bluuebunny/crossref_metadata_2025_split huggingface dataset:
DOP07 Chronic abdominal pain in IBD patients in remission: Real-world data on contributing factors
Authors: Rezazadeh Ardabili A , Janssen L M , Romberg-Camps M J L , Keszthelyi D , Jonkers D M A E , van Bodegraven A A , Pierik M J , Mujagic Z 
Published: January 2022

Abstract

Background
Chronic abdominal pain is highly prevalent in IBD patients in remission. The aetiology is incompletely understood, although persistent histologic inflammation, post-inflammatory visceral hypersensitivity, and altered gut-brain interaction are believed to contribute. Data on the characteristics of IBD patients suffering from chronic abdominal pain are sparse, yet essential for the identification of treatment targets. We investigated clinical, lifestyle and psychosocial factors associated with chronic abdominal pain in a real-world cohort of IBD patients in remission.

Methods
A prospective multicentre study was performed enrolling consecutive IBD patients, between Jan 1, 2020 and Jul 1, 2021, using myIBDcoach, an established remote monitoring platform for IBD. Patient reported outcome measures on disease activity, lifestyle and psychosocial factors (i.e. depressive symptoms, anxiety, stress, and life events) were assessed in three-monthly intervals. Chronic abdominal pain in IBD in remission (IBDremissionPain+) was defined as an abdominal pain score ≥3 (1–10 numeric rating scale (NRS)) at ≥1/3 of all assessments combined with faecal calprotectin &lt;150 μg/g in 90 days around periodic assessments. Multivariable logistic regression, adjusting for relevant confounders, was performed to identify risk factors for IBDremissionPain+ compared to patients in remission without chronic abdominal pain (IBDremissionPain-).

Results
In total, 559 patients were followed prospectively, of which 429 (76.7%) were in biochemical remission. Of these, 198 (46.2%) fulfilled the criteria for chronic abdominal pain. IBDremissionPain+ patients were characterized by female sex, higher BMI, and shorter disease duration compared to IBDremissionPain- (Table 1). IBDremissionPain+ patients reported significantly higher levels of stress, fatigue, depressive and anxiety symptoms, and occurrence of life events (Table 2). On multivariable logistic regression, female sex (aOR 2.58), shorter disease duration (&lt;10years, aOR 2.31), higher BMI (aOR 1.06), higher levels of stress (aOR 1.19), fatigue (aOR 4.73), and life events (aOR 1.65) were all significantly associated with chronic abdominal pain (Table 3). The univariable association between pain and anxiety and depressive symptoms was modulated by stress in the multivariable analysis.

Conclusion
In this real-world population of IBD patients in remission, 46.2% experience chronic abdominal pain, characterized by female sex, shorter disease duration, higher BMI, fatigue and psychosocial factors. The gut-brain interaction in this population is represented by higher levels of depressive and anxiety symptoms, but the relation to abdominal pain is potentially modulated through increased levels of perceived stress.
DOP10 Intestinal Ultrasound at IBD diagnosis predicts major disease events – A Copenhagen IBD cohort study
Authors: Madsen G R , Attauabi M , Wilkens R , Ilvemark J F K F , Theede K , Bjerrum J T , Dorn-Rasmussen M , Jansson S , Wewer A V , Bendtsen F , Seidelin J B , Boysen T , Burisch J 
Published: January 2022

Abstract

Background
The disease course of inflammatory bowel disease (IBD) is heterogeneous and highly unpredictable. Intestinal Ultrasound (IUS) is a non-invasive modality capable of assessing disease activity in IBD. IUS is reliable, patient-friendly, and allows frequent monitoring of disease activity. However, the evidence for IUS as a predictor of disease course is still limited. Here we present novel data on the predictive value of IUS performed at the time of IBD diagnosis.

Methods
Patients with new-onset IBD are currently being included in the ongoing multicentre prospective inception cohort study, the IBD Prognosis Study. During the first five years following diagnosis, patients undergo regular clinical, biochemical, endoscopic, and imaging assessments. IBD treatment and disease events are prospectively recorded. IUS is performed at diagnosis, after three months, and hereafter annually. Patients with proctitis do not undergo assessment with IUS. The newly developed IUS score, the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS), is calculated for the most inflamed segment, with a high score indicating severe disease activity. The score incorporates bowel wall thickness (BWT), bowel wall stratification, colour Doppler signal, and inflammatory fat. In this abstract, we report our preliminary results after including patients for six months.

