermore, this assay enables genotyping of individuals on a large scale while remaining flexible to implement newly identified genetic variants.
P822 Genetic analysis of ulcerative colitis in Japanese individuals using population-specific SNP array
Authors: Okamoto D , Kakuta Y , Takeo N , Moroi R , Kuroha M , Kanazawa Y , Hisashi S , Fuyuno Y , Umeno J , Hirano A , Torisu T , Nakamura M , Esaki M , Matsumoto T , Kinouchi Y , Masamune A
Published: January 2020

Background

Previous genome wide association studies (GWASs) have identified over 200 susceptibility loci for inflammatory bowel diseases (IBD), but studies in non-European population are limited. To clarify the genetic background of ulcerative colitis (UC) in the Japanese population, we conducted GWAS using a population specific SNP array (Japonica Array).

Methods

Discovery GWAS included 624 UC patients and 2004 healthy controls (HC) and replication study included 1075 UC patients and 419 HCs. We performed GWAS using a Japonica Array and the subsequent imputation with a Japanese population reference panel (referred to as 2KJPN). After GWAS, significant and candidate loci were identified and the representative top SNPs of each region were analysed in replication study and combined analysis. The probability of colectomy between genotypes of rs117506082, the top hit SNP at HLA loci, was analysed using the Kaplan–Meier method.

Results

In the GWAS, only the HLA loci showed genome wide significant association [rs117506082, p = 6.69E−28, OR=1.29, 95%CI=1.23–1.35]. 7 regions with nominal significance included 2 known loci: IL23R [rs76418789, p = 6.29E−7, OR=0.89, 95%CI=0.85–0.93], IRF8 [rs16940202, p = 1.03E−6, OR=1.07, 95%CI=1.04–1.10] and 5 novel loci: miR-622 [rs9560575, p = 8.23E−7, OR=1.06, 95%CI=1.04–1.09], 14q31 [rs117618617, p = 1.53E−6, OR=1.13, 95%CI=1.09–1.19], KAT6B [rs12260609, p = 1.81E−6, OR=1.06, 95%CI=1.04–1.09], PAX3-CCDC140-SGPP2 [rs7589797, p = 2.87E−6, OR=0.94, 95%CI=0.93–0.97], KCNA2 [rs118020656, p = 4.01E−6, OR=1.12, 95%CI=1.07–1.18]. Combined analysis revealed that the HLA loci [rs117506082, p = 1.10E−23, OR=3.43, 95%CI=2.99–3.83] and IL23R p.G149R [rs76418789, p = 9.03E−11, OR=0.51, 95%CI=0.42–0.63] had a genome wide significant association. The GG genotype of rs117506082 had a significantly lower probability for total colectomy compared with the GA+AA genotype (p = 1.72E−2).

Conclusion

IL23R p.G149R is a susceptibility locus for UC in Japanese individuals. The GG genotype of rs117506082 at HLA loci, a risk genotype for UC susceptibility, may predict a better clinical course.
P823 DNA methylation profiles accurately predict vedolizumab response and remain stable during induction and maintenance treatment in Crohn’s disease
Authors: Joustra V , Hageman I , Li Yim A , Gecse K , Lowenberg M , te Velde A , Satsangi J , de Jonge W , Henneman P , D’Haens G
Published: January 2020

Background

While the use of biologicals has revolutionised the treatment of Crohn’s disease (CD) in recent decades, many patients fail to respond or lose response over time. Predictors for treatment selection and/or success are lacking. Vedolizumab (VDZ) induces corticosteroid-free clinical remission in 29% and endoscopic remission in 36% of patients after 6 months. Accumulating evidence suggests that the epigenome, mainly DNA-methylation, is associated with certain CD phenotypes. Here, we investigated whether the DNA methylome of peripheral blood (PB) obtained from CD patients treated with VDZ was associated with clinical and endoscopic response or non-response to treatment.

