bluuebunny/crossref_metadata_2025_split huggingface dataset:
P241 Systemic redox status associates with disease activity and clinical phenotypes in Inflammatory Bowel Disease
Authors: Geertsema S , Bourgonje A R , Gacesa R , Fagundes R R , Spekhorst L M , Hu S , Kannan A K , Ruane D , de Jong S , Jansen B H , Bulthuis M L C , Reinders-Luinge M , Weersma R K , van Goor H , Dijkstra G , Faber K N 
Published: January 2024

Abstract

Background
Oxidative stress is a key pathophysiological mechanism in inflammatory bowel diseases (IBD). Systemic levels of oxidative stress are reflected by reduced levels of free thiols (FT) in circulating proteins, especially those in albumin, which associates with disease activity in IBD. Yet, clinal value of circulating FT level as biomarkers of disease and therapy response remains largely unexplored. Here we investigated the association between plasma FT levels and clinical parameters, the plasma inflammatory proteome and medication use.

Methods
Plasma samples from 1,028 patients with IBD (567 Crohn's disease [CD] and 461 ulcerative colitis [UC]), and 500 healthy controls (HCs) participating in the 1000IBD and LifeLines projects were profiled for free thiols (FT), uric acid, bilirubin and 92 inflammation-related proteins (Olink Inflammation panelÒ). All biomarkers were associated with clinical phenotypes using general linear models adjusting for age, sex, body mass index, smoking and medication use.

Results
Plasma FT levels were significantly lower in IBD compared to HCs (p&lt;0.05) (Figure 1A), with patients with UC showing even lower levels than patients with CD (p&lt;0.05). Patients with UC on induction therapy had lower FT levels compared to patients on maintenance therapy (p&lt;0.05). Furthermore, FT levels of patients with IBD were strongly associated with systemic inflammation (C-reactive protein [CRP], p&lt;0.05) (Figure 1B). In both patients withCD and UC, reduced FT levels were associated with elevated levels of inflammation-, apoptosis-, and growth factor-related proteins, including C-X-C motif chemokine 9 (CXCL9) (Figure 1C-D), CUB domain-containing protein 1 (CDCP1) and caspase-8 (CASP8), proteins previous associated with preclinical IBD1-3. Furthermore, specifically for patients with UC, reduced FT levels were associated with elevated eotaxin-1 (CCL11) (Figure 1C), monocyte chemotactic protein-1 (MCP-1), and several cytokine biomarkers like Interleukine-6 (IL6) and Interleukin-17A (IL17A).

Conclusion
Systemic FT levels associate with inflammatory disease activity and clinical therapy and may offer potential utility in clinical assessments. This study highlights the intricate involvement of oxidative stress in various inflammatory pathways and components, particularly in innate/adaptive immune balance, cell damage, and apoptosis. These findings contribute to a deeper understanding of the interplay between oxidative stress, inflammation, and IBD.
Funding: This study was supported by Janssen Research & Development LLC.
References:
1. Leibovitzh H, et al. Gut. 2023
2. Chen J, et al. JCC. 2023
3. Bergemalm D, et al. Gastroenterology, 2021
P253 Knowledge and acceptability of the Lémann Index to measure progressive intestinal damage in Crohn’s disease: results from an international cross-sectional survey
Authors: Wong C , Torres J , Burisch J , Ungaro R C , Colombel J F , Buisson A , Lambert J , Arebi N 
Published: January 2024

Abstract

Background
Chronic inflammation in Crohn’s disease (CD) predisposes to progressive structural bowel damage (SBD). The Lémann index (LI) is a prospectively validated tool that captures extent and severity of strictures, penetrating disease and surgery to generate a SBD score.1 It is earmarked as a potential outcome measurement tool for CD modification trials. Understanding perceived barriers and knowledge gaps is critical to its wider adoption.

Methods
We conducted a multinational, cross-sectional study (March to October 2023) to determine SBD and LI knowledge, and LI acceptability. An online survey link (REDCap) was distributed to clinicians by email through GI professional societies and snowball sampling. The questionnaire included 23 items, 5 sections (demographic, SBD knowledge, LI perception and knowledge, future LI adoption, and optional case) and responses (binary, 5-point Likert scale, 10-point visual analogue scale (VAS) and free-text) were captured on Excel.

