bluuebunny/crossref_metadata_2025_split huggingface dataset:
P688 Effect of golimumab induction therapy on histologic disease profile in patients with moderate to severe ulcerative colitis: Results from the randomised, placebo-controlled Phase 3 PURSUIT-SC trial
Authors: Johansson T , Weinstein C , MEEHAN A , Tzontcheva A , Xu P , Marano C , de Hertogh G 
Published: January 2020

Abstract

Background
Histologic improvement is an emerging goal in ulcerative colitis (UC) management. We previously demonstrated in the 6-week, multicentre, randomised, placebo-controlled, double-blind Program of Ulcerative colitis Research Studies Utilising an Investigational Treatment [PURSUIT-SC] Phase 3 trial that SC induction therapy with the tumour necrosis factor-α inhibitor, golimumab (GLM), led to statistically significant and clinically meaningful improvements in the signs and symptoms of UC compared with placebo, including clinical remission, mucosal healing, and improved health-related QoL, in patients with moderate to severe active UC.1 In the present report, we explored the histologic effects of GLM induction therapy in PURSUIT-SC by examining data from a prespecified histology sub-study.

Methods
The Phase 3 PURSUIT-SC trial evaluated the safety and efficacy of induction therapy with GLM in 774 patients with moderate to severe UC disease activity (defined as Mayo scores of 6–12, including an endoscopic subscore of ≥ 2). Patients were randomised 1:1:1 to receive SC induction treatment with placebo at Weeks 0 and 2, GLM 200 mg at Week 0 followed by 100 mg at Week 2 (GLM 200–&gt;100 mg), or GLM 400 mg at Week 0 followed by 200 mg at Week 2 (GLM 400–&gt;200 mg). Rectal biopsies were collected during endoscopy at screening and Week 6 in those randomised patients who consented to participate in the histology sub-study (N=98). During the screening endoscopy, two adjacent biopsies were collected 15 to 20 cm beyond the anal verge in an area that was most representative of the inflammation observed. At Week 6, two additional biopsies were to be obtained from the same location biopsied at screening. Biopsies were graded using the Geboes Score (GS) by a single expert gastrointestinal histopathologist, who was blinded to subject, treatment and study visit. The GS comprises seven histologic grades assessing structural changes and inflammatory disease activity. Higher GS grade scores indicate more severe histologic disease.

Results
Evaluable biopsy data were available in 89 patients (placebo, n = 30; GLM 200–&gt;100 mg, n = 30; GLM 400–&gt;200 mg, n = 29). At Week 6, compared with placebo, treatment with GLM induction therapy led to a decrease in the proportion of biopsies with GS grade scores of &gt; 1 and an increase in the proportion of biopsies with GS grade scores of ≤ 1, with the greatest improvements being observed in the GLM 400–&gt;200 mg group (figure).

Conclusion
The findings of this exploratory histologic sub-study in the PURSUIT-SC trial suggest that GLM induction therapy led to an improvement in histologic disease activity compared with placebo in patients with moderate-to-severe UC.

Reference
P698 IBD patients equally tolerate bowel preparation but need higher doses of sedation during colonoscopy in comparison with a population screening programme: Results from a prospective, single-centre study
Authors: Bezzio C , Andreozzi P , Schettino M , Arena I , Della Corte C , Devani M , Manes G , Omazzi B , Saibeni S 
Published: January 2020

Abstract

Background
IBD patients are intended to undergo several times colonoscopy during their lifespan. Adequate bowel preparation and sedation greatly contribute to high-quality colonoscopy and are even more important in this setting. However, few and low-quality studies addressed these issues. Aims: to prospectively evaluate the tolerability of bowel preparation and colonoscopy in ulcerative colitis (UC) and Crohn’s disease (CD) patients compared with subjects participating in a colorectal cancer population screening programme.

Methods
we consecutively enrolled CD and UC patients and screening subjects (SS) undergoing colonoscopy between August 2017 and August 2019. Bowel preparation was done by macrogol 4.000 + simethicone + sodium-sulphate-anhydrous. We recorded endoscopic, clinical and demographic features; quality of cleansing by Boston Bowel Preparation Scale (BBPS; from 0 the worst to 9 the best); sedation dose and need to increase the initial doses of midazolam (3.0 mg) and fentanyl (0.05 mg). Tolerability of bowel preparation, discomfort and pain during colonoscopy were assessed by Visual Analogue Scale (VAS) from 0 to 100 mm.