Methods

We prospectively recruited CD patients scheduled to start VDZ treatment at regular dosage and who underwent baseline endoscopy. PB was collected prior to treatment (T1) and at a median of 14 weeks (T2) into treatment. Additionally, a third PB sample was collected after a median of 79 weeks (T3) into treatment for 10 CD patients. DNA methylation was measured using the Illumina Infinium Methylation EPIC BeadChip. After a median 27 weeks of treatment, patients were characterised as responders (R) or non-responders (NR) based on endoscopic changes (R= ≥50% reduction in SES-CD score) combined with either steroid-free clinical remission (≥3 point drop in HBI, no systemic steroids) and/or biochemical response (≥50% reduction in C-reactive protein and faecal calprotectin).

Results

We analysed data of 16 R and 14 NR patients, 53% of which were female with a median age of 37. No significant differences in age, sex or smoking were observed between R and NR. All patients had measurable serum VDZ concentration at the second endoscopy. To identify response-associated biomarkers, we performed elastic net regression through repeated cross-validation. We identified 38 differentially methylated probes (DMPs) associated with response (Figure a), 7 of which were located in gene promoters. Performance-wise the DMPs displayed a sensitivity of 0.86 and a specificity of 0.8 in predicting response (Figure b). Notably, the degree of methylation for the response-associated DMPs did not change after 14 weeks of treatment (n = 30), or even after 79 weeks (n = 10).

Conclusion

Here, we show that the DNA methylome in peripheral blood is associated with response to VDZ. As the difference in methylation remained stable during induction and maintenance treatment with VDZ, inflammation did not appear to affect the response-associated DMPs. Our observations provide evidence towards the establishment of epigenetic marks with predictive biomarker capabilities, paving the road towards personalised treatment selection in CD.
P824 Molecular predictors of anti-TNF treatment response in patients with Crohn’s disease
Authors: WALCZAK M , Lykowska-Szuber L , Plucinska M , Michalak M , Krela-Kazmierczak I , Zakerska-Banaszak O , Stawczyk-Eder K , Eder P , Dobrowolska A , Slomski R , Skrzypczak-Zielinska M
Published: January 2020

Background

Anti-tumour necrosis factor (anti-TNF) therapy has revolutionised the treatment of Crohn’s disease (CD). These drugs induce clinical and mucosal remission with high effectiveness, however almost 20–40% of patients do not respond to initial treatment. The exact mechanism of primary non-response is still unknown. The aim of the study was to investigate the impact of genetic interindividual differences on patients’ response. This will allow to identify molecular predictors of variable reaction to anti-TNF treatment.

Methods

DNA samples were obtained from 107 diagnosed and clinically characterised CD patients following anti-TNF therapy, where 12 of patients were classified as nonresponders. Based on long-range PCR libraries and next-generation sequencing (NGS), a panel of 23 genes belonging to TNF superfamily, proinflammatory factors, apoptosis-related proteins, signal transmission factors and receptors was analysed. After NGS, bioinformatical and statistical analysis were performed.

Results

In total, 598 single-nucleotide variants (SNP) for all analysed targets were identified. Patients’ nonresponse was associated with genotypes in 12 following loci (p ≤ 0.05): rs1061624 (OR: 4.22; 95% CI: 1.33–13.34) in TNFRSF1B gene, rs7896789 (OR: 0.27; 95% CI: 0.09–0.78) in FAS gene, rs2041747 (OR: 0.17; 95% CI: 0.04–0.80) in IL1R gene, rs373184583 (OR: 0.29; 95% CI: 0.09–0.82), rs12128686 (OR: 0.29; 95% CI: 0.09–0.82), rs7539036 (OR: 0.31; 95% CI: 0.11–0.87) and rs6672453 (OR: 0.31; 95% CI: 0.11–0.87) in FCGR3A gene, rs1071676 (OR: 2.47; 95% CI: 1.04–5.85), rs1143639 (OR: 2.47; 95% CI: 1.04–5.85), rs1143637 (OR: 2.47; 95% CI: 1.04–5.85) and rs1143634 (OR: 2.47; 95% CI: 1.04–5.85) in IL1B gene as well as rs55790676 (OR: 2.64; 95% CI: 1.02–6.83) in ADAM17 gene.

