bluuebunny/crossref_metadata_2025_split huggingface dataset:
P166 Calprotectin in patients with perianal fistula: the CANALS study
Authors: Becker drs. M , Stevens T , de Voogd F , Wildenberg M , Gecse K , Buskens C 
Published: January 2023

Abstract

Background
Previous studies suggest that faecal calprotectin can be used to discriminate Crohn’s disease (CD) perianal fistulas from cryptoglandular (CG) perianal fistulas. The aim of this research was to prospectively validate these findings and further investigate local calprotectin production inside fistula tracts. The aim of the current study was to prospectively analyse the clinical value of calprotectin levels in both the faeces and the fistula tract.

Methods
In this prospective study, all consecutive patients with an active perianal fistula undergoing examination under anesthetics were included. Faecal and scraping calprotectin levels collected during surgery were measured. The primary objective was to differentiate between active CD perianal fistulas and CG perianal fistulas based on faecal calprotectin. Secondary outcome parameters were the levels of local calprotectin in fistula tracts and the correlation with fistula characteristics and clinical prognostic parameters like the Geldof Classification system.

Results
Sixty-three fistula patients were included in this study (CD n=45; CG n=18). Faecal calprotectin values were significantly higher in CD patients compared to CG patients (396.8 [61.9-1136.8] vs. 47.3 [14.6-233.6] ug/g, p=0.004). The Area Under the Curve (AUC) was 0.733 (95% CI [0.644 to 0.903] with an optimal FC cut-off value of 344ug/g. Faecal calprotectin was not related to calprotectin levels in fistula scrapings which was not significantly different in CD and cryptoglandular fistulas (p=0.893). Calprotectin in fistula scrapings was also not related to fistula characteristics like number of tracts, duration of disease or (previous) seton drainage. However, a significant correlation was found between scraping calprotectin and fistula disease severity and prognosis as defined by a new Geldof classification system: Patients in group 2a (amenable for fistula repair) had significantly lower calprotectin levels (140 [31.0-149.0])ug/g) when compared to class 2b (symptom control) (706 [198.5 – 1936]ug/g, p=0.054) and class 2c (gradually debilitating disease) (3464.0 [328.5-5692.0]ug/g, p=0.008). Patients in class 3 (exhausted perineum) had the highest calprotectin levels highest (5928.0 [2605.0-6000]ug/g).

Conclusion
CD and CG perianal fistulas can be distinguished by measuring faecal calprotectin levels. The difference can not be explained by local fistula calprotectin production as calprotectin in fistula scrapings is not predictive of CD. However, the results of this study suggest that scraping calprotectin levels may be used to classify fistula patients and predict outcome of fistula treatment.
P176 Clinical features of acute severe ulcerative colitis according to steroid dependency: A KASID multicenter study
Authors: Kim D H , Kim H S , Kim E S , Park S H , Kim S J , Kim K O , Lee Y J , Song E M , Kim D S ,   IBD Research Group in Korean Association for the Study of the Intestinal Diseases (KASID)
Published: January 2023

Abstract

Background
Intravenous steroid therapy is the main initial treatment for acute severe ulcerative colitis (ASUC). However, steroid dependence in patients who were treated with intravenous steroid therapy for ASUC is not fully evaluated. We aimed to determine the prevalence and risk factors of corticosteroid dependence after treatment of ASUC.

Methods
Adult patients who were admitted for the treatment of ASUC satisfying Truelove-Witts criteria from January 2015 to December 2020 were included in the study. Steroid dependence was defined as a failure to taper steroids below 10 mg within 3 months from initiating intravenous therapy or relapse within 3 months after steroid discontinuation.

Results
Among a total of 140 patients who received intravenous steroids as initial treatment for ASUC, 105 (75.0%) showed a response while 35 (25.0%) were refractory to steroids. Of 105 patients who responded to intravenous steroid therapy, 21 (20.0%) showed steroid dependence during the follow-period. Demographic and clinical variables were not significantly different between steroid-dependent and steroid response groups. However, initial C-reactive protein (CRP) levels in steroid-dependent groups were numerically lower compared with those in the steroid response group with statistical significance (4.4 ± 4.6 mg/dL versus 7.0 ± 6.4 mg/dL, p = 0.04).

