bluuebunny/crossref_metadata_2025_split huggingface dataset:
P385 Epithelial neutrophil localization and Claudin-2 immunohistochemical "leaky gut" expression are innovative predictors of outcomes in Ulcerative Colitis patients in endoscopic remission
Authors: Zammarchi I , Santacroce G , Hayes B , Crotty R , O’Driscoll E , Kaczmarczyk W , Maeda Y , McCarthy J , Sugrue K , O’Sullivan C , Burke L , Ghosh S , Iacucci M 
Published: January 2024

Abstract

Background
Patients with Ulcerative Colitis (UC) in clinical and endoscopic remission (ER) may still experience disease relapse, emphasizing the need to identify reliable predictors of outcome in clinical practice. Recently, neutrophil-based histological scores have highlighted the pivotal role of neutrophils in predicting disease outcome. Furthermore, the impairment of the intestinal barrier has been proposed as a crucial element in forecasting disease outcomes. Hence, this study aims to assess the predictive role of epithelial versus lamina propria neutrophil localization and barrier proteins expression in UC patients in ER.

Methods
UC patients in clinical remission who underwent colonoscopy between January 2020 and June 2022 at two tertiary referral centres were retrospectively enrolled. Patients in ER, defined by Mayo Endoscopic Score (MES) ≤1 and UC Endoscopic Index of Severity (UCEIS) ≤1 were included. Histological activity was assessed with Robarts Histopathology Index (RHI), Nancy Histological Index (NHI) and PICaSSO Histological Remission Index (PHRI). Neutrophil localization in the epithelium and lamina propria was accurately evaluated. Additionally, immunohistochemical expression of epithelial barrier proteins, namely Claudin-2 and JAM-A, was assessed to evaluate the integrity of intestinal barrier. Two pathologists experienced in IBD independently analysed all histological slides to ensure reliability. Kaplan-Meier were plotted to analyse survival free from adverse events such as flare-up, change/optimization of medication or hospitalization over a 12-month follow-up period.

Results
Out of 60 UC patients in ER (58.3% males, mean age 44.2±13.6 years), 36.7%, 38.3% and 36.7% were in histological remission according to RHI, NHI and PHRI, respectively. 25% of patients developed an adverse outcome within 12 months. Neutrophils in the epithelium significantly correlated with adverse outcomes compared with lamina propria localization (p=0.03) or their absence altogether (p&lt;0.01). Claudin-2 showed significantly higher expression according to endoscopic and histological activity (Table 1), while no significant difference was found for JAM-A. Notably, strong and diffuse claudin-2 expression was associated with a higher rate of adverse outcomes (p&lt;0.01), as well as the simultaneous presence of epithelial neutrophils and Claudin-2 (p=0.04). Substantial agreement between pathologists was found (K=0.67).

Conclusion
This multicentre retrospective study highlights the potential role of epithelial neutrophils localization and claudin-2 ‘leaky gut’ protein expression as practical clinical tools to predict outcomes in UC patients. These findings hold promise in guiding patient-tailored therapy in IBD.
P421 The faecal biomarker LDN-051 is a novel tool for monitoring disease activity and therapeutic response in Inflammatory Bowel Diseases
Authors: Jójárt B , Resál T , Diána K , Molnár T , Bacsur P , Szabó V , Varga Á , Szántó K J , Pallagi P , Földesi I , Molnár T , Maléth J , Farkas K ,   HCEMM-USz Molecular Gastroenterology Research Group
Published: January 2024

Abstract

Background
Crohn’s disease and ulcerative colitis, two forms of inflammatory bowel disease (IBD) require lifelong treatment and patient monitoring. Current predictors of relapse and therapeutic success have limitations, therefore there is high unmet need to identify novel biomarkers in IBD. Monitoring approaches for IBD are mostly invasive, time-consuming, and expensive. Therefore, a simple, rapid, and non-invasive test, with ability to differentiate IBD from other gastrointestinal conditions and to monitor disease activity, will have important clinical implications. Our previous mucosal cytokine profiling identified that Plasminogen activator inhibitor type 1 (PAI-1) is expressed in IBD patients with active disease, but not in control. Therefore, our aim was to assess the utility of PAI-1 in monitoring disease activity and therapeutic response of IBD patients in different biological samples.

