bluuebunny/crossref_metadata_2025 huggingface dataset:
P065 Altered B cell expansion and maturation in Crohn’s disease
Authors: Kappel-Latif S , Kotagiri P , Schuld G , Schlager L , Walterskirchen N , Schimek V , Jobst J , Murthy S , Messner B , Lyons P A , Oehler R , Bergmann M , Stift A , Unger L
Published: January 2023

Background

One of the hallmarks of Crohn’s disease (CD) is mesenteric thickening, accompanied by enlarged draining lymph nodes (LNs) in the affected areas. Descriptive studies imply that lymphatic architecture is altered in affected areas. Additionally, an altered IgA and IgG response towards commensal bacteria in CD patients compared to healthy controls has been described. Thus, we set out to investigate the B cell response in draining lymph nodes of patients with CD undergoing surgery.

Methods

We prospectively collected draining lymph nodes and serum samples in patients with Crohn’s disease during intestinal resections. LNs of affected and adjacent unaffected intestinal segments were processed for phenotyping by flowcytometry (n=18) and B cell receptor (BCR) sequencing (n=24). Histological analysis was performed to investigate size and number of germinal centers in affected and unaffected areas (n=10). Serum samples were collected from patients with CD undergoing surgery (n=18), and healthy individuals (n=16). The study was approved by the local ethics committee (EK #1480/2016) and all patients prospectively gave their written informed consent to participate in the study.

Results

Affected draining LNs showed a significantly increased fraction of CD45+CD19+ B cells (p=0.0055) compared to unaffected LNs. Fractions of double negative B cells (p=0.0394) and plasmablasts (p=0.0126) were significantly increased, and memory B cells significantly decreased (p=0.0127) in affected draining lymph nodes, respectively. Histological analysis revealed no difference in the numbers of germinal centers per high power field, but a significantly increased germinal center size (p<0.001). BCR sequencing demonstrated a reduction in IGHA (p<0.001) and IGHE (p=0.031), and a significant increase in IGHG1/2 (p<0.001) in affected LNs compared to unaffected LNs. Analysis of somatic hypermutation of BCRs and diversity analysis showed no significant increase in somatic hypermutation in IGHG1/2, and diversity analysis indicated significant diversity in specificity. Serum IgA of patients with CD recognized a significantly greater fraction of commensals in CD patients, and IgG binding towards commensals was almost universally detectable in CD patients but absent in healthy controls.

Conclusion

Our data indicate that a pathological IgG response in patients with severe disease is directed towards a broad set of antigens, most likely stemming from commensals. Additionally, expansion only at the site of inflammation may indicate a triggered immune response due to a leaky intestinal barrier. The relevance of pathological IgG antibodies on disease recurrence following surgery needs to be addressed in future studies.
P073 Let′s talk about sex: an unicentric cross-sectional study on sexual dysfunction, sexual satisfaction and body schema disorders in Inflammatory Bowel Disease
Authors: Lindenthal D , Kranzeder A , Hirning C , von Wietersheim J , Klaus J
Published: January 2023

Background

Patients with Inflammatory Bowel Disease (IBD) suffer from a variety of physical and psychological symptoms. Especially sexual health is an often underestimated but leading concern among patients. Despite its major impact, there has been little systematic research on this topic in the past. The aim of this study was to investigate sexual dysfunction, sexual satisfaction and body schema disorders in patients with IBD compared to a healthy control group.

Methods

A cross-sectional unicentric study was performed. 123 patients with IBD and 71 population controls were recruited for 12 months. Inclusion criteria for the patient group included a diagnosed IBD (Crohn's Disease or Ulcerative Colitis), age between 18 - 65 years and sufficient language skills to complete the questionnaires. For the control group inclusion criteria were similar but without a diagnosed IBD. Data was collected using standardised questionnaries (IBDQ, IBD-F, pMS, HBI, IIEF, BISF-W, FKKS, PHQ15, PHQ9, HADS-D). Sexual dysfunction, sexual satisfaction and body schema disorders were mainly assessed by the „Frankfurter Körperkonzeptskalen“ (FKKS) and „The Brief Index of Sexual Functioning for Women“ (BISF-W).

Results

Significant differences (p < 0.05) could be found within the individual questionnaire scales. Regarding the FKKS, the control group scored higher in three of the nine scales: Health and physical condition scale (SGKB), Sexuality scale (SSEX) and Body self-acceptance scale (SSAK). A similar result was also shown in the BISF-W: population controls had higher scores in two of the seven dimension scores: "Arousal" (D2) and "Pleasure/Orgasm" (D5). Overall, when comparing the total scores of FKKS and BISF-W between patients and population controls no remarkable distinctions were identified.

Conclusion

Sexual health seems to be impaired in patients with IBD. Patients suffer from reduced sexual arousal, orgasmic sensation and physical well-being. In addition, they are also more inhibited in sexual contact with their partners and devalue their own body in terms of aesthetics and biological functionality. Overall, these results can help to understand the disease′s complexity considering not only clinical but also psychological factors regarding sexual well-being and point to new therapeutical directions.
P074 Interferon-γ promotes antigen processing and presentation pathway in the intestinal epithelium of patients with Crohn’s disease
Authors: Hong S N , Lee C , Kim J E , Kim E R , Chang D K , Kim Y H
Published: January 2023

Background

Interferon-γ (IFN-γ) is a major driver of excessive immune response, leading to intestinal mucosal damage and contributing the pathogenesis of Crohn’s diseases (CD). In contrast to the inflammatory cells and immune system, IFN-γ-induced cellular responses has not been well documented in the intestinal epithelium. The intestinal epithelium consists of multiple cell types and patient-derived intestinal organoid model may be appropriate to evaluate the IFN-γ-induced epithelial cellular responses in patients with CD.

