bluuebunny/crossref_metadata_2025_split huggingface dataset:
P095 Anti-inflammatory effect of high acetate concentration on organoid-derived epithelial monolayer from patients with Ulcerative Colitis
Authors: Deleu S , Arnauts K , Machiels K , Huys G R B , Thevelein J , Raes J , Vermeire S 
Published: January 2022

Abstract

Background
Short-chain fatty acids (SCFA), such as acetate and butyrate, have gained increasing interest for their potential to suppress IBD inflammation1,4. Most data have been generated for butyrate, showing beneficial effects on the gut microbiome composition, intestinal barrier function and immune system1. The effects of acetate are less known, despite its lower toxicity on epithelial cells and its ability to support growth of butyrate-producing bacteria by metabolic cross-feeding2. Furthermore, the probiotic effect of the biotherapeutic yeast Saccharomyces cerevisiae var. boulardii might be linked to its high acetic acid production3. Here, we studied the effect of acetate on inflammatory markers and barrier integrity using an organoid-derived epithelial monolayer system obtained from Ulcerative Colitis (UC) patients.

Methods
Confluent Transwell® organoid-derived monolayers evaluated by Transepithelial electrical resistance (TEER) of 8 UC patients were basolaterally stimulated with control medium (CTRL) or with an inflammatory mix (INFL) [100 ng/ml TNF-α, 20 ng/ml IL-1β, 1 µg/ml Flagellin] (Fig. 1). After 24h, the monolayer was stimulated apically with control medium or with high acetate (HA) [100mM] and TEER was measured at 0, 24, and 48h post-stimulation. After 48h, RNA extraction of the epithelial cell monolayers and qPCR for selected target genes (IL8, TNFα, CLDN1, CLDN2, HIF1A, ZO1, OCLDN, MUC2 and MKI67) was performed. Cytokine measurement was performed using Mesoscale Discovery (Proinflammatory panel 1) on apical and basolateral media. Data were analyzed using GraphPad Prism 9 (D’Agostino & Pearson test for normality followed by Wilcoxon tests).

Results

Transcriptomic analysis of the monolayer cells showed a decrease in expression of IL8 (p=0.03), TNFα (p=0.08) and increase of HIF1A (p=0.03) upon HA administration in inflamed conditions (Fig. 2) whereas the proliferation marker MKI-67 was upregulated (p=0,03). Moreover, these findings were supported by significant decreases in pro-inflammatory cytokines measured apically after HA stimulation (Fig. 3A) such as IFNγ, TNFα, IL6, IL8 and IL1β (all p=&lt;0.01). Basolaterally, IL8 (p=0.02) and IL13 (p=&lt;0.01) increased significantly upon HA stimulation (Fig.3B). Administration of HA was associated with a numerical though non-significant increase in TEER-values (p=0.15) (Fig. 4) suggesting a potential for improved barrier integrity.

Conclusion
In this UC patient-derived epithelial cell culture model, high acetate administration positively affected barrier integrity gene expression and TEER-values and suppressed expression and production of pro-inflammatory cytokines.
References
1. Venegas, 2019
2. Gill, 2018
3. Offei, 2019
4. Deleu, 2021
P100 Serum inflammatory protein profiling to corroborate selection of therapy naïve moderate-to-severe pediatric Crohn’s disease patients eligible for first-line infliximab treatment
Authors: Jongsma M M E , Costes L M M , Tindemans I , Cozijnsen M A , Raatgreep R H C , van Pieterson M , Li Y , Escher J C , de Ridder L , Samsom J N 
Published: January 2022

Abstract

Background
Early intervention with biologic therapy, especially with anti-Tumor Necrosis Factor-a, is very effective and now more commonly used to prevent disease progression and complications in Crohn’s disease (CD). However, a rational approach to decide which patient should be treated First-line Infliximab (FL-IFX) is lacking. In this study, using serum from a randomized control trial, we assessed how changes in immune profiles prior to therapy and after the first standardized induction treatment with either FL-IFX or conventional treatment (CONV) related to maintaining disease remission at week 52.

