bluuebunny/crossref_metadata_2025_split huggingface dataset:
P244 Validation of the Red Flags index for early diagnosis of Crohn’s disease: A prospective general practitioner study
Authors: Fiorino G , Gilardi D , Bonovas S , Di Sabatino A , Angeli E , Gaffuri N , Allocca M , Furfaro F , Roda G , Lenti M , Nicola A , Mengoli C , Peyrin-Biroulet L , Danese S 
Published: January 2020

Abstract

Background
A diagnostic delay &gt;12 months is frequent in Crohn’s disease (CD), and associated with lower therapeutic response rates and worse outcomes. The Red Flags index, a simple tool to help to identify early CD and reduce diagnostic delay, was recently developed. We aimed to assess its accuracy for early diagnosis of CD patients.

Methods
Consecutive adult patients, suffering from intestinal symptoms and having no medical history of any gastrointestinal disease, referring to the General Practitioner (GP) were screened. Patients should have at least one of the following symptoms: chronic abdominal pain, chronic diarrhoea, nocturnal diarrhoea, unexpected weight loss, or perianal lesions. The GPs administered the Red Flags questionnaire to each eligible patient. Then, all patients were referred to the nearest participating Centre to confirm or exclude the diagnosis of CD. IBD specialists were blinded to the results of the questionnaire. The first-line examination systematically included blood cell count, serum C-reactive protein, faecal calprotectin (FC) and abdominal ultrasound, according to routine practice. If required to confirm CD, second-line examinations were planned (i.e. colonoscopy and cross-sectional imaging). Sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV, NPV) of the Red Flags index were estimated. Patients lost to follow-up were included in the analysis by a non-responder imputation assuming they were negative for CD.

Results
From 11/2016 to 11/2019, 64 GPs participated (Bergamo: 52, Pavia: 12, in charge of a population of 93,000 subjects) and 112 patients over a mean number of 53,568 subjects screened were included in the study (median age 35 years, range: 18–69, 37% males). Only 66 subjects (59%) completed the study. The prevalence of CD was 3.6% in the study population (4 of 112 subjects; 3 with B1, and 1 with B2 phenotype). The Red Flags index had Se=0.50 (95% CI: 0.07–0.93), Sp = 0.58 (0.49–0.68), PPV=0.04 (0.01–0.15), and NPV=0.97 (0.89–1.00). A combined diagnostic strategy with faecal calprotectin (in which a subject was considered ‘positive’ if having RFI ≥8 and/or FC &gt;250) resulted in significantly improved diagnostic accuracy: Se=1.00 (0.29–1.00), Sp = 0.72 (0.55–0.85), PPV=0.21 (0.05–0.51), NPV=1.00 (0.88–1.00); however, only 42 subjects (with 3 confirmed cases of CD) were available for this analysis.

Conclusion
The diagnostic accuracy of the Red Flags questionnaire was moderate when applied alone to a primary care setting. However, the combined diagnostic strategy of the Red Flags index and faecal calprotectin has given promising results. Further research is warranted on how to best identify patients with early clinical onset of CD.
P289 Biological therapies and the trajectories of biopsychological factors in inflammatory bowel diseases
Authors: Tavakoli P , Vollmer-Conna U , Vazquez Campos X , Hadzi-Pavlovic D , Grimm M 
Published: January 2020

Abstract

Background
Therapeutic aims in IBDs are to induce remission through rapidly effective treatment. Conventional therapeutic methods including immunosuppression have been available for more than half a century with biological therapies the treatment of choice in patients who fail immunosuppressive drugs. There has been little attempt to longitudinally examine the differences in biopsychological factors and their associations with treatment modalities in IBD patients.

Methods
50 IBD participants (24 UC, 26 CD) in clinical remission were followed for 12 months. Complete longitudinal datasets including demography, disease status (HBI, Mayo score), monthly stool and blood samples for inflammatory biomarkers, monthly validated scores of psychological state, baseline physiological state and autonomic function were collected for analysis of association. Microbiome analysis was performed using V4 16SrRNA for identification of microbial phylogenetic relationships. Patients were grouped on whether or not they were in remission on biological agents.

