bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0506 AZD7798, a monoclonal antibody depleting CCR9+ T cells, with the potential to target hard-to-treat small bowel Crohn’s disease
Authors: Powell N , Hedin C , Harper A R , MacKay J , Lundin P , Bock D , Spata E , Bouma G , Tian S , Lundahl A , Lund J , Eck S , Popińska A , Strömbeck A , Fowler A , Eberhardson M , Belvisi M , Marks D J B 
Published: January 2025

Abstract

Background
Crohn’s disease (CD) can affect any part of the gastrointestinal tract, but about 30% of patients have inflammation restricted to the ileum. In clinical trials, patients are typically enrolled irrespective of the disease localisation, with clinical outcomes focusing on a broad patient population. Anecdotally, small bowel healing in CD is often reported as challenging. Our aims were to investigate the unmet need in treating ileal CD and explore potential drug targets for this patient subpopulation.

Methods
A systematic review and meta-analysis was conducted of efficacy by disease location (Montreal classification L1 + L2) in placebo-controlled clinical trials in CD. As this revealed markedly different outcomes in ileal compared to colonic CD, transcriptomic data from 1185 small and large intestine biopsies of 594 CD patients were explored to identify potential small bowel specific drug targets, from which the chemokine receptor CCR9 emerged as high interest. AZD7798, a monoclonal antibody designed to deplete CCR9+ T cells, was evaluated in a randomized, placebo-controlled, double-blind first-in-human healthy volunteer study (NCT05452304), and in small bowel Crohn’s patients in a PET imaging study (NCT06053424).

Results
In the meta-analysis, marked differences were observed in efficacy of existing CD treatments in small compared to large bowel disease (Fig.1). Outcomes across mechanisms of action were not significantly different from placebo in small bowel CD (OR 1. 07, 95% CI 0.64-1.78, p=0.79) yet were superior in colonic CD (OR 3.86, 95% CI 2.75-5.42, p&lt;0.001). Next, transcriptomic analyses identified CCR9 and its ligand CCL25 as highly and selectively expressed in terminal ileum compared to large bowel. Subsequently AZD7798, a CCR9+ T cell depleting antibody, was evaluated in 106 healthy participants in a first-in-human study, and in 6 CD patients in a Phase 1b study. There were no SAEs or treatment discontinuations, and rapid and sustained depletion of CCR9+ T cells in blood was observed in both studies. Moreover, AZD7798 reduced target cells in small bowel in CD patients as detected using a novel CCR9 tracer (Fig.2).

Conclusion
Ileal CD represents a high unmet need patient subpopulation, where existing treatments appear less effective than for colonic disease. CCR9 is identified as an attractive target for small bowel-dominant inflammation. AZD7798, a first-in-class CCR9+ T cell depleting antibody, demonstrated acceptable safety and tolerability alongside sustained CCR9+ T cell reductions in blood and small intestine.
P0507 pTRACK generated normalised average T2 signal is an accurate and sensitive measure of Perianal Crohn’s disease activity
Authors: Naim I , Menys A , Bhatnagar G , Greer C , Lindsay L , Carter L , Moran G 
Published: January 2025

Abstract

Background
Magnetic resonance imaging (MRI) is the gold standard for diagnosing, classifying, and monitoring perianal Crohn’s disease (pCD). Fistula T2 signal intensity and volume/complexity are predictive of treatment response. We developed pTRACK, an interactive tool that enables radiologists to measure fistula volume, normalised average T2 signal intensity, and anatomical relationships to generate 3D digital models of pCD within minutes. This study aimed to evaluate pTRACK-generated MRI metrics against MAGNIFI-CD and assess their predictive value for clinical outcomes.

Methods
We retrospectively included consecutive adult patients (&gt;18 years) with pCD who underwent pelvic MRI and clinical assessment. Two independent, blinded abdominal radiologists scored MAGNIFI-CD and pTRACK metrics (figure 1) on axial T2 STIR TSE sequences. Clinical outcomes (remission, response, non-response) were scored using the fistula drainage assessment (FDA). Correlations, unpaired two-tailed t-tests, and leave-one-patient-out cross-validation (LOPOCV) performance metrics were used to compare MRI metrics (fistula volume, normalised average T2 signal intensity, MAGNIFI-CD score) and predict FDA categories. T2 signal intensity was normalised using an ROI in adjacent pelvic muscles.