Conclusion

Obtained results suggest that molecular changes in genes involved in TNF activity may play an important role in response to anti-TNF treatment and be useful as molecular markers indicating potential patients’ response. Additionally, these results may contribute to better understanding the mechanism of monoclonal antibodies action in IBD treatment.
P828 DNA methylation profile defines epigenetic characteristics and molecular targets of Crohn’s disease
Authors: Kim T O , Yi J , Jung S H , Baek D H , Lee H S
Published: January 2020

Background

Inflammatory bowel disease(IBD) is known to be caused by a genetic predisposition involving multiple genes; however, there is growing evidence that abnormal interaction with environmental, particularly epigenetic, factors can have a significant contribution during the development of IBD. Although many studies, particularly genome-wide association studies (GWAS), have been performed to identify the genetic changes underlying the pathogenesis of Crohn’s disease (CD), the role of epigenetic changes in the development of complications arising from CD is poorly understood.

Methods

Here, we employed an unbiased approach to define DNA methylation alteration in CD patients using the Human Methylation 450K Bead Chip platform. Compared to normal controls, the majority of differential DNA methylation in CD patient samples was in the promoter, intergenic, and gene body regions.

Results

The DNA methylation profile in CD revealed 134 probes (23 hypermethylated and 111 hypomethylated probes) that were differentially methylated. We validated the methylation levels of 19 genes that showed hypermethylation in CD patients compared with normal control. Technical validation was performed using quantitative MSP analysis and we finally identified that the Fragile Histidine Triad (FHIT) genes were hypermethylated in a disease-specific manner. Using a large cohort for CD patients samples (n = 207), we found that FHIT is frequently methylated in CD patients (71%) by MSP and significantly increasing methylation level in CD patient samples. In addition, we confirmed the methylation level of FHIT gene between normal colon and CD patients. Due to hypermethylation of FHIT gene promoter in CD patients, we observed that the level of FHIT protein is downregulated in CD patient samples compared with normal by IHC analysis. Gene network analysis by GO and metascape for hypermethylated genes in CD patients suggested putative cellular and molecular interactions relevant to IBD pathology.

Conclusion

Overall, our DNA methylation profile identifies newly hypermethylated genes in CD, as well as paves the way to a better understanding of the role of epigenetics in the pathogenesis of CD, and provides direction for future research in the diagnosis/prognosis or therapeutic treatments for CD.
P830 Genotype-based treatment with thiopurine reduces incidence of myelosuppression in patients with inflammatory bowel diseases
Authors: Chang J Y , Park S J , Jung E S , Jung S A , Moon C M , Chun J , Park J J , Kim E S , Park Y , Kim T I , Kim W H , Cheon J H
Published: January 2020

Background

Thiopurine-related myelosuppression (most frequently leukopenia) interferes with thiopurine therapy for patients with inflammatory bowel diseases (IBD). We investigated whether pre-treatment analyses genetic variants associated with thiopurine-induced leukopenia could be used to effectively identify patients who required dose adjustments.

Methods

We performed a multicentre, prospective study of patients with IBD at 5 tertiary medical centres in Korea, from January 2016 through September 2018. Seventy-two patients were randomly assigned to a group that underwent genotype analysis for the NUDT15 variant (rs116855232) and FTO variant (rs79206939) and 3 common TPMT variants (rs1800460, rs1800462, rs1142345) associated with myelosuppression and 92 patients were assigned to a group that did not undergo genotype analysis (non-genotyping group). Patients heterozygous for any variant received 50 mg azathioprine equivalents, whereas those who were homozygous for any variant received alternative drugs. Patients who did not carry any of the genetic variants and patients in the non-genotyping group received 50 mg azathioprine equivalents followed by dose escalation up to 2–2.5 mg/kg. Myelosuppression was defined as white blood cell counts below 3000/μL, levels of haemoglobin 10 g/dl, or platelet counts below 100 K/μl.

Results

Twelve patients (16.7%) in the genotype analysis group and 33 patients (35.9%) in the non-genotyping group developed myelosuppression (p = .005). A multivariate analysis revealed that body mass indices above 21 kg/m2 (hazard ratio [HR], 0.43; 95% CI, 0.22–0.81; p = 0.009), pre-treatment genotype analysis (HR, 0.37; 95% CI, 0.18–0.77; p = 0.008), and the maximum dose of thiopurines (HR, 0.34; 95% CI, 0.19–0.59; p < 0.001) independently decreased risk of myelosuppression. Pre-treatment genotype analysis reduced numbers of outpatient clinic visit and numbers of patients with drug discontinuation or dose reductions.

