bluuebunny/crossref_metadata_2025_split huggingface dataset:
P140 Serum Metabolomic Biomarkers Can Identify and Characterize Associated Subtypes and Phenotypes in Inflammatory Bowel Disease
Authors: Kim J , Suh D H , Park Y J , Oh S J , Kang H , Ji Y , Jung E S , Lee C K 
Published: January 2024

Abstract

Background
Metabolomics is increasingly recognized for uncovering pathophysiology and identifying diagnostic and prognostic biomarkers in inflammatory bowel disease (IBD). This study focuses on exploring comprehensive serum metabolomic profiles and corresponding specific metabolic pathways, in order to differentiate IBD patients from healthy individuals and to accurately identify IBD subtypes (Crohn's disease [CD], ulcerative colitis [UC]) through serum biomarkers with high patient acceptability.

Methods
Serum samples with matched clinical metadata were comprehensively collected from patients with IBD at Kyung Hee University Hospital, Seoul, Korea. Corresponding samples from normal controls (NCs) were obtained for comparison. Untargeted profiling was performed with Gas Chromatography-Time-Of-Flight-Mass Spectrometry, and targeted profiling of bile acids and tryptophan used Liquid Chromatography-Triple Quadrupole-Mass Spectrometry. The identification of distinct metabolites and potential biomarkers was achieved through extensive univariate and multivariate statistical analyses. Receiver operating characteristic (ROC) curves and metabolic pathway analyses were also conducted.

Results
A total of 346 subjects were analyzed, comprising 258 IBD patients (134 with CD and 124 with UC) and 88 NCs, Table 1. The patients with IBD were clearly clustered from the NCs, while IBD subgroups were not clearly separated from each other in the nontargeted profiling. Tryptophan and indole-3-acetic acid were elevated in both patients with CD and UC, while kynurenine and indole-3-propionic acid increased only in CD. Conversely, patients with UC had lower levels of indole-3-acetic acid, serotonin, and acetylcholine compared to CD. The ratio of primary and secondary bile acids was also significantly decreased in both patient groups compare with NCs. The ROC curves (Figure 1A) showed good discriminatory power for NCs vs CD (AUC:0.9738), NCs vs UC (AUC:0.9887), and UC vs CD (AUC:0.7140). Pathway analysis of the identified metabolites showed a sustained change in glyoxylate and dicarboxylate metabolism/alanine, aspartate and glutamate metabolism/glycine, serine and threonine metabolism associated with all comparisons (NCs vs UC, NCs vs CD, UC vs CD). Beta-alanine, arginine, and proline metabolism were linked to IBD compared to NCs. Glycerolipid metabolism distinctly differed between UC and CD (Figure 1B-1D). Network analysis revealed associations between metabolomic markers and specific clinical phenotypes of IBD subtypes.

Conclusion
This study demonstrates that serum metabolomic biomarkers are novel and effective tools for diagnosing IBD, as well as for identifying and characterizing its subtypes and associated phenotypes.
P141 Engineered probiotics treat inflammatory bowel disease by releasing all trans retinoic acid in the intestine
Authors: Gao M , Wang L , Kang G , Zhang Y , Huang H 
Published: January 2024

Abstract

Background
All trans retinoic acid (ATRA) is a potential candidate drug for the treatment of inflammatory bowel disease (IBD). ATRA can affect multiple pathways involved in the pathogenesis of IBD by binding to retinoic acid receptors. However, the shortcomings of poor compliance and significant side effects in patients who directly use ATRA limit its clinical application.

Methods
Here, we have developed a live biotherapeutic products (ELBPRA) based on synthetic biology methods for controllable delivery of ATRA on the gut. We first expressed four enzyme genes required for the synthesis of β-carotene, a precursor of retinoic acid, in Escherichia coli Nissle 1917 (EcN). In addition, we introduced the exogenous synthesis pathway of isopentane pyrophosphate into EcN to increase the yield of β-carotene. Then, β-carotene oxygenase and retinal dehydrogenase, were expressed in EcN to convert β-carotene into retinoic acid. However, considering the poor solubility of retinoic acid, we knocked out some genes related to vesicle formation in the EcN genome to increase extracellular production of retinoic acid. Finally, we investigated the therapeutic effect of ELBPRA using a colitis model induced by sodium dextran sulfate (DSS).