Results
CD: There was a larger magnitude of change in linear trends of anxiety (p = 0.007) in CD patients on non-biologic treatment. Quality of life (QOL), health-related quality of life (HRQOL) and faecal calprotectin measures were similar regardless of treatment. Longitudinal quadratic trends of CRP were significantly different between the two (p = 0.039) with the larger magnitude of change in non-biologic groups. CD patients had similar microbial profile when compared between two treatment groups. UC: Similar distributions of longitudinal psychological measures were found in two treatment groups, although results suggested significant linear trend (p = 0.019) in QOL scores but not with HRQOL. Faecal calprotectin had significant longitudinal linear trend (p = 0.016) with significant interaction between biologic therapy and this trend (p = 0.023). CRP had significant quadratic trend (p = 0.005) with strong interaction between biologic therapy and this trend (p = 0.009). Microbial α diversity was significantly different between two groups of treatments (Shannon; p = 0.041, evenness; p = 0.045) with biologic group having more diverse and more even microbial community.

Conclusion
Baseline biological and psychological factors were mostly similarly distributed between the two treatment options in remissive IBD patients, however biological therapy significantly influenced longitudinal trends of some psychological, inflammatory and microbiome dynamics, especially in UC. This suggests an underlying interrelationship between mode of treatment and biopsychological trajectories which might overshadow response to the treatment, requiring further assessment.
P299 A prospective randomised trial comparing dye-based chromoendoscopy with electronic virtual chromoendoscopy for detection of colonic neoplastic lesions during IBD surveillance colonoscopy
Authors: González-Bernardo O , Vivas S , de Francisco R , Pérez-Martínez I , Castaño-García A , Jiménez-Beltrán V , Flórez-Díez P , Martínez-González S , Rolle V , Suárez P , Suárez A , Riestra Menéndez S 
Published: January 2020

Abstract

Background
Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. Dye-based chromoendoscopy (CE) is the currently recommended method for the detection of dysplasia in IBD surveillance colonoscopy; the role of virtual chromoendoscopy (VCE) is not yet well defined. To compare CE with VCE using iSCAN1 digital image enhanced colonoscopy in the detection of colonic neoplastic lesions in IBD patients.

Methods
Randomised, single-centre trial to assess the detection rate of colonic neoplastic lesions in patients with long-standing IBD. Patients were randomised in two arms: dye-spraying CE using indigo carmine and electronic VCE using iSCAN1 digital image. Detection rates of dysplasia or any neoplastic lesion were compared by the two endoscopic techniques.

Results
A total of 129 patients were studied (67 by CE and 62 by VCE). Demographic and clinical characteristics were homogeneous in the two groups; 26 Crohn′s disease and 103 ulcerative colitis, 52% women, mean age 50 years, median duration of IBD 204 months, family history of colorectal cancer in 10 (8%), associated primary sclerosing cholangitis in 8 (6%), personal history of colorectal dysplastic lesions in 12 (9%), and more than 50% colonic involvement in 72 (56%). In total, 27 lesions (9 hyperplastic, 8 adenomatous and 10 low-grade dysplasia) were detected in 23 patients, without differences between CE and VCE arms (15 [22%] and 12 [19%] lesions, respectively; p = 0.98); on the other hand, neoplastic lesion (dysplasia or adenoma) detection rates was similar (12 [18%] in CE and 6 [10%] in VCE arms, p = 0.2). The duration of the withdrawal time of colonoscopy in minutes for patients in the CE group was median 14 min and in the VCE group was median 10 min (p &lt; 0.001).

Conclusion
There is no statistical difference between CE and VCE using iSCAN1 in the detection rate of colonic neoplastic lesions in IBD patients. Surveillance colonoscopy with VCE (iSCAN1) spends less time than conventional CE.
P300 Colectomy and health-related quality life in children with ulcerative colitis
Authors: DIPASQUALE V , Catena M A , Paiano L , Trimarchi G , Romeo C , Navarra G , Mattioli G , Romano C 
Published: January 2020

Abstract

Background
Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) is the recommended elective surgery for children with ulcerative colitis (UC). The aim of the present study was to evaluate health outcomes of children with UC and undergone restorative proctocolectomy with IPAA and to compare preoperative and postoperative health-related quality of life (HRQoL).