Methods
Serum, biopsy and faecal samples were collected from 132 IBD patients and 30 controls without IBD. ELISA method was used to define the level of PAI-1 in the mucosa, serum, and faecal samples and the serum CRP levels were also determined. For the mucosal gene expression analysis qRT-PCR was used. The correlation and ROC analyses were applied to observe the relationship between the disease activity and PAI-1 level.

Results
The applied screening approach detected significant higher expression of PAI-1 in active IBD. We demonstrated that the serum, mucosal and faecal PAI-1 concentration was significantly elevated in IBD patients showing clinical and endoscopic activity. Additionally, in responder patients the initial PAI-1 level decreased significantly upon successful therapy, whereas it remained unchanged in non-responders. We also showed that faecal PAI-1 selectively increases in active IBD patients, but not in other organic gastrointestinal diseases. In addition, the stability analysis of faecal PAI-1 showed that the protein was detectable up to one week at room temperature and 4ºC. The serum, mucosal and faecal PAI-1 level showed positive correlation to the endoscopic activity. ROC curves demonstrated that faecal PAI-1 showed a relatively high power to distinguish between active and control patients. However, the serum CRP level no reflected to the therapeutic response.

Conclusion
Our results suggest that serum, mucosal and faecal PAI-1 expression reflects to the disease activity in IBD, which could be used to disease monitoring and possibly therapeutic response. The correlation between the faecal PAI-1 level and the endoscopic activity promotes that it could be used as a novel non-invasive disease specific faecal biomarker in the IBD diagnosis.
P447 Anti-αvβ6 integrin antibody as a novel serum biomarker for diagnosis of ulcerative colitis; a nation-wide multicenter validation study in Japan
Authors: Okabe M , Yamamoto S , Kitamoto H , Kuwada T , Shiokawa M , Yamazaki H , Seno H ,   UCV6 Dx Study Group
Published: January 2024

Abstract

Background
There is no established diagnostic biomarker for ulcerative colitis (UC). Although we recently reported an anti-αvβ6 integrin antibody to diagnose UC, there is no large-scale validation study on this antibody to diagnose UC. This study aimed to validate the diagnostic value of anti-αvβ6 integrin antibody for UC in a nation-wide, multicenter cohort (UCV6-Dx Study).

Methods
We enrolled 1241 UC patients, 798 Crohn’s disease (CD) patients, and 207 other gastrointestinal disease patients from 28 Japanese high-volume referral centers. Anti-Integrin αvβ6 ELISA Kit (MEDICAL & BIOLOGICAL LABORATORIES CO., LTD., Tokyo, Japan) was used to measure the titer of anti-αvβ6 integrin antibody. The cut-off value was 1.64 U/mL (the mean +3SD of 83 serum samples from healthy volunteers determined by the manufacturer). The primary outcome was the diagnostic value of the anti-αvβ6 integrin antibody. Secondary outcomes were factors associated with false negative results in UC patients, factors associated with false positive results in non-UC patients, and the optimal cut-off values using receiver operating characteristic (ROC) analysis.

Results
The diagnostic sensitivity of the anti-αvβ6 integrin antibody in UC was 87.7% and the specificities were 82.0% in CD and 87.4% in other gastrointestinal diseases. Multivariate logistic regression analysis showed that false negative results in UC patients were associated with age at the time of sample collection [odds ratio (OR) 1.0242, p=0.034, 95% confidence interval (CI) 1.0018-1.0470], smoker (OR 2.5504, p=0.002, 95% CI 1.4216-4.5755), partial Mayo score (OR 0.8623, p=0.038, 95% CI 0.7495-0.9921), and advanced therapies (OR 0.5875, p=0.019, 95% CI 0.3765-0.9167) and false positive results in CD patients with disease location L2 (OR 2.6858, p=0.013, 95% CI 1.2323-5.8533). No factor was associated with false positive results in patients with other intestinal diseases. ROC analysis revealed that the optimal cut-off values estimated by the Youden method were 2.07 U/mL [area under the curve (AUC) 0.9003, sensitivity 85%, specificity 87%], and 1.78 U/mL (AUC 0.9206, sensitivity 87%, specificity 89%) for discriminating UC from CD and other gastrointestinal diseases, respectively.