Results
ELBPRA continuously produces retinoic acid and delivers it in the form of vesicles. ELBPRA reduced weight loss and disease activity index in DSS-induced colitis. Similarly, the spleen index also demonstrates the effectiveness of ELBPRA in treating colitis. The ELBPRA intervention group reduced the degree of colon shortening in mice. In addition, ELBPRA improved crypt loss and disorder of crypt structure. Finally, we also evaluated the inflammatory cytokines in the serum. ELBPRA significantly increased the concentration of anti-inflammatory cytokine IL-10 and decreased the concentration of pro-inflammatory cytokine IL-1β and TNF-α.

Conclusion
Engineered probiotics ELBPRA can deliver retinoic acid in the form of vesicles to alleviate DSS-induced colitis in mice, which provides a safe and effective treatment strategy for ulcerative colitis.
P184 Challenging Barriers in Inflammatory Bowel Disease: First Observational Analysis of Double Biological Therapy in Mexico
Authors: Sosa Martinez R , Garcia-Alonso D A , Lopez-Gomez J G , Cortes-Espinosa T 
Published: January 2024

Abstract

Background
Inflammatory bowel disease is a chronic inflammation of the GI tract, despite advances in treatment with biologic therapy, some patients may develop an inadequate response, known as refractory IBD (rIBD).Given this reality, the approach of double biological therapy (DBT) has emerged to effectively address and improve control of inflammation, providing them with an additional therapeutic option

Methods
Pilot prospective observational study evaluateing response to DBT in patients with refractory IBD

Results
A total of 7 patients with rIBD who received DBT were included, the average age was 29 ± 9, all female. The average duration of illness before starting dual therapy was 8 ± 2years. Patients had received an average of 2 previous biological treatments, 4 (57%) had a history of surgery related to IBD, 5 (71%) and 2(29%) had a history of stenosis and fistulas respectively and 100% used steroids and immunomodulators before starting DBT. Four DBT combinations were evaluated: CERTOLIZUMAB+VEDOLIZUMAB (group 1), USTEKINUMAB+VEDOLIZUMAB (group 2), INFLIXIMAB+USTEKINUMAB (group 3) and INFLIXIMAB+VEDOLIZUMAB (group 4).Group 1 included 1 patient with improvement in clinical activity, with a decrease in endoscopic activity from i4 to i2 by Rutgeerts criteria and Nancy index 1.Group 2 included 4 patients showed improvement in clinical and endoscopic activity, there was a reduction in clinical activity by CDAI from 225 to 66, and improvement in endoscopic activity from L1 B2 to L1 B1, i0 L2 B3P to i0 L1 B1 and i3 L3 B2 to i2 L3 B1 with different activity rates, Nancy's histology that varied from 0 to 3.Group 3 included 1 patient showed a reduction in clinical activity by CDAI from 210 to 166, endoscopic activity also decreased from i0 L2B3P to i0 L1 B1 with Nancy index of 2.Group 4 includes 1 with a decrease in clinical activity by Truelove-Witts from 2 to 2, endoscopic activity also decreased from 8 to 5 accordingto UCEIS with Nancy index of 1.In all groups, a reduction in the use of steroids was observed and no cases of infections associated with dual biological therapy were reported

Conclusion
This prospective observational pilot study represents the first analysis in Mexico and, to our knowledge, in Latin America, on the use of DBT in patients with rIBD who showed clinical, endoscopic and histopathological improvement in the majority of cases. It is important to recognize the limitations of this study, such as its pilot design and sample size. This pioneering study in refractory IBD presents encouraging results that suggest clinical and endoscopic benefits in the treated patients. These results justify the conduct of larger studies to strengthen the evidence and provide a solid basis for thepotential use of this therapy in clinical practice
P195 Prevalence and factors associated with fatigue in patients with inflammatory bowel disease
Authors: Kallel H , Elleuch N , Limam R , Dahmeni W , Hammami A , Braham A , Ben Slama A , Jaziri H , Ksiaa M 
Published: January 2024

Abstract

Background
Inflammatory bowel disease (IBD) is a group of pathologies characterized by symptoms that can be distressing and incapacitating. Fatigue is one of the complaints most frequently reported by patients. However, few studies have analyzed the determinants of fatigue in IBD. The aim of our work is to estimate the prevalence of fatigue, and to identify the factors associated with it in IBD patients.