Conclusion

In a randomised controlled study of patients undergoing thiopurine therapy for IBD, we found that selection of therapy based on genetic variants associated with thiopurine-induced leucopoenia significantly reduced the proportion of patients with myelosuppression during treatment.
P833 Bacterial mucosa-associated microbiome in inflamed and proximal non-inflamed ileum of patients with Crohn’s disease
Authors: Olaisen M , Flatberg A , van Beelen Granlund A , Røyset E S , Martinsen T C , Sandvik A K , Fossmark R
Published: January 2020

Background

The microbiota most likely has an essential role in the pathogenesis of Crohn’s disease (CD). While faecal diversion after ileocecal resection (ICR) protects against CD recurrence, re-exposure triggers inflammation. After ICR, the majority of patients develop recurrence in the neoterminal ileum and the ileal microbiome is of particular interest. We have therefore assessed the mucosa-associated bacterial microbiome in the inflamed and non-inflamed ileum of patients with CD.

Methods

Patients with an established diagnosis of CD undergoing ileocolonoscopy and healthy controls (HC) referred for colonoscopy due to rectal bleeding or screening for disease, but without any detected gastrointestinal pathology were invited to participate. Exclusion criteria included use of antibiotic treatment for the past 2 months. Mucosal pinch biopsies were sampled 5 cm and 15 cm orally of the ileocecal valve or ileocolic anastomosis for comparisons within the same patients. The biopsies were analysed by 16S rRNA sequencing, α- and β-diversity was assessed by Shannon entropy and Bray-Curtis dissimilarity index respectively. Histologic inflammation was graded.

Results

Fifty-one CD patients, where of 32 with previous ICR, and 40 HC were included in the study. Of the 51 CD patients, 20 had terminal ileitis, with endoscopically inflamed mucosa at 5 cm and normal appearing mucosa at 15 cm and no history of upper GI disease involvement. Seven CD patients had ileal stenosis. CD patients (n = 51) had lower α-diversity and separated clearly from HC on β-diversity plots (Figure 1). Twenty-three bacterial taxa were differentially represented in CD patients and HC, among these Tyzzerella 4 was found to be profoundly overrepresented in CD (p = 4.1 × 10–68). When comparing the microbiome in the inflamed ileal mucosa with the proximal non-inflamed mucosa within CD patients (n = 20) neither α- or β-diversity differed (Figure 2). Furthermore, no bacterial taxa were differentially represented in the inflamed vs. proximally non-inflamed mucosa. CD patients operated with ICR had lower α-diversity (p = 0.021), but β-diversity did not differ from CD patients without ICR. CD patients with stenosis had lower abundances of Bacteroides, Sutterella and Akkermansia species.

Conclusion

23 taxa were differentially expressed in CD compared with HC. The ileal mucosa-associated microbiome is similar assessed by both α- and β-diversity in the inflamed mucosa and the proximal non-inflamed mucosa within the same patients. Our results support the concept of CD specific microbiota alterations and demonstrate that neither ileal sub-location nor endoscopic inflammation itself influence the mucosa-associated microbiome.
P852 Introduction of Entamoeba histolytica serology testing in the management of inflammatory bowel disease patients at University Hospitals of Leicester, UK
Authors: O’Meara D , Tufail Q , Lim F , Richards C , Thi A A
Published: January 2020

Background

Amoebic colitis can mimic inflammatory bowel disease (IBD) in clinical presentation, endoscopic and (to some extent) histological findings. Four patients with amoebic colitis were misdiagnosed with IBD or an IBD flare at University Hospitals of Leicester (UHL), UK in 2018. This prompted a change in practise in our department and we began screening for Entamoeba histolytica in patients with newly-diagnosed IBD, a flare or those being considered for biologics. We analysed cases of possible amoebic colitis after this change by reviewing IBD patients with a positive E. histolytica immunofluorescence antibody test (IFAT).