Conclusion
The usefulness of anti-αvβ6 integrin antibody for diagnosing UC was validated in the Japanese large-scale, nation-wide multicenter study.
P456 Pragmatic trial design to compare real-world effectiveness of different treatments for inflammatory bowel diseases: the PRACTICE-IBD international consensus
Authors: Fantini M C , Fiorino G , Colli A , Laharie D , Armuzzi A , Caprioli F A , Gisbert J P , Kirchgesner J , Macaluso F S , Magro F , Ghosh S ,   The PRACTICE-IBD study group: Matthieu Allez Aurelien Amiot Raja Atreya Manuel Barreiro-de Acosta Livia Biancone Fabiana Castiglione María Chaparro Axel Dignass Glen Doherty Eugeni Domènech Walter Fries Jonas Halfvarson Uri Kopylov Sara Onali Daniela Pugliese Davide Giuseppe Ribaldone Simone Saibeni Edoardo Vincenzo Savarino
Published: January 2024

Abstract

Background
Pragmatic studies designed to test interventions in everyday clinical settings can successfully complement the evidence from registration and explanatory clinical trials. The international consensus project PRACTICE-IBD was developed to identify essential criteria and address key methodological issues needed to design valid comparative pragmatic studies in inflammatory bowel diseases (IBDs).

Methods
Statements were issued by a panel of 11 European experts in IBD management and trial methodology on four main topics: (I) study design; (II) eligibility, recruitment and organization, flexibility; (III) outcomes; (IV) analysis. The consensus process followed a modified Delphi approach, involving two rounds of assessment and rating of the level of agreement (1 to 9; cut-off ≥7 for approval) with the statements by 18 additional European experts in IBD (Fig.1)

Results
At the first voting round, 25 out of the 26 statements reached a mean score ≥7. Following the discussion that preceded the second round of voting, it was decided to eliminate two statements and to split one into two. At the second voting round, 25 final statements were approved: 7 for study design, 6 for eligibility, recruitment and organization, flexibility, 8 for outcomes, and 4 for analysis (Table 1).

Conclusion
Pragmatic randomized clinical trials can address important questions in IBD clinical practice, and may provide complementary high-level evidence, as long as they follow a methodologically rigorous approach. These 25 statements intend to offer practical guidance in the design of high-quality pragmatic clinical trials that can aid decision making in choosing a management strategy for IBDs.
P472 A Real World Practice of Intestinal Ultrasound in the Monitoring of Disease Activity in Ulcerative Colitis
Authors: Kim K W , Lee C H , Lee T , Kim S , Han Y M , Lee H J , Yoon H , Kang H W , Im J P , Kim J W , Park Y S , Kim J S , Koh S J ,   Seoul National University Inflammatory Bowel Disease Research Network (SIRN)
Published: January 2024

Abstract

Background
Intestinal ultrasound (IUS) has emerged as an important monitoring tool in the clinical course of ulcerative colitis (UC). Previously known factors about UC have been considered in terms of the associations with IUS. However, a few studies reported about the associations between the findings of IUS and clinical factors.

Methods
We performed a multi-center, cross-sectional study of patients with UC who received IUS and clinical exams including endoscopy simultaneously. The primary endpoint was the association between endoscopic disease activity as Mayo endoscopic score (MES) and IUS finding as Milan ultrasound criteria (MUC). The secondary endpoint comprised the various clinical factors associated with MUC. Patients with MUC&lt;6.2 were defined as low MUC group and others as high MUC group.

Results
A total of 35 patients were enrolled in this study. The numbers of Low- and high-MUC groups were 23 and 12, respectively. The median age in each group was 41 and 53 years old. The portion of male sex in each group was 57% and 75%. There were no significant differences in terms of body mass index, onset age, disease duration, current medication such as 5-aminosalicylic acid, steroid, immunomodulator, and biologics and small molecules between both groups.
Compared with low and high MUC groups, endoscopic remission was more significantly associated with the low MUC group than the high MUC group (35% vs. 0, p = 0.032). In addition, the rate of disease activity ranged from remission to mild, as tolerable clinical activity, was also significantly higher in the low MUC group than the high MUC group (91% vs. 58%, p = 0.033). Other outcomes such as symptomatic remission, histologic remission, and biochemical response revealed similar rates between the two groups.

Conclusion
Low MUC of IUS in the patients with UC showed significant clinical association such as endoscopic remission and tolerable clinical activity. This study is now ongoing prospective research and further investigation into the relationship between IUS and clinical outcomes of UC will elicit robust results.
P502 Multimodal profiling of peripheral blood identifies proliferating circulating effector CD4 T cells as predictors for response to integrin alpha4 beta7-blocking therapy in patients with Inflammatory Bowel Disease
Authors: Horn V , Cancino C , Steinheuer L , Obermayer B , Fritz K , Siegmund B , Thurley K , Hegazy A N ,   TRR241 IBDome Consortium
Published: January 2024

Abstract

Background
Despite the success of biological therapies in inflammatory bowel disease (IBD), patient management remains challenging due to a lack of therapy response predictors.