Methods

To evaluate the IFN-γ-mediated epithelial cellular responses, human small intestinal organoids (enteroids) derived from the controls (n=6) and patients with Crohn’s disease (CD, n=10) were constructed. We focused on the IFN-γ-induced cell death mechanism upregulated in CD enteroids and validated them in surgically resected small intestine in patients with active CD.

Results

As the concentration of IFN-γ increased in the culture medium, the organoid-forming efficiency decreased steadily, which did not differ between control and CD enteroids. The enteroid viability measured using MTT was estimated to be 83.10 pg/ml for EC50. In control and CD enteroids treated with 100 pg/ml IFN-γ, PANoptosis was the main inflammatory cell death mechanism. Bulk and single-cell RNA sequencing revealed that IFN-γ induced the expression of MHC class II-associated genes, co-inhibitory molecule CD274 (PD-L1), and IDO1 in control and CD enteroids, which may be associated with peripheral tolerance in the absence of exogenous antigens. Gene set enrichment analysis identified an up-regulated antigen processing and presentation pathway with increased expression of MHC class I molecules in IFN-γ-treated CD enteroids compared to IFN-γ-treated control enteroids (normalized enrichment score=2.13, p=0.002, q=0.005). IFN-γ-induced MHC class I pathway could result in T cell-mediated cytotoxicity in CD enteroids. The selective JAK1 inhibitor, upadacitinib, inhibited the IFN-γ-induced PANoptosis and T cell-mediated cytotoxicity in CD enteroids. The expression of HLA-A and B was higher in the inflamed small intestine in patients with CD than those in patients with ischemic enteritis.

Conclusion

IFN-γ promotes antigen processing and presentation pathway in the intestinal epithelium. In patients with CD, increased expression of MHC class I molecules may induce T cell-mediated cytotoxicity, which could contribute to the development of CD.
P106 Identification of urine and serum diagnostic biomarkers of inflammatory bowel disease using a proteomic approach
Authors: Baldan-Martin M , Azkargorta M , Lloro I , Soleto Fernández I , Orejudo M , Ramírez C , García S , Mercado J , Riestra S , Rivero M , Gutiérrez A , Rodríguez-Lago I , Fernández-Salazar L , Ceballos D , Benítez J M , Aguas M , Bastón-Rey I , Bermejo F , Casanova M J , Lorente R , Ber Y , Royo V , Esteve M , Elortza F , Gisbert J P , Chaparro M
Published: January 2023

Background

Inflammatory bowel diseases (IBD) are chronic, heterogeneous, and inflammatory conditions mainly affecting the gastrointestinal tract. Currently, endoscopy is the gold standard test for assessing mucosal activity and healing in clinical practice; however, it is a costly, time-consuming, invasive, and uncomfortable procedure for patients. There is, therefore, a need for sensitive, specific, fast and non-invasive biomarkers for the diagnosis of IBD.

Methods

Label-free quantification by nanoscale liquid chromatography coupled to tandem mass spectrometry (nLC MS/MS) was performed to profile the urinary and serum proteomes of 100 patients with newly diagnosed IBD, before starting any treatment [50 patients with Crohn′s disease (CD) and 50 patients with ulcerative colitis (UC)] and 50 healthy controls (HC). Data Mining and Pattern Recognition techniques were used to identify hidden relationships that are not detectable by using the classical and most commonly used lineal classifiers; and thus, identifying potential markers able to discriminate the studied cohorts. Finally, we applied Ingenuity Pathway Analysis (IPA) to analyze the pathways and functions of differentially expressed proteins.

Results

Serum proteomics results revealed 45 differentially expressed proteins in the comparison between UC and HC groups, 32 proteins significantly expressed in CD versus HC, and 12 proteins in CD compared with UC. In urine samples, 110 proteins were significantly changed in UC versus HC, 50 proteins were differentially expressed between CD and HC, and a total of 31 proteins were significantly changed in CD compared with UC patients. Receiver operating characteristic curve (ROC) analysis found multiple proteins with high area under the curve values, up to 0.94, indicating that these serum and urine proteins are of value as new non-invasive diagnostic classifiers of IBD patients. For each study comparative, the 5 most significant classifiers were selected (Figures 1 and 2). IPA revealed multiple signaling pathways, including prothrombin activation, acute phase response signaling, complement and coagulation system and liver X receptor/retinoid X receptor (LXR/RXR) activation, altered in IBD patients compared to HC (p-value < 0.05) (Figures 3 and 4).

Conclusion

Our findings indicate that analysis of the urine and serum proteome using nLC MS/MS is a feasible approach for biomarker discovery. We identified several serum and urine proteins that could serve as new non-invasive markers for the diagnosis of IBD patients after further validation. After bioinformatic analyses, we found multiple proteins that may play important roles in the pathogenesis of IBD.
P108 Development and evaluation of the i-Tracker Risankizumab and i-Tracker Anti-Risankizumab kits: rapid and innovative tests intended for monitoring patients treated with Risankizumab.
Authors: Khater G , Noguier G , Daviere S , Montaillier C , Guilbert V
Published: January 2023

Background

Risankizumab is a human monoclonal antibody directed against the cytokine IL-23. This drug is commonly used for the treatment of patients with chronic inflammatory diseases such as psoriasis. Risankizumab is about to get an indication in Crohn’s disease and Ulcerative Colitis. Theradiag has just developed new rapid (results in less than 40 minutes) and innovative assays allowing the quantification of Risankizumab: these tests are available on the new innovative i-Track10 chemiluminescence platform and allowing the rapid quantification of Risankizumab as well as anti-Risankizumab antibodies induced by the patient.