Results
IBUS-SAS at diagnosis was available in 60 patients. 32 patients were diagnosed with Crohn’s disease (ilieal: 7, colonic: 19, ileocolonic: 6) and 28 patients were diagnosed with ulcerative colitis (UC) or unclassified IBD (proctitis: 1, left-sided colitis: 8, extensive colitis: 19). The mean IBUS-SAS at diagnosis was 51.1, with a mean BWT of 5.2 mm. Major clinical outcomes were initiation of biologic therapy, n=12 (20.0%), IBD-related bowel resection, n=5 (8.3%), IBD-related hospitalisation, n=19 (31.7%). The mean IBUS-SAS at diagnosis was 66.2 among patients with the combined endpoint of any of these disease outcomes during follow-up vs. 34.7 for no major outcomes (p&lt;0.001), see Figure 1. Additionally, we found that all patients with an IBUS-SAS above 80 at diagnosis had been hospitalised and started on systemic steroids. So far, 20 patients had an IUS follow-up scan after three months showing a mean IBUS-SAS reduction by 17.0 points (p=0.008).

Conclusion
We present data on the predictive value of early IUS in new-onset IBD. IUS activity at diagnosis of IBD seems to have the capability to predict short term disease outcome. At diagnosis, high IBUS-SAS is associated with major disease events such as starting biological therapy, IBD-related bowel resection, and IBD-related hospitalisation. Furthermore, response to treatment is reflected by a decrease in IBUS-SAS after three months.
DOP12 Non-invasive assessment of intestinal inflammatory activity in Ulcerative Colitis by Multispectral Optoacoustic Tomography (MSOT)
Authors: Klett D , Jesper D , Vitali F , Federle A , Atreya R , Strobel D , Leppkes M , Neufert C , Rath T , Neurath M F , Waldner M J 
Published: January 2022

Abstract

Background
In order to guide therapy in Ulcerative Colitis (UC), repeated determination of intestinal inflammatory activity is essential. Endoscopy is the standard procedure to assess inflammation in UC. However innovative methods for non-invasive, uncomplicated and risk free estimation of inflammatory activity are needed as bowel preparation, patients discomfort and risk of procedural complications limit the (frequent) use of colonoscopy. Multispectral optoacoustic tomography (MSOT) is a promising new method to measure inflammation in UC. Using short and harmless impulses of NIR-lasers, it allows for determination of a specific hemoglobin-signal in the bowel-wall and therefore inflammatory activity in affected bowel segments. However, its informative value in UC has not been evaluated so far.

Methods
In 34 patients with confirmed UC, clinical activity parameters (e.g. clinical Mayo-Subscore, B-mode-sonography, C-reactive protein, white blood count) were collected and MSOT of the sigmoid was performed within 2 weeks before/after endoscopy. For MSOT, a commercially available clinical MSOT-system (Acuity Echo, iThera Medical, Munich) was used with sequential analysis of collected data on an external desktop PC. Finally, clinical data, ultrasound findings (Limberg) and MSOT-parameters (single wavelenghts 760 nm, 800 nm, 900 nm; multispectral signals hb, hbO2, hbT) were correlated with endoscopic findings (Mayo endoscopic Subscore, MES).

Results
We found strong and significant correlation between MES and MSOT parameters 800 nm (Spearman r = 0,6599; p &lt; 0,0001) and HbO2 (Spearman r = 0,6695; p &lt; 0,0001), superior to sonographic evaluation of the inflammatory activity in affected bowel segments (Spearman r = 0,4914; p = 0,0023). Simultaneously these MSOT parameters demonstrated excellent sensitivity and specifity in distinguishing moderately to highly active (MES 2,3) from inactive and mild disease (MES 0,1) (800nm: AUROC 0,9063 (p &lt; 0,0001); sensitivity = 93,75 %, specificity = 88,89 %; HbO2: AUROC 0,9063 (p &lt; 0,0001); sensitivity = 100 %, specificity = 88,89 %).