Methods
We reviewed the hospital records of all paediatric patients who had undergone surgery for UC between January 2009 and December 2016 in the Units of Paediatric Surgery and Gastroenterology of the University Hospitals of Messina and Genoa. Surgical treatment was represented by restorative proctocolectomy and laparoscopic IPAA. Patients and parents were interviewed by telephone before and after surgery, and responded to the modified IMPACT III questionnaire about health outcomes and HRQoL. The final version was made up of 15 closed questions of functional outcomes and HRQoL. All of the issues were grouped into 5 domains, such as gastrointestinal functional aspects (7 questions), school functioning (2 questions), social functioning (3 questions), emotional functioning (3 questions). The questionnaire was scored on a five-point scale with higher scores indicating a better HRQoL. The total score ranged from 35 (worst HRQoL) to 175 (best HRQoL).

Results
Data were obtained in 30 patients (16 males), who underwent surgery after a median post-diagnosis period of 3 years (range 1–4.5), at a median age of 12 (range 3–16). The most common indication for colectomy was acute severe colitis (63%, n = 19). Table 1 shows all the functioning total scores before and after IPAA. HRQoL scores showed a statistically signiﬁcant improvement after IPAA. This difference was observed in all dimensions of HRQoL (symptoms, school attendance, social activities, and emotional functioning). Overall, nearly all were completely satisﬁed with the outcome of colectomy. No operation-related mortality was reported. By the end of the follow-up, one patient developed pouchitis 1 month after colectomy, and responded well to antibiotic therapy.

Conclusion
Our data confirmed that HRQoL is low in children with UC referred for possible operation, and showed that surgical treatment may positively affect the overall HRQoL.
P325 A propensity score-weighted comparison of vedolizumab and adalimumab in Crohn’s disease: Real-life data from the Sicilian Network for inflammatory bowel disease (SN-IBD)
Authors: Macaluso F S , Ventimiglia M , Fries W , Viola A , Sitibondo A , Cappello M , Scrivo B , Busacca A , Privitera A C , Camilleri S , Garufi S , Di Mitri R , Mocciaro F , Belluardo N , Giangreco E , Bertolami C , Renna S , Orlando R , Rizzuto G , Cottone M , Orlando A 
Published: January 2020

Abstract

Background
Currently, there are no randomised controlled trials focussing on direct comparisons between biologics in Crohn’s disease (CD), while there is an unmet need to better understand and compare the effectiveness of these drugs. We performed a multicentre, real-life, comparison of the effectiveness of vedolizumab (VDZ) and adalimumab (ADA) in CD.

Methods
Data of consecutive patients with CD treated with VDZ and ADA from January 2016 to April 2019 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). A propensity score analysis was performed using the Inverse Probability of Treatment Weighting (IPTW) method. The effectiveness was evaluated at 12 weeks, 52 weeks, and as treatment persistence at the end of follow-up. The clinical endpoints were steroid-free clinical remission (Harvey–Bradshaw Index &lt; 5 without steroid use) and clinical response (reduction of the Harvey–Bradshaw Index ≥ 3 points with a concomitant decrease of steroid dosage compared with baseline). The sum of the two outcomes was defined as a clinical benefit. The achievement of endoscopic response (a reduction of Simple Endoscopic Score for CD ≥ 50% compared with baseline) or mucosal healing (Simple Endoscopic Score for CD ≤ 2) was assessed after at least 6 months of treatment.

Results
A total of 585 treatments (VDZ: n = 277; ADA: n = 308) were included, with a median follow-up of 56.0 weeks (IQR 24.0–104.0). After 12 weeks, a clinical benefit was achieved in 64.3% patients treated with VDZ and in 83.1% patients treated with ADA (p = 0.11 in propensity score analysis), while at 52 weeks a clinical benefit was observed in 54.0% patients treated with VDZ and in 69.1% patients treated with ADA (p = 0.33 in propensity score analysis). The median treatment persistences for VDZ and ADA were 52 weeks and 64 weeks, respectively. Cox survival analysis weighted for IPTW showed no significant difference in the probability of treatment discontinuation between the two drugs (HR for VDZ=1.20; p = 0.34). Post-treatment endoscopic response and mucosal healing rates were similar between the two drugs (endoscopic response: 35.3% for VDZ and 25.5% for ADA, p = 0.15; mucosal healing: 31.8% for VDZ and 33.8% for ADA, p = 0.85).