Results
From 170 respondants: 82 (48%) were female; 142 (82.4%) from Europe, 13 North America (7.6%) and 13 Asia (7.6%). Most were IBD specialists (121; 71.2%), General Gastroenterologists (36; 21.2%), managing &gt;40 CD patients per month (60; 35.3%). 88 (51.8%) questionnaires were incomplete (≥1 questions were unanswered). From completed responses, 99 (92.5%) knew about SBD, 97 (90.7%) rated it ‘’very’’ and ‘’fairly’’ important to measure SBD in clinical trials and 82 (76.6%) in clinical practice; 5 (4.7%) felt it was ‘’not important’’. Most agreed LI would improve long-term outcomes in CD (55; 55%) and show achievement of treatment targets (74; 74.7%). More (43; 42.6%) replied it was ‘’very difficult’’ or ‘’difficult’’ to complete the LI for each patient; 36 (36%) felt that it took ‘’significant’’ or ‘’a lot’’ of effort (Figure 1). Most (86; 80.4%) were untrained in calculating the LI; 73 (68.2%) felt it was ‘’very’’ and ‘’fairly’’ important to receive training. Most reported intestinal ultrasound instead of MR enterography to be important (VAS scores 8-10) for encouraging LI calculation in future clinical trials (53; 54.6%) and clinical practice (49; 52.7%) (Figure 2). Lack of time (80.2%), automated calculation methods (64.2%) and dedicated radiologist (50.6%) were the top 3 perceived barriers to wider adoption.

Conclusion
Most respondents had baseline knowledge of SBD and perceived the LI to be important in future long term CD research and clinical practice. Interventions to improve training and automation are needed to facilitate wider adoption of the LI.

Reference
1. Pariente B, et al.Validation and Update of the Lémann Index to Measure Cumulative Structural Bowel Damage in Crohn's Disease.Gastroenterology.2021 Sep;161(3):853-864.e13.
P268 Artificial Intelligence and Panendoscopy – Automatic Detection of Pleomorphic Lesions in Multibrand Device-Assisted Enteroscopy
Authors: Araújo Martins M P , Mascarenhas M , Afonso J , Ribeiro T , Cardoso P , Mendes F , Cardoso H , Andrande P , Mascarenhas Saraiva M , Ferreira J , Lopes S , Macedo G 
Published: January 2024

Abstract

Background
Device-assisted enteroscopy (DAE) stands as the sole diagnostic and therapeutic procedure capable of thoroughly examining the entire gastrointestinal (GI) tract. Nevertheless, its diagnostic yield falls short in ensuring a cost-effective panendoscopy and there is still a significant interobserver variability during the procedure. Multi-layered convolutional neural networks (CNN) have proven beneficial in numerous medical applications, yet there is a noticeable gap in research regarding their implementation in DAE. The aim of this study is to develop and a validate a multidevice CNN for panendoscopic detection of pleomorphic lesions (vascular lesions, hematic residues, protruding lesions, ulcers and erosions) during DAE.

Methods
In a retrospective analysis of 338 DAE procedures conducted at two specialized centers, frames from 152 single-balloon enteroscopies (Fujifilm®), 172 double-balloon enteroscopies (Olympus®), and 14 motorized spiral enteroscopies (Olympus®) were used to construct and validate the CNN. The dataset, comprising 40,655 images, was divided into a training dataset (90% of images, n=36,599) and a validation dataset (10% of images, n=4,066). We conducted a 5-fold cross validation, during training dataset. Primary outcomes were sensitivity, specificity, accuracy, and area under the precision recall curve (AUC-PR).

Results
During the training dataset's 5-fold cross-validation, the model demonstrated a mean sensitivity of 88.7% (88.0 – 89.5%), specificity of 98.0% (97.8 – 98.1%), PPV of 92.6% (92.0 – 93.1%), PPN of 97.0% (96.8 – 97.2%), with a mean accuracy of 96.0% (95.8 – 96.2%). During validation dataset, the CNN presented 88.9% sensitivity, 98.9% specificity, 95.8% PPV, 97.1% NPV, 96.8% accuracy and AUC-PR of 0.97. The CNN processed 124 frames per second.

Conclusion
This is the first CNN that can detect pleomorphic lesions in a panendoscopic and multidevice scenario (containing the majority of DAE devices used in medical practice). The model accurately identified pleomorphic lesions throughout the GI tract, featuring a short processing frame rate that may allow its application in real-time clinical procedures. The development and application of these systems could amplify the indications and benefits of DAE, increasing its diagnostic yield and cost-effectiveness.
P270 Male Genitourinary Dysfunction after Primary and Reoperative Ileoanal Pouch Surgery
Authors: Hernandez Dominguez O , Prien C , Almarzooqi R , Sanchetti H , Lavryk O , Somovilla J , Liska D , Kanters A , Gorgun E , Steele S , Holubar S 
Published: January 2024

Abstract

Background
Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the preferred surgical treatment for patients with IBD or FAP. As these diseases often manifest during adolescence or early adulthood, treatment effects on genitourinary function (GU) and sexual function are of paramount importance. However, the reoperative IPAA (R-IPAA) effects on male GU function and sexual function compared to primary IPAA (P-IPAA) are not known. Therefore, we conducted an observational survey to compare the long-term GU functionality of P-IPAA and R-IPAA long-term GU functionality male patients. We hypothesized that R-IPAA is associated with higher GU-dysfunction compared to R-IPAA.