Results
36 patients having 77 MRI scans were included. Mean C-reactive protein at the time of assessment was 12.9 ± 22 mg/L. 38.2% of patients had class 1 disease, 42.7% had class 2a disease with a minority having more complex disease. 58.4% of patients experienced non-response, with 14.3% experiencing response and 27.3% experiencing remission.
Significant differences were observed across metrics when dichotomized into remission and active groups (responding and non-responding): normalised T2 signal (1.65 ± 1.10 vs. 2.98 ± 1.52, p&lt;0.001), fistula volume (1.58 ± 3.08 mL vs. 4.55 ± 8.66 mL, p=0.03), and MAGNIFI-CD scores (5.86 ± 4.70 vs. 12.41 ± 5.80, p&lt;0.001). Fistula volume and average T2 signal intensity showed moderate correlation to MAGNIFI-CD (r=0.72, p&lt;0.001; r=0.49, p&lt;0.001 respectively). LOPOCV AUC for normalised average T2 and fistula volume were 0.77 and 0.74, respectively, with sensitivities of 87% and 95%, and specificities of 62% and 52%. For MAGNIGI-CD, LOPOCV AUC was 0.84, with a sensitivity of 77% and specificity of 81%.

Conclusion
pTRACK’s normalised T2 signal and fistula volume demonstrated comparable accuracy to MAGNIFI-CD, with higher sensitivity for predicting pCD activity and distinguishing active from non-active disease. These findings underscore pTRACK’s potential utility, warranting prospective validation in cohorts with more severe disease.
P0509 Fecal calprotectin diagnostic level gradient along the small bowel in patients with Crohn’s disease
Authors: Ukashi O , Kopylov U , Ungar B , Talan Asher A , Shachar E , Engel T , Albshesh A , Yablecovitch D , Lahat A , Eliakim R , Ben-Horin S 
Published: January 2025

Abstract

Background
Fecal calprotectin (FC) is known to be a sensitive biomarker of colonic inflammation but to a lesser degree of small bowel (SB) inflammation. Moreover, data on FC’s diagnostic levels in different SB segments are scarce. We aimed to examine FC’s diagnostic levels along the SB-axis in CD.

Methods
This was a post-hoc aggregated analysis of five prospective studies of adult CD patients, who underwent FC testing and SB video capsule endoscopy (VCE). Lewis score (LS) inflammation in different SB segments was tested for correlation with FC level after exclusion of colonic disease. The diagnostic levels of FC for SB inflammatory topographical-gradient were assessed using a receiver operating characteristic.

Results
214 patients were included (age:30 [24-43] year-old, males-57%). For a similar SB inflammatory-activity (LS≥135), FC levels incrementally increased from proximal to distal SB segments (63 [30-121] versus 190 [78-549], p=0.005) and from distal SB segment to the colon (190 [78-549] versus 542 [185-1000], p=0.010). The best FC cutoffs to identify isolated mild proximal/distal SB-inflammation (LS≥135) were 77 and 123, respectively. A cutoff of 234 was best to detect more significant proximal inflammation (LS≥350) when only mild distal SB-inflammation was present. In sensitivity analyses, this proximal-to-distal FC gradient was maintained when LS≥350 and LS≥790 were used as the inflammatory reference-values. Unlike FC, the magnitude of CRP elevation was unrelated to the topography of inflammation along the SB-axis.

Conclusion
FC may serve as a topographical biomarker of CD-activity, with its sensitivity to identify mucosal inflammation increases from proximal to distal SB segments.
P0517 Role of radiomics in predicting the degree of intestinal fibrosis in patients with Crohn’s Disease
Authors: Laterza L , Maresca R , Varca S , Tran H E , Boccia E , Larosa L , Sessa G M , Mignini I , Sacchetti F , Giustiniani M C , Boldrini L , Sofo L , Minordi L M , Cammarota G , Papa A , Gasbarrini A , Scaldaferri F 
Published: January 2025