Conclusion
MSOT is a promising approach to non-invasively assess intestinal inflammation in UC and therefore monitor anti-inflammatory therapy in these patients. Further studies are required to validate these findings.
DOP16 Categorizing endoscopic severity of Crohn’s Disease using the Modified Multiplier SES-CD (MM-SES-CD)
Authors: Narula N , Pray C , Wong E , Colombel J F , Marshall J , Daperno M , Reinisch W , Dulai P 
Published: January 2022

Abstract

Background
Current endoscopic scoring indices such as the Simple Endoscopic Score for Crohn’s Disease (SES-CD) quantify the degree of mucosal inflammation in Crohn’s disease (CD) but lack prognostic potential. The Modified Multiplier of the Simple Endoscopic Score for Crohn’s Disease (MM-SES-CD) is an internally validated endoscopic scoring tool that quantifies the endoscopic burden of CD and can be accessed online (https://www.mcmasteribd.com/mm-ses-cd).1 This analysis aims to establish thresholds of the MM-SES-CD that classify CD endoscopic burden into inactive or very mild disease, mild, moderate, and severe disease based on the probability of achieving endoscopic remission (ER) on active therapy at one-year.

Methods
This post-hoc analysis included pooled data from three CD clinical trials (n=350 patients, baseline SES-CD ≥3 with confirmed ulceration). Maximum Youden Index calculations were used to determine thresholds for severity. Chi-square tests of trend were used to compare achievement of ER between severity categories, and Kaplan-Meier survival curve analysis was used to compare time to clinical remission (CR).

Results
Table 1 demonstrates the baseline characteristics of the 350 participants included in this analysis. MM-SES-CD severity categories were established as inactive or very mild (score &lt;14), mild (score ≥14 to &lt;31), moderate (≥31 to &lt;45), and severe (score ≥45), which were predictive of one-year ER (50%, 30.3%, 21.7%, 8.8% respectively p&lt;0.001) (Table 2). Lower MM-SES-CD scores had numerically higher rates of one-year CR, and time to CR over 52 weeks was superior to those with higher scores (p=0.0492) (Figure 1). MM-SES-CD thresholds for the achievement of ileal ER at one-year among 75 patients with isolated ileal disease were also established as mild (score &lt;14), moderate (score ≥14 to &lt;33), and severe (score ≥33), which were predictive of one-year ER (66.7%, 33.3%, 13.3%, respectively p=0.027) (Table 3).

Conclusion
We have established numerical cut-offs of the MM-SES-CD that categorize endoscopic disease severity and are prognostic for one-year ER and CR. These cut-offs could help ensure adequate balance between study arms (e.g. in prevalence of mild or moderate endoscopic disease) and identify patients with severe endoscopic disease and low probability of achieving ER.

Reference
1. Predicting endoscopic remission in Crohn’s disease by the modified multiplier SES-CD (MM-SES-CD). Gut, 2021: p. gutjnl-2020–323799.
DOP35 Increasing incidence of pouchitis among patients undergoing ileal pouch-anal anastomosis between 1996 and 2018: A population-based Danish cohort study
Authors: Barnes E , Allin K , Iversen A , Herfarth H , Jess T 
Published: January 2022

Abstract

Background
Current knowledge regarding the epidemiology of pouchitis is based on highly selected, mostly single-center, patient cohorts. Our objective was to prospectively determine the population-based incidence of pouchitis in patients with ulcerative colitis (UC) in the first 2 years after ileal pouch-anal anastomosis (IPAA) and analyze time trends of the incidence of pouchitis.

Methods
We used national registries to establish a population-based cohort of all Danish patients undergoing proctocolectomy with IPAA UC between 1996 and 2018. The primary outcome was the development of pouchitis within the first 2 years after IPAA, evaluated by time period of IPAA. The period of IPAA was categorized as follows: 1996–2000 (pre-biologic-1), 2001–2005 (pre-biologic-2), 2006–2010 (early-anti-TNF), 2011–2014 (expanding anti-TNF), 2015–2018 (current biologic). Pouchitis was defined using a previously developed case-finding definition for use in administrative claims data. Kaplan Meier and Cox Proportional Hazard modeling were utilized in the evaluation of time to development of pouchitis.

Results
We identified 1,664 patients that underwent an IPAA for UC. The cumulative incidence of pouchitis in the 2 years after IPAA increased throughout the study period, from 40% in 1996–2000, (95% CI:35%-46%) to 55% in 2015–2018, (95% CI:48%-63%, Table 1). Patients undergoing surgery between 2015–2018 also demonstrated an increased risk of pouchitis compared to the earliest study period (1996–2000) after adjusting for sex, age, and socioeconomic status (Hazard Ratio [HR] 1.57, 95% CI:1.20–2.05, Table 2, Figure 1). In a separate model adjusting for the same clinical and demographic factors, there was no significant relationship between the preoperative use of anti-tumor necrosis factor alpha therapy use and the risk of pouchitis when evaluated in the entire population (HR 1.14, 95% CI:0.93–1.40) and when evaluated by time period of surgery.