Methods
All adult male patients who underwent IPAA at a single tertiary hospital between 1983 and 2022 were identified and demographics and clinical data were obtained from our prospectively maintained pouch registry. Patients were surveyed using validated questionnaires (Table 1). The primary outcome was composite survey scores. Patients were stratified into P-IPAA or R-IPAA groups; R-IPAA was defined as IPAA excision, reconstruction, or revision. Patients status-post prostatectomy were excluded.

Results
A total of 1,836 male patients were surveyed, and 457 (24.9%) submitted a response. After exclusion criteria, 339 responses were analyzed:296 (87.3%) P-IPAA and 38 (11.2%) R-IPAA, which included 22 redo IPAA, 9 excisions, and 7 revisions. In both groups, most patients had ulcerative colitis (89 vs. 90%). P-IPAA compared to R-IPAA had a similar age at surgery (40.8 vs. 42, p=0.59), similar age at survey (56.2 vs. 56.4, p=0.94), and a similar interval between surgery and survey (15.4 vs. 14.4, p=0.51). The P-IPAA group had less severe sexual dysfunction than the R-IPAA group (IBD-MSDS, 2.0 vs. 7.0, p=0.002). No significant difference was observed between P-IPAA and R-IPAA in erectile dysfunction (SHIM score 21 vs. 18.5, p=0.24), urinary tract symptoms (CLLS, 5.5 vs. 8.0, p=0.06), use of therapeutic aids for sexual activity (6 vs. 7, p=0.29), or orgasm ability (4 vs. 4, p=0.3). Patients with P-IPAA had a higher CGQoL (0.83 vs. 0.7, p=0.02). There were no differences between patients who had difficulty conceiving a child (4 vs. 7, p=0.5) and those who experienced infertility (3 vs. 1, p=0.43). In patients with fertility problems, no quality-of-life differences were observed between the groups (FertiQoL, 85.9 vs. 88.5, p=0.62).

Conclusion
Primary-IPAA was associated with increased sexual function and overall higher global quality of life compared to R-IPAA. No difference in erectile function, LUTS, and the need for therapeutic aids for sexual function, orgasm ability, or fertility were observed.
P296 Preclinical protein signatures in blood predict Crohn's disease and Ulcerative colitis several years before the diagnosis
Authors: Grännö O , Salomon B , Lindqvist C M , Hedin C R H , Carlson M , Dannenberg K , Andersson E , Söderholm J D , Keita Å V , Öhman L , Magnusson M K , D’Amato M , Eriksson C , Hultdin J , Kruse R , Cao Y , Repsilber D , Bergemalm D , Grip O , Karling P , Halfvarson J 
Published: January 2024

Abstract

Background
We aimed to identify protein signatures predictive of a future diagnosis of inflammatory bowel disease (IBD).

Methods
We conducted a case-control study, nested within large population-based cohorts with biorepositories. Samples were obtained from individuals who later in life were diagnosed with IBD (preclinical cases) and compared with age and sex-matched individuals who remained free from IBD during follow-up (controls). Using proximity extension assays (Olink, Uppsala), we measured 176 proteins. We applied regularized logistic regression to identify protein signatures of preclinical disease in serum from the discovery cohort (n=312). Their performance was validated in an external preclinical cohort (n=222). The biological relevance of identified proteins was further assessed in an inception cohort (n=144). Finally, we used an IBD twin cohort (n=327) to examine the impact of genetic and shared environmental factors on identified proteins.

