bluuebunny/crossref_metadata_2025_split huggingface dataset:
DOP003 Cromoendoscopy versus second generation Narrow band Imaging for dysplasia detection in IBD. A prospective randomized controlled trial
Authors: Martin Arranz E , Suarez Ferrer C , García Ramirez L , Sanchez Azofra M , Rueda Garcia J L , Poza Cordon J , Martín-Arranz M D 
Published: January 2025

Abstract

Background
Neoplastic risk is increased in long-standing colitis. Dye chromoendoscopy (CE) and virtual chromoendoscopy are surveillance methods. The aim of this trial is to compare methylene blue chromoendoscopy (CE) with second generation narrow band imaging (NBI) virtual chromoendoscopy in the detection of IBD-associated colonic neoplasia.

Methods
Prospective randomized controlled trial (NBICromo NCT04403997) including patients with clinical indication for surveillance (&gt;8 years of disease, left-sided or extensive colitis, colonic Crohn´s disease with &gt;2 colonic segments affected or associated primary sclerosing cholangitis). Patients were randomized on 1:1 ratio to CE with methylene blue 0,1% or NBI. All procedures were performed with Olympus HQ190 endoscopes by endoscopists with experience in IBD and chromoendoscopy. All visible lesions were resected or biopsied depending on the optical diagnosis. The primary endpoint is the difference in total number of neoplastic lesions detected in each group. Neoplastic lesions include dysplasia and serrated lesions. Secondary endopoints include withdrawal time, total number of lesions, adverse events. The study has been approved by the Hospital Ethics Committee and patients signed informed consents.

Results
200 patients were included, 26 were excluded due to presence of inflammation or poor bowel preparation and finally 174 were randomized, 81 to CE arm and 93 to NBI Basal characteristics are shown in Figure 1.
118 (67,8%) patients had at least one lesion. 59 (72,8%) in the CE group and 59 (63,4%) in the NBI group p=0.22. 51 patients (29,5%) had neoplastic lesions, 24 patients in CE group (29,6%) and 25 patients with NBI (26,8%)
299 lesions were detected. 173 with CE and 126 with NBI. Of these 75 (25,1%) were neoplastic. 37 neoplastic lesions were found in NBI group and 38 in CE group p ns. 10 lesions were serrated, 6 in the NBI group and 4 in CE group p ns. No invasive cancer was detected.
Lesion characteristics are shown in figure 2
Total withdrawal time (including staining and/or therapeutics) was significantly shorter in the NBI group (median 15 min (Interquartile range 11-21 vs 24 (IQ range 18-32 p&lt;0.001).AE were 1 post moderate resection bleeding and 1 mild fever, both in the CE group.

Conclusion
In patients with IBD undergoing colitis associated neoplasia screening we found no difference between virtual chromoendoscopy with NBI and methylene blue chromoendoscopy in neoplasia detection. NBI reduces procedure time significantly.
DOP005 Long-term efficacy and safety of mirikizumab treatment for Crohn’s Disease: Results from the VIVID-2 open-label extension study
Authors: Vermeire S , Sands B E , D’Haens G , Hisamatsu T , Kelly C R , Lu N , Morris N , Moses R , Durand F , Protic M , Hozak R R , Lopes M U , Regueiro M , Laharie D 
Published: January 2025

Abstract

Background
VIVID-2 (NCT04232553) is an ongoing open-label long-term extension study of efficacy and safety of mirikizumab (MIRI), a selective interleukin-23p19 inhibitor, in patients with moderately to severely active Crohn’s disease (CD). We present efficacy and safety results from patients randomised to MIRI in the phase 3 VIVID-1 study (NCT03926130) who received MIRI for a second year in VIVID-2, with or without reinduction.

Methods
In VIVID-1, the MIRI group received induction with 900 mg intravenously (IV) at weeks (W) 0, 4, and 8, then 300 mg subcutaneously (SC) every 4W. Week 52 endoscopic responders (≥50% reduction from baseline in Simple Endoscopic Score for CD [SES-CD]) continued the same MIRI SC dosing in VIVID-2. Endoscopic non-responders received reinduction with MIRI IV at the start of VIVID-2 followed by SC dosing (IV-SC) as described. Outcomes at W104 of MIRI treatment included endoscopic response and endoscopic remission (SES-CD ≤4 and ≥2-point reduction from baseline with no subscore &gt;1 for any individual variable). The cutoff date was 02 August 2024; VIVID-2 patients entered after 01 August 2023 were excluded from this interim analysis. Safety was assessed from the first dose in VIVID-2 through the cutoff date. Discontinuations or missing data were handled using modified nonresponder imputation (mNRI) and observed cases (OCs).