Methods

The analytical performance was studied using two types of samples: human serum samples spiked with Risankizumab or anti-Risankizumab antibodies, and human serum samples from patients with inflammatory diseases treated with Risankizumab. For drug assay, Risankizumab was captured using IL-23-coupled magnetic microparticles and detected using an acridinium ester-conjugated anti-Risankizumab polyclonal antibody. For the assay of anti-Risankizumab antibodies, microparticles coupled to Risankizumab were used. The anti-Risankizumab antibodies thus captured were detected by Risankizumab conjugated to the acridinium ester. Light emission from acridinium ester conjugates is directly related to the amount of Risankizumab or anti-Risankizumab antibodies present in the sample.

Results

The quantification of Risankizumab by the i-Tracker Risankizumab kit shows very good accuracy (the percentages of recovery are between 84% and 108%). The intra-test and inter-test reproducibility is very good (CV <7.3% for the Risankizumab assay and CV <8.0% for the anti-Risankizumab antibody assay). No interference from biological agents (bilirubin, hemoglobin, triglycerides, rheumatoid factors) was detected. The assay measurement ranges are 1 µg/mL to 80 µg/mL for Risankizumab and 10 ng/mL to 2000 ng/mL for anti-Risankizumab antibodies.

Conclusion

The i-Tracker Risankizumab and anti-Risankizumab kits are rapid tests (results obtained in less than 40 minutes) and highly accurate. Monitoring Risankizumab plasma levels could provide clinicians with relevant information to improve treatment efficacy.
P114 Increased serum levels of the migraine biomarker calcitonin gene related peptide alpha in a newly diagnosed inflammatory bowel disease population: a new mediator for the gut-brain-axis
Authors: Pascual M , Gárate G , Serrano M S , García García M J , Castro B , González Quintanilla V , Crespo J , Rivero M , Pascual J
Published: January 2023

Background

Calcitonin gene related peptide (CGRP) is known to be the most potent vasodilator of the body, and it promotes migration of inflammatory cells. CGRPβ isoform is located along the enteric nervous system, and CGRPα is mainly present in the central nervous system. CGRPα is known to be the key molecule in migraine, an entity with digestive symptoms. It has been suggested that migraine prevalence is increased in inflammatory bowel disease (IBD).

The aim of the study was to assess CGRPα serum levels in patients with newly diagnosed of IBD, stratified by migraine diagnosis, to unravel its potential role in the disease.

Methods

CGRPα serum concentrations were measured by ELISA (CUSABIO, China) in early morning samples of newly diagnosed patients with IBD. Classification of the disease (ulcerative colitis- UC, Crohn’s disease- CD or unclassified inflammatory bowel disease- U-IBD), demographic data and treatment during sample collection were also collected. To establish a migraine diagnosis, patients were interviewed about prior migraine diagnosis and validated ID-migraine questionnaire was used to diagnose patients with migraine. The results were compared with healthy controls (HC) matched by age and sex. Statistical analysis was performed using SPSS and CGRPα levels were compared with Mann-Whitney and Dunn’s tests.

Results

Sixty-two patients with newly diagnosed IBD (mean age 47.9±16.3 years, 62.5% females) were matched with 71 HC (mean age 48.2±16.7 years, 64.8% females). Samples were collected between 0 and 249 days after IBD diagnosis was stablished (median 50.5 days, interquartile range 26.75-64.5 days).

We included 27 patients with CD, 31 with UC and 4 with U-IBD. Baseline characteristics are shown in table 1. Fifteen female patients met migraine criteria (22.7%).

Serum CGRPα levels in patients with IBD were significantly increased (59.7±26.3 pg/mL), compared to HC (43.6±25.3 pg/mL, p<0.0001). CGRPα remained significantly elevated as compared to HC both in IBD patients with migraine (74.8±27.3 pg/mL, p< 0.001) and without migraine (58.6±24.4 pg/mL, p<0.05), though those with migraine were significantly increased as compared to IBD patients without migraine (p<0.05). These results are shown in figures 1 and 2.

Conclusion

Serum CGRPα levels are increased in patients with IBD, regardless of migraine diagnosis, which could indicate a role of this peptide in the pathophysiology of IBD. These results, and especially the higher levels in IBD patients with migraine, suggest a bidirectional, shared pathophysiology between migraine and IBD, which could be a further example of the clinical relevance of the gut-brain axis. Supported by Instituto de Salud Carlos III (PI20/01358).
P116 RIPK3 - a new marker for assessment of ulcerative colitis severity
Authors: Panayotova E , Atanassova A
Published: January 2023

Background

Necroptosis is a novel form of regulated necrotic cell death that is dependent on Receptor interacting protein kinase-3 (RIPK3). It leads to cell lysis and directly triggers inflammation. Several clinical and preclinical studies have implicated necroptosis in the etiopathogenesis of inflammatory bowel disease.

Methods

The aim of the study was to evaluate the expression of RIPK3 according to the activity and severity of ulcerative colitis (UC). Tissue expression of RIPK3 was determined immunohistochemically in intestinal biopsies from 85 patients with ulcerative colitis. Тo evaluate the severity and activity of UC were used the Montreal classification for disease severity (S), full Mayo score (MS) and Mayo endoscopic score (MES).