Methods
Serum samples from therapy naive moderate to severe CD patients from the TISKIDS study1 were used at time of diagnosis and at 10–14 weeks after induction therapy with FL-IFX (n=48) and CONV (n=43). FL-IFX consisted of 5 IFX infusions (5 mg/kg) combined with azathioprine (AZA) maintenance. CONV consisted of induction therapy with Exclusive Enteral Nutrition or oral prednisolone combined with AZA maintenance. Concentrations of 92 inflammatory proteins were determined with Olink Proteomics®. Significant differences in mean protein NPX after FDR adjustment with log2fold &gt; 0.5 were considered meaningful.

Results
After 10–14 weeks of induction therapy, FL-IFX suppressed a larger number inflammatory proteins and induced stronger suppression compared to CONV. Of the 30 significantly modulated FL-IFX target proteins 18 were differentially regulated by FL-IFX only. Hierarchical clustering of patients based on their baseline profiles of the 30 IFX-modulated proteins revealed 2 patient clusters, a CD-hi cluster with significantly higher baseline clinical disease activity, CRP and blood neutrophil concentrations compared to the CD-lo cluster. The CD-hi cluster had an increased abundance of 23/30 proteins amongst which Oncostatin-M, TNFSF14, HGF and TGF-alpha compared to the CD-lo cluster (Figure 1A). Of the CD-lo patients treated with FL-IFX, 58% reached clinical disease remission without treatment escalation at week 52, while this was only 24% for CD-hi patients treated with FL-IFX. Only 20% of the CD-lo patients treated with CONV reached remission while this was only 6% for the CONV treated patients in the CD-hi group (Figure 1B). Strikingly, similar clustering using the immune profiles after 10–14 weeks induction therapy did not predict remission at week 52.

Conclusion
FL-IFX achieves stronger reduction and modulates more inflammatory serum immune protein concentrations than CONV. Stratification of patients according to profiles of IFX-modulated proteins prior to therapy identifies patients with a lower chance of reaching clinical remission without treatment escalation at week 52.

Reference
1. Jongsma MME et al. Gut. 2020 Dec; DOI:10.1136/ PMID:33384335
P102 Changes in serum immune protein profiles following vedolizumab therapy in Inflammatory Bowel Disease
Authors: O’Connell J , O’Connell F , O’Sullivan J , Kevans D 
Published: January 2022

Abstract

Background
Vedolizumab(VDZ) is a monoclonal antibody targeting α4β7-integrin which has demonstrated efficacy as induction and maintenance therapy for inflammatory bowel disease(IBD). We aimed to characterise changes in serum immune protein profiles following VDZ induction therapy and evaluate the association between serum immune protein profiles and outcome of VDZ therapy.

Methods
IBD patients commencing VDZ induction therapy were prospectively recruited. Patients received VDZ induction as per standard protocol. Week 0 and week 6 pre-infusion serum samples were collected from each patient. Serum samples were analysed using human multiplex panels (Meso Scale Discovery, Rockville, MD, USA) which quantifies 54 discrete inflammatory proteins. Corticosteroid-free remission(SFR) was assessed at week 14 and 30. Changes in serum immune protein profile were compared between baseline(week 0) and following two VDZ infusions(week 6). Serum immune proteins which demonstrated a significant week 0 to 6 change were evaluated as candidate biomarkers of week 14 and 30 SFR. Continuous variable are presented as median[range]. P values &lt; 0.05 were considered significant.

Results
N=39 IBD patients were included: age 50.4[18.2–75.8] years, UC phenotype 51%, male 51%; disease duration 13.4[0.4 – 40.8] years, clinical Mayo subscore 4[0 – 9] and HBI 7[1 – 20]. 7 of 54 analytes demonstrated a significant change from baseline to week 6. Eotaxin(p=0.001), Eotaxin-3(p=0.001), TNF-b (p&lt;0.008), TARC(p=0.015), bFGF(p=0.034) and MIP1-b(p=0.043) increased from baseline to week 6. IL-15(p&lt;0.001) reduced from baseline to week 6. There was no association between any of these 7 immune proteins and VDZ therapy outcome at week 14 or 30.

