bluuebunny/crossref_metadata_2025_split huggingface dataset:
P094 Differences in expression of PPARγ in small intestine vs. colon impact the effect of 5-aminosalicylates in inflammatory bowel disease
Authors: Bakke I , Bruland T , Eriksen K S , Skovdahl H K , Gopalakrishnan S , Thorsvik S , Granlund A V B , Sandvik A K , Østvik A E 
Published: January 2020

Abstract

Background
The nuclear receptor peroxisome proliferation-activated receptor γ (PPARγ) harbours anti-inflammatory effects. There is evidence that PPARγ mediates the effect of 5-aminosalicylic acid (5-ASA). 5-ASA is the first-line drug in ulcerative colitis (UC, while its use in Crohn`s disease (CD) is debated and not recommended according to guidelines. We hypothesise that the inconsistent therapeutic effect of 5-ASA in Crohn’s disease is caused by different expression of PPARγ between the large and small intestine.

Methods
Levels of PPARγ mRNA were measured by RNASeq in mucosal biopsies from (1) active/inactive ileal CD (n = 14/17) and healthy controls (n = 9) and (2) colonic biopsies from patients with active/inactive UC (n = 24/24) and active/inactive CD (n = 24/21) and healthy controls (n = 20). Subsets of ileal and colonic biopsies were examined by western blot, immunohistochemistry (IHC) and in situ hybridisation (ISH). The effects of 5-ASA on PPARγ expression and TNF/IL17/polyI:C induced cytokine release were examined in the colonic cell-line HT29 and primary human IECs (colonoids) using RNASeq and ELISA in.

Results
PPARγ mRNA was strongly downregulated in colonic biopsies from inflamed mucosa of UC (log2 = −1.65, fold change 0.319 (p &lt; 0.001)) and CD (log2 = −1.3, fold change 0.406 (p &lt; 0.001)) compared with healthy controls. In ileal biopsies from CD and controls, PPARγ mRNA was not differentially expressed between inflamed and non-inflamed or healthy mucosa. These findings were confirmed by ISH in a subset of biopsies. Western blot analysis and IHC revealed almost undetectable levels of PPARγ protein in ileum, in the colon however, PPARγ was strongly expressed in healthy controls and inactive IBD; with significantly lower levels in active IBD. PPARγ was downregulated by TNF, TNF+IL17 and TNF + poly(I:C) in colonoids derived from IBD-patients (n = 3) and non-IBD controls (n = 3). 5-ASA attenuated the release of TNF-induced proinflammatory cytokines such as CXCL1, CXCL8 and CXCL10 from both HT29 cells and colonoids. This effect was reversed by the PPARγ antagonist GW9662.

Conclusion
5-ASA harbours anti-inflammatory effects on intestinal epithelial cells mediated by epithelial PPARγ. We suggest that the previously observed lack of effect of 5-ASA in CD is related to differences in PPARγ expression in small intestine vs. colon. These results suggest that patients with Crohn’s colitis may benefit from 5-ASA similarly to UC patients and challenge the current view on use of 5-ASA in CD.
P096 Specific plasma micro-RNA profiles for prediction of recurrence in Crohn’s disease in pre-surgery and established recurrence scenarios
Authors: Moret I , Cerrillo E , Saez-Gonzalez E , Hervas D , Iborra M , Tortosa L , Nos P , Gadea J , Beltran B 
Published: January 2020

Abstract

Background
Crohn’s disease (CD) patients who undergo ileocolonic resection are at high risk of postoperative recurrence (POR). Both environmental and genetic factors are known to influence CD pathogenesis. MicroRNAs (miRs) are important epigenetic regulators in CD, but their role in the progression to POR is still unknown. Thus, we aimed to identify differential miRs profiles and their potential use to predict POR in CD patients.

Methods
A cohort of 33 CD patients who underwent a resection was consecutively and prospectively followed for at least 1 year. Patients were classified according to the presence or absence of POR during the follow-up. POR was assessed by ileocolonoscopy (Rutgeerts’ index ≥ i2b) or MRI enterography within 6–12 months after surgery. Patients received postoperative therapy to prevent POR (thiopurines 47%; anti-TNFα 25%; mesalamine 9%; combination therapy 3%; none 16%). Peripheral blood samples were taken at fixed times. Total RNA was obtained from miRNeasy Serum/Plasma Advanced Kit (Qiagen) and run on the miRCURY LNAtm Universal RT microRNA PCR with a miRs panel selection (32) based on previous experiments. The predictive accuracy of the possible predictors was assessed by using receiver operating characteristic curves with the R software.