Conclusion
This first population-based study demonstrated a 15% absolute and 38% relative increase in the incidence of pouchitis among patients undergoing surgery between 1996 and 2018, with the greatest cumulative incidence of pouchitis demonstrated in the most recent era (2015–2018). The striking increase in the incidence of pouchitis highlights the need for further research into causes and prevention of pouchitis.
DOP38 Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1
Authors: Vermeire S , Colombel J F , Takeuchi K , Gao X , Panaccione R , Danese S , Dubinsky M , Schreiber S , Ilo D , Finney-Hayward T , Zhou W , Phillips C , Yao X , Zhou Q , Loftus E 
Published: January 2022

Abstract

Background
Upadacitinib (UPA), an oral, reversible JAK inhibitor engineered for increased selectivity for JAK1 over JAK2, JAK3, or tyrosine kinase 2 (TYK2), demonstrated significantly greater efficacy compared with placebo (PBO) for induction of remission in patients with moderately to severely active ulcerative colitis (UC) in two phase 3 trials, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026). This analysis evaluated the efficacy of UPA on early symptomatic improvement for the first 14 days, using pooled data from U-ACHIEVE Induction and U-ACCOMPLISH.

Methods
U-ACHIEVE and U-ACCOMPLISH were multicentre, double-blind, PBO-controlled trials that enrolled patients who have had moderately to severely UC with an Adapted Mayo Score of 5 to 9 points and centrally reviewed endoscopy subscore of 2 to 3. A total of 998 patients were randomized to receive UPA 45mg once daily (QD) (n=658) or PBO (n=328) for 8 weeks (wks) in a 2:1 ratio. First dose of study drug was administered on Day 0. Improvement in symptoms including stool frequency subscore (SFS), rectal bleeding subscore (RBS), abdominal pain, and bowel urgency were analysed from daily symptom diary data. Multivariate regression analysis was used to determine if early changes in UC symptoms could be used to evaluate a potential correlation with patients’ likelihood of achieving clinical response or clinical remission per Adapted Mayo score at the end of induction.

Results
Baseline characteristics were similar between both treatment groups. Patients treated with UPA 45 mg QD experienced significant improvement in daily symptoms, with significantly more subjects achieving SFS≤1 (p&lt;0.001), RBS of 0 (p&lt;0.05), and SFS of 0 (p&lt;0.05) as early as day 1 and maintained through day 14 (Figure 1). A significantly higher percentage of patients who received UPA 45 mg QD compared to PBO, achieved abdominal pain=0 and the absence of bowel urgency within 3 days of beginning treatment through day 14 (p&lt;0.05). Multivariate analysis revealed that patients who achieved day 7 SFS≤1 (OR 2.42, 95% CI, 1.53–3.82) were more likely to attain clinical response (Table). Patients who attained day 7 SFS≤1 (OR 2.53, 95% CI 1.59–4.00) or day 7 bowel urgency absent (OR 2.40, 95% CI 1.52–3.79) were more likely to achieve clinical remission at week 8.

Conclusion
UPA 45 mg QD significantly improved UC symptoms as early as day 1, providing patients with rapid symptom relief. Patients who achieved early symptom improvement were more likely to attain clinical remission or clinical response at week 8. [Clinicaltrials.gov, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026)]
DOP56 Histologic disease activity correlates with endoscopic severity in patients with moderate to severe Crohn’s Disease
Authors: Reinisch W , De Hertogh G , Protic M , Chan L S , Magro F , Pollack P , Feagan B G , Harpaz N , Pai R 
Published: January 2022

Abstract

Background
The role of histopathology evaluation in Crohn’s disease (CD) is not precisely defined. Due to the heterogeneity of phenotypes, the discontinuity of distribution, and the transmural nature of inflammation, the interpretation of histologic outcomes is complex. To analyze how histology relates to established outcomes in CD, we examined association between histologic and endoscopic disease activity measured by frequently used scores (simple endoscopic score for Crohn’s disease [SES-CD], Robarts histopathology index [RHI], global histological activity score [GHAS]) and the association between histologic or endoscopic severity with inflammatory biomarkers in a cohort of patients with moderate-to-severe CD.