Methods
Fatigue and nine other dimensions of IBD-related disability were assessed in a cross-sectional survey, including patients followed and hospitalized between March and September 2023, using the IBD-Disk questionnaire. Fatigue and severe fatigue were defined by an "Energy" sub-score &gt; 5 and &gt; 7 respectively. The correlation between Energy and the other IBD-Disk items was analyzed using Pearson's correlation coefficient. Determinants of fatigue were assessed using the Chi-2 test and multinomial logistic regression.

Results
We included 166 patients, 53.6% were men, and 69.3% were Crohn's disease carriers. Mean age was 39 ± 12.7 years. More than two-thirds (69.9%) lived in urban areas. IBD was active in 48.8% of cases. A total of 59% of patients were on biotherapy for maintenance treatment. The mean IBD-Disk total score was 36.4 ± 21. The Energy subscore obtained the highest score (4.9 ± 2.9). The prevalence rates for fatigue and severe fatigue were 42.2% and 22.9% respectively. Significant correlations were observed between fatigue and all other dimensions of IBD-related disability assessed by the IBD-Disk (p&lt;0.001). The strongest correlations were observed between fatigue and defecation regulation (r=0.642), fatigue and work and study (r=0.630), and between fatigue and sleep (r=0.620) (Table 1). In univariate analysis, factors significantly associated with fatigue and severe fatigue were female gender (p=0.040 and 0.047 respectively), disease activity and hospitalization (p&lt;0, 001 each), anemia (p=0.005 and 0.014 respectively), elevated CRP (p&lt;0.001 and 0.030 respectively), hypoalbuminemia (p&lt;0.001 and 0.042 respectively) and absence of biotherapy treatment (p=0.02 and 0.01 respectively). Living in an urban area was also associated with fatigue (p=0.015). In multivariate analysis, the independent risk factors predictive of fatigue were female gender, urban origin, hospitalization at the time of interview, and clinical disease activity. Independent risk factors for severe fatigue in multivariate analysis were female gender and clinical disease activity (Table 2).

Conclusion
The causes of fatigue are multiple and go beyond the clinico-biological elements associated with IBD, also encompassing social, geographical and sleep disturbance aspects. This underlines the need for a holistic approach to the management of IBD patients.
P200 Oral Mannitol for bowel preparation in IBD patients: a post-hoc analysis of a multicentre, controlled, randomized clinical trial
Authors: Tontini G E , Rimondi A , Caprioli F , Radaelli F , Spada C , Vecchi M 
Published: January 2024

Abstract

Background
Bowel preparation is the most burdensome part of the whole colonoscopy procedure according to patients. A diagnosis of Inflammatory Bowel Disease (IBD) implies the need for lifelong repeated colonoscopies, therefore amplifying the problem. Bowel preparation with oral Mannitol, a sugar alcohol with a sweet taste, could significantly improve the patients’ tolerance as it has a quick onset, is single dose and has a low volume.1-3

Methods
This is a post-hoc analysis of IBD patients included in the SATISFACTION study, a third phase multicentre, international, randomized, endoscopists-blinded controlled trial4. Patients were randomized (1:1) to 750mL of oral mannitol (OM, 100 g in 750 mL water) to be drunk in a single dose 4 hours before colonoscopy versus a standard split preparation with 2L PEG-ASC (PEG). An intention to treat analysis was performed on patients who underwent colonoscopy and who took bowel preparation even partially. Biological important parameters summarising the rate of bowel cleansing and patients’ satisfaction were collected.

Results
A total of 55 IBD patients (M = 24, P = 31, Crohn’s = 12, Ulcerative Colitis = 40, Microscopic colitis =3) from 7 centres were ruled in for this post-hoc analysis. The two population were comparable in terms of age and sex and diseases (Table 1). A statistically significant preference of OMl over PEG was found in terms of taste (numerical rating scale – NRS, p &lt; 0.001), willingness to reuse the preparation (p = 0.03), and of time of first evacuation (M 56.6 minutes, P 90.7, p = 0.01). No differences were found in terms of adequate bowel cleansing as assessed by the Boston bowel preparation scale (96% OM, 97% PEG), adherence to bowel preparation (complete in 100% OM, 94% PEG) and easy of use (88% OM, 71% PEG). Minor and expected adverse events of special interest such as nausea and abdominal pain were comparable in the two courts (12% OM, 3% PEG).

