Introduction

Dutch society has witnessed significant societal and demographic changes over the decades. With 28% of the Dutch population having a migration background in 2023, understanding diversity within the gastroenterology workforce is imperative. This study examines the evolution of sex, ethnic, and socio-economic diversity among Dutch gastroenterologists from 2005-2023.

Aims & Methods

This repeated cross-sectional study utilized pseudonymized data from the BIG-register, paired with demographic variables from Statistics Netherlands (CBS), covering the years 2005, 2010, 2015, 2020, and 2023. The total population sample in each year consisted of all individuals registered as gastroenterologists for at least one day in a respective year. Variables such as sex, migration background, year of birth, and parental socio-economic status indicators were analyzed to assess trends and identify factors associated with being a
gastroenterologist. Descriptive and logistic regression analyses were employed to explore these trends and compare generational differences.

Results

The study revealed a narrowing sex gap with an increase in female gastroenterologists (28% to 43% from 2005-2023), particularly among the younger cohort (60% female). However, ethnic diversity has not kept pace, with a decline in the representation of gastroenterologists from migration backgrounds among younger professionals (27% to 18% for gastroenterologists < 1979 and ≥ 1980, respectively). Socio-economic analysis indicated that approximately 75% of gastroenterologists have parents from top-20% assets category.

Conclusion

The gastroenterology field in the Netherlands shows significant advancements in gender diversity, but lags in ethnic and socio-economic diversity. The increasing trend of gastroenterologists from medical families highlights the need for policy adjustments, to ensure access to candidates from more diverse socio-economic backgrounds. Policies should focus much more on promoting comprehensive diversity to enhance healthcare outcomes and reflect the demographic changes within society.

References

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Disclosure

OKB, ABB, PK and LM have no conflict of interests, CJJM is consultant for Douglas (New Zealand) and HLW (The Netherlands). All outside submitted work.

Introduction

Linked Color Imaging (LCI) is an endoscopic system that emphasizes the red mucosal color to identify subtle areas of inflammation. Endoscopic imaging, including LCI classification and LCI index, has been reported as a predictor of histological healing (HH) in ulcerative colitis (UC). Endoscopic changes (LCI classification, LCI index) in vedolizumab treatment have not been reported to date.

Aims & Methods

This study aimed to evaluate endoscopic remission and HH using LCI endoscopy at week 22 of vedolizumab treatment in patients with moderate to severe UC. This was a phase 4, multicenter, open-label, single-arm, prospective study involving 12 patients with moderately to severely active UC receiving vedolizumab. Vedolizumab was administered for 54 weeks. Endoscopy and mucosal sampling from most inflamed sites or the patient’s rectum when all sites had equal endoscopic severity were performed at weeks 0, 22, and 54 to assess the LCI index, LCI classification, Mayo endoscopic score (MES), Nancy score (If MES = 0, it was collected from the rectum). This study was also evaluated a variety of possible factors such as fecal calprotectin, serum vedolizumab concentration and mucosal gene expression associated with changes induced by vedolizumab. LCI index was numerically evaluated for the redness of a 40-pixel square area within the LCI image. LCI classification was defined by assigning one of the three categories (A, no redness; B, redness with visible vessels; C, intense redness without visible vessels). HH was defined as a Nancy score ≤1, and clinical outcomes were compared between HH and non-HH groups. Correlation coefficients between LCI endoscopy and other clinical markers (MES, Nancy score, fecal calprotectin and vedolizumab concentration) were analyzed at weeks 0, 22, and 54. Gene expression analysis was performed on 374 genes, comparing HH (n=8) vs. non-HH (n=3) and LCI classification A (n=5) vs. LCI classification B and C (n=6) at week 22. Biomarkers common to HH and LCI-A were identified as LCI-Deep remission (L-DR) markers.
The study was registered with the Japan Clinical Trial Registry (Identifier: UMIN000042855).

