bluuebunny/crossref_metadata_2025_split huggingface dataset:
OP21 Predictive value of Milan Ultrasound Criteria in Ulcerative Colitis: A prospective observational cohort study
Authors: Allocca M , Dell’Avalle C , Furfaro F , Craviotto V , Zilli A , D’Amico F , Peyrin-Biroulet L , Fiorino G , Danese S 
Published: May 2021

Abstract

Background
Endoscopic remission is associated with better outcomes in ulcerative colitis (UC). However, colonoscopy (CS) is invasive and poorly tolerated by patients. Recently, we developed and externally validated non-invasive ultrasonography based criteria [Milan ultrasound criteria (MUC)] to assess and grade endoscopic activity in UC. We also confirmed that a MUC score &gt; 6.2 is a valid cut-off to discriminate endoscopic activity, defined by a Mayo endoscopic subscore &gt; 2.
Aim of this study was to assess the predictive role of MUC on disease course in a prospective cohort of UC patients.

Methods
UC consecutive patients were followed for at least 12 months after performing baseline bowel US. UC-related outcomes, including need of treatment escalation (defined as the need of corticosteroids or change/optimization of immunosuppressants), hospitalization and surgery, were assessed at 1 year by logistic regression analysis, and were analyzed after long term follow-up (5 years) using Kaplan-Meier survival analysis.
Fig. 1A and 1B. Kaplan–Meier curves for the cumulative probability of hospitalization and surgery in patients with Milan ultrasound criteria (MUC) &lt; 6.2 (solid line) or MUC &gt; 6.2 (dotted line). (p= 0.046; p= 0.023; respectively).
Fig. 1C and 1D. Kaplan–Meier curves for the cumulative probability of hospitalization and surgery in patients with Mayo endoscopic subscore 0–1 (solid line) or 2–3 (dotted line). (p= 0.035; p= 0.071; respectively).

Results
87 UC consecutive patients were included in the study, 31 (36%) were in endoscopic remission (Mayo endoscopic subscore 0–1) and 56 (64%) in endoscopic activity (Mayo endoscopic subscore 2–3). MUC and Mayo endoscopic subscore significantly correlated at baseline (Spearman’s rank correlations [rho]= 0.642; 95% confidence interval (CI) 0.499 to 0.751; p &lt; 0.001). The multivariable analysis identified as independent predictors of need of treatment escalation throughout the 12-month period as being: MUC &gt; 6.2 (OR: 5.95, 95% CI: 1.32–26.76, p &lt; 0.020) and a partial Mayo score (PMS) &gt; 2 (OR: 26.88, 95% CI: 5.01–144.07, p &lt; 0.001). Kaplan-Meier survival analysis of long-term follow up demonstrated a lower cumulative probability of need for surgery and hospitalization in patients with MUC &lt; 6.2 compared to MUC &gt; 6.2 (Fig. 1A and 1B), as well as in patients with a Mayo endoscopic subscore of &lt; 1 compared to Mayo endoscopic subscore of 2–3 (Fig. 1C and 1D).

Conclusion
MUC is a novel non invasive tool that predicts the course of UC in the short and long term follow-up.
OP30 Lyophilised orally administered faecal microbiota transplantation for Active Ulcerative Colitis (LOTUS study)
Authors: Haifer C , Saikal A , Paramsothy S , Borody T J , Ghaly S , Kaakoush N O , Leong R 
Published: May 2021

Abstract

Background
Faecal microbiota transplantation (FMT) administered via the lower GI tract effectively induces remission in ulcerative colitis (UC). Orally administered FMT capsules may improve patient tolerability and facilitate maintenance therapy while it is unclear if pre-FMT antibiotics enhance therapeutic efficacy.

Methods
We performed a dual-centre randomised, double blind, placebo-controlled trial of oral lyophilised FMT in adults with mild-moderately active UC (total Mayo 4–10). All subjects received 2-weeks of pre-FMT antibiotics (amoxycillin, metronidazole and doxycycline) before 1:1 randomisation to either oral FMT (0.35g stool content per capsule from 1 of 2 healthy donors) or identical placebo for 8 weeks. Enforced tapering and cessation of corticosteroids was mandated. The primary endpoint was week 8 steroid-free clinical remission with endoscopic remission or response (total Mayo score ≤2 with subscores ≤ 1 for rectal bleeding, stool frequency and endoscopic appearance, and ≥1-point reduction from baseline in endoscopy subscore). Responders to FMT induction were re-randomised to either continue maintenance FMT or withdrawal of FMT with final outcomes assessed at week 56.