Results

A moderate direct correlation was found between disease severity and RIPK3 expression (r=0.354; p=0.001), with severe disease (S3) being characterized by overexpression of the marker (199.67). A moderate right-proportional relationship was also found in the analysis of RIPK3 expression and UC activity, measured by the full Mayo score (r=0.481; p<0.001). RIPK3 expression increased with increasing disease activity (p<0.001), and patients with severe disease activity (MS =11-12) had overexpression of the marker (211.71). A moderate correlation between RIPK3 expression and the degree of endoscopic activity was also found (r=0.363; p=0.001), with patients with severe endoscopic activity (MES=3) having high expression of the marker (198.27).

Conclusion

High expression of RIPK3 in UC patients was associated with severe disease activity assessed by the Montreal classification and full Mayo score and marked endoscopic activity.
P117 Low-Intensity Pulsed Ultrasound as a new approach of gut disruptive liquid biopsy to boost the release of mucosal extracellular vesicles in Ulcerative Colitis
Authors: Pineda Chavez S E , Rizzo G , Cafarelli A , Sorriento A , Loy L , dal Buono A , Gabbiadini R , Meanti L , Allocca M , Danese S , Repici A , Armuzzi A , Ricotti L , Vetrano S
Published: January 2023

Background

Ulcerative Colitis (UC) is a chronic, idiopathic intestinal inflammatory disease whose diagnosis requires colonoscopy with biopsy. There is an unmet need for sensitive, and easy-to-detect biomarkers helping a rapid and non-invasive diagnosis, and suitable for following disease progression. Extracellular vesicles (EVs) have been proposed as promising carriers of biomarkers. Nevertheless, their plasma levels remain very low and thus difficult to detect. We explored Low-Intensity Pulsed Ultrasound (LIPUS) as a novel and safe approach to enhance the mucosal release of EVs in experimental models of UC.

Methods

LIPUS was applied at a frequency of 38 kHz and at an intensity of 150 mW/cm2 for 3 min, using devices dedicated to in vitro or in vivo studies. Primary intestinal fibroblasts, Human Intestinal microvasculature endothelial cells (HIMEC) and peripheral blood mononuclear cells (PBMC) were isolated from UC patients and healthy volunteers (n=6). Cell viability was tested in Caco-2 and all primary cells using MTT assay. Computer acoustic simulations, allowing a reliable control of the energy dose in the colon, were carried out using k-Wave software to translate in vivo the LIPUS. Acute and chronic colitis models were induced in C57BL/6N mice by administration of dextran sodium sulfate (DSS) respectively 2 and 2.5% ad libitum in their drinking water for seven days for the acute and three cycles of DDS for the chronic. Mice were monitored daily for body weight loss, bleeding and stool consistency. EVs were characterized in supernatants, plasma and mucosa at NanoSight and inflammatory mediators detected 1, 2 and 24 h after LIPUS by ELISA assay. Apoptosis and cell proliferation were evaluated by TUNEL and Ki67 stainings.

Results

After LIPUS, all cells appeared 100% viable and no pro-inflammatory changes were observed. In Caco-2 cells, fibroblasts and HIMEC, LIPUS significantly decreased the levels of IL-8. The maximum release of EVs, range in size from 100 to 120 nm, was recorded after 60 min in resident cells from both UC and healthy-derived cells. Conversely, PBMC displayed a progressive decrease. In both acute and chronic models, the physiological cellular turnover of the mucosa resulted unchanged after LIPUS. A significative increase of EVs was observed after 2 h of stimulation, and dropped down after 24 h. The levels of EVs were higher (p<0.01) in the chronic rather than acute phase of colitis.

Conclusion

LIPUS proved to be a safe and non pro-inflammatory approach to boost the release of EVs accumulated into the mucosa increasing their levels in the bloodstream. This feature is transient and more evident in the short term. Overall, the LIPUS could pave the way to a new era of a gut disruptive liquid biopsy.
P123 Development of an end-to-end Mayo endoscopic score machine learning algorithm for use in clinical trials of ulcerative colitis
Authors: Vieira M , Mishkin D S , Gaither K W , Safran M , Dashuta A , Tarakanov A , Zfira L , Fuerst T
Published: January 2023

Background

Scoring colonoscopy videos of UC patients requires a high level of expertise, but even among trained expert readers there are disagreements. In clinical trials, this can negatively impact both subject selection and assessment of treatment response. Consistency among central readers might be improved by algorithms that automatically process videos to identify salient features and estimate the level of disease activity using established scoring methods.

Methods

We propose an end-to-end system using machine learning (ML) models to process colonoscopy videos, both shortening the time required for a human expert reader to score a video by filtering out non-informative parts and supplying a second-opinion of Mayo Endoscopic Score (MES) on each informative frame and the full video. Our dataset included videos from UC patients with a representative range of disease activity acquired at a Ukrainian hospital (n=505) and an Israeli hospital (n=227). Video annotation was performed by 12 reviewers, trained and supervised by an expert gastroenterologist (DM) with >10 years central reading experience. Out of almost 3 million frames over ~34% were classified by human reviewers as non-informative (e.g., out of focus, motion blurring, stool). The remaining informative frames were further annotated by the reviewers as containing ulcers (6%) and hence classified as MES=3, erosions (22%) as MES=2, loss of vascularity or erythema (23%) as MES= 1, or none of the above (49%) classified as MES=0. Informative frames were split to 80% training set, 10% validation set and 10% test set. The data set included low quality frames on which the reviewers could still estimate the MES. Models consisting of image processing algorithms, Convolutional Neural Networks (CNN), CNN+Long Short Term Memory (LSTM) model and classical ML classifiers were trained to filter out non-informative frames and score independently each frame and the full video for MES.

Results

Model performance was evaluated using Cohen’s Quadratic Weighted Kappa (QWK) with 95% Confidence Interval [95% CI]..Model agreement with humans is shown in the middle column. Inter-reviewer agreement based on a subset of ‘clear frames’ from various videos of the test set is shown in the last column.