Conclusion
This is the first real-life study comparing VDZ and ADA in CD patients via propensity score-adjusted analysis. Even if crude rates of all clinical outcomes were higher for ADA compared with VDZ, such differences were not significant when patients’ characteristics at baseline were weighted by propensity score.
P337 Usefulness of drug-level monitoring in therapeutic guidance in patients with ulcerative colitis on anti-TNF-α maintenance therapy
Authors: Oh E H , A-Ran Y , Ye-Jee K , Jeongseok K , Namseok N , Sang Hyoung P , Dong-Hoon Y , Jeong-Sik B , Seung-Jae M , Suk-Kyun Y , Byong Duk Y 
Published: January 2020

Abstract

Background
While treatment optimisation using therapeutic drug monitoring (TDM) of anti-TNF-α agents has become more common in clinical practices, studies comparing its correlation with clinical remission (CR), biochemical remission (BR) and mucosal healing (MH) in patients with ulcerative colitis (UC) are still lacking

Methods
Trough levels of infliximab/adalimumab (TLIs/TLAs) and levels of antibody to infliximab/adalimumab (ATI/ATA levels) were measured using serum samples collected between August 2017 and September 2019 from patients with UC on anti-TNF-α maintenance therapy. CR, BR and MH were defined as partial Mayo score of 0–1, within normal range of both ESR and serum C-reactive protein (CRP) level, and Mayo endoscopic subscore of 0–1, respectively.

Results
This study included 115 patients (72.8%, 91 [76.5%] on infliximab and 24 [61.5%] on adalimumab) in CR and 43 patients (27.2%) in non-CR. ATI/ATA were positive in 31 (26.1%) and 2 (5.1%) patients on infliximab/adalimumab therapy, respectively. TLI showed significant differences according to stats of CR (2.146 [0.273–4.296] vs. 0.405 [0.001–2.962], p = 0.019), BR (2.843 [0.282–4.835] vs. 0.987 [0.022–2.914], p = 0.007) and MH (2.411 [0.282–4.439] vs. 0.240 [0.001–1.674], p = 0.001), however, TLA didn’t (p = 0.783, 0.893 and 0.853, respectively) (Table 1 and Figure 1). In receiver operating characteristics (ROC) curve analysis, TLI of 2.314 μg/ml was identified as cut-off value discriminating MH (area under ROC 0.705, p = 0.001, sensitivity 0.527, specificity 0.885, negative predictive value [NPV] 0.343, positive predictive value [PPV] 0.942). After excluding 36 patients with MH even though their TLI &lt; 1ug/ml, AUROC increased to 0.931 (p &lt; 0.001, sensitivity 0.860, specificity 0.885, NPV 0.742, PPV 0.942) while cut-off TLI remained same. In incremental graph by ranges of TLI, MH rates showed plateau over 4 μg/ml of TLI. In multivariate logistic regression analysis, extensive colitis (hazard ratio [HR] 0.289, 95% confidence interval [CI] 0.079–1.060, p = 0.061) and TLI (HR 1.282, 95% CI 0.974–1.687, p = 0.076) were marginally associated with MH (Table 2).

Conclusion
In this study, TLIs correlated with CR, BR and MH, while TLAs did not. TLI should be targeted to be above 2.3 μg/ml.
P367 Real-life long-term effectiveness and treatment persistence of vedolizumab in a single tertiary care cohort of Crohn’s disease patients
Authors: Calandrini L , Salice M , Privitera Hrustemovic H , Peruzzi G , Rizzello F , Calabrese C , Scaioli E , Belluzzi A , Gionchetti P 
Published: January 2020

Abstract

Background
Long-term effectiveness of vedolizumab (VDZ) in real-life clinical practice is unknown. We aimed to evaluate clinical efficacy and treatment persistence of VDZ in a real-world cohort of patients with Crohn’s disease (CD).

Methods
CD patients from a single tertiary IBD referral centre receiving VDZ treatment outside clinical trials between September 2016 and August 2019 were included. Data were collected prospectively at baseline, weeks 22, 54, and 108. Disease activity was assessed using the Harvey Bradshaw index (HBI). The primary endpoint was steroid-free clinical remission, defined as HBI of 4 or lower without the need of corticosteroids. Secondary endpoints were treatment persistence and durability of VDZ response.