Results
Among MIRI endoscopic responders (N=251) who continued MIRI SC, 81.8% (mNRI)/87.6% (OC) maintained endoscopic response at W104 (Fig. 1A). At W104, endoscopic remission was maintained by 72.5% (mNRI)/78.6% (OC) of the 137 patients also in endoscopic remission at W52 and gained by a further 33.3% (mNRI)/35.4% (OC) of the 112 patients not in endoscopic remission at W52 (Fig. 1A). Among MIRI endoscopic nonresponders (N=179) who received reinduction with MIRI IV at the start of VIVID-2 followed by MIRI SC, 30.9% (mNRI)/36.1% (OC) gained endoscopic response; 12.1% (mNRI)/13.7% (OC) of the 174 patients not in endoscopic remission at W52 gained endoscopic remission at W104 (Fig. 1B). Treatment-emergent adverse events (AEs) were reported in 64.3% (MIRI SC) and 65.3% (MIRI IV-SC) of patients, and serious AEs were reported in 6.8% (MIRI SC) and 9.0% (MIRI IV-SC) of patients (Table 1).

Conclusion
In VIVID-2, high maintenance rates of endoscopic response and endoscopic remission were observed in patients with moderately to severely active CD who were endoscopic responders at 1 year, with additional patients gaining endoscopic remission in year 2 of MIRI treatment. Over 30% of endoscopic nonresponders at 1 year gained endoscopic response with MIRI reinduction. Overall, safety was consistent with the known MIRI safety profile.
DOP006 Long term maintenance treatment with vedolizumab in pediatric IBD: a three-year follow-up of the prospective multicenter VEDOKIDS study
Authors: Atia O , Shavit-Brunschwig Z , Orlanski-Meyer E , Stein R , Efrat B , Hyams J , Granot M , Rosh J , Hussey S , Markowitz J , Russell R K , Turner D 
Published: January 2025

Abstract

Background
Long-term data on the use of vedolizumab in children with Crohn’s disease (CD) and ulcerative colitis (UC) are lacking and the drug is not yet approved in pediatrics. The VEDOKIDS prospective multicenter cohort study aimed to assess the effectiveness and safety of vedolizumab as maintenance therapy in children with CD and UC; this study reports the 3-year final visit outcomes (ClinicalTrials.gov, NCT02862132).

Methods
Children commenced on vedolizumab at any disease duration and with any degree of disease activity were enrolled in 17 pediatric centers in Europe, the USA and the Middle East and followed prospectively through 3 years. The primary outcome was complete remission at 3 years (i.e. steroid-free clinical remission and normal ESR/CRP with sustained vedolizumab treatment and without a surgery). Secondary outcome was loss of response (PUCAI ≥ 10 or wPCDAI ≥ 12.5 for children with UC and CD, respectively) in those achieving clinical remission at week 6.

Results
Altogether, 137 children were enrolled, of whom 53 (39%) continued vedolizumab treatment through three years. Sustainability rate was higher in UC (35/73 [48%]) than in CD (18/64 [28%]; OR 2.4 [95%CI 1.2-4.8]). Complete remission at three years was achieved in 19/73 (26%) children with UC vs. 9/64 (14%) with CD (OR 2.2 [95%CI 0.9-5.2]) using ITT analysis.
The best predictor of complete remission at 3 years was clinical remission at week 6 measured in CD by wPCDAI ≤12.5 (AUROC 0.78 [95%CI 0.64-0.963]), and in UC by PUCAI&lt;10 (AUROC 0.74 [0.63-0.85]). Similarly, in adjusted multivariable logistic regression, complete remission at 3 years was more likely in week-6 remitters or responders compared to non-responders (HR 2.6 [95%CI 1.1-7.2]). Of the 51 (37%) children who achieved clinical remission at week 6 (32 UC and 19 CD), the likelihood of achieving complete remission at 3 years was 41% for UC and 26% for CD (OR 1.9 [95%CI 0.6-6.6]). Of those achieving clinical remission at week 6, 22%, 28%, 31% and 38% lost response by 30, 54, 108 and 162 weeks, respectively, for UC, while for the fewer children with CD who achieved remission at week 6, 5%, 5%, 11% and 16%, respectively, lost response (Figure).
Forty adverse events were recorded in 23 children (17%) as possibly related to vedolizumab, none were serious, with the most common being headache, myalgia and fever.