Conclusion

We developed a full end-to-end pipeline for processing colonoscopy videos that estimated MES with accuracy comparable to human-human agreement. Such a model has the potential to make human readers more efficient by highlighting frames with relevant pathology. It can also aid inter-reader agreement by providing a second-opinion MES. Future work will expand model training and testing with new data sources and explore paradigms to combine the model with human readers to improve clinical trial central reading.
P125 LCI/BLI chromoendoscopy plus CAD-EYE artificial intelligence for the detection and characterization of endoscopic visible lesions in ulcerative colitis
Authors: Cassinotti A , Zadro V , Parravicini M , Ferraris M , Balzarini M , Sessa F , La Rosa S , Segato S , Cortelezzi C C , Segato S
Published: January 2023

Background

LCI/BLI chromoendoscopy and CAD-EYE artificial intelligence have been developed for the detection and characterization of colorectal neoplasia in the general population. In this study, we analyzed their diagnostic accuracy in the detection and characterization of endoscopic visible lesions (EVL) during endoscopic surveillance of ulcerative colitis (UC).

Methods

A prospective tandem study on consecutive UC patients was performed, using Eluxeo white light endoscopy (WLE), LCI and LCI+CAD-EYE during a back-to-back withdrawal phase. Lesion characterization of all EVL was performed according to three classifications (Kudo, NICE and Kudo-IBD) and, finally, by BLI+CAD-EYE. The lesion/neoplasia miss rates were analyzed during the detection phase. Sensitivity (SE), specificity (SP), positive- and negative-predictive values (PPV/NPV) and accuracy (ACC) for lesion characterization by Kudo, NICE and Kudo-IBD were calculated when applied to BLI and compared with CAD-EYE, using histology as reference test.

Results

62 patients (mean age 54 years, mean disease duration 18 years) were included; 133 lesions (mean size 6 mm, 18 neoplastic) were found in 35 patients. The lesion miss rate was significantly higher (p<0.05) with WLE (9.8%) and LCI (5.3%) than CAD-EYE (0%), with no differences in neoplasia miss rates. For lesion characterization, the SE, SP, PPV, NPV and ACC of BLI+CAD-EYE (83%, 65%, 27%, 96%, 68%, respectively) were not inferior to the conventional Kudo (67%, 71%, 27%, 93%, 71%) and NICE (72%, 68%, 26%, 94%, 68%) classifications, while Kudo-IBD had higher SE (89%) and significantly (p<0.05) higher SP (83%) and ACC (84%) than Kudo, NICE and CAD-EYE.

Conclusion

LCI+CAD-EYE and the Kudo-IBD criteria applied to BLI can improve, respectively, the detection and characterization of EVL in UC.
P134 Pediatric granulomatous appendicitis, how can it be precursor of Crohn Disease?
Authors: Bakkaloglu I Guvendir , Calim Gurbuz B , Zemheri I E , Bakkaloglu O Kagan
Published: January 2023

Background

Granulomatous appendicitis (GA) in pediatric age is an entity that is difficult to evaluate, diagnose, and may present with unexpected symptoms, and overlap with other diseases. Since there may be many different causes in its etiology, detailed histopathological examination with clinical correlation is very important. Our aims are to analyse detailed histomorphological features of GA in children, understand the etiology and investigate if it may be a precursor of inflammatory bowl disease (IBD) in the follow ups.

Methods

The detailed histopathology and etiology of pediatric and adult GA’s were evaluated retrospectively in two centers between 2016 and June 2022. All cases diagnosed with granulomatous appendicitis in the given date range were included in the study.

Serological, radiological and histomorphological findings of the patients were evaluated within at least 6 months of follow-up and compared with adults.

Results

Of the 2144 pediatric appendectomy specimens, 25 (0.01%) were GA, 12(48%) of them are female and the mean age was 13.96. While interval appendicitis was the most common cause in GA etiology (n:12, 48%), IBD (n:5, 20%) was the second. 4 pediatric patients were diagnosed with Crohn Disease (CD) and one with Ulcerative Colitis in their follow-ups, none of the adults had IBD.

During the follow-ups, mycobacteria was detected in the serology of one case, while actinomycesis was observed in the lumen of another. Crohn's disease may tend to involve the appendix more severely in younger patients. And it may present as the first finding of IBD. It is known that granulomas are more specific for Crohn's disease. In the detailed histopathological examination of cases, non-necrotizing granuloma structure is seen more frequently in CD. Besides, non-necrotizan type granulomas, mucosa involvement of the wall, accompanying exaggerated reactive lymphoid aggregates, and eosinophil count were more common in CD .

Conclusion

Granulomatous appendicitis may be more associated with IBD, especially in childhood patients than in adults. Detailed histopathological examination of CD-specific features can be alarming. However, when a case with GA is encountered, all conditions that may cause granulomatous inflammation should be ruled out serologically and radiologically, and system scanning should be performed very carefully before considering IBD.
P143 Outcomes of ulcerative colitis-associated dysplasia patients treated with endoscopic submucosal dissection: An extended analysis of a single center cohort
Authors: Park S , Hong S W , Hwang S W , Park S H , Ye B D , Byeon J S , Myung S J , Yang S K , Yang D H
Published: January 2023

Background

Total proctocolectomy has been recommended for patients with ulcerative colitis (UC)-associated dysplasia due to the risk of its progression to colorectal cancer or metachronous recurrence. Recently, endoscopic resection has been considered as a therapeutic option for dysplasia in UC, and endoscopic submucosal dissection (ESD) has been recommended for lesions where endoscopic mucosal resection is unsuitable. We aimed to investigate the long-term outcomes of UC patients who underwent ESD for dysplasia or early colorectal cancer

Methods

We retrospectively reviewed 47 patients with UC-associated dysplasia/cancer referred for potential ESD to treat non-polypoid or sessile dysplasia between August 2009 and August 2022 at Asan Medical Center, a tertiary hospital in Seoul. Indications for ESD were determined according to the criteria applied for sporadic colorectal neoplasms based on magnifying endoscopy.