Methods
Here we prospectively sampled two cohorts of IBD patient cohorts receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry, single-cell RNA sequencing, single-cell V(D)J sequencing, serum proteomics, and multidimensional flow cytometry to comprehensively assess vedolizumab-induced immunological changes in the peripheral blood and their potential associations with treatment response.

Results
Vedolizumab induced changes in the abundance of both circulating innate and adaptive immune cell compartments and modified the T cell receptor diversity of circulating gut-homing CD4+ memory T cells. Through integration of multimodal parameters and machine learning, we identify that pretreatment activated proliferating CD4+ memory T cell abundance is associated with treatment failure, independent of clinical variables, thereby providing a reliable predictive classifier with significant implications for the personalized management of IBD patients.

Conclusion
Our study provides a comprehensive framework for assessing therapy response and understanding the mechanisms underlying resistance in chronic immune-mediated inflammatory diseases such as IBD. Identifying personalized treatment strategies based on individual patient characteristics, as exemplified by our "stratify to target" approach, can significantly improve IBD management.
P538 Platelet-rich stroma during surgery for treatment-refractory perianal fistulizing Crohn’s disease: long-term outcomes of a pilot study
Authors: Bak M , Witjes C , Arkenbosch J , Dwarkasing R , van Dongen J , Fuhler G , Schouten R , van der Woude J , de Vries A , van Ruler O 
Published: January 2024

Abstract

Background
Platelet-rich stroma (PRS), a combination of stromal vascular fraction and platelet-rich plasma, proved to be safe and feasible for the treatment of treatment-refractory perianal fistulizing Crohn’s disease (pCD). This study aimed to assess the long-term outcomes in patients with pCD treated with PRS.

Methods
Long term results from adult patients with pCD, who underwent fistula curettage, closure of the internal fistula opening and PRS injection, included in an earlier conducted pilot study (n=25) were assessed up to October 2023. The primary outcome was complete clinical closure at long-term follow-up (closure of all treated external opening[s]). Secondary outcomes comprised complete radiologic closure (absence of fluid-containing tracts on MRI), partial clinical closure (closure of ≥ 1 treated external opening[s]), recurrence (reopening of the external opening after complete clinical and/or radiological closure) and the need for unplanned re-intervention(s).

Results
The majority of the patients was female (56.0%)(mean age 34.4 years [SD: 0.9], and mean follow-up 3.7 years [SD: 0.6])(Table 1). 68% of the patients were concomitantly treated with a biological. During follow-up, ≥1 unplanned re-intervention(s) were necessary in 44% of the patients which were minor (e.g. incision and drainage) in the vast majority (83%)(Table 2). Complete clinical closure at long-term follow-up was reached in 88%. Complete radiologic closure was reached in 75% of patients. Partial clinical closure was reached in all patients (100%). Recurrence was reported in 8% of patients, all whom reached (partial/complete) clinical closure, whereas no recurrence was experienced in patients with complete closure on MRI. All patients with complete radiologic closure achieved clinical closure. Vice versa, patients with clinical closure achieved complete radiologic closure in 82% of the cases.

Conclusion
In this pilot study with treatment-refractory pCD patients treated in a tertiary referral center, all patients had benefit from surgical treatment and an additional injection of PRS. At long-term follow-up, treatment with PRS injection during surgery is promising as complete clinical and radiological closure is achieved in the majority of these patients. In addition, complete radiologic closure seems a valuable prognostic parameter for long-term success for fistula closure. Future (randomized) research is warranted to further assess the effectiveness of PRS in patients with pCD.
P612 Switching from intravenous to subcutaneous VEDOlizumab formulation in ulcerative colitis patients in clinical remission: the SVEDO Study, a multicenter IG-IBD study
Authors: Ribaldone D G , Parisio L , Variola A , Bossa F , Castiglione F , Marzo M , Piazza N , Aratari A , Savarino E V , Bodini G , Mastronardi M , Micheli F , Mazzuoli S , Ascolani M , Viganò C , Cappello M , Bezzio C , Ciccocioppo R , Scardino G , Sarli E , Pugliese D , Scaldaferri F , Napolitano D , Todeschini A , Geccherle A , Colaci N , Guerra M , Annese M , Testa A , Caiazzo A , Conforti F S , Festa S , Lorenzon G , Marra A , Magiotta A , Baccini F , Amato A , Vernero M , Caprioli F , Caviglia G P ,   Italian Group for the study of Inflammatory Bowel Disease (IG-IBD)
Published: January 2024