Results
We identified 34 proteins associated with preclinical Crohn’s disease (CD) in the discovery cohort (Pfalse discovery rate &lt;0.10), with 9 confirmed in the validation cohort (Pfalse discovery rate &lt;0.05). For preclinical ulcerative colitis (UC), 45 proteins were identified and 12 validated (Fig. 1A-B). In the discovery cohort, a signature of 29 proteins differentiated preclinical CD cases from controls with an AUC of 0.85 (Fig. 1G). Its performance was confirmed when applied to the preclinical validation cohort (AUC=0.84, Fig. 1H). Moreover, the signature had excellent capacity to differentiate newly diagnosed CD from healthy controls in the inception cohort (AUC = 0.99, Fig. 1I). The preclinical UC signature had a significant, but albeit lower, predictive capacity in the discovery (AUC=0.77), validation (AUC=0.67) and inception cohort (AUC=0.90, Fig. 1G-I).15 of 17 proteins associated with preclinical IBD demonstrated significantly higher intra-pair correlation coefficients in healthy monozygotic- compared to dizygotic twin pairs, indicating an influence from genetic factors on the regulation of these protein markers. The preclinical signature for CD demonstrated an AUC of 0.87 when comparing twins with preclinical CD (n=10) to matched external healthy twins. However, its predictive capacity was lower when comparing preclinical CD twins with their healthy twin siblings (AUC=0.58), i.e., when accounting for genetic and shared environmental factors. The difference in AUC estimates in the twin cohort was not significant (P=0.07).

Conclusion
We identified protein signatures for predicting clinical onset of CD and UC, validated across independent cohorts. Specifically for CD, the preclinical signature offers significant potential for early detection.
P299 Ulcerative Colitis Severity Assessment through Abdominal Ultrasonography: A Diagnostic Accuracy Meta-analysis
Authors: Elhadi M , Faraj H , Ala K 
Published: January 2024

Abstract

Background
Ulcerative colitis, a prevalent form of inflammatory bowel disease, necessitates a precise evaluation of disease severity. While effective, traditional diagnostic methods like colonoscopy are invasive and uncomfortable for patients. Abdominal ultrasonography offers a non-invasive alternative for this assessment, but its differential accuracy in evaluating disease severity in the right and left colon is not fully explored.This study aims to assess the diagnostic accuracy of abdominal ultrasonography in determining the severity of ulcerative colitis, focusing on its performance in the right and left colon.

Methods
A systematic review was conducted in PubMed, EMBASE, and the Cochrane Library, targeting studies up to June 2023. The selection criteria included studies that used abdominal ultrasonography for ulcerative colitis severity assessment, compared against histopathology or combined clinical, endoscopic, and radiological findings. Data analysis was performed using R software (version 4.0.3) with the mada package. This analysis focused on calculating sensitivity, specificity, diagnostic odds ratio, and positive and negative Likelihood Ratios for both the right and left colon, each with a 95% Confidence Interval.

Results
The search identified 5 studies with a total of 383 ulcerative colitis patients. In the right colon, the pooled sensitivity was 73.7% (95% CI, 57.6-85.2%, I2=0%), and specificity was 99.5% (95% CI, 1.6-100%, I2=0%). The diagnostic odds ratio was extremely high at 560.1 (95% CI, 0.04-6966551), with a positive Likelihood Ratio of 148.14 (95% CI, 0.01-1713586.1) and a negative Likelihood Ratio of 0.26 (95% CI, 0.15-0.45). In the left colon, sensitivity was higher at 93.7% (95% CI, 87.2-97%, I2=49.1%) with a specificity of 73.3% (95% CI, 41.8-91.3%, I2=70.9%). The diagnostic odds ratio for the left colon was 40.96 (95% CI, 8.67-193.62), with a positive Likelihood Ratio of 3.51 (95% CI, 1.31-9.42) and a negative Likelihood Ratio of 0.08 (95% CI, 0.04-0.19).

Conclusion
Abdominal ultrasonography shows promising results in assessing disease severity in ulcerative colitis, particularly in the left colon. The high specificity in the right colon is notable, but the wide confidence intervals suggest caution in interpretation, likely due to the small sample sizes and study variability. The left colon's more consistent and reliable performance indicates its suitability for routine clinical use in this region. This study highlights the need for further research with larger patient cohorts and standardized methodologies to solidify these findings and optimize ultrasonography’s role in ulcerative colitis management.
P305 The serum protein profile across the IBD spectrum: Results from the COLLIBRI consortium
Authors: Salomon B , Sudhakar P , Verstockt B , Ungaro R C , Aden K , D'Haens G R , Silverberg M S , Repsilber D , Vermeire S , Halfvarson J 
Published: January 2024

Abstract

Background
Inflammatory bowel disease (IBD) is a heterogeneous disorder. Both subtypes, i.e., Crohn’s disease (CD) and ulcerative colitis (UC), differ in disease behaviour and inflamed gastrointestinal segments. Despite this, randomized controlled trials stratify patients based on CD and UC. Molecular characterization could uncover subtype-specific differences that could guide treatment and thereby overcome current therapeutic limitations. Therefore, we aimed to examine differences in serum inflammatory protein profiles across the IBD spectrum.