Conclusion
A total of 20.0% of responders to intravenous steroid treatment for ASUC had a steroid dependency during follow-up. The demographic and clinical features of ASUC according to the presence or absence of steroid dependency were similar. Initial CRP levels were low in patients with steroid dependence.
P179 Comparative benefit-risk profile of induction and maintenance therapy with upadacitinib versus placebo in patients with moderately to severely active ulcerative colitis
Authors: Blumenstein I , Xuan S , Panaccione R , Baert F , Barreiro-de Acosta M , Ye B D , Klaff J , Vladea R , Levy G , Holweg C T J , Sanchez Gonzalez Y , Dubinsky M C 
Published: January 2023

Abstract

Background
Upadacitinib (UPA) demonstrated efficacy and safety as induction and maintenance therapy for ulcerative colitis (UC) in Phase 3 trials U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026). This post-hoc analysis aims to characterise the benefit-risk profile of UPA induction and maintenance therapy vs placebo (PBO) in patients (pts) with moderately to severely active UC based on a number needed to treat/harm (NNT/NNH) analysis.

Methods
Efficacy and safety data from the pooled intention-to-treat population of U-ACHIEVE and U-ACCOMPLISH trials were included. Pts received UPA 45 mg (UPA45) once daily (QD) or PBO for 8 weeks (induction trials). Clinical responders (per Adapted Mayo score) at Week 8 of induction were re-randomised to receive UPA 15 mg (UPA15) or 30 mg (UPA30) QD, or PBO in the 52-week maintenance study. The primary efficacy endpoint was clinical remission per Adapted Mayo score. Secondary outcomes are listed in Table 1 and safety outcomes are listed in Table 2. N, percentages, and outcome differences compared by Z test were reported. NNT/NNH was calculated as the inverse of the difference in proportions achieving efficacy/safety outcomes for UPA vs PBO. Positive NNT values indicate greater efficacy and negative NNH values imply lower safety risk for UPA vs PBO.

Results
A significantly greater proportion of pts achieved clinical remission at induction (UPA45 29.9% vs PBO 4.4%) and maintenance (UPA15 40.4%, UPA30 53.6% vs PBO 10.8%) with UPA vs PBO, as well as all secondary endpoints (all p&lt;0.001; Table 1). The NNT for clinical remission at Week 8 was 4.0, ranging from 2.1 to 9.6 for secondary endpoints. At Week 52, the NNT for clinical remission was 2.4; NNTs for secondary endpoints ranged from 1.8 to 5.9 (Table 1). At Week 8, adverse events (AEs) were lower for worsening of UC for UPA45 vs PBO-treated pts and greater for creatine phosphokinase (CPK) elevation, acne, neutropenia, and lymphopenia (p≤0.01). At Week 52, AEs were lower for UPA15 and UPA30 vs PBO for worsening of UC, AEs leading to discontinuation (UPA15 only), and arthralgia (UPA30 only), and greater for CPK elevation, herpes zoster, hepatic disorder (UPA15 only), and neutropenia (UPA30 only) (p≤0.05; Table 2). All other AEs were similar between UPA and PBO. Among the safety outcomes significantly different between UPA and PBO, the NNH for UPA vs PBO ranged from –16.1 to 25.6 (Table 2).

Conclusion
This post-hoc Phase 3 analysis demonstrates greater efficacy and generally comparable safety of UPA vs PBO, indicating a favourable benefit-risk profile for UPA in pts with moderately to severely active UC.
P185 Global perception of normal life by healthcare professionals and IBD patients: mind the gap
Authors: Van Oostrom J , Anjie S , Braad M , Horrigan J , Karimi N , Adi B , Ganesh G , Yang S K , Lasa J , Broër C , de Kruif A , Olivera Sendra P , Ye B D , Banerjee R , Connor S , Siegel C , Peyrin-Biroulet L , Gecse K , D’Haens G 
Published: January 2023

Abstract

Background
For patients living with inflammatory bowel diseases (IBD), the ultimate treatment goal is “normal life”. However, no patient-reported outcome measurement (PROM) exists to measure the level of life normality in IBD. We previously asked patients across the world (5 continents) to identify and rank-order items important to their “normal life”. The top-25 ranked items are being used for subsequent PROM development. In this study, we aimed to compare the perception of healthcare professionals (HCP) and patients with IBD on normal life.