Abstract

Background
The administration of biologic drugs in inflammatory bowel diseases (IBD) is increasingly moving from intravenous to subcutaneous formulations. Limited data is available on the effectiveness of subcutaneous vedolizumab in patients switching from long-term intravenous therapy. The aim of the study was to evaluate the efficacy and safety of vedolizumab subcutaneous administration after switching from intravenous administration in ulcerative colitis patients in corticosteroid-free clinical remission.

Methods
An observational, multicentre, prospective study was conducted by the Italian Group for the study of IBD in Italy (IG-IBD). Ulcerative colitis patients in clinical remission (pMAYO &lt; 2) not receiving steroids for &gt; 8 months before the switch, and with at least 6 months of follow-up were included. Switch from intravenous to subcutaneous vedolizumab was defined as successful in patients not experiencing a disease flare (pMAYO ≥ 2) or needing oral steroids or stopping vedolizumab during the 6 months of follow-up after the switch.

Results
One hundred sixty-eight patients were included. The switch was a complete success in 134 out of 168 patients (79.8%). In particular, vedolizumab retention rate was 88.7% at month six. No predictor of complete switch success was found at multivariate analysis. C-reactive protein and faecal calprotectin values did not significantly change after the switch (p = 0.07 and p = 0.28, respectively). Ten of the 19 patients who stopped subcutaneous formulation switched back to intravenous formulation, with a success in recapturing clinical remission in 80%. Twenty-two out of 168 patients (13.1%) experienced side effects while on subcutaneous formulation, including 4 cases of rheumatological side effects, 4 cases of injection site reactions, 3 allergic reactions, 3 cases of cancers.

Conclusion
Effectiveness of switching from intravenous to subcutaneous vedolizumab formulation in UC patients in steroid-free clinical remission is confirmed in a real-world setting.
P613 Dietary intervention as a novel tool to improve diagnostic accuracy of patency capsule in Crohn’s Disease patients
Authors: Talan Asher A , Lahat A , Ukashi O , Yablecovitch D , Engel T , Shachar E , Selinger L , Ungar B , Kopylov U , Eliakim R , Ben- Horin S ,   for the Israeli IBD Research Nucleus (IIRN)
Published: January 2024

Abstract

Background
Patency capsule (PC) is recommended to confirm the patency of the small bowel before ingestion of video capsule endoscopy (VCE). However, in some patients non-expelled PC could be due to slow transit time and not due to small bowel stricture. We examined if dietary intervention during the PC could improve passed PC rate and reduce false positive results.

Methods
A retrospective study of patients who received diet-modified protocol of PC test, introduced into routine clinical practice on February 2023, compared with standard protocol. Dietary-modification comprised individualized dietary advice on the consumption of personally-conceived laxative foods after PC ingestion. Abdominal X-ray at 30 hours post-ingestion was performed to ascertain passage of PC in patients who did not see an intact PC in stool, followed by low-dose limited computed tomography (CT) in patients with evident PC on X-ray to assure passage to colon.

Results
A total of 52 Crohn's patients who ingested PC were included (median age 32.4, 28.8% with previous intestinal resection). 26 of the patients followed the dietary-modified personalized protocol and 26 followed the standard protocol. In total, 38/52 PC passed and 14/52 (26.9%) failed. Patients on dietary modification had significantly reduced rate of a failed PC compared to patients receiving standard protocol (7.7% versus 46.1%, respectively, odds ratio 0.1, 95% confidence interval 0.02-0.49, P=0.005). 12/14 patients with a failed PC underwent low-dose CT, which showed PC was in the colon (false positive PC) in 11/12 patients (92%, 9/11 in standard group, 2/11 in dietary group). All 11 patients with a passed PC in colon subsequently ingested a VCE without complications.

Conclusion
Majority of failed PC are falsely positive, stemming from slow-transit of PC in the colon. Personalized dietary intervention to promote colonic transit may serve as a novel practical tool to reduce false positive tests and improve the diagnostic accuracy of patency capsule.