Results
65 UC (26 women, mean age 50.6 ± 15.4 years), 65 CD (29 women, mean age 44.7 ± 3.9) and 94 SS (47 women, mean age 61.9 ± 6.9) enrolled. Bowel preparation was similarly tolerated in UC (70.3 ± 17.7 mm), CD (73.1 ± 12.7 mm) and SS (73.2 ± 12.6 mm) (p = 0.397). Complete colonoscopy was similarly done in UC (61/65, 93.8%), CD (60/65, 92.3%) and SS (91/94, 96.8%) (p = 0.364). BBPS did not show significant differences between UC (6.5 ± 1.0), CD (6.4 ± 1.1) and SS (6.4 ± 1.0) (p = 0.824). The need to increase sedation doses was significantly higher in CD (26/65, 40.0%) and UC (16/65, 24.6%) than in SS (4/94, 4.3%) (p &lt; 0.0001). The mean increases in midazolam and fentanyl doses were significantly higher in CD (0.446 ± 0.660 mg and 0.009 ± 0.019 mg, respectively) and UC (0.300 ± 0.620 and 0.008 ± 0.018 mg) than in SS (0.042 ± 0.250 mg and 0.001 ± 0.007 mg) (p &lt; p &lt; 0.0001 in both cases). Discomfort and pain during colonoscopy were similar in UC (35.0 ± 23.0 mm and 27.6 ± 24.6 mm, respectively), CD (37.5 ± 22.2 mm and 28.8 ± 22.5 mm) and SS 33.7 ± 18.7 and 26.9 ± 19.8 mm) (p = 0.530 and p = 0.866, respectively).

Conclusion
in IBD patients, higher sedation doses are needed in order to warrant a tolerated colonoscopy. Bowel preparation is equally tolerated and efficacious in IBD patients and in screening subjects.
P701 New onset spondyloarthropathy in vedolizumab treated IBD patients
Authors: Tetley A M , Lobaton T , Truyens M , Katsanos K H , de Boer K H N , Pattinson A , Molnar T , Filip R , Michalopoulos G , Sebastian S 
Published: January 2020

Abstract

Background
Patients with IBD may have associated spondyloarthropathy. Vedolizumab is used for IBD with its actions considered to be gut specific but the impact of this treatment on existing arthritis or development of arthritis is uncertain. Integrins and adhesion molecules play a role in the interception of recirculating activated lymphocytes between the gut and the synovial membrane due to the inhibition of the alpha4beta7 integrin homing at the level of the gut. We aimed to describe characteristics and outcomes of spondyloarthropathy in IBD patients treated with vedolizumab.

Methods
We retrospectively collected data on a multicentre cohort of IBD patients with arthropathy which developed following use of Vedolizumab for IBD. This was a part of the European Crohn`s and Colitis Organisation (ECCO) initiated CONFER (Collaborative Network for Exceptionally Rare case reports) project. Data were recorded on a standardised case report form and analysed with descriptive statistics.

Results
We report data on 14 cases of new onset spondyloarthropathy and 1 case of worsening of pre-existing arthropathy from 7 contributing centres. Vedolizumab was used for 6 patients with CD and 8 patients with UC. IBD was in remission in all but 3 patients at the time of development of the joint features. Sacroiliitis was the manifestation in 10 patients, 3 of whom had both sacroiliitis and peripheral arthritis. Three patients had peripheral arthritis alone and one patient had peripheral arthritis with enthesitis. One patient had worsening of peripheral arthropathy following use of vedolizumab. Raised inflammatory markers (CRP, ESR or both) were recorded only in one-third of the patients. MRI was abnormal in 9 patients being the marrow oedema in SI joints the commonest feature. One patient had abnormal bone scintigraphy and in another patient plain X-ray and ultrasound was used in confirming diagnosis. Eight of the patients developed arthropathy within days after a single infusion of vedolizumab. five patients needed hospitalisation for treatment The treatments used included systemic steroids (11 patients), Intraarticular steroids (3) NSAID (2 patients), Cox inhibitor (1), methotrexate (2) Hydroxychloroquine (1). Vedolizumab was discontinued in 11 of the patients. In the majority of patients (11/15) it took many months to resolve the arthropathy. On re-challenge with vedolizumab, the arthropathy recurred in 2 out of the 3 patients.