Conclusion
Changes in serum immune protein concentrations with pro-inflammatory, immunoregulatory and chemotactic functions are observed following VDZ induction therapy. Further study is required to identify serum biomarkers of VDZ therapy response.
P107 IL10 secretion endows intestinal human iNKT cells with regulatory functions towards pathogenic T lymphocytes in Crohn’s disease patients
Authors: Burrello C , Strati F , Diaz-Basabe A , Lattanzi G , Lopez G , Trombetta E , Conforti F S , Botti F , Vecchi M , Fantini M C , Caprioli F , Facciotti F 
Published: January 2022

Abstract

Background
Invariant Natural Killer T (iNKT) cells perform pleiotropic functions in different tissues by secreting a vast array of pro-inflammatory and cytotoxic molecules. However, the presence and function of human intestinal iNKT cells capable to secrete immunomodulatory molecules such as IL-10 has never been reported so far. Here we describe for the first time the presence of IL10-producing iNKT cells (NKT10 cells) in the intestinal lamina propria of healthy individuals and of Crohn’s Disease (CD) patients.

Methods
Frequency and phenotype of NKT10 cells were analyzed ex-vivo from intestinal specimens of Crohn’s disease (n=17) and controls (n=7). Stable CD-derived intestinal NKT10 cell lines were used to perform in vitro suppression assays and cocultures with patients’-derived mucosa-associated microbiota. Experimental colitis models were performed by adoptive cell transfer of murine splenic naïve CD4+ T cells in the presence or absence of IL10-sufficient or deficient iNKT cells. In vivo induction of NKT10 cells was performed by administration of SCFA by oral gavage.

Results
Patient’s derived intestinal NKT10 cells demonstrated suppressive capabilities towards pathogenic CD4+ T cells. The presence of increased proportions of mucosal NKT10 cells associated with better clinical outcomes in CD patients. Moreover, an intestinal microbial community enriched in SCFA-producing bacteria sustained the production of IL10 by iNKT cells. Finally, IL10- deficient iNKT cells failed to control the pathogenic activity of adoptively transferred CD4+ T cells in an experimental colitis model.

Conclusion
These results describe an unprecedent IL10-mediated immunoregulatory role of intestinal iNKT cells in controlling the pathogenic functions of mucosal T-helper subsets and in maintaining the intestinal immune homeostasis.
P109 Risk of cervical cancer in incident Ulcerative Colitis during the first 10 years after diagnosis: A nationwide population-based study
Authors: Kim J , Kim H , Park S C , Lee J K , Kang D R , Kim S Y , Kim H S , Kim H M 
Published: January 2022

Abstract

Background
Several studies suggested association between inflammatory bowel disease (IBD) and risk of cervical cancer in women. We investigated the risk of cervical cancer in patients with ulcerative colitis (UC) using the nationwide population-based claims data in South Korea.

Methods
We analysed the claims data of the Korean National Health Insurance (2006–2015). UC and cervical cancer were defined using International Classification of Diseases-10 codes and UC-specific prescription. Age- and sex-matched individuals without UC (control group) were randomly selected from the general population. Hazard ratios (HRs), adjusted for different covariates, were calculated using multivariate Cox proportional hazard regression.

Results
In total, 30,546 and 88,829 individuals with UC and without UC, respectively, were enrolled. Cervical cancer developed in 26 (0.21%) among UC patients, and 51 (0.14%) among control group, respectively. The standardized incidence ratio (SIR) of cervical cancer in the UC and non-UC groups were 2.04(95% confidence interval [CI], 1.33–2.98), and 1.35(95% CI, 1.00–1.77). The HR of cervical cancer in UC group, with reference to the non-UC group, was 1.56 (95% CI, 0.97–2.50). Further, UC groups were stratified according to age (HR=9.89, 1.62, 0.79 and 3.65 for 0–19, 20–39, 40–59, and ≥60 years, respectively). HR was significantly higher for early-onset UC (0–19 years) and late-onset UC (≥60 years). Among UC, age≥40, low socioeconomic status, rural residence, cerebral vascular disease are risk factors for cervical cancer.