Conclusion
Vedolizumab was safe and effective for maintaining long-term remission in children with UC and CD. Remission rates were higher in UC compared to CD at the end of induction, but UC patients experienced a higher rate of loss of response over time. Achieving clinical remission by week 6 after initiation of the drug was the best predictor of long-term effectiveness in both UC and CD.
P0209 Unraveling the microbial dynamics in Crohn’s Disease-associated Fibrosis: insights from RNA-seq and Spatial Transcriptomics
Authors: Nicolo’ S , Massimino L , Parigi T L , Errico C , Salvatore S , Bozzetti V , Facoetti A , Cagliani S , Riva M , Danese S , Ungaro F 
Published: January 2025

Abstract

Background
In Crohn’s disease (CD), over 50% of cases develop fibrosis, often resulting in strictures. Despite advances in anti-inflammatory therapies, these complications persist due to chronic inflammation, which causes tissue injury and disrupts mucosal functions. Recent studies highlight microbiota dysbiosis as a potential inflammation-independent driver of fibrosis in CD 1,2, but specific microbial signatures across fibrosis stages remain underexplored.

Methods
We performed a meta-analysis of RNA-seq data from fibrotic CD-associated and healthy tissues. Cells, including immune, fibroblast, endothelial, and epithelial populations, were isolated via flow cytometry (FACS) and analyzed at the transcriptomic level. Co-culture experiments were conducted to explore cellular-bacterial interactions in fibrosis progression, and fibrosis markers (alpha-SMA, vimentin, and FAP) in fibroblasts were evaluated through immunofluorescence (IF).

Results
Gene ontology analysis revealed activation of antimicrobial immune processes, indicating a targeted response to microbiota during fibrosis progression. Microbiota analysis showed an increased abundance of Roseomonas mucosa in CD patients compared to controls across multiple cell types (endothelial, epithelial, fibroblast, and immune cells). Moreover, fibroblast co-cultures with Roseomonas mucosa (50 MOI/cell) displayed elevated fibrosis markers in IF compared to unstimulated controls.

Conclusion
Our findings suggest that Roseomonas mucosa, or its products, may modulate the transcriptional state of mucosal cells, including fibroblasts, contributing to intestinal fibrosis. To further elucidate the role of bacterial proteins in the progression from healthy to fibrotic tissue, we are performing spatial transcriptomics analysis on ileo-cecal resection tissues, followed by RNA-scope with bacteria-specific probes. This integrative approach aims to map the temporal progression of fibrosis in relation to microbiota, offering deeper insights into its development.

References
1.Massimino, L. et al. The Inflammatory Bowel Disease Transcriptome and Metatranscriptome Meta-Analysis (IBD TaMMA) framework. Nat. Comput. Sci. 1, 511–515 (2021).
2.Watanabe, D. & Kamada, N. Contribution of the gut microbiota to intestinal fibrosis in crohn’s disease. Front Med (Lausanne) 9, 826240 (2022).
P0213 Salivary Veillonella parvula from Crohn’s Disease Patients Exacerbates Intestinal Inflammation
Authors: Xiang B , Hu J , Zhi M , Xu Z , Zhang M , Peng X 
Published: January 2025

Abstract

Background
The gut microbiota plays a significant role in the development of inflammatory bowel disease (IBD). There is a close interaction between the oral and gut microbiota. However, the role of the "oral-gut" microbial axis in the development of IBD is not yet clear.

Methods
1. Analyzed oral-gut microbiota patterns in 97 IBD patients using 16S rDNA sequencing and bioinformatics methods.
2. A mouse colitis model with DSS was used. It was gavaged with oral microbiota from CD patients to assess the impacts on colitis and gut microbiota.
3. Isolated specific differential bacteria, Veillonella, from CD patient saliva and evaluated their effects on DSS-induced colitis in mice.

Results
1. IBD patients had a reduced core gut microbiota, lower diversity (P &lt; 0.05), and increased abundance of potential pathogens such as Escherichia-Shigella.
2. CD patients showed more correlations between saliva and fecal microbiota, with the most significant correlation between Veillonella in saliva and Escherichia-Shigella in fecal (P=0.00018) .
3. The mice which were gavaged with saliva from CD patients showed significant weight loss (P &lt; 0.0001), reduced colon length (P=0.03), increased histopathological scores (P=0.01), decreased expression of colonic mucosal barrier proteins ZO-1 and E-cadherin, and exacerbated gut microbiota dysbiosis .
4. The mice which were gavaged with Veillonella parvula from CD patients showed significant weight loss (P &lt; 0.0001), reduced colon length (P=0.02), increased histopathological scores (P=0.02), decreased expression of colonic mucosal barrier proteins ZO-1 and E-cadherin, and exacerbated gut microbiota dysbiosis.