Results
MicroRNAs profiles were studied at two different times: presurgery (PS) and at the time of the morphological POR or, in those who remained in remission, 1 year after surgery (1 year). The miRs whose fluorescent signal did not differ from background noise were excluded from the analysis [8 in PS (25%); 5 in 1 year (16%)]. Using elastic net regression, five miRs (hsa.miR.191.5p, hsa.miR.15b.5p, hsa.miR.106b.5p, hsa.miR.451a and hsa.miR.93.5p) were selected for discriminating the two patient groups at the time pre-surgery. Seven miRs (hsa.miR.15b.5p, hsa.miR.126.3p, hsa.miR.451a, hsa.let.7b.5p, hsa.miR.93.5p, hsa.miR.423.5p and hsa.miR.125b.5p) were selected for discriminating the two patient groups at the time of 1 year. Using a predictive model with these miRs, an overall AUC of 0.86 (95% confidence interval, 0.75–0.97) was achieved for PS, and 0.96 (0.92–1.0) for 1 year.

Conclusion
This study shows that plasma microRNAs are useful biomarkers in the POR scenario. When recurrence is already established, a group of plasma miRs is also specifically expressed, thus assessing them could prevent patients from receiving and endoscopic procedure for POR evaluation. Furthermore, microRNA assessment PS could predict which patients will develop recurrence within 1 year of surgery. This could also have an impact on clinical management, selecting patients who can avoid immunosuppressive treatment and the ones who may need more intensive therapeutic strategies.
P103 The treatment effect of tonsil-derived mesenchymal stem cells (T-MSCs) via regulating programmed death-1/programmed death ligand-1 (PD-1/PD-L1) in ulcerative colitis
Authors: Song E M , Joo Y H , Lim J Y , Choe A R , Tae C H , Moon C M , Kim S E , Jung H K , Shim K N , Jung S A 
Published: January 2020

Abstract

Background
The programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway has not been fully evaluated in inflammatory bowel disease. We evaluated the level of PD-1/PD-L1 in the mucosa of patients with ulcerative colitis and revealed the role of PD-1/PD-L1 in the immunomodulatory mechanism of tonsil-derived mesenchymal stem cells (T-MSCs).

Methods
We used chronic murine colitis model induced by dextran sodium sulphate (DSS). We measured the PD-1 and PD-L1 levels in inflamed colonic tissues before and after the treatment with T-MSC. We also measured the levels of PD-1 and PD-L1 in the colonic tissues from patients with ulcerative colitis and compared with those from normal controls.

Results
In chronic colitis model, the level of PD-L1 was decreased than normal controls (fold change) (1.0 vs. 0.46 ± 0.08, p = 0.05). However, the level of PD-1 was increased than normal controls (1.0 vs. 6.84 ± 8.16, p = 0.142). After treatment with T-MSC which showed significant improvement in body weight, disease activity index and colon length, the levels of PD-1 and PD-L1 were recovered; PD-L1 was significantly increased (1.04 ± 0.77 vs. 0.46 ± 0.08, p = 0.031) and the level of PD-1 was decreased (3.63 ± 1.94 vs. 6.84 ± 8.16, p = 0.537). When measuring the level of PD-1 and PD-L1 in both soluble medium and cell lysate of T-MSC, we found that the PD-1 and PD-L1 were expressed in both forms (182.63 pg/ml in soluble medium and 11.85 pg/protein (μg) in cell lysate after 7 days of differentiation period). In the analysis using human colonic tissues, a significantly increase in the levels of PD-1 and PD-L1 was observed in the colonic mucosa of patients with UC compared with normal controls (PD-1: 2.09 ± 3.95 vs. 7.93 ± 14.21, p = 0.034 and PD-L1: 2.24 ± 2.91 vs. 10.08 ± 18.13, p = 0.044).