Methods
IBD patients without an ostomy, pouch or significant comorbidities were interviewed in their mother tongue in 5 continents about “normal life” using a semi-structured interview guide. All items indicated as important were extracted from translated transcripts using directed content analysis (1) until saturation of items occurred. Categorisation was guided by the Wilson’s & Cleary’s Quality of Life model. (2) Second, in an online Delphi procedure, interviewed patients and HCP from each participating centre scored importance of each item on a 0-10 scale. Items scored 7 or higher by &gt;75% were considered important to the respective group. Patient-ranked items were then presented to a patient focus group to clarify wording and merge similar items. Items merged in the patient focus group were merged similarly in HCP rankings. Third, HCP- and patient-rankings were compared. We compared top-25 items selected for PROM development and top-3 items per category.

Results
45 CD and 40 UC patients spread over 6 countries were interviewed (median age 36, 56% male, 68% employed, median disease duration 7 years [IQR 4-15]) (table 1). Saturation occurred after 33 CD and 36 UC interviews, yielding 156 unique items. In the Delphi procedure, 54 patients considered 31 items important for normal life with IBD of which 25 remained after focus group discussion. 34 HCP (12 IBD nurses, 16 IBD gastroenterologists, 6 colorectal surgeons) considered 72 items important.
Top-25 rankings overlapped in 15 items between patients and HCP, being 5 of 12 physical, 1 of 4 activities, 2 of 3 social, 4 of 11 psychological items and 3 of 5 circumstances (table 2). Top-3 rankings per category overlapped in 2 physical, 1 activities, 2 social, 1 psychological items and 2 circumstances (table 3).

Conclusion
We identified discrepancies in the perception of normal life with IBD between patients living with IBD and healthcare professionals (HCP). Of top-25 selected items for PROM development, 15 items overlapped between patients and HCP. Of top-3 items per category, the least overlap was seen in activities and psychological items. PROM development and international validation is ongoing.
P187 Intestinal ultrasound is accurate for detecting intra-abdominal complications in Crohn’s disease: a meta-analysis
Authors: Pruijt M , de Voogd F , Montazeri N , Jamaludin F , D’Haens G , Gecse K 
Published: January 2023

Abstract

Background
The clinical course of Crohn’s disease (CD) is associated with development of complications including strictures and penetrating lesions such as fistulas and abscesses. Close disease monitoring and optimizing therapy can prevent these complications. Intestinal ultrasound (IUS) is a non-invasive cross-sectional imaging method ideal for frequent assessment of disease activity and intra-abdominal complications. In this meta-analysis we provide an updated assessment of the diagnostic accuracy of IUS and its advanced modalities in the detection of intra-abdominal complications in CD compared to endoscopy, MRI/CT, surgery and pathology.

Methods
We conducted a literature search in Pubmed/MEDLINE and EMBASE databases from 01-01-1970 up to and including 17-10-2022 for studies describing diagnostic accuracy of IUS in adult patients with CD related intra-abdominal complications. Quality of the included studies was assessed with the QUADAS-2 tool. A univariate random-effects model was used to calculate the diagnostic test accuracy variables, including the log diagnostic odds ratio and area under the pooled ROC (AUC for SROC). All data were calculated with 95% confidence intervals (CIs). Chi-squared (χ²) test was used to assess study heterogeneity with p &lt; 0.05 indicating significant heterogeneity. Funnel plots were created to assess publication bias. All meta-analysis were performed using the R-package mada. We calculated pooled sensitivity and specificity in Meta-DiSc.

Results
We identified 1506 studies of which 68 were used for the systematic review. Twenty-three studies with 3863 patients were included in this meta-analysis with an overall moderate to high risk of bias. In total 6 meta-analyses were performed, both for conventional IUS (B-mode) and oral contrast IUS (SICUS) for diagnosing CD-related complications. Pooled overall log diagnostic odds ratio for strictures, fistulas and inflammatory masses by B-mode IUS were 3.56 (2,90-4.21), 3.84 (3.28-4.41) and 3.97 (3.30-4.64) and the AUC were 0.926, 0.896 and 0.960 respectively. Pooled overall diagnostic odds ratio for the diagnosis of strictures, fistulas and inflammatory masses by SICUS were 4.51 (3.28-5.73), 4.80 (3.46-6.14) and 5.46 (3.61-7.30) and the AUC were 0.955, 0.982 and 0.985, respectively. Significant heterogeneity was seen between studies reporting data on diagnosing strictures by B-mode IUS.