Conclusion
This case series demonstrates the potential risk for development of spondyloarthropathy with vedlizumab in IBD patients which is unrelated to the activity of IBD and can have significant impact including need for use for systemic steroids and hospitalisation. Larger prospective cohorts are needed to confirm these results.
P720 Recurrent rectovaginal fistula in patients with Crohn’s disease: How can we improve the success rate of graciloplasty? A bi-centric European study in 30 patients
Authors: Frontali A , Rottoli M , Chierici A , Poggioli G , Panis Y 
Published: January 2020

Abstract

Background
Graciloplasty (GP) is indicated in case of recurrent rectovaginal fistula (RVF), even in patients with Crohn’s disease, after failure of previous local treatments. The aim of this study was to evaluate risk factors for GP failure performed for recurrent RVF in these patients.

Methods
We realised a retrospective study based on a prospective database of GP, realised in two Tertiary expert Centers in Italy (Bologna) and France (Clichy).

Results
Thirty-two patients undergoing 34 GP (2 patients have undergone 2 GP for failure of first GP): we excluded second GP and 2 patients without available follow-up: 30 patients undergoing a first GP for RVF (n = 29) or ileal-vaginal fistula after ileal-pouch-anal-anastomosis (IPAA) (n = 1) with a mean age of 41 ± 10 years (range, 25–64) were analysed. After a mean follow-up of 65 ± 52 months (2–183), a success of GP (considered as absence of diverting stoma and RVF healing) was noted in 17/30 patients (57%). We evaluated risk factors for failure of the procedure and we found only 2 risk factors on univariate analysis: (1) absence of a postoperative prophylactic antibiotherapy: only 2/13 (15%) patients with a GP failure had a postoperative antibiotic-prophylaxis vs. 9/15 (60%) patients with success of GP (p = 0.0238); (2) a postoperative perineal infection: 7/13 (54%) with a GP failure developed a postoperative perineal infection vs. 2/17 (12%) patients (p = 0.0196).

Conclusion
Graciloplasty for recurrent rectovaginal fistula in patients with Crohn’s disease is effective in 57% of patients. Our study underlines the possible benefit of a postoperative antibiotic-prophylaxis because it seems to increase significantly the success rate of the procedure.
P732 The clinical efficacy and safety of indigo naturalis in induction & maintenance therapy for moderate-to-severe ulcerative colitis: A single-centre prospective uncontrolled open-label study
Authors: Matsuno Y , Hirano A , Torisu T , Fuyuno Y , Okamoto Y , Shin F , Tomohiko M , Umeno J , Hirakawa Y , Esaki M , Kitazono T 
Published: January 2020

Abstract

Background
Recently, several studies have shown the high efficacy of Indigo naturalis (IN) in the induction therapy for ulcerative colitis (UC). However, the efficacy and safety in the maintenance therapy remain unclear. Thus, we performed this prospective study to investigate the efficacy and safety of IN for induction and maintenance therapy in patients with moderate to severe active UC.

Methods
We conducted a prospective uncontrolled open-label study at Kyushu university hospital. A total of 33 patients with moderate to severe active UC (clinical activity index (CAI) ≥8) received 2 g per day of IN for 52 weeks. We assessed CAI at week 0, 4, 8, 52, and Mayo endoscopic score (MES) was evaluated at weeks 0, 4, 52. We calculated the clinical remission (CAI ≤4) rate and mucosal healing (MES ≤1) rate at each point. Overall adverse events (AEs) during the follow-up were also estimated.

Results
Clinical remission rates at weeks 4, 8, and 52 were 67%, 76%, and 73%, respectively. Mucosal healing rates at weeks 4 and 52 were 48% and 70%. Seventeen patients experienced adverse events (AEs) during the follow-up. Seven severe AEs, including intussusceptions, acute severe colitis, infectious colitis, portal thrombosis, appendicitis, were observed in 4 patients.

Conclusion
Our prospective study indicated that IN was a promising option for induction and maintenance therapy in UC. However, possible AEs of IN should be paid attention.
P752 A nationwide survey of chronic enteropathy associated with SLCO2A1 gene in Japan
Authors: Umeno J , Fuyuno Y , Torisu T , Hirano A , Esaki M , Yanai S , Ohmiya N , Hisamatsu T , Watanabe K , Hosoe N , Ogata H , Hirai F , Hisabe T , Matsui T , Yao T , Kitazono T , Matsumoto T 
Published: January 2020

Abstract

Background
Chronic enteropathy associated with SLCO2A1 gene (CEAS) is an autosomal recessive disease caused by mutations in the SLCO2A1 gene which encodes a prostaglandin transporter. It is a rare intractable disease characterised by persistent blood and protein loss due to the small intestinal ulcers. Because CEAS mimics Crohn’s disease (CD) concerning ileal ulcers and stenoses, it is often difficult to distinguish CEAS from CD based on gastrointestinal findings alone. Furthermore, SLCO2A1 gene mutations are also known to cause primary hypertrophic osteoarthropathy (PHO) and some CEAS patients manifest digital clubbing, periostosis, acroosteolysis, and thickened skin as extra-intestinal manifestations. Since little is known about the clinical features of CEAS, we conducted a nationwide survey in Japan.