Conclusion
Bowel preparation with a very low volume of oral mannitol in a single dose 4 h before colonoscopy provides better satisfaction among IBD patients and showed an excellent efficacy and safety profile as compared to the standard split preparation with 2L PEG-ASC. Same day bowel preparation with oral mannitol is a reliable option for colonoscopy in IBD and an effective strategy to improve the patients’ acceptance.

Funding/Acknowledgment
The Satisfaction study was funded by NTC, Milan, Italy.

References
1. Spada C et al. Eur J Clin Pharmacol. 2022 Dec;78(12):1991-2002.
2. Fiori G et al. Clin Transl Sci. 2022 Oct;15(10):2448-2457.
3. Carnovali M et al. Clin Transl Sci. 2023 May;16(5):759-769.
4. Tontini G.E. et al. Endoscopy 2023; 55; s64
P213 ArgesMES: A high-performance, generalizable AI model for scoring Ulcerative Colitis severity from endoscopy videos
Authors: Chaitanya K , Zemlianskaia N , Damasceno P , Scherer E , Ulloa Cerna A , Mobadersany P , Parmar C , Surace L , Yarani S , Huang K H G , Germinaro M , Kwon J , Ghanem L R , Mansi T , Oana Cula G , Standish K 
Published: January 2024

Abstract

Background
The Mayo endoscopic subscore (MES) is widely used to assess endoscopic disease severity assigned by human readers in Ulcerative Colitis (UC) clinical trials. AI-based automation of the MES could reduce inter-rater variability and allow for the development of more sensitive endoscopic measures. This report assesses whether a previously trained (locked) algorithm is suitable for automating full colon or segment-level MES scoring on a prospective UC clinical trial.

Methods
Endoscopy videos from two UC clinical trials (UNIFI: NCT02407236, Phase 3, 965 subjects, 3128 videos; and JAK-UC: NCT01959282, Phase 2, 211 subjects, 448 videos) were used to train an AI-based MES classifier, where 20% of the total data was retained as a holdout set. This AI model training had two steps: 1) training a feature extraction module using self-supervised learning (SSL), and 2) supervised training of a small transformer network with an attention-based classifier using SSL features to estimate full colon MES. Videos from an independent, prospective UC trial (QUASAR: NCT04033445, Phase 2b induction study, 313 subjects, 615 videos) were used to validate the locked AI model. MES scoring in QUASAR included full colon MES values and additional MES values for three left colon segments: descending colon, sigmoid colon, and rectum. Comparisons between AI-model and human reader scores were performed using AUC, Accuracy, F1 score, and Fleiss kappa. A non-inferiority test was also conducted to determine interchangeability between AI- and human-derived full colon MES values.

Results
Full colon MES on the QUASAR data showed AUC, Accuracy, and F1 scores of 0.810, 0.687, and 0.693, respectively, comparable to results obtained on the UNIFI holdout data (0.803, 0.645, and 0.647). The Fleiss kappa score was 0.682, comparable to the inter-rater agreement between two human readers-local and central readers (Fleiss kappa = 0.712). The non-inferiority test (p-value &lt; 0.05) indicated that the AI-computed full colon MES readout was interchangeable to that of human readers. Similar performance was observed for the AI-computed segment-level MES: descending colon, sigmoid colon, and rectum as shown in Table 1. This result demonstrates the model's effectiveness at scoring the segment-level MES despite not being trained with segment level ground truth.

Conclusion
ArgesMES, an AI-based model, underwent successful prospective validation, demonstrating proficiency in automating full colon and segment-level MES scores. ArgesMES has the potential to facilitate rapid, reliable, and reproducible MES scoring at full colon and segment levels in prospective clinical trials.
P217 Rate of undetected dysplasia at colectomy in patients with IBD - What are we missing?
Authors: Centorrino E , Ferrari D , Larson D W , Coelho-Prabhu N 
Published: January 2024

Abstract

Background
Patients with Inflammatory Bowel Diseases (IBD) are at higher risk of developing dysplastic lesions and colorectal cancer (CRC). Despite the use of high-definition endoscopes, dysplasia is not always detected at colonoscopy. This study aims to determine the rate of dysplastic lesions detected only at colectomy in IBD patients and to identify the characteristics of patients with undetected dysplasia.

