bluuebunny/crossref_metadata_2025_split huggingface dataset:
P089 Long ncRNA Landscape in the Rectum of Treatment Naïve Early Onset Ulcerative Colitis Highlights Association with Severity and Early and Late Disease Outcome, with Potential Role in Epithelial Metabolic Functions
Authors: Haberman Ziv Y , Braun T , Sosnovski K , Amir A , VanDussen K , Igor Ulitsky I U , Griffiths A , Walters T , Mack D , Boyle B , Kugathasan S , Jegga A , Hyams J , Denson L 
Published: January 2022

Abstract

Background
Long non-coding RNAs (lncRNAs) are tissue-specific and regulate cellular functions. We previously reported a dramatic inhibition of epithelial metabolic mitochondrial functions in mucosal biopsies from the UC PROTECT cohort. We aimed to define lncRNAs that are dysregulated in UC, linked with attenuated epithelial metabolic functions, and associated with worse outcome.

Methods
Transcriptomics of pre-treatment rectal biopsies in PROTECT UC [206 UC and 20 controls (Ctl)]. Weighted gene co-expression network analysis (WGCNA) to identify modules and gens associated with UC severity, week 4 remission after 5-ASA/steroids (W4R), week 52 steroid-free remission (W52SFR), and colectomy within 3 years. Epithelial mechanistic data of prioritized lncRNA.

Results
PROTECT transriptomics included 2,826 lncRNA genes with TPM&gt;1 in 20% of samples. Principal components analysis (PCA, Fig 1) using these lncRNA showed distinct clusters of UC and Ctl, and PC2 values were linked (p&lt;0.01) with endoscopic (Mayo score) and clinical (PUCAI) disease severities. Random forest classifiers using the 2,826 lncRNA trained to distinguish UC from Ctl using PROTECT, predicted the correct diagnosis in PROTECT (AUC=1) and in RISK (AUC=0.88) connecting lncRNA to UC pathogenesis in two independent cohorts. WGCNA on the 2,826 lncRNA resulted in 6 modules (M1-M6) associated with UC (p&lt;0.01, Fig 2). M1, which contained lncRNA reduced in UC, was associated with lessW4R (p=0.01) less W52SFR (p=0.04) and increased colectomy (p=0.02). In contrast, M6, which contained lncRNA elevated in UC, was linked with W4R (p=0.008). The hub genes in the M1 and M6 modules included GATA6-AS1 and LINC01272 lncRNAs, respectively. Re-analysis of single cell datasets supported epithelial expression of GATA6-AS1 and myeloid expression of LINC01272. GATA6-AS1 co-expression with protein-coding genes in PROTECT showed significant enrichment for mitochondrial functions (p&lt;1E-40). Reduction of GATA6-AS1 expression with 2 shRNAs resulted in reduced mitochondrial complex IV MT-CO2 mRNA and protein and reduction of LGR5, linking mitochondrial genes and function with epithelial renewal. We recently showed pronounced reduction of the mitochondrial membrane potential (MMP) by JC-1 staining in UC epithelia. Consistent with this finding, GATA6-AS1 inhibition reduced MMP levels from 0.22 in control to 0.08 (p=0.01), similarly to MMP of cells treated with CCCP that is known to depolarize and reduce MMP.

Conclusion
LncRNA are significantly linked with UC and disease severity, and the M1 epithelial enriched module shows significant association with worse outcome. GATA6-AS1 within the M1 hub genes show potential role in epithelial metabolic functions and renewal.
P101 Isosteviol Attenuates Dextran Sulfate Sodium-Induced Colitis by Maintaining the Intestinal Barrier Through PDK1/AKT/NF-κB Signaling
Authors: Yao L , Cao Q 
Published: January 2022

Abstract

Background
Inflammatory bowel disease (IBD) is a chronic debilitating inflammatory disorder of the gastrointestinal tract that is characterized by intestinal epithelial barrier dysfunction and excessive activation of the mucosal immune system. Isosteviol (IS) has been reported to possess anti-inﬂammatory properties. Thus, in this study, we aimed to investigate the therapeutic effects and detailed mechanisms of IS use against intestinal inflammation using both in vivo and in vitro models.

Methods
C57BL/6 mice were randomly divided into sham, dextran sodium sulfate (DSS), and DSS+IS groups. Colitis was established using 3.0% DSS through oral gavage for five consecutive days. In vitro, tumor necrosis factor-α (TNF-α)-treated Caco-2 cells were used as an inflammatory model. Clinical characteristics, histological performance, proinflammatory cytokine expression, and intestinal barrier function were measured. In addition, activation of the pyruvate dehydrogenase kinase 1/protein kinase B/nuclear factor-κB (PDK1/AKT/NF-κB) signaling pathway was determined by western blotting, quantitative polymerase chain reaction, and immunofluorescence assays.