Results

The median age at UC diagnosis was 45 years, and 24 patients (51%) were male. The median duration of UC was 13 years. Colectomy was recommended for 11 patients, and the remaining 36 patients underwent ESD. The en bloc resection rate was 88.9% (32/36), and the histologic complete resection rate was 77.8% (28/36). Five patients underwent colectomy after ESD due to missed adenocarcinoma, deep submucosal cancer, and multiple dysplasia. A total of 31 patients were followed-up after ESD. Their mean (standard deviation) follow-up period was 45.9 (±30.6) months, and the mean number of post-ESD surveillance endoscopies was 3 (±2). Local recurrence of dysplasia occurred in 3 (3/31, 9.6%) patients; metachronous recurrence occurred in 7 patients (7/31, 22.6%). There were no cases of metachronous colorectal cancer.

Conclusion

ESD for discrete dysplastic lesions in UC patients is feasible and shows favorable outcomes in terms of colorectal cancer prevention. However, surveillance colonoscopy with short intervals is warranted due to the high metachronous recurrence rate.
P148 Work Ability Index (WAI) as a suitable instrument to assess work ability among IBD patients
Authors: Mtir M , Mechergui N , Kchir H , Cherif D , Dabbabi H , Yacoub H , Hassine H , Maamouri N
Published: January 2023

Background

Inflammatory bowel disease(IBD) is a chronic disease usually diagnosed in early adulthood and characterized by unpredictable flare-ups and debilitating symptoms that can interfere with the patient's ability to work and perform daily activities. In fact, since work disability is difficult to quantify, several scores have been developed for this purpose. The Work Ability Index(WAI) is a validated practical tool to measure the work capacity of patients.

The objective of this study was to assess work performance in patients followed for IBD using the WAI psychometric tool, and to identify predictive factors of work disability.

Methods

We conducted a cross-sectional study including working patients followed for IBD, over a 9-months period. We collected sociodemographic, clinico-biological and evolutionary data. Quality of life was assessed by the IBDQ questionnairy. Work capacity was assessed using the WAI, a short 7-item questionnairy, which classified work performance into four categories: poor (score between 7-27), moderate(28-36), good(37-43) and excellent(44-49).

Results

We included 45 patients: 80% Crohn disease and 20% ulcerative colitis. The mean age was 44 years[20-72], the sex-ratio M/F was 0.7, and the mean of follow-up time was 9 years[1-18]. The average number of working hours per week was 38.84 [9-60]. The mean absenteeism during the last twelve months was 49.6 days [0-240] and the average number of hospitalization days was 30.7 [0-150]. The mean WAI value was 32.58, which corresponds to a moderate work performance.

Assessment of work performance according to the WAI questionnaire showed that 38% of patients (N=17) had poor work ability, 24% (N=11) moderate work ability, 33% (N=15) good work ability and only two patients had an excellent work ability.

In univariate and multivariate study, predictive factors of disability at work in IBD patients were:

Furthermore, the assessment of health-related quality of life by the IBDQ questionnairy showed a mean IBDQ value of 160.78 which corresponds to a moderate score relating a quality of life; 224 being the maximum score obtainable reflecting an optimal quality of life. In the analytical study and using Spearman's test, a statistically significant correlation was found between the WAI and IBDQ with a p-value <0.0001 and a correlation coefficient r=0.7, reflecting the impact of work life on quality of life.

Conclusion

In our study, one third of patients had poor work capacity. Risk factors for poor performance were disease severity, presence of osteoarticular extraintestinal manifestation, and patients with children. The only protective factor identified was a high level of education. Thus, the Work Ability Index can be used as a screening tool to identify the need for rehabilitation.
P153 Association between ustekinumab trough concentrations and clinical, biochemical, and endoscopic outcomes in patients with Inflammatory Bowel Disease
Authors: Serra-Ruiz X , Claudia H D G , Mayorga Ayala L , Robles Alonso V , Céspedes Martínez E , Casellas F , Miarons M , Garcia-Garcia S , Pérez Martínez Z , Oller E , Borruel Sainz N
Published: January 2023

Background

Ustekinumab (UST), an inhibitor of the p40 subunit of interleukins 12 and 23, is an effective treatment for patients with Crohn’s disease (CD) and ulcerative colitis (UC). There is limited data on therapeutic outcomes and UST trough levels (UTL). We aimed to evaluate the association between UTL and corticosteroid-free clinical remission. We also assessed the relationship between UTL and endoscopic remission as a secondary outcome.

Methods

We performed a cross-sectional study on IBD patients receiving maintenance therapy with UST (>6 months). We included UTL, C reactive protein (CRP), faecal calprotectin (FC), and clinical and endoscopic indexes (Harvey Bradshaw [HBI] and simple endoscopic score [SES-CD] for CD patients; and partial Mayo score [PMS] and endoscopic Mayo score [EMS] for UC patients). Corticosteroid-free clinical remission (CSF-CR) was defined as HBI<5 or PMS<2 plus normal CRP and/or FC values without corticosteroids. Endoscopic remission was defined as SES-CD<3 or EMS<2.