Methods
We retrospectively identified IBD patients that underwent total or sub-total colectomy at Mayo Clinic, between January 2013 and December 2022. Patients with a confirmed IBD diagnosis, with at least one colonoscopy report prior to surgery available, were included. Data collected was demographics, comorbid conditions, colonoscopy, surgery, and their pathology reports. Concordance between dysplasia found at colonoscopy and dysplasia found at surgery was evaluated, noting dysplasia sites and grade. Patients were then divided into three groups: those with at least one undetected dysplastic lesion at surgery, those with dysplasia detected at colonoscopy and no further lesions at surgery, and those without dysplasia at both.

Results
Seven hundred-four patients were included: 387 (55%) were male, 450 (64%) had ulcerative colitis, 197 (28%) had Crohn’s disease and 57 (8%) had indeterminate colitis.
In 42 patients (6%) dysplasia was undetected at colonoscopy, 136 (19.3%) had dysplasia detected at colonoscopy, and 526 (74.7%) had no dysplasia at both.
In the group with dysplasia detected, 40 patients (30%) had dysplasia only at colonoscopy while 96 (70%) had dysplasia at surgery as well.
Among those with undetected dysplasia, in 17 (40%) dysplasia was identified only at surgery: 14 (82%) had low grade dysplasia and 3 (18%) had cancer. All cancers were stage 1. Three of these patients (18%) had primary sclerosing cholangitis and 4 (23%) had a family history of cancer. In the other 25 patients (60%), dysplasia was detected at colonoscopy but further dysplastic foci were identified at surgery. In 13 (52%) patients dysplasia was upgraded, in 2 (8%) was downgraded and in 10 (40%) the grade was confirmed. Compared to those with detected dysplasia, these patients more frequently had moderate-severe disease activity, and less frequently a prior history of dysplasia. There was no difference in age at surgery, but those with undetected dysplasia had less years of disease at colectomy.
Further results are shown in Table 1.

Conclusion
The rate of dysplastic lesions found at colectomy and missed at colonoscopy is 6%. Dysplastic lesions tend to be undetected when endoscopic disease activity is more severe and regardless of the use of extensive nontargeted biopsies.
P235 Correlation of mental and psychological status to disease activity in patients with Inflammatory Bowel Disease using The Symptom Checklist -90- Revised Questionnaire (SCL90R)
Authors: Abdelaty K 
Published: January 2024

Abstract

Background
Inflammatory Bowel Disease can affect mental health. There is no evidence that stress is a direct cause of the disease. Most Inflammatory Bowel Disease patients describe an emotional impact, mainly feelings of depression and anxiety. Many questionnaires used to assess anxiety in those patients including Symptom Checklist -90-Revised Questionnaire. This research aimed to investigate Correlation of mental and psychological status to disease activity in patients with Inflammatory Bowel Disease using Symptom Checklist -90-Revised Questionnaire.

Methods
The study included one hundred patients (50 Crohn's Disease patients – 50 Ulcerative Colitis patients). Detailed history taking, systemic physical examination, laboratory investigations, Colonoscopy, Symptom Checklist -90-Revised Questionnaire. A self-report psychometric instrument (questionnaire) for every patient.

Results
The mean age of Crohn’s Disease patients was 24,2 years +/- SD 3,6 years. In Ulcerative Colitis patients the mean age was 28,5 years +/- SD 7,3 years. No age or gender relation could be detected with Symptom Checklist -90-Revised Questionnaire score in both groups, The study showed a direct correlation of Crohn's Disease Activity Index (CDAI) and endoscopic activity (Simple Endoscopic Score) (SES) to Symptom Checklist -90-Revised Questionnaire. There was direct correlation of Ulcerative Colitis disease activity (Simple Clinical Colitis Activity Index) (SCCAI) and Endoscopic activity (Ulcerative Colitis Endoscopic Index of Severity) (UCEIS) to Symptom Checklist -90-Revised Questionnaire.

Conclusion
There is a direct correlation of disease activity and Endoscopic activity in Ulcerative Colitis and Crohn's Diseases to Symptom Checklist -90-Revised Questionnaire.