Conclusion
UC patients had an increased risk of cervical cancer, especially with early-onset (0–19 years) and late-onset (&gt;59 years). Since cervical cancer incidence is higher in UC patients than in the general population, UC patients should receive the human papillomavirus vaccine prophylactically.
P112 The road to disease control: Combination of histologic and endoscopic remission predicts long-term disease outcome in ulcerative colitis
Authors: Bretschneider F , Kormilez D , Sari S , Pflaum T , Le H D , Nikolaus S , Lassen A , Rosenstiel P , Roecken C , Szymczak S , Schreiber S , Aden K 
Published: January 2022

Abstract

Background
Independent assessments of histologic and endoscopic scores are two commonly used parameters as therapeutic endpoints in ulcerative colitis. However, our individual goal for patients is to achieve (long-term) disease-control. It has been recently shown that the individual combination of histologic and endoscopic remission is related to favorable long-term outcomes1. However, real world evidence for the benefit of using combined endoscopic and histologic remission endpoints is scarce.

Methods
We collected data from a retrospective cohort study of n=398 patients with active UC who underwent clinical assessment and routine colonoscopy. All patients donated data and biomaterials at the University Hospital Schleswig-Holstein (Kiel) using the broad consent2. The patients were observed over a minimum of 6 months and three individual outcomes were pre-defined as outcome-endpoints: i) therapy escalation (systemic steroids/new targeted MoA), ii) long-term hospitalization and iii) IBD-related surgery.

Results
398 UC patients (female: n=166, 41.7%, male: n=232, 58.29% with a median age of 47 years at time of routine colonoscopy) were analyzed. We observed therapy escalation in 134 cases (42.27%), hospitalization in 70 cases (21.21%) and IBD-related surgery in 34 cases (10.66%). Remission at the time of colonoscopy was assessed by endoscopic Mayo (eMayo=0) or Nancy-Index (=0) and used for prediction of long-term outcome.We investigated the benefit of combined endoscopic and histologic remission on long-term outcome by comparing a combination of both eMayo=0 and Nancy=0 against eMayo=0 and Nancy&gt;0. Patients with combined histologic and endoscopic remission show a significantly reduced hazard ratio for all three outcome endpoints, such as therapy escalation (HR 0.20, CI 0.10–0.39, p&lt;0.001), hospitalization (HR 0.24, CI 0.09–0.59, p=0.002) and IBD-related surgery (HR 0.20, CI 0.05–0.84, p=0.028).

Conclusion
We show that the combined assessment of endoscopic and histologic remission substantially increases the identification of patients with favorable long-term outcome in UC. However, even in patients with combined endoscopic and histologic remission approx. 20% underwent therapy escalation within 6-month period. These data highlight the need of combined endpoints using histology, endoscopy and probably other parameters (e.g. inflammatory biomarkers, patient reported outcomes) to define disease control and predict favorable disease trajectories in the future course of patients with UC.
P121 Second-Line Biologic Therapy Persistence in a Multicentre Cohort of Inflammatory Bowel Disease Patients
Authors: Doherty J , Stack R , O Morain N , Corcoran R , Ryan B , Doherty G , Mc Namara D , Kevans D 
Published: January 2022

Abstract

Background
Anti-TNF agents are effective treatments for Inflammatory Bowel Disease (IBD), however, a significant proportion of patients require second-line biologic therapy. Real-world data on the outcome of second line biologic therapy can inform clinical decision-making.

