bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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 &lt; 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

Abstract

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

Abstract

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 &gt;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

Abstract

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

Abstract

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 (&lt;150) moderate (&lt;400), and high (&gt;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

Abstract

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

Abstract

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.