Methods
This was a cross-sectional multicentre study of adult patients (≥18 years) with IBD from one Belgian and eight Swedish hospitals in the COLLIBRI consortium. IBD diagnosis and classification was based on international criteria, according to the Montreal classification. Relative serum protein levels were assessed using proximity extension assay technology (Olink Proteomics, Uppsala, Sweden; inflammation panel). We adopted smoothly clipped absolute deviation penalized logistic regression models to discriminate CD and UC patients. Using fitted CD vs UC logistic models, we estimated probability scores of CD vs UC for each patient based on their serum protein profiles. Scores ranged from 0 to 1, where lower scores indicated a higher molecular resemblance to UC. We evaluated the performance using leave-one-out cross-validation and the area under the curve (AUC).

Results
Relative levels of 86 serum inflammatory proteins were available from 1,551 patients with IBD (CD, N=883; UC, N=639 and IBD-U, N=29) (Table 1). CD vs UC probability scores based on protein estimates for patients with UC, IBDU and different CD phenotypes (ileal CD, L1; colonic CD, L2; ileocolonic CD L3) are shown in Figure 1A. We observed a spectrum of IBD patients based on their CD vs CD probability scores with most pronounced differences between ileal CD and UC. Probability scores also differed significantly between colonic CD and ileal CD, but not between ileal and ileocolonic CD. The model performance to discriminate CD and UC yielded an AUC of 0.75. Restricting the samples to only one CD phenotype vs UC respectively resulted in the highest AUC for ileal CD (0.81), followed by ileocolonic CD (0.75) and colonic CD (0.65). Key proteins in the CD vs. UC model with higher protein estimates in UC were IL-17A, MMP10, FGF19. Contrary, CSF1, and SLAMF1, were higher in CD (Figure 1B).

Conclusion
Our results on inflammation related serum proteins advocate for a more nuanced classification of CD into ileal-predominant and colonic-predominant subtypes. Such stratification could advance our understanding of IBD pathophysiology and may provide guidance for future therapeutic approaches.
P307 Novel proteomic analysis of 11,000 serum proteins distinguishes between Crohn’s disease and ulcerative colitis in pediatric patients
Authors: Wu M C , Dillon S , Omede M , Gu X , Otu H , Ngo L , Winter H , Libermann T 
Published: January 2024

Abstract

Background
While the two main inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), share various clinical features, they differ in clinical, endoscopic and histological features, and may have different underlying etiopathological mechanisms, resulting in different treatment options. Consequently, the development of reliable, highly accurate, non-invasive biomarkers that differentiate CD and UC in pediatric IBD are an unmet need of paramount importance in terms of medical care, surgical intervention, and prognosis. The most advanced proteomics technology, the aptamer-based SomaScan, enables measurement of 11,000 biologically relevant proteins, including very low abundant proteins, and was tested to discover serum protein biomarkers capable of differentiating between pediatric CD and UC.

Methods
SomaScan (SomaLogic; Boulder, CO) quantitative serum protein profiles were generated from pediatric subjects diagnosed with CD (n=56) and UC (n=25) using standard diagnostic criteria. The disease location for patients with CD was 18 L1 (ileal), 9 L2 (colonic), 27 L3 (ileo-colonic) and 2 L4 (small bowel); Inflammatory phenotype (B1) occurred in 40, stricturing (B2) in 8, penetrating (B3) in 6, and B2B3 in 2. To develop highaccuracy predictors with the lowest number of proteins for discriminating CD from UC, we used machine learning and conditional logistic regression to calculate odds ratios(OR) and 95% confidence intervals(CI) per one standard deviation increase in protein levels. Area under the curve (AUC) was calculated to determine the performance of the multi-protein model in discriminating CD cases from UC cases. Ingenuity pathway analysis was conducted to identify pathophysiological pathway differences between CD and UC.

Results
There were 256 proteins that were discriminating between CD and UC with fold change &gt;1.3 and an unadjusted p-value &lt;0.05. Of these, 38 proteins were associated with increased odds and 218 proteins were associated with decreased odds of CD diagnosis. Compared to UC, CD cases had decreased neutrophil movement and degranulation, inflammatory response, and metabolism of reactive oxygen species but enhanced apoptosis. When we developed a multi-protein model and assessed its performance to discriminate CDs cases from UC cases, a 4-protein model showed an AUC=0.97.

Conclusion
Using the most comprehensive proteomics platform, we identified serum proteins and developed a high accuracy multi-protein model discriminating between pediatric CD and UC. The utility of SomaScan demonstrates not only the value of these diagnostic biomarkers, but also the potential to discover immune and metabolic pathways that distinguish CD from UC.