Results
IS mitigated DSS-induced colitis by significantly reducing body weight loss, colonic shortening, and the disease activity index score via inhibition of colonic proinflammatory cytokine production of IL-1β, IL-6, and TNF-α. IS restored impaired barrier function by regulating tight junctions and intestinal epithelial barrier permeability. Furthermore, we found that IS ameliorated intestinal barrier injury by regulating the PDK1-dependent AKT/NF-κB signaling pathway.

Conclusion
Our results demonstrate that IS attenuates experimental colitis by preserving intestinal barrier function, probably mediated by the PDK1/AKT/NF-κB signaling pathway. These findings highlight the potential of IS as a novel therapeutic agent for IBD.
P117 point-of-care intestinal ultrasound for the detection of postoperative Crohn’s disease endoscopic recurrence
Authors: Dolinger M , Stauber Z , Spencer E , Kayal M , Pittman N , Colombel J F , Dubinsky M 
Published: January 2022

Abstract

Background
In patients with Crohn’s disease (CD), following an ileocolic resection (ICR), colonoscopy is the gold standard for the detection of endoscopic recurrence (ER). Colonoscopy, however, is invasive and not easily accepted by patients, particularly for repeated monitoring. In contrast, intestinal ultrasound (IUS) has the advantage of being non-irradiating, non-invasive, well-tolerated, and easy to repeat. The goal of this study was to assess the accuracy of IUS for ER in CD.

Methods
This was a cross-sectional study of CD patients who underwent IUS during a postoperative clinic visit within 30 days of a planned colonoscopy. Parameters on IUS included bowel wall thickness (BWT), bowel wall hyperemia (BWH; modified Limberg score 0-III), layer stratification, inflammatory fat, and complications. C-reactive protein (CRP), fecal calprotectin (FC), endoscopic healing index (EHI; Prometheus Labs, CA) and Harvey Bradshaw Index (HBI) were also measured. ER was defined as a Rutgeerts Score (RS) &gt; i2. Primary outcome was the association between IUS parameters and ER. Secondary outcomes were the association of IUS parameters with other markers of disease activity.

Results
Eighteen CD patients (9 female; 29 [19–40] years old), underwent IUS examination 45 [29–99] months post-ICR during a routine clinic visit. Seven (39%) patients were on ustekinumab, four (22%) on adalimumab, two (11%) on infliximab, one (6%) on vedolizumab, and four (22%) on no therapy. ER was found in eight (44%) patients. BWT and BWH in the neo-terminal ileum and BWH at the ileocolic anastomosis were the only IUS parameters associated with ER (Table 1). Neo-terminal ileum BWT was 4.0 [3.2–4.8] mm in patients with ER compared to 2.0 [1.5–2.6] mm without (p=0.04). Neo-terminal ileum BWH was abnormal in six (75%) patients with ER compared to 0% without (p=0.007). BWT of 3.2 mm was the optimal cut point for predicting ER with an: AUROC of 0.82, positive predictive value of 100%, negative predictive value of 97.3%, sensitivity of 75%, and specificity of 100% (Figure 1) vs. a CRP of 10.4 mg/L (AUROC = 0.54) or FC of 1146 µg/g (AUROC = 0.56). Significant correlations were observed between neo-terminal ileum BWT and RS (ρ=0.51, p=0.04) and between BWT and CRP (ρ=-0.56, p=0.023). No correlation was observed between BWT and FC (ρ=-0.04, p=0.91), BWT and EHI (ρ=-0.04, p=0.91), or BWT and HBI (ρ=0.09, p=0.75).

Conclusion
IUS is a feasible, accurate, non-invasive monitoring tool for detection of postoperative CD recurrence. Larger prospective studies are needed to determine how IUS can be integrated in the monitoring of CD patients after surgery.
P123 Characteristics of small bowel involvement and association with clinical outcome in patients with Crohn’s disease
Authors: Yoon H , Park J , Kim H Y , Lee Y J , Shin C M , Park Y S , Kim N , Lee D H 
Published: January 2022

Abstract

Background
The location and number of involved sub-segments in small bowel Crohn’s disease (CD) vary on each patient. This study aimed to evaluate the distribution and characteristics of involved small intestine lesions through a detailed image review at the time of diagnosis and to evaluate the relationship between them and clinical outcomes.