Results
Recruitment was paused due to the COVID-19 pandemic. 37 patients were randomised. Baseline patient and disease characteristics were balanced between the randomised groups. The primary outcome was achieved in 8/16 (50%) receiving FMT versus 3/19 (16%) receiving placebo (OR: 4.63; 95%CI: 1.74–12.30; P=0.002). Steroid-free clinical remission rates and endoscopic remission rates were 69% vs 26% (P=0.012) and 44% vs 16% (P=0.074) in the FMT and placebo arms, respectively. Reported SAE were worsening colitis (2 FMT, 1 placebo) and PR bleeding relating to previous anal surgery (placebo). Ten patients entered the maintenance withdrawal study. Steroid-free clinical, endoscopic and histologic remission was achieved in 4/4 patients who continued daily oral FMT, with all 6 patients randomised to FMT withdrawal having a flare of disease with a median time to relapse of 6 months.

Conclusion
Oral lyophilised FMT following antibiotic pre-treatment for mild-moderately active ulcerative colitis was associated with a significant increased rate of clinical remission with endoscopic remission or response versus antibiotic treatment alone at week 8. Pre-treatment antibiotics had an additive impact upon treatment efficacy compared with previous studies utilising FMT. Maintenance FMT therapy was associated with sustained clinical, endoscopic and histologic remission at week 56. Treatment was well tolerated and there were no new safety signals related to FMT therapy.
P022 Pathologic involvement of the farnesoid X receptor/fibroblast growth factor 19 axis to the Crohn’s disease early postsurgical recurrence
Authors: Suau R , Garcia-Jaraquemada A , Lorén V , Torres P , Jou E , Llaves M , Aterido A , Julià T , Zabana Y , Lozano J J , Domènech E , Mañosa M , Manyé J 
Published: May 2021

Abstract

Background
Crohn’s disease (CD) is a chronic inflammatory bowel disease that normally requires bowel surgical resection due to intra-abdominal inflammatory complications such as fistulae and stenosis. However, 90% of patients that underwent surgery and did not receive prophylaxis, suffer from postsurgical endoscopic recurrence within one year.

Methods
The objective of this study is to understand the de novo postsurgical lesion formation in order to stablish a potential mechanism of action and its derived predictive signals to devise preventive strategies. To achieve it, transcriptome analyses of the inflamed and macroscopically unaffected zone of the ileocecal resection from 20 patients from a hospital cohort and 10 controls were performed. Patients were classified for early postsurgical recurrence by means of Rutgeerts index (i0&lt;i1&lt;i2&lt;i3&lt;i4) and transcriptome was analysed using different comparatives and clustering strategies. In order to replicate the results from the transcriptome analyses, the statistically significant genes and rationally related genes have been tested by qPCR in a corroboration cohort formed by 24 different patients.

Results
The transcriptome results showed there were no differences neither between i0, i1 and i2a (anastomotic lesions) nor when comparing i2b (non-anastomotic lesions) vs ≥i3. However, when comparing i0+i1+i2a vs. i2b+i3+i4 there were differently expressed genes highlighting ADIPOQ in the inflamed zone and the FXR/FGF19 axis in the unaffected zone. When replicating the results in the corroborative cohort, we identified FXR and other xenobiotic nuclear receptors as the genes differentially expressed in i2a vs i2b, i3 and/or i4, mainly in the macroscopically unaffected zone. Specifically, the differentially expressed genes were: MOGAT2, PXR, FXR and AHR (i2a vs i4), PPARα and FXR (i2a vs i3), TMIGD1, PPARα, FXR and AHR (i2a vs i3+i4) and FXR (i2a vs i2b+i3+i4).