Results

At week 22, 66.7% (8/12) achieved histological healing (HH), while 50.0% (6/12) met LCI classification A criteria. The LCI index change from baseline showed a statistically significant difference between HH and non-HH (week 22: p=0.021; week 54: p=0.011).Correlation analysis demonstrated that LCI index was significantly associated with: MES (week 22: ρ=0.729, week 54: ρ=0.789), Nancy score (week 22: ρ=0.695, week 54: ρ=0.725), fecal calprotectin (week 22: ρ=0.555, week 54: ρ=0.783), vedolizumab concentration (week 22: ρ=0.758, week 54: ρ=-0.418). Gene expression analysis identified IL1B, CXCL11, CD38, CSF2RB, PTPN6, CD86, NFKB2, IFNAR2, STAT1, GNAI2, FES and IRF9 as L-DR markers, as they were commonly associated with both HH and LCI classification A. There are genes involved in NF-κB signaling pathway and JAK-STAT signaling pathway associated with UC. HH and LCI endoscopy have been found to correlate well but do not perfectly align.
In this study, we proposed a definition of L-DR, which encompasses both HH and LCI endoscopic remission.

Conclusion

This study introduces L-DR as a novel definition for combined endoscopic (LCI-A) and HH (Nancy score ≤1) in UC patients receiving vedolizumab. Additionally, we identified candidate L-DR biomarkers that may serve as potential indicators of deep remission.

Disclosure

Tomohisa Takagi, Male, (Kyoto Prefectural University of Medicine, Kyoto, Japan):
Scholarship funds from Mitsubishi Tanabe Pharma Corporation,
Collaborative research fund from PreMedica Inc.,
Lecture fees by Mochida Pharma. Co., Ltd., Yanssen Pharmaceutical K.K., EA Pharma. Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Towa Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Pfizer Japan Inc.
Kazuhiko Uchiyama, Male, ( Kyoto Prefectural University of Medicine, Kyoto, Japan):
Collaboration research fund from Janssen Pharma. K.K.
Lecture fee by Mitsubishi Tanabe Pharma. Co. Ltd. and Janssen Pharma. K.K.
Yuji Naito, Male, (Kyoto Prefectural University of Medicine, Kyoto, Japan):
Scholarship funds from Taiyo Kagaku Co. Ltd., Morinaga Co. Ltd., Miyarisan Pharma Co. Ltd, Morishita-Jintan Co. Ltd., Fujikko Co. Ltd., Mizkan Co. Ltd., Mykinso Co. Ltd.
Collaboration research fund from Takeda Pharma. Co. Ltd. and Taiyo Kagaku Co., Ltd.
Lecture fees by Takeda Pharma. Co. Ltd., Mochida Pharma. Co. Ltd., Biofermin. Co. Ltd., Otsuka Pharma. Co. Ltd., and Miyarisan Pharma. Co. Ltd.

Introduction

Inflammatory Bowel Diseases (IBD) are chronic immune-mediated disorders of the gastrointestinal tract. Fibrosis is a frequent manifestation in IBD driven by inflammatory cytokines. During fibrosis, extracellular matrix proteins accumulate in the tissue, causing the disruption of the epithelial barrier and stenosis, ultimately causing malabsorption and intestinal motility issues. This can eventually lead to further serious complications, strictures, fistulas, or ileus. No drugs are available targeting fibrosis, in these cases, only surgical intervention can be used. A defined primary in vitro cell culture model is not available for intestinal fibrosis modeling.

Aims & Methods

Therefore, we aimed to establish and characterize human primary fibroblast cell culture from intestinal biopsies of control and IBD patients.
Human primary fibroblast cell cultures were generated from colonic biopsy of patients with IBD (N=4) and control (N=4). All downstream analyses were applied in passage number 3. For the phenotype observation, immunofluorescent staining was used. Targeted proteins were COL1A1, TGF-ß1, PAI-1, α-SMA, and PHH3. Proteome Profiler Human Cytokine Array Kit was used for the secreted cytokine pattern observation. For the gene expression analysis, RNA was isolated, and the qRT-PCR technique was utilized for the following target genes: COL1A1, ACTA2, TGF-ß1, FN1, PAI-1, H3C4. Scratch assay was used to examine wound closure, we monitored the closing for 48 hours taking photographs throughout. We evaluated the collected data and performed statistical analysis.