Conclusion
The interplay between the oral and gut microbiota potentially influences the progression of IBD, with oral bacteria such as Veillonella possibly intensifying intestinal inflammation in IBD patients by disrupting the gut microbiota balance. Targeted modulation of the gut microbiota and interference with oral-gut microbial interactions may offer a promising therapeutic strategy for managing IBD.
P0217 Colonic stromal cells are a source of sphingosine-1-phosphate and may be defining responsiveness to sphingosine-1-phosphate receptor modulators in Ulcerative Colitis
Authors: Drygiannakis I , Damianaki A , Filidou E , Theodoraki E , Coucoutsi C , Foteinogiannopoulou K , Spathakis M , Kandilogiannakis L , Dovrolis N , Kolios G , Valatas V , Koutroubakis I 
Published: January 2025

Abstract

Background
Sphingosine-1-phosphate (S1P) receptor (S1PR) modulators (S1PRMs) block chemotaxis of cells of immunity to the locus of inflammation. S1PRM effectiveness depends on the extent of the pathway activation. We explored the contribution of colonic stromal cells (CSC) to S1P production in patients with ulcerative colitis (UC) and healthy controls (HC).

Methods
We looked into the two S1P-producing kinases (SPHK1, SPHK2), the transporter exocytosing S1P (SPNS2) and the lyase degrading it (SGPL1). Basal mRNA transcription in primary CSC in culture from UC patients and from HC was assayed with quantitative reverse-transcription PCR. The effect of each one of the principal T helper (Th) 1 (ΤNF-α, IFN-γ), Th2 (IL-4, IL-13) or regulatory T (Treg; TGF-β, IL-10) cytokines was also tested. Medians of ΔΔCT and statistical significance between groups of unpaired, paired or between scale variables with Mann-Whitney, Wilcoxon or Spearman’s rho test, respectively, are reported.

Results
Eleven patients with UC (mean age: 49 years; 9 males; 7 with left-sided and 4 with extensive disease; mean UC duration: 180 months) and 9 HC were included. CSC from both UC and HC had a basal expression of SPHK1, slightly lower in UC (0.56x10-3 vs 2.18x10-3, p&lt;0.04), and of SPHK2 (8.04x10-4, 1.05x10-3, respectively). However, CSC from UC patients with an endoscopic Mayo component of 3 vs 2 and from UC patients with higher erythrocyte sedimentation rate expressed more SPHK1 (3.69x10-3 vs 0.45x10-3, p&lt;0.05; r 0.762, p&lt;0.04). Similarly, both UC and HC CSC expressed SPNS2 (5.96x10-5, 3.46x10-4, respectively) and SGPL1, with the latter overexpressed in UC (5.41x10-2 versus 2.68x10-3, p&lt;0.001).
CSC from UC, in sharp contrast with those from HC, were responsive to proinflammatory cytokines. In detail, SPHK1 was upregulated by TNF-α (x5 times, p&lt;0.034; Figure 1A). SPHK2 was downregulated by TGF-β (/3 times, p&lt;0.042). SPNS2 was downregulated by IFN-γ (/18 times, p&lt;0.001; Figure 2B) and by TGF-β (/8 times, p&lt;0.02; Figure 2B). SGPL1 was downregulated by IFN-γ (/16 times, p&lt;0.001; Figure 2C) and by IL-10 (/7 times, p&lt;0.04; Figure 2C).

Conclusion
In health and UC, CSC express the machinery synthetizing, exocytosing and catabolizing S1P. In UC the transcription of these genes is controlled by cytokines. Hence, activity of the pathway in CSC should be further investigated as a parameter to the direction of personalised treatment with S1PRMs in UC.
P0325 Is the augmentation index a good marker of cardiovascular risk in Crohn’s disease?
Authors: Fissah M , Rechach A , Charifi M , Menzou F , Djouhri M , Chibane A 
Published: January 2025

Abstract

Background
The axiom which defines that the high prevalence of cardiovascular risk factors is by definition correlated with the risk of cardiovascular events does not seem to apply to subjects with IBD, according to several studies which have reported that the prevalence of classic cardiovascular risk factors is lower in subjects with IBD than in the general population. This leads us to look for other markers to identify this risk at an early stage. The Augmentation index (Aix) is one such marker, based on the reflection of the pulse wave in the blood, and is a recognised measure of arterial stiffness and a risk factor for cardiovascular disease

Methods
This was a prospective cross-sectional study of 107 patients with Crohn’s disease (CD) diagnosed on the basis of clinical, endoscopic, morphological and histological criteria. Classical cardiovascular risk factors were analysed, as well as data concerning CD: duration, location, phenotype, clinical relapse, extradigestive manifestations, ano-perineal lesions (APL) and C-reactive protein (CRP). The augmentation index (Aix) was assessed using the SphygmoCor-XCEL Sydney. The Chi2 test was used for qualitative variables and the Kruskal Wallis test for quantitative variables. The informed consent of all patients was obtained.