Conclusion
Nuclear receptor FXR is activated in the ileum by bile acids action and it is key in the lipid metabolism regulation and in the bile acids production by means of FGF19. Moreover, ileal FXR, as well as other xenobiotic nuclear receptors, actively participates in the enhancement of the intestinal barrier function and in the innate immunity regulation. In conclusion, the results obtained in this study suggest a link between bowel xenobiotic metabolism and the de novo lesion formation in previously unaffected areas in the postsurgical recurrence in CD.
P046 Disease modelling of Inflammatory Bowel Disease by human colon organoids
Authors: Molnár T , Jójárt B , Resál T , Szántó K , Kata D , Földesi I , Molnár T , Maléth J , Farkas K 
Published: May 2021

Abstract

Background
Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the gastrointestinal tract which is associated with the imbalanced pro- and anti-inflammatory cytokines. Anti-TNF-α is widely used as a therapeutic agent, but 10–30% of the patients are not responding to the treatment or in time it become less affective. In vitro organoid cultures generated from stem cells can mimic the cellular diversity and function of the organ of origin and might be used as a predictive tool for patient specific response. However, the in vitro cytokine expression pattern of the IBD colon organoid cultures have never been determined or compared with the cytokine expression of the colon mucosa.

Methods
Our aim was to determine and compare the cytokine profiles of the colon biopsy samples in IBD patients and organoid cultures generated from these biopsies.
In this study samples from 5 IBD patients were used. Biopsies were taken during colonoscopy from inflamed part of the colon. Crypts were isolated from the biopsy samples to start colon organoid culture. Total protein was isolated from the biopsies and the organoids. Cytokine Array was used to determine the cytokine patterns in both samples. ELISA was used to measure the TNF-α concentrations and immunofluorescence staining to localize it in the organoids.

Results
We determined the cytokine profile of the biopsy samples and the colon organoid cultures. The cytokine patterns were remarkably similar until the first passage. The major pro-inflammatory cytokines, IL-1β, IL-6, IL-8, were detected in the organoids after the first passage. After the second passage the cytokine expression decreased or disappeared. ELISA revealed that TNF-α was also expressed in the organoid cultures, however a similar decrease in the expression was observed, which was also confirmed by immunofluorescence staining. TNF-α positive cells were present in the organoids, but it decreased after every passage.

Conclusion
Our results suggest that the colon organoid cultures maintain the cytokine profile of the tissue of origin until a limited time (until the first passage). Therefore, organoids might be used to determine patient specific therapy for drug tests.
P066 Exploration of critical molecules for optimizing treatment by analyzing in flammatory cytokines in the intestinal mucosa of patients with Inflammatory Bowel Disease
Authors: Yokoyama Y , Yamakawa T , Hayashi Y , Kazama T , Hirayama D , Nakase H 
Published: May 2021

Abstract

Background
Inflammatory cytokines initiate and sustain the perpetuation of processes leading to chronic inflammatory conditions such as inflammatory bowel diseases (IBD). Research into the cytokine biology of IBD has nurtured the dogmatic view that distinct immunotypes characterize different IBD subtypes. Recently, many biologics have emerged as the treatment options for IBD patients. Still, it is challenging to establish biomarkers for predicting their effectiveness because the cytokines that determine the IBD clinical phenotype vary in individual patients. Therefore, this study aims to explore critical molecules for optimizing treatment by analyzing inflammatory cytokines in the intestinal mucosa of IBD patients.

Methods
From September 2019, to February 2020, patients with ulcerative colitis (UC) and Crohn’s disease (CD) who underwent colonoscopy or flexible sigmoidoscopy, and the control group, patients who received colorectal polypectomy at our institution, were enrolled in the study. We took biopsies from inflamed ileal or colonic mucosa. We analyzed the gene expression of various inflammatory cytokines by real-time PCR using RT2 Profiler PCR Array (96-Well Format) Human Inflammatory Cytokines & Receptors (QIAGEN). Cytokines not included in this array were subjected to real-time PCR separately. Based on these data, we investigated the relationship between mucosal cytokines and clinical characteristics.

Results
The total number of patients was 23 (control 5, UC 12, CD 6) cases, the median age was 51 years (18–78), genders were fifteen males and eight females. Disease phenotype was divided into extensive colitis/ left-sided colitis/proctitis (10/1/1) in UC patients, and A1/A2/A3 (2/3/1), L1/L3 (2/4), B1/B1+p/B2/B3 (3/1/1/1) in CD patients. Seven patients were steroid-dependent, and six patients were refractory to the anti-TNFα agent. The higher gene expressions of CCR2/CXCL1/CXCL3/CXCL13, IL-8, IL-33, and SPP1 in inflamed mucosa of UC compared to those of CD (p&lt;0.05). The positive correlation between Mayo score and IL-1R1 expression in intestinal mucosa was observed (r=0.68, p=0.028). The expression of IL-1β, IL-6, IL-8, and oncostatin M (OSM) was higher in steroid-dependent UC patients, and the primary non-responders to anti-TNFα therapies had higher expressions of IL-7 in colonic mucosa than the secondary non-responders in UC.