Results

We included 105 patients; the mean age was 50 years, and 59% were female (Figure 1). Eighty-seven patients had CD, and 92% had previously received an anti-TNF. The median time on UST was 121 weeks at inclusion. Sixty-four patients received 90mg subcutaneous (SC) every 4 weeks, 40 patients 90mg SC every 8 weeks, and 1 patient 90mg SC every 12 weeks. Eighty percent were in CSF-CR, and 53% were in endoscopic remission.

Median UTL were 2,7µg/mL (IQR: 1,7-4,1µg/mL); UST antibodies were not detected. Patients in CSF-CR and endoscopic remission did not show significantly higher UTL (3,4µg/mL vs. 2,5µg/mL, p=0,147; and 3,6µg/mL vs. 3,7µg/mL, p=0,903, respectively). No differences in UTL were detected between patients on monotherapy and combination therapy (2,9µg/mL vs. 3,3µg/mL, p=0,456).

Conclusion

No association between UTL and clinical or endoscopic activity was observed in our predominantly biologic-experienced cohort. Further prospective studies are needed to determine the role of therapeutic drug monitoring while on UST.
P155 Natural history of anal stricture in pediatric-onset Crohn’s disease: a two-decades population-based study
Authors: Mortreux P , Leroyer A , Ley D , Dupont-Lucas C , Bertrand V , Wils P , Coevoet H , Paupard T , Gower-Rousseau C , Siproudhis L , Guillon N , Sarter H , Savoye G , Turck D , Fumery M
Published: January 2023

Background

The natural history of anal stricture complicating pediatric-onset Crohn’s disease (CD) is poorly known. The aims of this study were: to determine in a population-based study the risk of anal stricture in pediatric-onset CD; to identify risk factors for anal stricture; and to evaluate the natural history of anal stricture at the population level.

Methods

All patients with a diagnosis of CD made before the age of 17 years between 1988 and 2011 in a population-based registry were followed retrospectively until 2013. A specific collection of additional data was performed in patients with anal stricture at diagnosis or during follow-up. Variables collected included: proctological examination, diagnostic management and treatment. Multivariate Cox models were used to identify factors associated with anal stricture.

Results

Among the 1,007 included CD patients (females, 451 (44.8%); median age at diagnosis 14.4 years (IQR, 12.0-16.1), median follow-up 8.8 years (IQR, 4.6-14.2)), only one (0.1%) had anal stricture at diagnosis while 26 (2.6%) presented anal stricture during follow-up. Cumulative incidence of anal stricture at 5 and 10 years after diagnosis was 0.6% (CI95%, 0.1-1.1) and 1.4% (CI95%, 0.5-2.3), respectively. Among the 27 patients with anal stricture, 25 (92.6%) had already at least one episode of anal ulceration or fistulizing perianal CD (pCD). In multivariable analysis, the presence of extra-intestinal manifestations (Hazard Ratio (HR) 2.2, CI95% 1.0-4.8, p=0.027), colonic location (L1 vs L3 HR 0.0 (-); L2 vs L3 HR 1.2, CI95% 0.6-2.7, p=0.006) and history of fistulizing pCD (HR 9.9, CI95% 4.3-22.8, p<0.0001) were significantly associated with anal stricture. Eleven (41%) patients needed at least one dilation. After a median follow-up of 16.9 years (IQR, 11.5-20.2), healing of anal stricture was observed only once. One patient (3.7%) presented an anal cancer 7 years after the diagnosis of anal stricture. Nine (33.3%) patients needed a stoma. Among them, 8 already had a fistulizing pCD and 4 needed an abdominoperineal amputation. Anal stricture was significantly associated with an increased risk of stoma (HR 5.8, CI95% 2.3-14.3), p=0.0002).

Conclusion

Anal stricture is a rare event in pediatric onset CD, occurring in 1.5% of patients over a 10 year-period after diagnosis. However, anal stricture had a negative impact on disease prognosis with a five-fold increase of the risk of stoma.
P159 Development of a core set of quality of care measurements for patients with inflammatory bowel disease in Belgium
Authors: Fierens L , Bossuyt P , Baert F , Baert D , Lavaerts M , Weltens C , Ferrante M
Published: January 2023

Background

Uniform and standardized quality indicator (QI) measurement allows to assess quality of care (QoC) and set up quality improvement initiatives. To date there is no uniform measurement of QoC in IBD centres in Belgium. We therefore aimed to adapt existing standards of QoC to practical local needs, and to define a core set of quality measurements (QM) through a multi-stakeholder consensus.

Methods

A Core Team (4 IBD expert clinicians, 3 researchers) prepared and coordinated the Delphi process (Figure). Through a literature review, 221 existing QIs for IBD were identified. Second, an importance rating scale exercise was performed, leading to 58 QIs that were reformulated into practical QMs. Next, a variety of experts from different centres in Flanders were invited to rate the importance of these 58 QMs on a 10-point Likert scale. In between two consecutive online voting rounds, expert and patient (n=93) perspectives were provided. Furthermore, participants could also suggest items that were missing in the pre-selected list. A consensus threshold of ≥80% of the participants scoring the item 7, 8, 9 or 10 in voting round 2 was applied as the cut-off criterion for an item to be directly included in the final set of QMs. Newly suggested items and items that did not reach the cut-off criterion were discussed and reconsidered for inclusion in the final set during a closing consensus meeting. In order to come to a workable selection of items, participants to the consensus meeting were requested to estimate the potential for improvement of each of the selected QMs.