Results

We can successfully generate and maintain human colon primary fibroblast cell cultures from colonic biopsies of healthy and Crohn’s disease (CD) origins. Morphological differences were observed between control and diseased patient samples. In the protein examinations, the fluorescent intensity of fibrotic markers (COL1A1, TGF-ß1, PAI-1) and the mitosis marker PHH3 were significantly higher in the CD samples, indicating that the cells maintained fibrotic phenotype and the diseased fibroblasts had a higher proliferation rate. The myofibroblast marker, α-SMA, didn’t show a significant difference. In the cytokine pattern analysis, 22 cytokines showed a twofold increase or decreased by half between the two groups. HGF and DPPIV showed higher quantities in the CD-originated fibroblast. These cytokines are connected to the induction of fibrosis. However, the ANG, BDNF, PTX-3, VEGF, and VCAM-1 were higher in the control samples. Interestingly, no significant differences were noted between the two groups in the targeted genes examined by qRT-PCR measurements. We observed the closure of the artificial wound was faster and more effective in the Crohn’s disease culture compared to the control.

Conclusion

In conclusion, we can generate primary human intestinal fibroblast cell cultures and maintain them to passage number 3, approximately a month long. Fibrotic markers, secreted cytokines and morphological differences distinguish the diseased cultures from the healthy subjects; therefore, it could be useful for in vitro fibrosis modeling in the future. On the other hand, the gene expression analysis doesn’t discriminate between the two groups at passage number 3. To continue with our work, we will observe the fibrotic properties in earlier passage numbers.

Introduction

The Mayo Endoscopic Subscore (MES) is the most widely used endoscopic index for assessing disease activity in ulcerative colitis (UC). Although artificial-intelligence　(AI)–assisted colonoscopy is expected to reduce inter-observer variability, the MES 4-point scale (0–3) lacks sufficient sensitivity to detect subtle changes in mucosal activity, limiting its ability to capture incremental improvement or deterioration. Moreover, because MES focuses on qualitative features—such as bleeding and erosions—without considering the extent or surface area of inflammation, it provides an incomplete estimate of a patient’s overall inflammatory burden.

Aims & Methods

We sought to develop and validate a quantitative, AI–driven colonoscopic score—Quantitative Ulcerative Colitis Assessment using Deep-learning (QUAD)—and to determine whether it predicts clinical relapse in patients with UC. The QUAD system was trained on 84 743 colonoscopic images from 998 UC patients at three centers and comprises three main functions: i) Image filtering: Automatic exclusion of low-quality images that are unsuitable for analysis owing to light saturation (halation), inadequate insufflation, excessive proximity to the mucosa, chromoendoscopy, or virtual chromoendoscopy. ii) Frame-level scoring: Each frame is divided into four quadrants; inflammation in each quadrant is graded from 0 to 3, and the quadrant scores are summed to yield a QUAD score of 0–12. iii) Video-level aggregation: Full-length withdrawal videos are processed to generate (i) an Entire QUAD score (0–60), representing pan-colonic inflammation, and (ii) a Distal QUAD score (0–12) for the rectosigmoid segment (final 20 % of the video).
The QUAD system contains mainly three function: i) automatically exclude low quality images that is ineligible for analysis in cases of halation, inadequate air de­livery, proximity to mucosa, chromoendoscopy, and virtual chromoendoscopy; ii) fully auto­mated twelve-class score output based on frame analysis: Each frame was divided into four quadrants; inflammation in each quadrant was graded 0–3 and summed to yield a QUAD score of 0–12; and iii) full-length withdrawal videos were processed to generate (I) an Entire QUAD (0–60) for considering whole-colon inflammation status and (II) a Distal QUAD (0–12) for the distal rectum–sigmoid segment (final 20 % of the video). An open-label cohort of adults with quiescent UC (partial Mayo score ≤ 2 for ≥6 months) was prospectively enrolled at a single center (August 2022–February 2023), and followed for 24 months after baseline colonoscopy; clinical relapse was defined as partial Mayo score > 2. The predictive value of QUAD scores for relapse was evaluated.