Methods
All study participants provided written informed consent for genetic analysis. The present study was approved by the ethics committee of each institution. During the period between 2012 and 2019, 141 patients suspected of CEAS were enrolled in this study and checked to have SLCO2A1 gene mutations. We reviewed the clinical information of genetically confirmed CEAS patients.

Results
We confirmed 61 CEAS patients (21 males and 40 females) and found 14 different types of recessive SLCO2A1 mutations. The median age at disease onset and diagnosis was 18.5 (range 1–69) and 40 (range 7–70) years, respectively. Parental consanguinity was present in 16 patients (26%). Although anaemia was present in almost all patients, only two patients experienced gross haematochezia. The median haemoglobin and serum protein levels at diagnosis were 9.7 (range 2.3–13.7) and 5.2 (2.7–8.2) g/dl, respectively. Thirty-three patients (54%) had undergone intestinal surgery. They showed relatively low inflammatory markers in blood tests (median CRP, 2.9 mg/l). The most frequently involved gastrointestinal site was ileum (93%), but the terminal ileum was rarely involved (Figure). Mild digital clubbing or periostosis was found in 16 patients (26%), with six male patients fulfilling the major diagnostic criteria of PHO. The major manifestations of PHO were more frequently found in males than in females (digital clubbing 57% vs. 10%; periostosis 52% vs. 11%; pachydermia 62% vs. 0%).

Conclusion
Although CEAS frequently causes intestinal strictures like CD, its clinical features seem to be distinct from those of CD. Also, a gender difference in clinical symptoms needs to be considered, because concurrent PHO can be frequently seen especially in male patients with CEAS.
P755 Congenital chloride diarrhoea and inflammatory bowel disease: an emerging association
Authors: Norsa L , Berni Canani R , Duclaux- Loras R , Bequet E , Koeglmeier J , Russell R K , Ulhig H , Koletzko S , Rodrigues A , Deflandre J , Dembinski L , Castaldo G , Grimaldi G , Shah N , Heinz-Erian P , Janecke A , Leskinen S , Wedenoja S , Lachaux A , Kolho K L , Ruemmele F 
Published: January 2020

Abstract

Background
Congenital chloride diarrhea (CLD) is a rare autosomal recessive disease caused by the mutation in member 3 of the solute carrier 26 (SLC26A3). The phenotypic expression is a life-long severe watery Chloride rich diarrhea. Anecdotal association with inflammatory bowel disease (IBD) has been reported suggesting that underlying molecular mechanisms could represent part of an evolving association between IBD and channelopathies. We aimed to investigate this association in a cohort of CLD pediatric patients.

Methods
A European-based call for cases was made in CLD patients followed up in five different countries. A case report form for each patient was then completed.

Results
A total of 74 patients with CLD with a range of different CLD mutations were enrolled in the study. Twelve patients of 64 (16%) demonstrated colonic inflammation and were finally diagnosed with IBD: 8 patients with Crohn’s Disease, 2 with Ulcerative Colitis, and 2 IBD-like colitis (IBD-U). The diagnosis was made at a median of 12 years old (IQR: 6–30). Patients had different ethnicities (7 European, 2 Middle East, 1 North Africa, 1 Pakistan, 1 Central Africa). Among the 12 IBD, 2 had a 5-ASA-based treatment, 3 required immunosuppressant and 6 had biologics (Infliximab, Adalimumab and Vedolizumab). Three patients underwent surgery for ileostomy formation for CD that was non-responsive to multiple line of biologics (anti-TNF and anti-integrin): one had colectomy the remnant two colon preservation. Clinical characteristics, such as premature delivery, low weight at birth, fecal Cl- at diagnosis and amount of Cl- supplementation (mmol/kg) did not differ between patients with or without IBD. All patients underwent genotyping for CLD diagnosis and we did not find any specific genetic mutation linked to the development of IBD.