Conclusion
These results indicate that IUS is an accurate tool for the diagnosis of intra-abdominal complications related to CD. IUS as a non-invasive, point-of-care modality is recommended as the first-line imaging tool if there is a suspicion of CD-related intra-abdominal complications.
P189 Prospective Validation Study Regarding Disease Complications of the Toronto IBD Global Endoscopic Reporting (TIGER) Score in Ulcerative Colitis and Crohn’s Disease Patients
Authors: Zittan E , Levy M , Saban L , Vered S , Steinhart A H , Milgrom R , Gralnek I M , Silverberg M S , Zelber-Sagi S 
Published: January 2023

Abstract

Background
The recently developed TIGER endoscopy score was established to reliably describe disease severity as it can be utilized for both Ulcerative Colitis (UC) and Crohn’s disease (CD) patients.1 The aim of this study was to assess the TIGER score’s ability to predict outcomes regarding complications such as surgeries, hospitalizations, and drug or disease-related side effects in a sample of both UC and CD patients.

Methods
A cohort of 78 patients with UC (n=40) and CD (n=38) were included in a 52-week multiple visit prospective study. Each visit included patient interviews, IBD disk questionnaire, blood draws for C-reactive protein (CRP), and fecal calprotectin (FC). Endoscopy was performed at baseline. Baseline total TIGER scores were dichotomized as &lt;100 (remission-mild activity) or ≥100 (moderate-severe activity) as a predictor of complications such as surgeries, hospitalizations, and side effects.

Results
At baseline, compared to patients with TIGER scores &lt;100, UC patients with TIGER scores ≥100 had significantly higher CRP, FC, and IBD disk. In CD patients, at baseline, compared to patients with TIGER scores &lt;100, patients with TIGER scores ≥100 had significantly higher CRP, FC, and IBD disk. In terms of hospitalizations, at 52-weeks, compared to patients with baseline TIGER scores &lt;100, UC and CD patients with baseline TIGER scores ≥100 had a significantly increased likelihood of being hospitalized (p&lt;0.02). More specifically, at 52-weeks, 38.5% and 34.5% of UC and CD patients with baseline TIGER scores ≥100 experienced at least one disease-related hospitalization, respectively. Comparatively, there were zero hospitalizations in UC or CD patients with baseline TIGER scores &lt;100. In terms of surgeries, at 52-weeks, 0% and 11.1% of UC and CD patients with baseline TIGER scores &lt;100 had surgery compared to 3.9% and 24.1% of UC and CD patients with baseline TIGER scores ≥100, respectively. In terms of side effects, at 52-weeks, compared to patients with baseline TIGER scores &lt;100, UC and CD patients with baseline TIGER scores ≥100 had a significantly increased likelihood of reporting a side effect from both medications and the disease (p&lt;0.006). More specifically, 0% and 11.1% of UC and CD patients with baseline TIGER scores &lt;100 reported medication and disease side effects compared to 11.5% and 19.2% of UC and CD patients with baseline TIGER scores ≥100, respectively.

Conclusion
The TIGER endoscopic score demonstrates significant association with CRP, FC and IBD disk in both UC and CD patients. Moreover, the TIGER score can be utilized as a measure to predict the likelihood of UC and CD patients with moderate-to-severe disease burden experiencing a disease complications.
1. Zittan E, et al. J Crohns Colitis 2022;16:544-553.
P192 Comparison of Endoscopic Scoring System and Simplified Magnetic Resonance Index of Activity in Patients with Small Bowel Crohn’s Disease: Basis for Therapeutic Plan?
Authors: Na J E , Sung Noh H , Young-Ho K , Tae-Oh K , Sang-Bum K , Sung Hoon J 
Published: January 2023

Abstract

Background
The newly derived simplified magnetic resonance index of activity (MARIAs) has not been verified in comparison with balloon-assisted enteroscopy (BAE) for patients with small-bowel Crohn’s disease (CD). We studied the correlation of MARIAs with simple endoscopic score for Crohn's disease (SES-CD) of ileum based on magnetic resonance enterography (MRE) and BAE, respectively, in patients with small-bowel CD. In addition, we determined the impact of these tools on clinical decision-making.

