bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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&lt;0.0001). CGRPα remained significantly elevated as compared to HC both in IBD patients with migraine (74.8±27.3 pg/mL, p&lt; 0.001) and without migraine (58.6±24.4 pg/mL, p&lt;0.05), though those with migraine were significantly increased as compared to IBD patients without migraine (p&lt;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

Abstract

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&lt;0.001). RIPK3 expression increased with increasing disease activity (p&lt;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

Abstract

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&lt;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

Abstract

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 &gt;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

Abstract

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&lt;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&lt;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

Abstract

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

Abstract

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

Abstract

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 &lt;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

Abstract

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 (&gt;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&lt;5 or PMS&lt;2 plus normal CRP and/or FC values without corticosteroids. Endoscopic remission was defined as SES-CD&lt;3 or EMS&lt;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.