Methods

We conducted a retrospective electronic and case note review of patients with IBD and positive amoeba IFAT serology >1:80 from April 2019 through September 2019. We collected information including Crohn’s disease (CD), ulcerative colitis (UC), IBD treatment, histological findings, travel history, stool E. histolytica DNA polymerase chain reaction (PCR) and amoebic serology including IFAT and Cellulose Acetate Precipitin test (CAP). The histology of endoscopic biopsies for 16 of the IFAT positive patients was reviewed specifically for amoebic trophozoites.

Results

During the study period we identified 26 IFAT positive patients, excluded 3 patients that were felt to be non-IBD; 23 were included in the study. The median age was 37.8 (range 16–86); 43.5% were male. Four had a diagnosis of UC; 19 had CD. 12 were new IBD presentations. Seven patients had a relevant travel history (Jamaica, Thailand, Turkey, Italy, Greece, and Spain). Four did not have a travel history. Travel history was unknown for 12. Three patients were on biologics, one on biologics and thiopurines. Five were on thiopurines, three on thiopurines and steroids. Four were on steroids only, four on 5-ASAs. Three were on no treatment. Two out of 16 patients reviewed had amoebic trophozoites on endoscopic biopsy, unfortunately stool PCR was not sent on these two patients. Stool E. histolytica DNA PCR, was sent for 19 patients and was negative in those cases. All 24 patients were negative for CAP.

Conclusion

While IFAT is helpful in detecting past exposure it is only 75% sensitive for amoebic colitis. Even if IFAT and CAP are combined it is difficult to differentiate amoebic colitis from IBD. It is not clear if these cases represent past infections, early infections that precipitated an IBD flare, early infections that arose in the setting of immunosuppression, or false positive IFATs. The risk of infection in the immunosuppressed patient is high and the consequences of misdiagnosis are significant therefore a comprehensive screening method is merited; this may encompass IFAT ± CAP, stool E. histolytica DNA PCR, and possibly histological review.
N02 The IBD-BOOST programme: developing a digital self-management intervention for symptoms of fatigue, pain and urgency in inflammatory bowel disease
Authors: Windgassen S , Artom M , Norton C , Sweeney L , Moss-Morris R
Published: January 2020

Background

Fatigue, pain and urgency are among the most commonly reported and burdensome symptoms of inflammatory bowel disease (IBD). A disconnect between symptoms and inflammation has been documented and medical management does not always adequately resolve symptoms. Extensive research shows the relationship between IBD symptoms and psychosocial factors. This poster describes the development of a facilitator-supported, theory-driven, tailored web-based intervention for fatigue, pain and urgency in IBD.

Methods

The Medical Research Council (MRC) guidance and the person-based approach were used to guide intervention development. Literature reviews of psychosocial factors related to fatigue, pain and urgency in IBD and trials of behavioural interventions were used to create a cognitive-behavioural model of symptom perpetuation and impact. The model was tested and refined in large cross-sectional and qualitative studies to understand patients’ experiences of these symptoms and intervention needs. The refined model was mapped onto an intervention logic model to define the psychosocial processes to target in intervention techniques. Patient feedback on the logic model and session content was obtained. Usability of the website was assessed using think-aloud methods and survey data were collected on session content, design and functionality.

Results

87 people with IBD and 68 IBD nurses participated in Patient and Public Involvement activities for intervention development. Five interviews were carried out to develop guiding principles and two focus groups provided feedback on a logic model and session plan. 54 people with IBD and 45 IBD nurses completed an initial discovery online survey. Results indicated preferences to receive facilitator support via email/online-messages rather than telephone. Five focus groups included 68 IBD-nurses to assess barriers/facilitators in supporting the intervention. Desirable functionalities included diagrams/aids, email reminders and links to external resources. 31 people with IBD were included in feasibility and acceptability testing. The final intervention includes 8 core sessions with tasks and 4 symptom-specific sessions, and facilitator support of one 30-minute call and in-site messaging. Core to all sessions is understanding and ‘breaking’ personal ‘vicious cycles’ of symptom interference.