Abstract

Background
During their lifetime, patients with Crohn’s disease (CD) frequently develop strictures as a complication, where various degrees of inflammation and fibrosis coexist. Distinguishing between inflammatory and fibrotic strictures is crucial for deciding on surgery or treatment changes, yet it is currently challenging in clinical practice. Cross-sectional imaging techniques (e.g. magnetic resonance imaging MRI) provide a reasonably accurate estimate of bowel wall fibrosis. However, only histopathological examination can determine its true extent. Radiomics uses artificial intelligence to analyze quantitative features from diagnostic images and can predict clinical outcomes. This study aims to assess the role of radiomics in classifying patients according to the degree (no/mild vs severe) of intestinal fibrosis in a cohort of CD patients who underwent surgery for strictures disease

Methods
We retrospectively selected 48 CD patients who underwent MR-enterography and subsequent surgery within 4 months between 2017-2023. An expert pathologist evaluated the degree of fibrosis in histopathological specimens from surgical samples using the Chiorean scoring system from 0 (no fibrosis) to 2 (severe fibrosis), and the degree of inflammation using Geboes score. For each MR-enterography, typical lesions of CD were searched by an expert radiologist on T2-weighted axial images generating a region of interest (ROI) segmentation for each lesion. We extracted 100 radiomic features from each ROI of the pre-processed MRI images using Pyradiomics. Feature selection included univariate analysis (Wilcoxon-Mann-Whitney test) and Spearmann correlation to exclude highly correlated features. A logistic regression model with stepwise regression was built with the selected features and evaluated by computing the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Model’s sensitivity and specificity were calculated using the best cut-off according to the Youden index method.

Results
Among the 48 patients, 48% (n=23) showed severe fibrosis on the surgical specimen, whereas 52% (n=25) had either no or mild fibrosis. Two radiomic features were selected and resulted statistically significant in the fitted logistic regression model(p &lt; 0.05): original_shape_Maximum2DDiameterColumn and original_firstorder_90Percentile. Results with their 95%CI were: AUC 0.79(0.64-0-90), sensitivity 0.69(0.50-0.75) and specificity 0.84(0.66-0.94). Bootstrap corrected (mean optimism) values of AUC and metrics were: AUC 0.77 (0.02), sensitivity 0.68(0.01), specificity 0.81(0.02).

Conclusion
Our study suggests that MRI-based radiomics modeling could help predict the degree of intestinal fibrosis. Future research will confirm these findings in a larger cohort
P0518 Study of the prevalence of defecatory disorders in patients with quiescent ulcerative colitis using high resolution anorectal manometry
Authors: Abdelaty K ,   Hussein Saad Eman Abu El-Soud Ezzat Ali
Published: January 2025

Abstract

Background
Ulcerative colitis is characterized by recurring episodes of inflammation limited to the mucosal layer of the colon. Initially, it affects the rectum, and it may progress in a proximal and continuous manner to encompass other sections of the colon. Anorectal manometry quantifies and evaluates various aspects of the intricate and multifactorial mechanisms that regulate defecation and continence.

Methods
This study was carried out on 50 ulcerative colitis patients aged from 19 to 76 years old, both sexes, patients who have documented disease remission or mild activity clinically and by colonoscopy for the last six months and had persistent defecatory disorder symptoms. All patients were subjected to detailed history taking, systemic physical examination, laboratory investigations, colonoscopy showing remission or mild activity for the last six months based on Mayo score, and high-resolution anorectal manometry.

Results
There were statistically significant differences regarding relation between fecal incontinence and duration of the disease (P=0.008), while no significant differences were observed with the ulcerative colitis extension, and the treatment used. Regarding constipation, urgency, incomplete evacuation and proctalgia; there was no statistically significant differences with the duration of the disease, the ulcerative colitis extension, and the treatment used.

Conclusion
Many ulcerative colitis patients still experience defecatory disorders even at the quiescent stage, and this could be explained by the long-term neuromuscular effect of prolonged inflammation. High resolution anorectal manometry is the most important test to assess anal tone and contractility, recto-anal coordination and rectal sensation. Fecal incontinence in quiescent ulcerative colitis patients is significantly associated with the duration of the disease.