Conclusion
Sixteen percent of patients enrolled with CLD in our cohort developed IBD. Despite different presentations (CD, UC, IBD-U) all patients had colonic without ileal/small bowel involvement, in line with preliminary murine models of CLD demonstrating a role of colonic mucous layer in the development of colonic inflammation (Xiao et al Acta Physiol Oxf Engl 2014; 211:161–175). Patients’ IBD treatment included a wide range with variable success. Patients with IBD did not differ in their clinical characteristics or genetic mutations compared with non-IBD CLD patients. The role of genetic variants outside the CLD-gene and the microbiome in this association are under investigation.
P759 Correlation of quality-of-life components with sexual function scores and disease duration in patients with inflammatory bowel disease
Authors: Domislović V , Brinar M , Vujičić L , Novosel M , Grgić D , Krznarić Ž 
Published: January 2020

Abstract

Background
Inflammatory Bowel Disease (IBD) has a negative impact on quality of life (QOL), and sexuality is one of its major determinants. The impact of disease characteristics on sexuality and intimacy is one of the main concerns of IBD patients. Despite the obvious relevance of this problem, knowledge of the extent and the determinants of sexual dysfunction in persons with IBD is limited. The main goal of the study was to determine the correlation of quality of life (QOL) and it’s components in patients with IBD, and to investigate the impact of disease duration on QOL components.

Methods
In this cross-sectional study patients fulfilled anonymous validated questionnaire on their sexual function. In International Index of Erectile Function (IIEF) for males, five domains were evaluated through questions on erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction. In women were six domains assessed, desire, arousal, lubrication, orgasmic function, satisfaction and pain. For both scores, higher scores indicated a better function. Patients also fulfilled IBDQ-32, a validated questionnaire for assessing quality of life in IBD patients that consists of four main components (social, emotional, systemic and bowel function).

Results
In this study we have enrolled 202 patients who fulfilled the questionnaire (133 CD, 69 UC). Among them 122 were men and 80 women. Average age of included patients was 39.2 ± 11.02. Prevalence of SD in women was 70% (n = 60) and 18% (n = 22) in males. Female patients with sexual dysfunction had lower emotional and social QOL (p = 0.035 and p = 0.03, respectively). Total male IIEF sexual function score correlated significantly with all of the components of IBDQ; emotional (rho=0.36, p &lt; 0.001) systemic (rho=0.24, p = 0.006), social (rho=0.28, p = 0.002), bowel (rho=0.27, p = 0.002) and with total IBDQ (rho=0.36, p &lt; 0.001). Regarding erectile function score, there was also correlation with all of the components of IBDQ. Total female sexual function FSFI score correlated significantly only with systemic component of IBDQ (rho=0.25, p = 0.02). Interestingly, in male patients disease duration correlate negatively with emotional and social component of IBDQ (rho = −0.21, p = 0.02 and rho=-023, p = 0.01, respectively), which was not the case in female patients.

Conclusion
The results show correlation of sexual function score with components of QOL, which were more correlated in male patients. Our results suggest that longer disease duration might have positive impact on emotional and social life in male patients, which could be connected with achieving disease control and accepting the disease. It is important to provide proper psychological support, medical treatment and educational information.
P762 Prevalence association between HPV and fistulising perianal Crohn’s disease
Authors: RODRIGUES BOARINI L , Sobrado C W , Guzela V R , Pozzebon Gonçalves A , Lina Villa L , Nadal S R , Da Costa Lino Costa A , Nahas S C 
Published: January 2020

Abstract

Background
Perianal Crohn’s disease (PCD) is the main risk factor for squamous cells carcinoma (SCC). The incidence of SCC in PCD patients is 0.26 per 1000 patients-years, affects females more than males, develops on average at 42 years of age, which is earlier than general population. Although epidemiological studies have shown that most anal cancers are associated with HPV infection, predominantly oncogenic types 16 and 18.1 prevalence of HPV on perianal Crohn`s disease (PCD) remains unknown. We aimed to estimate the Prevalence of HPV and the subtypes more frequently associated with PCD.

Methods
Adults with fistulising PCD under immunosuppressed medications who have required surgical intervention, were transversally recruited. A biopsy sample was obtained from perianal fistula tract during under anesthesia exam. INNO-LiPA test was performed on paraffin blocks containing fistula path for HPV testing.

Results
A total number of 45 PCD patients were recruited and underwent surgical intervention. All patients were under biologic therapy, 42.2% Adalimumab, 40.1% Infliximab, 11.1% Certolizumab, 4.4% Ustekinumab and 2.2% Vedolizumab. The prevalence of fistula tract HPV infection in PCD patients was 37.8% and 22.2% for high-risk HPV in particular. The subtypes more frequently identified were HPV-11 (15.5%), HPV-16 (8.9%) and HPV-53 (6.7%).

Conclusion
This study shows a high point-prevalence of HPV, specially high-risk subtypes in fistulising PCD population. More studies are necessary to define a screening for cancer in this population.