Results
Up to August 2019 114 patients had received at least one VDZ infusion, 79% had prior anti-TNFα drug exposure. Of the 90 patients who reached 54 weeks of follow-up, 68 patients (75,5%) were still under VDZ therapy. 38 of them (55,9%) were in steroid-free clinical remission. We compared the initial response to VDZ at week 22 and at week 54. Among the 29 patients in steroid-free clinical remission at week 22, 25 (86.2%) were still in steroid-free clinical remission at week 54. Three out of 29 patients discontinued VDZ therapy before week 54, for insufficient response and adverse events in two cases and for pregnancy in one. Of the 34 patients who reached 108 weeks of follow-up, 17 (50%) were still under VDZ therapy. 11 of them (64.7%) were in steroid-free clinical remission. We compared the initial response to VDZ at week 22 and at week 108. Among the 11 patients in steroid-free clinical remission at week 22, 6 (54.5%) were still in steroid-free clinical remission at week 108. Two out of 11 patients discontinued VDZ therapy before week 108 for worsening of perianal disease.

Conclusion
After 1 year, 75.5% of patients were still on treatment, of whom more than 55% achieved remission. 86% of patients maintained a response after the first year of treatment. After 2 years the rate of patients who presented with steroid-free clinical remission and who maintained response tended to decrease, consistent with previously published data. However, half of the patients persisted with VDZ treatment. These data support the long-term effectiveness and favourable safety profile of VDZ.
P399 Endoscopic and histologic outcome in tofacitinib treated refractory moderate-to-severe ulcerative colitis: A prospective real-life cohort
Authors: Verstockt B , Outtier A , Lefrère J , Sabino J , Vermeire S , De Hertogh G , Ferrante M 
Published: January 2020

Abstract

Background
The pan-Janus kinase inhibitor tofacitinib (TFC) has recently been approved for treatment moderate-to-severe ulcerative colitis (UC). Real-life data are limited, especially on endoscopic and histologic outcome. We report the efficacy and safety of TFC in refractory UC patients, and assessed potential clinical predictors of response.

Methods
Thirty-five UC patients, all refractory to anti-TNF and vedolizumab, were prospectively included (Table 1). All received TFC 10mg BID till week 8, and were endoscopically assessed at baseline (Mayo endoscopic sub-score ≥2) and week 8. Biological response was defined as a 50% decrease in faecal calprotectin (fCal) or fCal &lt;250 mg/g, and biological remission as a fCal &lt;250 mg/g at week 8. The endoscopic response was defined as Mayo endoscopic sub-score of ≤1, endoscopic remission as a sub-score of 0. Histologic remission was defined as a numeric Geboes score ≤6 (similar to ≤2A.0). A non-response imputation and last observation carried forward analysis was applied.

Results
The Mayo endoscopic sub-score decreased significantly by week 8 (p = 0.004), resulting in an endoscopic response and remission rate of 22.9% and 17.2% respectively. Histological remission was seen in 14.8% of patients. Faecal calprotectin decreased from 1386 mg/g down to 568 mg/g by week 4 (p = 0.03) (Table 2), but not further down by week 8 (703 mg/g, p = 0.5) with a biological response and remission rate of 52.9% and 38.2%. Half of the patients with a PNR to one anti-TNF (10 out of 20) did discontinue TFC because of PNR. However, PNR to two anti-TNF agents almost exclusively (4 out of 5) resulted in PNR to TFC. In contrast, only 3 out of 8 vedolizumab PNR experienced PNR to TFC. Ultimately, 48.6% of all included patients discontinued TFC therapy after a median of 15.9 [12.4–26.6] weeks, all but one due to PNR, of whom 9/17 (52.9%) required colectomy. In multivariate analysis, a higher baseline albumin and a lower Mayo endoscopic sub-score were independent predictors of endoscopic (OR 1.06, p = 0.02; OR 0.59, p = 0.003) and biological remission (OR 1.06, p = 0.03; OR 0.57, p = 0.01). By week 8, creatinine kinase significantly increased (p = 0.001), whereas the lipid profile was not significantly affected. One patient suffered from vaginal herpes infection, and one patient treated with TFC and high dose steroids developed disseminated nocardia, pneumocystic jiroveci, cutaneous zoster and varicella pneumoniae.

Conclusion
TFC can induce biologic, endoscopic and histologic remission in refractory UC, though clinical and predictive molecular markers are required to identify the right patients. In patients with prior PNR to 2 anti-TNF agents, TFC does not seem an alternative treatment strategy.