Methods
Fifty patients with small-bowel CD who underwent BAE and MRE concurrently within three months from September 2020 to June 2021, followed by the reference date of December 2021, were enrolled. The primary outcome was correlation between the active score of ileal SES-CD (ileal SES-CDa)/ileal SES-CD and MARIAs based on BAE and MRE in segmented ileum. The active/severe disease index was set as ileal SES-CDa/ileal SES-CD of 5/7 and MARIAs of 1/2. The secondary outcome was the basis for step-up treatment.

Results
The ileal SES-CDa/ileal SES-CD and MARIAs showed strong associations (R=0.76, p&lt;0.001/R=0.78, p&lt;0.001). The AUROC of MARIAs for ileal SES-CDa ≥ 5 was 0.92 (95% CI: 0.88-0.97). The AUROC of the MARIAs for ileal SES-CD ≥ 7 was 0.92 (95% CI: 0.87-0.97). Among the 26 patients who experienced step-up treatment after BAE and MRE, 23 patients showed active disease on both BAE and MRE.

Conclusion
We validated the applicability of MARIAs compared to the BAE-based ileal SES-CDa/SES-CD. Assessment of disease activity based on both BAE and MRE could optimize the management of small-bowel CD patients.
P215 Deep immune phenotyping of unconventional T cells reveals a depletion in Mucosa Associated T Cells (MAIT) in IBD patients with extraintestinal manifestations
Authors: Catalàn-Serra x I , Xu W , Bruland T , Larbi A , Sandvik A K 
Published: January 2023

Abstract

Background
Extraintestinal manifestations (EIM) are common in IBD and they affect importantly the quality of life of patients. Although the pathogenesis of EIM is still poorly understood, an altered immune response involving T cells has been proposed. In addition, the presence of EIM during disease course will impact the therapeutic choices with new biologics.
In the present work we aim to characterize T cell populations -with focus on Uncoventional T cells- in IBD patients presenting EIM using advance flow cytometry and proteomics.

Methods
A total of 184 individuals (106 F/78 M) and were prospectively included: 149 IBD patients (84 UC/65 CD) and 25 healthy matched controls. Biologic samples including Peripheral Blood Mononuclear Cells (PBMC) and plasma were consecutively stored and classified in an established cross sectional IBD biobank at the Norwegian University of Science and Technology. Patient characteristics including age, sex, smoking status, current medication, Montreal Classification phenotype and inflammation biomarkers (CRP) and fecal Calprotectin were recorded.
PBMC were stained with antibodies and acquired using BD FACS Symphony flow cytometer using automatic compensations and Multiplex ELISA for 65 proteins was performed using Immune Monitoring 65-Plex Human ProcartaPlex™ Panel at Singapore Immunology Network (SIgN), as previously described.
Statistical analysis was performed using GraphPad Prism (San Diego, CA). p≤ 0.05 was considered statistically significant.

Results
Of the 184 IBD patients included, the presence or not of EIM was registered in 149 (mean age 37 +/-7.2; 86 female) of which 84 had UC and 65 CD. Of them, 21 (14.1%) presented EIM at inclusion. We analyzed the differences in all subsets of unconventional T cells: gammadelta T cells (VD1, VD2, VD3), MAIT cells, innate NKT cells and CD4/CD8 positive T cells between IBD patients with or without EIM (Fig1A). MAIT cells were selectively depleted in patients with EIM (p&lt;0.01), while there was no statistically significant change in the ratios of other T cell subpopulations.
We then studied the concentrations of plasma proteins between the two groups. We found a significant increase in IL-2, GM-CSF, IL-6, Eotaxin, Leukemia Inhibitory Factor Protein (LIF), TNF-RII and Monocyte Chemoattractant Protein-1 (MCP), all p&lt;0.05 in patients with EIM (Fig1B).
In order to address the potential use of MAIT as marker of EIM we constructed a ROC curve showing an AUC 0.752 (95% CI 0.639-0.865, p= 0.0002) Fig. 1C

Conclusion
MAIT cell depletion associated strongly with the presence of EIM and could be used as a clinical marker for EIM in IBD. A deeper understanding of its role in the pathogenesis of EIM, as well as an external validation as a marker, deserves further investigation.