Conclusion
Our results suggest that UC exhibits different cytokine patterns in the intestinal mucosa from CD as reported previously. Exploration of cytokine expressions in the intestinal mucosa may lead to predicting refractory IBD. The identification of molecules that can predict therapeutic effectiveness helps to optimize IBD treatment in the future.
P072 The involvement of extracellular Nicotinamide Phosphoribosyltransferase (eNAMPT) and Nicotinate Phosphoribosyltransferase (eNAPRT) in inflammatory bowel disease
Authors: Colombo G , Ribaldone D G , Caviglia G P , Genazzani A , Travelli C 
Published: May 2021

Abstract

Background
Nicotinamide phosphoribosyltrasferase (NAMPT) is a pleiotropic enzyme which catalyses the first and rate-limiting step in the biosynthesis of NAD. It is present in two different forms: an intracellular form, called iNAMPT, (Chiarugi et al., 2012), and an extracellular form, eNAMPT. eNAMPT is considered an important factor for granulocyte-colony stimulating factor-(G-CSF)-induced myeloid differentiation, with paracrine and autocrine effects on different cell types (i.e. immune and cancer cells), binding TLR4. NAMPT is structurally and functionally related to the enzyme nicotinate phosphoribosyltransferase (iNAPRT), which is rate-limiting in the NAD salvage pathway that starts from nicotinic acid. The NAD biosynthetic pathways controlled by NAMPT and NAPRT are closely interconnected and can compensate for each other. Also, NAPRT is identified as an extracellular ligand (eNAMPRT) for TLR4 and a mediator of inflammation (Managò et al., 2020).
Importantly, iNAMPT and eNAMPT levels are increased in several pathologies, included inflammatory bowel disease (IBD). It has been reported that serum eNAMPT levels correlate with the stage of the pathology: in an active state of the disease the levels of NAMPT are very high, however its levels are partially reduced in a remission stage (Moschen et al., 2007).

Methods
First, we investigated the role of eNAMPT and eNAPRT in murine IBD models (especially in DNBS and DSS model). We took into account phenotypic effect as weight loss and colon shortening, but also the reduction of mRNA of inflammatory genes with RT-PCR, tissue damage with H&E and IHC analysis and systemic and local production through colon explant. Secondly, we determined serum eNAMPT and eNAPRT levels in a cohort of adult IBD patients.

Results
Both eNAMPT and eNAPRT have been found elevated in 180 IBD patients, as proinflammatory marker of the pathologies. These levels are also elevated in serum and colonic explant of DSS and DNBS preclinical models, associated to an active state of the disease, as a pro-inflammatory response developed locally and systemically.
Moreover, we performed ELISA analysis on sera of 100 IBD patients, eligible for anti-TNF treatment, both pediatric and adults. Serum eNAMPT levels are increased before the treatment, responsive patients verified a reduction of these levels, while no-responsive ones verified higher levels.

Conclusion
eNAMPT and eNAPRT could be considered pro-inflammatory markers of IBD and possible druggable targets.
P096 Which patients with known Crohn’s disease after an ileo-colonoscopy will benefit most from small bowel capsule endoscopy?
Authors: Viazis N , Mountaki A , Koustenis K , Veretanos C , Arvanitis K , Georgiadi T , Karampekos G , Manolakis A , Archavlis E , Christidou A , Mela M , Mantzaris G 
Published: May 2021

Abstract

Background
Ileo-colonoscopy with biopsies is considered the gold standard for the diagnosis and management of Crohn’s disease (CD). In contrast, the role of small bowel capsule endoscopy (SBCE) is limited currently in cases where ileo-colonoscopy and imaging techniques raise doubts on the diagnosis or cannot explain certain clinical manifestations of Crohn’s disease. The aim of our study was to determine whether there are patients with endoscopically confirmed established CD who could get additional benefit by SBCE.