Conclusion

We have used a person-based approach and systematic application of theory, evidence and stakeholder involvement to guide intervention development. BOOST is the first web-based intervention with the primary aim of targeting fatigue, pain and urgency and improving the quality of life of people with IBD. This is now being tested in a large randomised controlled trial.
N05 IBDoc® Faecal calprotectin self-test retrospective audit in a District General Hospital (DGH)
Authors: Avery P , Blackmore K , Angel C
Published: January 2020

Background

In 2016, a DGH in England commenced the IBDoc® Faecal calprotectin test. Using smart phone technology, the test can provide results as quickly as 2 hrs. An audit of patients who trialled the test was presented at ECCO in 2017; this abstract looked at the value of the tests and helped to show the investigations worth to the DGH trust. The continued use of the test at the trust has recently been audited and these data are presented by the authors to help further understand the benefit.

Methods

A retrospective audit of patients enrolled on the IBDoc® between July 2017 and October 2019 was carried out by the IBD nursing team. Electronic patient records were searched and corresponding endoscopic assessments that had been carried out within 6 months of the most recent IBDoc® results, were documented for each patient. The terms normal/mild, moderate and severe were used to categorise inflammation seen at colonoscopy, flexible-sigmoidoscopy (C/FS) and/or histopathology (HP). The IBDoc® uses the categories normal (<150) moderate (<400), and high (>400); these values have been set locally easy comparison of these data is possible due to the three levels of stratification. The reason for the endoscopic investigation was also documented. In the sample where no endoscopic investigation was recorded, outcomes were categorised into three groups; well (W), increase monitoring (IM), and treatment adjustment required (TAR).

Results

134 patients are signed up to the IBDoc®, 23 patients failed to carry out the test successfully (CD 14 and UC 9). 6 did not accept a test in clinic due to changing their mind or failure in smart phone technology, 12 did not do the test before expiry* and 5 failed to give a result due to difficulties completing the test. *Myriad of reasons were given for not doing the test and another paper could be written to attempt to understand the persons motivation for not completing the test. Of the 111 patients’ (CD 55, UC 56, IBDU 2 and non-IBD 2), 80 patients did not undergo a C/FS, of the 31 that did, correlation between calprotectin, C/FS and/or HP result was 84%. at 100% best correlation was seen in the severe C/FS results and high IBDoc® results. C/FS were carried out for diagnosis (n =10) surveillance (n =4) and disease assessment (n = 17). In the 80 patients with no colonoscopy’s were assessed for outcomes and are: W. n = 39; IM. n = 19; TAR. n = 23.

Conclusion

The above data shows continuing value of the IBDoc® faecal calprotectin self-test, and there is correlation seen in the comparative results. This data also helps separate well from unwell patients, offering further opportunities to promote supported self-management in people with IBD and prioritisation of clinic appointments.
N11 Pregnancy Outcomes in Patients with inflammatory bowel disease: A single-centre experience
Authors: BAILEY Y , Hanna C , O’Connor A , Breslin N , Ryan B , McNamara D
Published: January 2020

Background

This study aimed to examine the current management and outcomes in pregnancy in our cohort of inflammatory bowel disease (IBD) patients.

Methods

Following ethical approval patients with at least one pregnancy with known Crohn’s Disease (CD) or Ulcerative Colitis (UC) were identified. Using a self-assessment questionnaire basic demographic, clinical data and pregnancy outcomes were recorded.

Results

Eighty-five patients were recruited between January and October 2019; 38 CD, 26 UC and 1 Indeterminate (ID). The mean age was 28.6 years (range 14–46 years) at diagnosis. In total there were 199 pregnancies: 168 live births, 2 stillbirths (1%); lower than the national rate of 3.0 per 1000 and 29 miscarriages (14.5%) compared with national rates of 1 in 5. The majority attended routine combined GP and maternity services, only 17 (20%) attended a specific high-risk maternity clinic. Biologic usage was similar pre and during pregnancy; 16 (22%), 11 (16%) with a slight increase post pregnancy 19 (30%). Overall 26% continued to smoke and 7% drank alcohol during their pregnancy. The total of reported flares were less frequent during pregnancy 45% (n = 35) vs. pre-partum 61% (n = 47) and post-partum 79% (n = 61), p = 0.021. In all there were 138 vaginal deliveries and 32 (19%) caesarean sections (CS). CS rates did not differ by disease type, UC 9/26 & CD 26/58, p = 0.4 There were 12 (7%) preterm deliveries 3 of which had low birth weights. 2 congenital abnormalities 1 % (cleft palate and spina bifida) lower that the national rate of 2–3% of live births and 14–24% of stillbirths, were recorded. Breast feeding rates were reported at 34% (n = 28), significantly lower than the national average rate of 46.3%. 81% of patients reported having had a recent smear test and 18% reported an abnormal smear. Seventy per cent of patients who reported having an abnormal smear were on immunosuppressant therapy.