Methods
Patients (N=191) who were enrolled in a phase 2 randomized clinical trial (NCT02891226) in patients with moderate-to-severe CD were assessed at baseline (BL) for endoscopic disease location and severity as measured by SES-CD. Biopsies were obtained during BL endoscopy from the edge of the ulcers and the most inflamed mucosa in terminal ileum and 4 colonic segments (ascending, transverse, descending, rectum; N=10/patient, 2 per location with the more severe score used), and scored by central readers blind to study treatment, timepoint, and response status using RHI and both modified and active GHAS (mGHAS: Q1, 3, 4, 5, 6; aGHAS: Q1, 4, 5, 6; see Fig. 1). Inflammatory biomarkers included fCLP and CRP; log-transformed values are used. Linear correlations between measures were determined using Pearson correlation coefficients (PCC) as exploratory analyses. Nominal p values are presented.

Results
SES-CD correlated well with all 3 histologic measures examined (Fig. 1). While both fCLP and CRP correlated more closely with endoscopy than with histologic measures, fCLP had higher correlation with each histologic measure than CRP (Fig. 2). 64% of patients had the same disease location at BL when measured by endoscopy or histology. Patients with endoscopic colonic disease displayed histologic ileal involvement in up to 20% of cases, while 13% of patients with endoscopic ileal disease demonstrated histologic colonic involvement (Table 1).

Conclusion
Although histologic disease activity in CD, as determined by 3 different measures, correlates well with endoscopic assessment of disease, histologic involvement provides complementary information on disease distribution and extension. Further analyses are required to understand the additive role of mucosal histology in CD.
DOP68 CD-TREAT diet induces remission and improves quality of life in an open label trial in children and adults with active Crohn’s Disease
Authors: Svolos V , Hansen R , Russell R , Gaya D R , John Paul S , Macdonald J , Nichols B , Papadopoulou R , Logan M , Mckirdy S , Gervais R , Ijaz U , Milling S , Shields S , Wilson D , Henderson P , Din S , Ho G T , Gerasimidis K 
Published: January 2022

Abstract

Background
Exclusive enteral nutrition (EEN) is an established induction treatment for active Crohn’s disease (CD) with a proposed mechanism of action involving the gut microbiome. We have previously shown that CD-TREAT diet, a food-based diet with similar dietary profile to EEN, improves rat ileitis and replicates the effect of EEN on the gut microbiome of healthy volunteers and animal models. Here, we test the efficacy of CD-TREAT diet to induce clinical remission in active CD.

Methods
This is an open-label study in children (wPCDAI≥12.5) and adults (HBI≥5) with active CD. Primary outcome was clinical response (wPCDAI fall≥17.5; HBI fall≥3) or clinical remission (wPCDAI&lt; 12.5; HBI&lt;5) after 8 week treatment with CD-TREAT. Secondary outcomes included improvement of quality of life (QoL) and reduction in faecal calprotectin (FC) levels. Since CD-TREAT diet is gluten-free, adherence to treatment was assessed by the detection of the gluten immunogenic peptide (GIP) in faeces. Data are presented with median (IQR).

Results
25 children, [age, 14.4 (12.5,15.7) years] and 32 adults, [age, 32.6 (24.2,43.9) years] were treated. 7 (12%) failed treatment and n=10 (18%) dropped out during the first 2 weeks of treatment due to palatability issues. In patients who completed 8 weeks of CD-TREAT course (n=40), 85% and 78% achieved clinical response and remission, respectively. CD-TREAT diet improved QoL in children [IMPACT-III score, baseline: 136 (122,143) vs 8weeks: 148 (133,153), p&lt;0.01] and in adults [sIBDq score, baseline: 30 (26,45) vs 8weeks: 60 (48, 64), p&lt;0.001]. Faecal GIP decreased during treatment [ng/g stool, baseline: 1250 (589, 1250), 4weeks: 0 (0,269), 8weeks: 0 (0,329), mg/mg, p&lt;0.001 for both] showing adherence with the CD-TREAT diet. However, 33% and 40% of the patients had detectable faecal GIP at 4 and 8 weeks, respectively, revealing at least partial non-adherence. 30% of patients who completed CD-TREAT (n=12/40) experienced &gt;50% FC reduction. Median FC levels decreased significantly? in the group of patients (n=22) who had undetectable GIP at 4 or 8 weeks [mg/kg FC, baseline: 1190 (361,1129); 8weeks: 534 (92,1230), p&lt;0.01].

Conclusion
CD-TREAT diet improved disease activity indices and QoL in the majority of patients who completed treatment and decreased FC in those who were most likely to be compliant. Future RCT should aim to compare CD-TREAT with other induction treatments and improve meal variety and palatability to improve compliance and reduce drop-out rates.