Methods
Retrospective analysis of prospectively collected data from 6301 patients subjected to SBCE in our department from 1st March 2003 to 18th February 2021. Patients with CD diagnosed by ileo-colonoscopy or total colonoscopy only (because the ileo-caecal valve could not be intubated) prior to SBCE were included in the study and biopsies. SBCE had been performed only in patients who lacked any clinical and/or imaging (CT/MRE) evidence of bowel obstruction. The presence and extent of mucosal lesions, namely local and/or diffuse erythema, erosions and ulcers (aphthous, superficial and/or deep) throughout the small intestine, which may be difficult to identify by traditional imaging, could either explain clinical manifestations unrelated to the findings of colonoscopy or led onto reassessment of applied treatments were sought by SBCE.

Results
The study sample consisted of 1002 patients (males/females: 511/491, mean age ± SD: 52.6±27.3). Among these, CD had been diagnosed with colonoscopy (and not ileo-colonoscopy) in 293 (29.2%) subjects and small bowel involvement was seen in 104 (35.5%) patients. The vast majority of these patients had lesions only in the terminal ileum (n=81, 77.8%), while the remaining patients (n=23, 22.2%) had additional lesions in more proximal parts of the small bowel. Among the 709 (70.8%) patients in whom CD had been diagnosed by ileo-colonoscopy, lesions in the terminal ileum were found in 407 (57.4 %) patients; SBCE revealed more proximal lesions in 104 patients (25.5%). In the remaining 307 patients (43.3%) in whom ileo-colonoscopy did not reveal terminal ileum involvement, more proximal small bowel lesions were seen in 35 (11.4%) patients. These lesions were mainly apthoid ulcers or larger ulcers, findings that led to a change in therapeutic management in 17 patients (48.6%).

Conclusion
SBCE identifies more proximal small bowel lesions in a substantial number of patients with CD established by traditional endoscopic techniques. When these lesions are more severe and extensive they may lead onto re-evaluation of the personalized therapeutic strategies.
P105 Coping in Inflammatory Bowel Disease: insights from the Crohn’s and Colitis UK national survey
Authors: Marshall Mr J , Rowse G , Hollobone S , Afhim S , Oliver P 
Published: May 2021

Abstract

Background
Inflammatory bowel disease (IBD) is a chronic condition that adversely affects quality of life (QoL) and well-being. Factors associated with coping in IBD include disease activity, the presence of arthropathy and illness perceptions such as personal control. The evidence in this field is, however, limited by small sample sizes. The aim of this study was to use data from a national survey to identify factors associated with coping in a large sample of IBD patients. Identification of factors associated with coping may help inform the development of targeted interventions to improve psychological well-being.

Methods
A national postal and online survey was conducted by the charity Crohn’s & Colitis UK of its members in 2018. Participants were asked to complete a questionnaire which was co-produced by the charity and University of Sheffield, following focus groups of key stakeholders. The survey collected demographic and disease-related information as well as Likert item responses to questions relating to well-being, including coping. The response rate was 22.2%. To examine factors associated with coping, ordinal regression analysis was performed. Results are presented as adjusted odds ratios (ORs).

Results
8012 respondents were included in the analyses. The mean age of respondents was 45 years (SD =16 years) with 69% being female. The majority of respondents had a diagnosis of Crohn’s disease (78%) with 53% of participants self-reporting that they were in remission at the time of the survey. In multivariable analyses, the adjusted odds of females reporting difficulty in coping was 1.6 times higher than that for males (95% CI 1.43–1.79). The odds of those with active disease reporting more difficulty in coping were approximately twice that of those in remission (95% CI 2.38–2.93). Several well-being factors were found to be associated with coping, even after adjusting for personal and disease related characteristics (such as severity of symptoms and disease activity). Participants who had reported less understanding and felt they had less control of their IBD, had higher odds of difficulty in coping with their disease (95% CI 0.76–0.85 & 0.64–0.72 respectively). Participants who experienced disease-related stigma were also more likely to have difficulty in coping (95% CI for 1.99–2.26).

Conclusion
In this large survey of IBD patients, coping was associated with gender, disease characteristics and a number of psychological factors, which may be amenable to intervention to improve the QoL and well-being of patients with IBD. Efforts are required to improve public awareness of the impact of IBD in order to reduce stigma. Further research is required to understand these relationships and constructs through the use of validated measures.