Conclusion

The results from our ongoing study have found less disease activity during pregnancy possibly associated with continued use of biological therapy. However, there were higher rate of flares reported post-partum possibly related loss to immune tolerance developed during pregnancy, or lifestyle and environmental factors. Despite not attending a specific IBD pregnancy service outcomes in our cohort were good with lower than National average rates of miscarriage, stillbirths and congenital abnormalities. Worryingly rates of over a quarter of patients continued to smoke during pregnancy and only a third of patients breastfed; factors which could be targets for future education. High rate of abnormal smear tests, low rate of HPV vaccination warrants further research.
N14 Patient-identified symptom management techniques to inform the content and functionality of an online self-management programme: an exploratory qualitative study
Authors: Fawson S , Dibley L , Smith K , Batista J , Artom M , Windgassen S , Syred J , Moss-Morris R , Norton C
Published: January 2020

Background

As part of the IBD-BOOST programme of research (www.ibd-boost.org), we aimed to understand how people manage fatigue, pain and urgency in inflammatory bowel disease (IBD), and their preferences for an online self-management intervention for this triad of symptoms.

Methods

Using exploratory qualitative methods we recruited people with IBD from clinic and community sources and conducted focus groups and interviews in different UK locations. Focus groups and interviews were facilitated by experienced qualitative researchers, recorded on a digital audio device and professionally transcribed. Participants were asked to talk about the techniques they have found helpful for managing fatigue, pain, and/or urgency, and their preferred design and functionality of an on-line intervention to support self-management. Individual interviews were used to explore and elaborate on issues raised in focus groups in greater depth. We conducted framework analysis of focus group data and applied it over three rounds of analysis. Interview data were analysed thematically and then integrated with the focus group data.

Results

Thirty-nine participants (16 females; ages 23–60 years) each attended one of five focus groups (N = 3, 7, 6, 6 and 3), or an individual interview (n = 14). Twenty-four had CD, 13 had UC and three had IBD-U. Duration of disease was three–49 years. Three core themes emerged:

Participants discussed the importance of learning to manage all three symptoms simultaneously, and of using techniques to track the link between factors such as food, fluids, stress and exercise, and symptoms. They wanted an accessible online intervention which would work across several platforms (mobile phone, tablet, laptop or desktop computer), to include symptom, medication and activity-tracking features, with options for support from IBD clinicians.

Conclusion

Fatigue, pain, and urgency commonly occur together, and patients want these managed simultaneously, rather than separate interventions for each symptom. Findings are informing the development of online intervention self-management programme, reflecting patient requests regarding content, access, functionality, and usability.
39 Overview of tricuspid regurgitation (tr). new classification of tr. when severe tr is too severe?
Authors: Vieitez Florez J M , Monteagudo J M , Mahia P , Perez L , Lopez T , Marco I , Perone F , Gonzalez T , Sitges M , Bouzas A , Gonzalez V , Li P , Alonso D , Fernandez-Golfin C , Zamorano J L
Published: January 2020

Introduction

Tricuspid regurgitation (TR) importance is growing in the last years. Its presence is associated with a worse prognosis. A new severity classification has been published, adding massive and torrential to the classical TR classification. However, it is not know how many of the patients classified as severe TR, corresponds to the new Torrential or massive classification that for sure will lead to different treatment strategies. Also few published studies have addressed the aetiologies, mechanisms and severity in large cohorts.