Results
57.9% were men, mean age was 36.9 ± 11.7 years, 5.6% of patients had coronary heredity, 11.2% hypertensive, mean systolic blood pressure: 120.1 ± 12.7 mm/hg, mean diastolic blood pressure: 74.4 ± 8.1 mm/hg, pulse pressure: 45.7 ±9.3 mm/hg, AIx was positive in 31.8% of patients, 7.5% of women were postmenopausal, mean BMI was 22 ± 5.91 Kg/m2, 9.3% were obese, 11.2% were sedentary, 20.6% were active smokers, only two patients were diabetic. 57.9% had dyslipidaemia, and 13.1% had a low cardiovascular risk according to the Framingham score. 74% had an ileal location, 6.8% colonic and 19.2% ileocolic, 19.8% had an inflammatory form, 43,4% stenosing and 36,8% penetrating, 25.5% with ano-perineal lesions, 31.4% had an extradigestive manifestation, 59.4% of patients were in clinical relapse, 47.2% of whom had a CRP &gt; 6mg/l, 38% of subjects had had at least one relapse in the year prior to recruitment, and the mean duration of the disease was 57.3 ± 57 months. Statistical analysis showed a significant association between AIx and clinical relapse (p=0.03), disease duration (p=0.008), and no significant association with phenotype, location, APL, extradigestive manifestations and CRP (p&gt;0.05).

Conclusion
Our results suggest that the augmentation index could be a good tool for detecting subclinical cardiovascular damage in Crohn’s disease. Clinical relapse and the duration of the disease would be two predominant factors in the increase in this index
P0536 Clinical profile and treatment outcomes in patients receiving advanced therapies for ulcerative colitis – the READ-UC real-world study
Authors: Fernandes S R , Tavares de Sousa H , Portela F , Ministro P , Lago P , Branquinho D , Freitas I , Martins Machado N , Magro F 
Published: January 2025

Abstract

Background
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that requires effective treatment with the main goal of inducing and maintaining remission. This study aimed to characterize UC patients receiving advanced therapies (AT), by describing their demographic and clinical characteristics and remission outcomes.

Methods
Cross-sectional and retrospective study in 5 IBD referral centres. Eligible subjects (≥18 years-old with UC diagnosis and receiving AT for ≥16 weeks) were consecutively enrolled at a standard of care appointment (study appointment). The primary endpoints were the proportion of patients achieving remission, defined as both symptomatic [Mayo subscores stool frequency of 0 or 1 and rectal bleeding of 0] and faecal biomarker remission [faecal calprotectin &lt;150 µg/g]. Data on patients’ demographic and clinical characteristics, including extraintestinal manifestations (EIMs), comorbidities and treatment patterns, and on healthcare resource utilization were also collected.

Results
The study included 219 patients (50.9% female, median [P25;P75] age 46 [36;58] years) presenting a median disease duration of 9 [5;14] years. History or current evidence of EIMs and comorbidities were reported in 13.7% and 43.8% of patients, respectively. At diagnosis, 17.0% of patients had ulcerative proctitis, 38.1% had left-sided UC, and 44.8% had extensive UC. Over half (58.4%) were diagnosed with moderate or severe UC. Most patients (57.1%) were on their first AT, mostly on infliximab (47.5%) and vedolizumab (37.4%), while a minority received ustekinumab (5.9%), adalimumab (5.5%), tofacitinib (2.3%), and golimumab (1.4%). After treatment (26 [14; 47] months), symptomatic and faecal biomarker remission was achieved in 35.2% of patients, while 83.9% presented symptomatic remission and 46.1% of patients attained faecal biomarker remission (). There were no significant differences between patients who achieved symptomatic and faecal biomarker remission and those who did not (Table 1). Patients were prescribed concomitant specific therapies [5-ASA derivatives (78.0%), immunosuppressants (34.7%), and steroids (6.4%)]. Steroid-free remission was achieved in 34.9% of patients (Figure 1), who were off this medication for a median of 26 [15;45] months. Since AT initiation, 20.6% of patients relapsed, 11.9% were hospitalized, and 27.4% visited an emergency department.

Conclusion
The READ-UC study provides a detailed real-world characterization of UC patients on AT. The high proportion of patients not achieving symptomatic and faecal biomarker remission or steroid-free remission, highlights the urgent need for implementing strategies that improve UC management and outcomes of these patients.