Conclusion
The altered expression of PD-1 and PD-L1 in colonic mucosa may a possible mechanism of ulcerative colitis and T-MSC-derived PD-L1 could repress the colitis.
P110 Identification of the tryptophan metabolite 3-hydroxyanthranilic acid as a novel tool for the differentiation of Crohn’s disease phenotypes
Authors: Huhn M , Herrero San Juan M , Melcher B , Dreis C , Schmidt K , Pfeilschifter J M , Vieth M , Stein J , Radeke H H 
Published: January 2020

Abstract

Background
The widely varying therapeutic response of patients with inflammatory bowel disease (IBD) continues to raise question regarding the unclarified heterogeneity of disease pathomechanisms. While biomarkers for the differentiation of Crohn’s disease (CD) vs. ulcerative colitis (UC) have been suggested, specific markers for a subclassification of CD phenotypes are still rare. Since an altered signature of the tryptophan metabolism is associated with chronic inflammatory disease, we sought to characterise potential biomarkers focusing on the downstream metabolites of kynurenine metabolism. The widely varying therapeutic response of patients with inflammatory bowel disease (IBD) continues to raise question regarding the unclarified heterogeneity of disease pathomechanisms. While biomarkers for the differentiation of Crohn’s disease (CD) vs. ulcerative colitis (UC) have been suggested, specific markers for a subclassification of CD phenotypes are still rare. Since an altered signature of the tryptophan metabolism is associated with chronic inflammatory disease, we sought to characterise potential biomarkers focusing on the downstream metabolites of kynurenine metabolism.

Methods
Using immunohistochemical staining, we analysed and compared the mucosal tryptophan immune metabolism in biotic samples from patients with UC (n = 11), CD (n = 11) and healthy control (n = 12). Localisation-specific quantification of immune cell infiltration, tryptophan-metabolizing enzyme expression and mucosal tryptophan downstream metabolite levels was performed.

Results
As expected, we found generally increased immune cell infiltrates in the tissue of all patients with IBD. However, in patients with CD, significant differences were found between regulatory T-cell markers in the ileum compared with the colon. In line with this finding, we identified kynureninase as a modulator of immunosuppressive kynurenine levels specifically in the ileum of patients with CD. Correspondingly, significantly elevated levels of the kynurenine metabolite 3-hydroxyanthranilic acid were detected in CD ileum samples.

Conclusion
Highlighting the heterogeneity of the different phenotypes of CD, we identified 3-hydroxyanthranilic acid as a potential mucosal biomarker allowing the localisation-specific differentiation of ileum or colon inflammation in patients with CD. Moreover, we characterised the kynurenine-degrading enzyme kynureninase as a modulator of immunosuppression and chronic inflammation with potential therapeutic relevance.
P122 High correlation between faecal calprotectin and a Novel Integral Index for evaluating disease activity in ulcerative colitis patients
Authors: Yamamoto-Furusho J K , Mendieta-Escalante E A 
Published: January 2020

Abstract

Background
Ulcerative colitis (UC) is a chronic and incurable disease characterised by periods of activity and remission. There are several indexes that evaluate the UC activity from clinical, biochemical and endoscopic parameters. The faecal calprotectin is a non-invasive marker for detecting intestinal inflammation in UC patients. A new novel integral disease index (Yamamoto-Furusho index) includes clinical, biochemical, endoscopic and histological findings that evaluate the full spectrum of activity in UC patients. The aim is to correlate the Novel Index Activity index (Yamamoto-Furusho Index) with faecal calprotectin levels in UC patients and compare with other indexes.

Methods
A total of 158 patients with confirmed diagnosis of UC from the IBD Clinic were recruited in the period between July 2017 and June 2019. All demographic and clinical characteristics were collected from clinical charts. The faecal calprotectin was measured at least 1 week before the colonoscopy and biopsies. The Spearman’s Rho was used for the correlation. A p-value of &lt;0.05 was considered as significant.

Results
We analysed 185 patients with UC, 85 patients (51.8%) were women and 73 (44.5%) men, with an average current age of 43.53 years (+14.35), an age at diagnosis of 36.6 + 15.1 years and disease duration of 11.27 ± 8.1 years. The extension was distributed on proctitis (E1) in 13.3%, left colitis (E2) in 19.6% and pancolitis (E3) in 31.6%. The treatment was based on mesalazine in 93.9%, steroids in 26.2% and azathioprine in 15.9%. The correlation between faecal calprotectin and the Yamamoto–Furusho index was high (rho = 0.730, p &lt; 0.0001) compared with other indexes such as endoscopic Mayo sub-score (rho = 0.705, p = &lt;0.001); Truelove–Witts (rho = 0.644, p = &lt;0.001), Full Mayo score (rho = 0.708, p = &lt;0.001) and Montreal (rho = 0.551, p = &lt;0.001).