Methods
CD patients who underwent computed tomography (CT) at the initial diagnosis were retrospectively enrolled. Two abdominal radiologists reviewed the CT images of all patients. They independently rated the presence of “bowel wall thickening”, “stricture”, and “fistula or abscess” in the jejunum, distal jejunum/proximal ileum, ileum, and terminal ileum, respectively. Score 1 was assigned if both radiologists concurred regarding the presence of a lesion. Based on the total score summed across different locations in the small bowel (e.g., imaging score), we divided the patients into three groups as 0, 1–2, and 3–4. Major clinical outcomes were compared among these groups.

Results
A total of 152 patients were enrolled. The proportion of the patients involved in the jejunum, distal jejunum/proximal ileum, ileum, and terminal ileum was 2.0%, 30.3%, 82.2%, and 71.7%, respectively; 32.3% of the patients had Montreal classification L4 (involvement of jejunum or distal jejunum/proximal ileum). Agreement on fistula or abscess was almost perfect (kappa value = 1.0 for most segments); the degree of agreement on bowel wall thickness and stricture varied according to involved segments (kappa value = 0.690–0.936). There were 15 (9.9%), 100 (65.8%), and 37 (24.3%) patients in groups 0, 1–2, and 3–4, respectively. In Kaplan-Meier survival analysis, there was no difference in the major clinical outcomes among three groups based on the imaging score (emergency room visit p = 0.093; operation p = 0.080; new use of corticosteroid p = 0.139; and new use of biologics p = 0.126). In the multivariable analysis, disease behavior was the only risk factor associated with all clinical outcomes after adjusting other factor (emergency room visit, HR 2.127 [1.356–3.337], p = 0.001; operation, HR 8.216 [2.629–25.683], p &lt; 0.001; new use of corticosteroid, HR 1.816 [1.249–2.642], p =0.002; and new use of biologics, HR 2.352 [1.492–3.708], p &lt; 0.001).

Conclusion
As a result of a detailed CT review, about one-third and one-fourth of patients newly diagnosed as small bowel CD had L4 lesions and multiple lesions (&gt; 2 segments), respectively. However, the location and number of involved sub-segments in small bowel CD did not affect the clinical outcomes. Initial disease behavior is a more critical factor associated with clinical outcomes than characteristics of disease location.
P142 Inflammatory bowel diseases associated with primary immunodeficiency: a multicenter study
Authors: Malamut G , Simon M , Nachury M , Uzzan M , Serrero M , Fumery M , Trang-Poisson C , Zallot C , Abitbol V , Charbit-Henrion F , Gornet J M , Picard C , Cerf-Bensussan N , Chaussade S , Sokol H 
Published: January 2022

Abstract

Background
Inflammatory bowel diseases (IBD) associated with primary immunodeficiency (PID) remain poorly known. We aimed to isolate characteristics of IBD associated with PID.

Methods
Using a GETAID register, we reviewed medical files of recorded patients with PID and IBD (Crohn’s disease, ulcerative colitis (UC) or microscopic colitis) followed in 9 adult university hospitals. Results of genetic investigations were available for 46 patients (62%).

Results
74 patients (30 F, 44M) were included with a mean age of 26 years (median: 24 years) at diagnosis of IBD. Forty-four (59%) patients had Crohn’s disease with anoperineal lesions in 12, 26(35%) patients had microscopic (mainly lymphocytic) colitis and 4 patients had UC. PID was predominantly antibody deficiency in 40(54%) patients [34 common variable immunodeficiency, 4 X-linked agammaglobulinemia, 2 selective IgA deficiencies], disease of immune dysregulation in 18(24%) patients [CTLA4, LRBA, NFKB1, TNFAi3, XIAP deficiencies, STAT3 and STAT1 hyperactivation], phagocytosis deficiency in 15(20%) patients (12 chronic granulomatous diseases (CGD), 3 congenital neutropenia] and C1s deficiency (n=1). In order of frequency, Crohn’s disease was associated with antibody deficiencies (52%), phagocytosis deficiencies (29%) and immune dysregulation (18%), microscopic colitis with antibody deficiencies (65%), immune dysregulation (27%) and more rarely with phagocytosis deficiencies (8%) and UC with antibody deficiencies (75%) and immune dysregulation (25%). 46% of patients received immunoglobulin supplementation, 70% steroids, equally corticosteroids and budesonide, 49% biotherapy mainly anti-TNF-alpha antibody (38%) and ustekinumab (16%), 23% immunosuppressive drugs, mainly azathioprine and sirolimus and 18% aminosalicylates. Three patients (2 CGD, 1 XIAP) had been treated with allogeneic stem cell transplantation (SCT) and one patient (TNFRS13B deficiency) with autologous SCT. Eleven (15%) patients had intestinal surgery, mainly ileocecal resection. During follow-up [mean: 16 years], 51% of patients had transient or sustained clinical remission mainly with an anti-TNF-alpha antibody, ustekinumab, steroids (budesonide) and specific therapy (targeted therapy such as abatacept and ASCT), 41% of patients had severe infections, 22% developed neoplasia mainly gastrointestinal dysplasia and/or cancers (n=8), B cell lymphoma (n=3) and 4 patients died.