Purpose

To evaluate the burden of TR in a large cohort of patients referred for an echocardiography.

Methods

Prospective study where consecutive patients undergoing an echocardiographic study in 10 Spanish hospitals within a three-month period were included. All studies with at least moderate TR were selected for analysis. The evaluation was conduced according to the usual practice of the laboratory. TR assessment was performed as recommended by the European Association of Cardiovascular Imaging. TR was quantified according to Hanh & Zamorano new published classification.

Results

A total of 35088 consecutive echocardiographic studies were performed in the participant hospitals during the recruitment period. TR of at least moderate degree was detected in 2124 studies (6,05%). Mean age was 77,1 years and 62.8% were women.

Mitral or aortic valvulopthy was the most common cause, present in almost half of cases (48.4%). The second cause of TR was idiopathic with 22.2% of cases. Primary TR was found in 7.2% of patients, the most frequent aetiology in these group was cardiac implantable devices with 4.2% of total of TR. Aetiology and severity according to the new classification can be seen in the figures

Atrial fibrillation was present in 47.6% of cases. 56.4% of patients had symptoms at the time of the study (NYHA≥2 at the time of study).

Right ventricle (RV) was dilated (telediastolic basal diameter >42mm) in 39.4% of patients). RV function was impared (TAPSE <17mm) in 30.6% of patients.

Conclusions

In these larger multicentre study, significant TR may is present in up to 6% of the echocardiographic studies and is often symptomatic[m1] . 4,91% of patients had a massive or torrential grade. Most TR are secondary to mitral or aortic valvulopathy. Idiopathic TR has taken the second place.

Abstract 39 Figure. Severity and aetiology of TR
44 Determinants of functional tricuspid regurgitation progression
Authors: Aronson D , Lessick J , Agmon Y , Mutlak D
Published: January 2020

Background

Tricuspid regurgitation has been the focus of increasing interest and research in recent years. However, few data are available with regard to risk factors associated with the evolution of TR.

purpose

The aimed to determine the risk factors for the development of hemodynamically significant functional TR.

Methods

We studied 1552 subjects with an index echocardiogram demonstrating trivial or mild TR. Risk factors for TR progression to moderate or severe TR during a median follow-up time of 38 months (IQR 26 to 63 months), were determined using logistic regression.

Results

In the multivariable logistic regression model, older age, female gender, pacemaker electrode and indicators of left heart disease (LA enlargement, increased pulmonary artery pressure (PAP), atrial fibrillation, and left-sided valvular disease) were associated with future development moderate or severe TR (Table). The strongest predictors of TR progression were PAP, LA size, AF, and age.

The final echocardiographic examination demonstrated a marked worsening in the severity of left-sided myocardial and valvular disease, that was more prominent in subjects with TR progression (Figure). Compared with subjects in whom TR did not progress, subjects with TR progression demonstrated an increase in PAP and in the severity of mitral and aortic valve disease, larger increases in LA and reductions in LVEF (Figure). Lager proportions of subjects progressing to significant TR developed AF, were implanted with pacemakers or defibrillators or underwent valvular interventions (Figure). The mean PAP change between the baseline and final echocardiographic examination was 16 ± 15 mm Hg and 3 ± 11 mm Hg with and without TR progression, respectively (P < 0.0001).

Conclusion

Predictors of TR progression are mostly indicators of more advanced left heart disease. In addition, progression to significant TR is associated with a more acceleration course of left hear disease.

Independent Predictors of TR Progression Characteristics HR (95% CI) P value Age (per 10 years increase) 1.35 (1.31-1.50) <0.0001 Female sex 1.50 (1.13-1.99) <0.0001 Heart failure 2.76 (1.43-5.32) 0.002 LA enlargement ≥ Moderate 1.86 (1.29-2.67) 0.001 Atrial fibrillation 2.34 (1.57-3.49) <0.0001 Pacemaker/ICD 2.93 (1.48-5.78) 0.002 Pulmonary artery pressure (per 10 mm Hg increase) 1.47 (1.29-1.69) <0.0001 Valvular heart disease≥ Moderate 1.50 (1.11-2.04) 0.009

Abstract 44 Figure. Proportion of new abnormalities