Conclusion
The novel integral index showed a high correlation with faecal calprotectin compared with other UC indexes for evaluating disease activity in UC patients.
P123 Sarcopenia is a predictor for severe disease course in paediatric inflammatory bowel disease
Authors: Atlan L , Pratt L T , Cohen S , Shiran S , Yerushalmy-feler A 
Published: January 2020

Abstract

Background
Inflammatory bowel disease (IBD) is a chronic immune-mediated disease with high impact on nutritional status. Sarcopenia was related to higher risk of intestinal resection and rescue therapy in adult IBD patients; however, data in paediatric population is missing. The aim of this study was to evaluate muscle mass as a predictor of disease outcome in paediatric IBD.

Methods
All paediatric IBD patients that underwent a magnetic resonance enterography (MRE) study for disease assessment at the Tel Aviv Sourasky Medical Center in 2008–2019 were retrospectively included. Muscle mass was assessed by measuring the area of the psoas muscle at the upper level of L3 on MRE by a freehand region of interest (ROI). Psoas index was defined as the average psoas area divided by body surface area, and then was divided into quartiles. Disease location and radiological signs of IBD were documented. Clinical data including disease activity and course, medications, exacerbations and laboratory results were documented.

Results
We included 101 patients, 69 (68.3%) Crohn’s disease patients and 32 (31.7%) ulcerative colitis patients. The mean age was 13.05 ± 3.48 years at diagnosis and 15.03 ± 3.27 years at MRE. The psoas index was significantly lower in patients with presence of fatty proliferation (p = 0.021), comb sign (p = 0.001) and extensive disease in MRE (p = 0.012) and in radiologic evidence of disease complications such as abscess or fistula (p = 0.027). In a univariate analysis, patients with psoas index in the lower quartile had significantly higher risk of need for biologic therapy during follow-up (HR = 35.1, p &lt; 0.001; Figure 1) and higher risk of disease exacerbation (HR = 25.1, p &lt; 0.001; Figure 2) compared with patients with psoas index in the upper quartile. In a multivariate analysis adjusted for age, gender, disease type, haemoglobin, C-reactive protein, albumin, disease activity and interval from diagnosis to MRE, patients with psoas index in the lower quartile had significantly higher risk of need for biologic therapy (HR = 12.1, p = 0.046) and of disease exacerbation (HR = 9, p = 0.047) compared with patients with psoas index in the upper quartile.

Conclusion
Sarcopenia correlates with the radiological severity of IBD and was found to be an independent predictor for severe clinical disease course. Muscle mass in MRE studies may be used as a possible marker for disease outcome in paediatric IBD.
P129 Value of diffusion-weighted magnetic resonance enterocolonography for assessing Crohn’s disease activity
Authors: Straksyte V , Kiudelis G , Kupcinskas L , Zaboriene I 
Published: January 2020

Abstract

Background
We aimed to determine diffusion-weighted imaging (DWI) value to predict active Crohn’s disease (CD) and compare apparent diffusion coefficients (ADC) with endoscopic and conventional magnetic resonance imaging (MRI) CD activity indices.

Methods
Overall, 229 patients with suspected CD prospectively underwent magnetic resonance enterocolonography (MR-EC) with DWI sequence and ileocolonoscopy. Magnetic resonance activity index (MaRIA), Clermont index, and CD endoscopic index of severity (CDEIS) were calculated.

Results
Out of 229 investigated patients, the clinical diagnosis of CD was confirmed in 100 persons. Using receiver operating characteristic curve, we showed that DWI score ≥2 had 96.9% sensitivity and 82.3% specificity for diagnosing CD. A threshold of ADC value of 1.30×10–3mm2/s can distinguish between normal and inflamed bowel segments with a sensitivity of 73.8% and a specificity of 98% using Copenhagen diagnostic criteria as the reference standard. While using MaRIA, the threshold of ADC value was established of 1.32 × 10–3 mm2/s with sensitivity and specificity (97.9%, 97.8%). ADC correlated with MaRIA-G (global) (r = -0.69, p = 0.001), Clermont-G (r = -0.722, p = 0.001) and CDEIS (r = -0.69, p = 0.001).