Conclusion
At adulthood in our series, IBD associated with PID are mainly Crohn’s disease and lymphocytic colitis. The first most frequent associated PID is antibody deficiency. Biotherapies (anti-TNF-alpha antibody, ustekinumab), steroids and specific therapies are commonly used to induce clinical remission.
P144 Changes of fecal metabolic and lipidomic features by anti-tumor necrosis factor treatment and prediction of clinical remission in patients with ulcerative colitis
Authors: Shin Shin S , Kim S Y , Park S J , Im J P , Kim H J , Lee K M , Kim J W , Jung S A , Lee J , Kang S B , Shin S J , Kim E S , Kim Y S , Kim T O , Kim H S , Park D I , Kim H K , Kim E S , Kim Y H , Teng D , Kim J H , Kim W , Saeed M , Moon J M , Kim K , Choi C H , Choi H K 
Published: January 2022

Abstract

Background
Tumor necrosis factor (TNF) antagonists are recommended for patients with ulcerative colitis (UC) for the effectiveness in inducing and maintaining clinical remission. We investigated the altered fecal metabolites and lipids by anti-TNF treatment and prediction model of remission in patients with UC.

Methods
A prospective, observational multicenter study was conducted at 17 academic hospitals in Korea. Fecal samples were collected from adult patients with moderately to severely active UC (n=116) before and after 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n=37). Clinical remission was assessed using Mayo score. Metabolome and lipidome analyses were performed using gas chromatography-, and nano electro spray ionization-mass spectrometry, respectively. Prediction models of remission were developed using baseline fecal samples by Fourier transform-infrared (FT-IR) spectroscopy combined with machine learning algorithms.

Results
Fecal metabolites and lipids in UC were different from HC at baseline and were changed similarly to HC during treatment. Fecal metabolites and lipids in remitters (RM) after treatment were more grouped and clustered with those of HC compared with non-remitters (NRM). In RM, 2-aminobutyric acid, galactose and dodecanoate levels which were previously decreased at baseline compared to HC increased to the levels of HC, whereas benzoate, stigmasterol, 3-hydroxybutyrate, diacylglycerol and triacylglycerol levels which were previously increased at baseline compared to HC decreased to the levels of HC after 56 weeks of treatment. The best model predicting short-term remission was developed by applying logistic regression (LR) and radial basis functions (rbf) support vector machine (SVM) with an accuracy of 0.99 (95% confidence interval [CI], 0.98–1.01). For long-term remission, the best prediction model was developed by rbf-SVM revealing 0.99 [CI 0.98–1.01]. LR and K-nearest neighbors also showed excellent performance for prediction of long-term remission (accuracy of 0.96 [CI 0.90–1.02] and 0.96 [CI 0.92–1.00], respectively.

Conclusion
Fecal characteristics in UC were changed after anti-TNF treatment and became similar to those of HC. Potential therapeutic target compounds were suggested to develop novel therapeutic strategies for UC. Novel remission prediction models by FT-IR spectroscopy were also established.
P147 Do IBD Patient Treatment Outcomes Expectations Differ by Ethnicity and Gender?
Authors: Broide E , Richter V , Mari A , Khoury T , Shirin H , Naftali T 
Published: January 2022

Abstract

Background
Understanding IBD Patient’s expectations of treatments outcomes may improve understanding of patient’s needs. These expectations may differ in different ethnic groups. Awareness of the patient’s expectations and preferences will decrease the gap between patients and physicians.
We aimed to investigate patient’s preferences and priorities for treatment outcomes among Jewish and Muslim IBD patients in Israel.

Methods
A prospective survey of Muslim IBD patients was compared to historical data of Jewish IBD patients. Data included demographics, socioeconomics, and disease parameters. Patients were asked to rank ten items regarding their preferences for treatment outcome, based on the ten IBD disk items.