References
Gajendran M, Loganathan P, Jimenez G, Catinella AP, Ng N, Umapathy C, et al. A comprehensive review and update on ulcerative colitis. Dis Mon. 2019; 65:100-51.
Kang HR, Lee JE, Lee JS, Lee TH, Hong SJ, Kim JO, et al. Comparison of high-resolution anorectal manometry with water-perfused anorectal manometry. J Neurogastroenterol Motil. 2015; 21:126-32.
Torresan F, Mandolesi D, Bonventre S, Usai P. Differences between conventional anorectal manometry and high resolution\high-definition anorectal manometry. In: Bellini M, editor. High resolution and high-definition anorectal manometry. 5. Cham: Springer; 2020. p.49-68.
P0530 Relationships and sexuality in patients with inflammatory bowel disease – The perspective of healthcare professionals
Authors: Jäghult S , Druvefors E , Bello F , Florwald E , Forsell A , Myrelid P , Almer S 
Published: January 2025

Abstract

Background
Previous studies have shown that inflammatory bowel disease (IBD) has a negative impact on intimacy and sexuality related questions, and many IBD-patients experience that the disease impair the possibility of creating relationships. A recent Swedish study revealed that a large part of IBD-patients experience difficulties concerning relationships and sexuality, and many wish for a more active support from healthcare professionals. The aim of this Swedish follow up study was therefore to explore the current situation concerning intimacy and sexuality from the perspective of the healthcare professionals.

Methods
A digital, anonymous questionnaire was sent to healthcare professionals in Sweden through the different professional associations working with IBD-patients. The questionnaire contained 19 questions concerning problems that patients raise concerning intimacy and sexuality and how they are handled.

Results
A total of 118 respondents answered the questionnaire, the majority were women (73%), the mean age was 51 years. About half of the respondents (54%) were nurses, while 28% were gastroenterologists, 11% were surgeons, and 7% had another profession. The different professions were overall consistent in their answers why the results are presented for the whole group.
Half answered that they raise questions concerning relationships and sexuality on single occasions, while 23% stated that they never raise the topic with their patients (Figure 1). A total of 56% indicated that their patients ask questions concerning intimacy on single occasions, while 19% stated that it never happens (Figure 1). About 16% of the respondents stated that they had access to sexologist and 42% answered that they had possibility to refer to a psychologist or psychotherapist.
Many of the responders indicated that IBD-patients rarely raise questions concerning relationships and sexuality. Issues still being raised are mainly concerns about fertility in women, and erection problems in men. According to the healthcare professionals, both male and female patients report decreased sexual desire, a sense of not feeling attractive, and concerns about intestinal leakage. Women, also mentioned concerns regarding pain during intercourse, related to perianal fistulas and abdominal pain.

Conclusion
Healthcare professionals state that conversations concerning relationships and sexuality rarely happen. The conversations are mainly focused on fertility and erection problems. In our previous study, 78% of the patients stated problems concerning intimacy and 64% requested more active support from the healthcare professionals. Our results indicate a need for an increased knowledge and awareness about these questions among healthcare professionals.
P0532 Exploring biomarkers of systemic oxidative stress and placental insufficiency in pregnant women with Inflammatory Bowel Disease
Authors: Holstein H J , Bouwknegt D G , Visschedijk M C , Bulthuis M L C , Reinders-Luinge M , Schoots M H , van Goor H , Gordijn S J , Dijkstra G , Bourgonje A R 
Published: January 2025

Abstract

Background
Inflammatory bowel disease (IBD) often presents during the fertile age and may affect pregnancy outcomes. Both IBD and selected pregnancy complications involve oxidative stress. Soluble FMS-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) serve as biomarkers of placental insufficiency, while free thiols (FT) reflect systemic oxidative stress. This study aimed to assess the dynamics of FT, sFlt-1, and PlGF before, during, and shortly after pregnancy, and their relationships with disease- and pregnancy outcomes in patients with IBD.

Methods
This retrospective cohort study included pregnant women with and without IBD (Figure 1). FTs were measured with colorimetric detection; sFlt-1 and PlGF were measured using immunofluorescent assays. Extensive clinical data were collected, including pregnancy complications and IBD parameters. Differences between groups during pregnancy were assessed using nonparametric tests. Linear mixed-effects models were used to assess longitudinal changes of biomarkers before, during, and after pregnancy.