Conclusion
DWI is a valuable tool which is able to identify inflamed bowel segments as accurate as conventional MARIA score and to discriminate between mild and moderate and severe CD activity.
P133 Pregnancy in inflammatory bowel disease: experience of a Chilean cohort
Authors: Núñez P , Sepúlveda E , Simian D , Figueroa C , Flores L , Ibáñez P , Kronberg U , Lubascher J , Pizarro G , Quera R 
Published: January 2020

Abstract

Background
In inflammatory bowel disease (IBD), a high percentage of women are diagnosed during their reproductive age. IBD in remission is the ideal scenario when planning a pregnancy. Here, we describe the demographic, clinical and pregnancy/childbirth characteristics in patients with IBD treated at a tertiary centre in Chile between 2017 and 2019.

Methods
Observational, analytic study. We retrospectively reviewed women diagnosed with IBD who were pregnant or delivered during the study period. Demographic, clinical, obstetric and delivery data were obtained from the IBD registry, approved by the local IRB. Descriptive statistics and association tests performed (χ2, p &lt; 0.05).

Results
Forty-six women with IBD were included (Tables 1). At the beginning of pregnancy, 19 (41%) had active disease and 27 (59%) were in remission. Of those with active disease, 8 (79%) remained active and six had spontaneous abortions. In those who were in remission, 20 (74%) remained in this condition. Six patients (13%) discontinued treatment (four based on external medical advice, two on her own). Preconception counselling was performed in 16/40, group with a higher percentage of remission during pregnancy (69% vs. 25%, p = 0.006). Pregnancy outcomes by disease activity are presented in Figure 1. Patients who had a flare during pregnancy had newborn with lower weight compare with the group that always remained in remission (2,945 vs. 3,323 g; p = 0.007).

Conclusion
In this cohort, we observed that pregnancy during remission presents better outcomes and that preconception counselling would allow a better IBD control during pregnancy.
P134 Patient empowerment in inflammatory bowel disease (IBD): early education at a new diagnosis IBD clinic (NDC)
Authors: Fenech V A , Kamperidis N , Tyrrell T , Dyall L , Fofaria R , Misra R , Barber S , Randall S , Shah J , Arebi N 
Published: January 2020

Abstract

Background
IBD is a chronic condition that affects young and older people. Co-existing diseases are common. Patient-centred care includes education and support to empower patients and is a recognised dimension of high-quality care. Patient empowerment with knowledge, skills and confidence (‘patient activation’) is associated with better outcomes in many chronic diseases. We aimed to measure patient activation in recently diagnosed IBD patients and to identify factors associated with levels of activation.

Methods
A NDC was set up at St Mark’s Hospital to offer patients education, information resources and signposts to verified information sources. Patient activation was measured using the Patient Activation Measure (PAM®) tool (Insignia Health) before and after the first consultation. PAM® is a validated questionnaire with 13 questions to generate an activation score ranging from 1 to 4. Non-activation was defined as PAM levels 1 and 2. Demographic (age in years (SD)), disease specific characteristics and anxiety (Generalised Anxiety Disorder Scale, GAD-2) and depression [Patient Health Questionnaire (PHQ-2)] data were collated at the first visit. The National Statistics Socio-economic classification (NS-SEC) was used to classify socio-economic status (SES). Categorical variables were analysed with chi-square test and numerical variables with Student’s t-test.

Results
Twenty-nine patients (51.7% male) attended NDC (ulcerative colitis = 15, Crohn’s disease = 10, unclassified IBD = 4). 28 completed PAM questionnaires. Mean age was 43.2 ( ± 16.4). 5/28 had a family history of IBD, 6/28 were smokers, 11/28 had another chronic condition, and 16/28 were of non-White ethnic background. Sixty-nine% had active disease. SES and psychological scores were available for 14/28 and 16/28 patients, respectively. Fifty per cent (14/28) of patients were non-activated before NDC; 57.1% (8/14) showed an improvement in activation after NDC. Mean age for activated and non-activated patients was 40.6 ( ± 19.0) and 46.6 ( ± 13.9), respectively (p = 0.35). There was no association between gender, family history, smoking, co-morbidity, ethnic background and SES with activation. None of the four patients (4/16) who scored for anxiety or depression were activated compared with 50% (6/12) of non-anxious/depressed patients (p = 0.07). No patients (0/7) in intermediate or higher SES were activated compared with 43% (3/7) of lower SES (p = 0.05).

Conclusion
Most non-activated patients had improved activation after attending NDC. Anxiety and depression may contribute to non-activation. Early assessment of patient activation may guide healthcare providers to offer individualised support. Further studies to evaluate the sustainability of patient activation and its effect on clinical outcomes are ongoing.