Results
121 Muslim patients were compared to 240 Jewish patients. Both groups were equal regarding age and IBD type (Crohn’s or ulcerative colitis). The Jewish IBD patients were characterized by including more female (p&lt;0.001), higher education level (p=0.02), more urban residence (p&lt;0.001), less unemployment (p=0.012), higher income level (p&lt;0.001), and less relationship with a partner (p&lt;0.001).
Patient’s priorities stratified according to the 10 IBD disk items revealed that disease symptoms including abdominal pain, energy, and regular defecation ranked highest in both Muslims and Jews. The scores given by the Muslim patients were significantly lower (range 6.69 - 4.29) than the scores given by the Jewish patients (range: 9.03 – 6.25) regarding all items, except for body image. Jewish women attached higher priority to abdominal pain, energy, education and work, sleep, and joint pain compared to Muslim women.
Cluster analysis and multivariable regression analysis revealed that factors associated with higher patients’ preferences (cluster 2) were Jewish religion [OR, 4.77; 95% CI, 2.36–9.61, p&lt;0.001], and disease activity [1–2 attacks: OR, 2.13; 95% CI, 1.02–4.45, p=0.043; primarily active disease: OR, 5.29; 95% CI, 2.30–12.18, p&lt;0.001].
Factors unlikely to be associated with higher patient’s preference (cluster 2) were male gender [OR, 0.5; 95% CI, 0.271–0.935, p=0.030], and income level above average [OR, 0.267; 95% CI, 0.124–0.577, p=0.001].

Conclusion
Ethnic, gender, and socioeconomic disparity have a high impact on patient’s ranking of priorities for treatment outcome. Despite the ethnic and cultural differences, symptoms relief is in the highest priority in both patient groups. Understanding patient’s priorities will improve communication and enable a better personalized approach.
P149 Prioritising colonoscopy by faecal immunochemical test result does not delay the diagnosis of inflammatory bowel disease
Authors: White K , Makin A 
Published: January 2022

Abstract

Background
Due to the Covid-19 pandemic there has been unprecedented pressure on endoscopy services. Faecal immunochemical tests (FIT) are designed to detect small amounts of blood in stool samples using antibodies specific to human haemoglobin. This test is highly specific and sensitive for colorectal cancer (CRC) and has been shown to detect mucosal healing in ulcerative colitis(1). FIT was utilised at our hospital to prioritise urgency of colonoscopy referrals. We aimed to determine whether this caused a delay in the diagnosis of inflammatory bowel disease (IBD) in this cohort.

Methods
Consecutive colonoscopy referrals (urgent, semi-urgent and routine) from September 2020 to April 2021 were prioritised by FIT result. Any patient with a FIT&gt;/=10mcg were deemed category 1 (colonoscopy within 30 days) and FIT&lt;10mcg were deemed category 2 (colonoscopy within 90 days). Demographic data were collected along with procedure result and histology.

Results
One hundred and twelve patients (52% female) had a FIT test and a subsequent diagnostic test (96 had a colonoscopy, 12 had a flexible sigmoidoscopy, 3 had a CT colonography and 1 patient declined a colonoscopy but later had a CT abdomen and pelvis. Patients who did not go on to have a diagnostic test were excluded. Sixty four patients had a FIT&lt;10 (mean age 61), 35 had a FIT 10–400 (mean age 64) and 13 patients had a FIT&gt;400 (mean age 52).
Median number of days from FIT result to diagnostic test was 56 (range -9–163) in the group with FIT&lt;10, 44 (-28–93) in the group with FIT 10–400 and 44 (10–89) in the group with FIT&gt;400.
There were no cancer diagnoses in the FIT&lt;10 group. No patients in this group had colonic inflammation. Of the patients with FIT 10–400; 4 had colonic or ileocaecal valve inflammation, 12 had polyps and 2 had a CRC. Of the patients with inflammation one had mild right sided inflammation (FIT 228), one had colitis (FIT 367), one had proctitis (FIT 87) and one had ileitis of the ileocaecal valve (FIT 119).
Of the patients with FIT&gt;400; 4/13 had a colorectal malignancy (one of which was a polyp cancer), 4/13 had colonic polyps and 3/13 had active colonic inflammation. Of the patients with inflammation one had right sided inflammation, likely crohns disease, one had severely active ulcerative colitis (UC) and one had mild proctitis, likely UC.

Conclusion
In this cohort there were no CRC or IBD diagnoses in the patients with FIT&lt;10. Therefore there was no delay in investigation of any patient subsequently diagnosed with IBD. This suggests that FIT may be safely used to stratify the priority of referrals for colonoscopy in symptomatic patients. Further work is required to confirm this.