Results

In total 40 stakeholders of which 29 IBD clinicians, 7 IBD nurses, 2 paediatricians, 1 abdominal surgeon and 1 chief medical officer from 24 different Flemish centres participated in both Delphi voting rounds. Of this group, 21 IBD clinicians, 3 IBD nurses and 2 paediatricians also participated in the virtual consensus meeting. In total, 50 items reached the cut-off criterion for direct inclusion in the final QM set, the other 8 items and also 3 new items were discussed and re-voted during the consensus meeting of which 8 additionally reached the cut-off criterion to include in the final set. Based on the estimated improvement potential, 19 of these 58 QMs were prioritized and agreed to measure in clinical practice (Table).

Conclusion

We defined a core set of 58 QMs for IBD based on multi-stakeholder consensus. In the next phase of this project, a more condensed subset of 19 QMs with potential for improvement will be measured in IBD centres across Belgium, allowing QoC assessment, benchmarking and quality improvement initiatives.
P169 Copy number variation of alpha defensin 1-3 is a predictive marker of therapeutic response in ulcerative colitis
Authors: Kanmura S , Tanaka A , Maeda N , Kuwazuru K , Komaki F , Sameshima Y , Komaki Y , Ido A
Published: January 2023

Background

Alpha-defensin 1-3 (DEFA1A3) is an antimicrobial peptide found in phagocytic cells such as neutrophils, functioning as an effector factor in innate immunity. Reports suggest that copy number variation (CNV) of the DEFA1A3 gene is associated with the severity of ulcerative colitis (UC). However, the impact of DEFA1A3 on the pathogenesis of UC, and treatment response has not been fully investigated. Therefore, we aimed to evaluate the relationship between DEFA1A3-CNV and UC treatment response.

Methods

This was a retrospective and two medical centers study. The study included UC patients with DEFA1A3-CNV measurements, who attended our department and related facilities between 2020 and 2022. Clinical background and white blood cell count and serological marker were collected from the medical records of included patients. DEFA1A3-CNV was measured using droplet digital PCR after DNA extraction from peripheral blood mononuclear cells. Mayo score was used to determine the response to treatment and severity of UC.

Results

In total, 197 UC patients were included in the study. The median DEFA1A3 copy number was 7.36, and there was a significant correlation between DEFA1A3 copy number and Mayo score. The high DEFA1A3 copy number group had a significantly higher severity of UC during the observation period, compared with the low copy number group. In the analysis of the relationship between prednisolone/immunosuppressive therapy and DEFA1A3-CNV, the DEFA1A3 copy number was significantly higher in the non-remission group than in the remission group following prednisolone treatment. However, there was no correlation between other immunosuppressive therapies and DEFA1A3 copy number.

Conclusion

DEFA1A3 copy number is a predictive marker of disease severity and prednisolone treatment response.
P172 Metabolic disorders with non-alcoholic fatty liver disease in people with inflammatory bowel disease
Authors: Walker C , Stapleton E , Dempsey M , Carroll A , Connaughton R , Breslin N , McNamara D , O'Donnell S , Ryan B , O'Connor A
Published: January 2023

Background

Globally rising rates of obesity and consequent metabolic diseases have been reflected in the inflammatory bowel disease (IBD) population. Non-alcohol fatty liver disease (NAFLD) is a common liver disorder associated with obesity, that occurs more frequently in people with IBD.

Methods

A prospective single-centre cohort study. In total, we recruited 203 patients from our IBD service in a tertiary academic hospital. 7 participants were excluded due to later diagnosed non-NAFLD liver disease. Following informed consent, participants underwent a fibroscan for liver stiffness (LSM) and controlled attenuation parameter (CAP) measurement, and blood tests for HbA1c and fasting lipids.

Basic demographics, past medical history, exercise measured on the Godin-Shepard Leisure Time Physical Activity Questionnaire, physical functioning on SF-36 Questionnaire, blood pressure, CAP and LSM were recorded. T-test and Fishers exact test were used to test for statistical significance as appropriate.

Results

Of the 196 IBD patients included, 34.7% (n=68/196) had a healthy BMI, 34.7% (n=68/196) were overweight (BMI≥25-29.9), and 30.6% (n=60/196) were obese (BMI≥30). Overall, 16.3% (n=32) had a CAP score >294dB/m consistent with NAFLD, and 2.55% (n=5) had a LSM >8.1kPa consistent with fibrosis.

When compared to those without NAFLD, those with NAFLD had higher BMIs, 26.9 vs 32.3 p<0.05. They also had a much higher incidence of diabetes 28.1% vs 0% p=0.0001, higher overall rates of abnormal HbA1C (≥6%), 21.9% (n=7/32) vs 6.4% (n=10/156) p=0.0121, and higher rates of abnormal HbA1c without a diagnosis of diabetes 13% (n=3/23) vs 6.45% (n=10/155) p=0.4043. Additionally, they had non-significant higher mean systolic blood pressure and higher rates of diagnosed hypertension.

Compared to those without NAFLD, the NAFLD cohort had higher rates of diagnosed hypercholesterolaemia 34.4% (n=11/32) vs 15.3% (n25/163) p=0.022 and there were higher rates of elevated total cholesterol (>5mmol/L) in those not previously diagnosed with hypercholesterolaemia, 42.9% (n=9/21) vs 31.8% (n=47/148) p=0.3292.

Participants with NAFLD also had lower exercise scores 17 vs 24.9 p=0.03543, and lower scores for physical functioning 71.9 vs 83.2 p=0.00676.

Of particular note, they had more than double the 10-year risk of myocardial infarction or death determined by the Framingham risk scores for hard coronary heart disease, 2.48% vs 5.75%, p=0.00012.

Conclusion

Our study shows that people with concurrent NAFLD and IBD have a significant cardiovascular risk profile. With increased awareness of this, metabolic syndrome conditions should be screened for and treatment initiated where appropriate, to decrease cardiovascular related mortality in this cohort.