Results
A total of 40 patients and 14 non-IBD controls participated, covering 57 IBD and 14 control pregnancies. Serum FT levels were significantly lower in patients with ulcerative colitis during pregnancy (p=0.007, Fig. 2A) and decreased compared to pre-conceptional levels (p=0.005, Fig. 2B), indicating increased oxidative stress. Conversely, sFlt-1/PlGF ratios were not significantly different across groups (Fig. 2C). sFlt-1/PlGF ratios were higher in patients with small-for-gestational-age infants (p=0.015, Fig. 2D). Post-pregnancy FT levels were lower in patients experiencing disease exacerbations during pregnancy (p=0.046, Fig. 2E), whereas sFlt-1/PlGF ratios were numerically higher (p=0.063, Fig. 2F). IBD severity correlated with lower FT levels, as reflected in patients with a surgical history (p=0.066, Fig. 2G) and those using biologics at time of sampling (p=0.033, Fig. 2H).

Conclusion
This study demonstrates increased systemic oxidative stress in patients with IBD during pregnancy, as reflected by lower FT levels compared to pre-conceptional values and non-IBD controls. This was especially pronounced in patients with higher disease activity and severity. Prospective validation is required to evaluate the utility of these biomarkers in predicting pregnancy complications and informing clinical decision-making.
P0535 Crohn’s Anal Fistula - Quality of Life (CAFQOL) for disease control and remission in patients with perianal fistulizing Crohn’s disease: a new standard in assessing clinical outcome?
Authors: Mulders L , Beek K , Tielbeek J , Zwart M , Rietdijk S , Jansen J , Stoker J , Buskens C , D’Haens G , Gecse K ,   AMFIBIO study group
Published: January 2025

Abstract

Background
Perianal Fistulizing Crohn’s Disease (PFCD) has a major impact on quality of life (QOL). QOL improvement is a key clinical goal, whether the aim is surgical repair, or symptom control. This prospective study evaluated the CAFQOL (Crohn’s Anal Fistula-QOL) questionnaire for disease monitoring in PFCD patients.

Methods
This study included patients with PFCD starting on anti-TNF therapy, mesenchymal stem cell injection, or hyperbaric oxygen therapy followed by surgical closure. We collected patient-reported CAFQOL and IBDQ-32, as well as Fistula Drainage Assessment (FDA), Perianal Disease Activity Index (PDAI) and MRI (MAGNIFI-CD) outcomes at baseline, and at weeks 9, 26, and 52. QOL changes over time were analyzed using a linear mixed-effects model, and correlations between outcomes were assessed using Spearman correlation coefficients. Internal consistency was assessed with Cronbach’s alpha. The underlying structure of CAFQOL was evaluated with exploratory factor analysis (EFA) to identify distinct dimensions of quality of life. Responsiveness of CAFQOL and PDAI were reported in standardized response mean (SRM). Target CAFQOL values at week 52 for patients in complete remission by week 26 (PDAI≤4, MAGNIFI-CD=0) were calculated with a linear mixed-effects model. Receiver Operating Characteristic (ROC) model was used to evaluate CAFQOL in relation to clinical remission (FDA).

Results
We included 62 patients with a mean CAFQOL of 59.8 (SD 16.4) at baseline (Table 1). CAFQOL showed significant improvement over time, with average improvements of 8 points (95% CI 4 – 11) at week 9, 12 points (95% CI 8 - 16) at week 26, and 22 points (95% CI 18 - 26) at week 52 (all p&lt;0.0001) (Figure 1). CAFQOL was strongly correlated with IBDQ-32 (r = -0.78; p&lt;0.001) supporting convergent validity, while correlations with FDA (r = 0.48; p&lt;0.0001), PDAI (r = 0.33; p=0.131), and MAGNIFI-CD (r = 0.11; p=0.548) were weak to negligible, supporting discriminant validity. A Cronbach’s alpha of 0.80 supported internal consistency. EFA revealed three main factors: social-practical impacts, emotional-mental health impacts, and physical discomfort explaining 53% of the QOL variance. By week 52, SRM of CAFQOL and PDAI were -1.26 and -1.79 respectively, suggesting large effect sizes. CAFQOL ≤ 37 was associated with complete fistula remission (PDAI≤4, MAGNIFI-CD=0), and was able to detect clinical remission with 80% (95% CI: 58–92) sensitivity and 56% (95% CI 39–71) specificity (AUROC=0.735; p=0.0038).

Conclusion
The CAFQOL is a reliable and consistently responsive tool that captures meaningful changes in quality of life over time regardless of the treatment modality.