Results

Frame-level QUAD scores correlated strongly with expert-assigned MES values (Spearman r = 0.68, p < 0.01). Among 156 participants (median age, 51 years; 49 % male), 22 experienced relapse during follow-up. Relapse occurred in 19.4 % (19/98) of patients with a QUAD score > 3 versus 5.2 % (3/58) with a score ≤ 3 (log-rank p = 0.01).
In video analysis, an Entire QUAD > 6 did not significantly stratify relapse risk (16.8 % [17/101] vs 9.1 % [5/55]; log-rank p = 0.17). In contrast, a Distal QUAD > 3 was strongly associated with relapse (43.8 % [7/16] vs 10.7 % [15/140]; log-rank p < 0.01).

Conclusion

AI-generated QUAD provides a sensitive, fully quantitative measure of mucosal inflammation and stratifies relapse risk in clinically quiescent UC. In particular, the automatically derived Distal QUAD—focused on the distal colon and independent of operator image selection—offers a practical, objective tool for longitudinal monitoring and treatment tailoring in UC.

Introduction

Intestinal ultrasound (IUS) is increasingly used as a point-of-care tool for patients with ulcerative colitis (UC). Non-invasive monitoring is essential for managing disease progression and therapeutic intervention in pediatric UC patients. The Milan Ultrasound criteria (MUC), ulcerative colitis intestinal ultrasound score (UC-IUS), and Civitelli score show promise as real-time disease activity assessment tools, potentially reducing the need for invasive procedures like endoscopy.

Aims & Methods

A prospective cohort of 34 pediatric UC patients underwent IUS and colonoscopy to assess disease activity using MUC, UCIUS, and Civitelli scores. Assessments were conducted within a 7-day interval, with no therapeutic changes between procedures. Diagnostic accuracy was determined using receiver operating characteristic (ROC) curves, with endoscopy as the reference
standard, and histological parameters assessed in a subset of patients using the Nancy Index.

Results

The study included 34 pediatric UC patients (median age: 14.7 years; 65% male) with varied disease severities and durations (median duration: 12.6 months; median PUCAI: 30; median fecal calprotectin: 1041 μg/g). Bowel wall thickness (BWT) correlated significantly with all IUS scores; however, no correlation was observed between BWT and baseline Mayo endoscopic disease activity. The area under the curve (AUC) was 0.528 (CI:0.348–0.704) for MUC, 0.602 (CI: 0.418–0.768) for UC-IUS, and 0.572 (CI: 0.388–0.742) for the Civitelli score, indicating moderate diagnostic accuracy. While differences among scores were not statistically significant, UC-IUS demonstrated the highest accuracy. In 16 patients with available Nancy Index data, the AUC values were 0.500 for MUC, 0.579 for Civitelli, and 0.563 for UC-IUS, further supporting moderate accuracy (Table 1).

Conclusion

Both MUC, Civitelli, and UC-IUS scores provide moderate diagnostic accuracy in assessing pediatric UC, though potentially less effective than in adult populations. UC-IUS, with its emphasis on vascularization, haustration and wall thickness, may offer enhanced sensitivity in pediatric patients. Lowering the cut-off for bowel wall thickness may improve accuracy in children, given their thinner, yet highly vascularized bowel walls, particularly in early disease stages.

References

1. van Wassenaer EA, van Rijn RR, Zwetsloot SLM, et al. Intestinal Ultrasound to Assess Ulcerative Colitis Disease Activity in Children: External Validation and Comparison of 2 Intestinal Ultrasound Activity Indices. Inflamm Bowel Dis. 2023;29:1217-1222.
2. Allocca M, Dell'Avalle C, Craviotto V, et al. Predictive value of Milan ultrasound criteria in ulcerative colitis: A prospective observational cohort study. United European Gastroenterol J. 2022;10:190-197