Methods
To evaluate prescribing practice and second-line biologic therapy persistence in IBD patients. IBD patients, who had received one prior anti-TNF agent and commenced a second-line biologic, at participating centres, were identified. Baseline demographic data, concomitant medication and biologic therapy history were characterised by retrospective review of patients records. Adalimumab(ADA) and golimumab(GOL) were considered subcutaneous(SC) anti-TNF agents. Date of commencement and discontinuation of therapies were documented. Kaplan-Meier survival curves were constructed for time based analyses. P values &lt; 0.05 were considered significant in analyses.

Results
N=395 IBD patients were included; 30%, 68% and 2% had UC, CD and IBD-U respectively; age (median[IQR]) 26[18–35] years; 56% female; 35% receiving a concomitant immunomodulator (IMM); follow-up time (median [IQR]) 1.5[0.7–3.3] years. Second-line biologic therapy with SC anti-TNF, infliximab(IFX), vedolizumab(VDZ), and ustekinumab(USTK) was used in 36%(n=143), 38%(n=151), 10%(n=38), and 16%(n=63) of patients respectively. Follow-up time (median[IQR]) was significantly longer for SC anti-TNF and IFX compared with VDZ and USTK groups: 1.7 [0.7–3.6], 1.7 [0.7–3.5], 1.1[0.3–2.5], 1.3[0.5–2.3] years respectively, p=0.03. A greater proportion of patients receiving anti-TNF therapy versus alternate class biologic therapy received a concomitant IMM: 42%, 34%, 18% and 29% of SC anti-TNF, IFX, VDZ and USTK treated patients respectively, p=0.03. In a univariate survival analysis there was no significant difference in survival-free of drug discontinuation comparing second-line biologic agents, p=0.8. In a multivariate analysis, including second-line biologic agent type, concomitant IMM use, gender and IBD phenotype the only factor significantly associated with time to drug discontinuation was UC phenotype, Hazard ratio (95%CI): 1.5 (1.1 – 2.1), p=0.007.

Conclusion
While follow-up time was shorter for VDZ and USTK treated patients, the durability of response to second-line biologic therapy, assessed by drug persistence, appeared similar between agents. UC phenotype was associated with a shorter time to therapy discontinuation.
P131 Impact of Inflammatory Bowel Disease on patients’ caregivers: Results from a French cohort
Authors: El Hajj MD W , Buisson A , Olympie A , Ravel M H , Devos C , Trang C , Nahon S 
Published: January 2022

Abstract

Background
Inflammatory Bowel Disease (IBD) has an important impact on patients’ quality of life (QOL). Data on its impact on patients’ close relatives are limited. This study aims at exploring the effect of IBD on patients’ caregivers (PC).

Methods
We have conducted an online survey about the impact of IBD on PCs via the social network of the French association of IBD patients (Association François Aupetit) between october 16th and november 23rd 2020. The burden the disease had on their psychological, professional and social life was evaluated through a computerized questionnaire.

Results
Eight hundred and fifty-three PCs aged &gt; 16 years were interrogated. 77% were females. Their relatives had Crohn’s disease (CD) in 63% and Ulcerative colitis (UC) in 35% of cases. Patient was the child in 57% or the partner in 31% of cases. Fifty four percent of PCs had never heard about IBD before the diagnosis of their relatives, and upon disease announcement, 86% experienced a feeling of worry, sadness or anxiety. They were regularly searching informations about the disease through internet websites, IBD associations or health care professionals in 72, 68 and 53% of cases, respectively. Main concerns included novel therapies (55%), treatment side effects (45%), long term disease consequences (52%) and dietary limitations (47%). Twenty percent considered that they were still not well informed about the disease. The most significant impact on daily PCs’ life was psychological as they were regularly experiencing anxiety and incapacity in 94% of cases. Concerning professional impact, 36% of PCs needed to reduce or to adjust their work time, to work from home or even to change or leave their work. Among partners, the disease impacted their sexual life as 22% reported a decrease in their desire/libido and 14% reported an absence of sexual relation for weeks or months. Sixty four percent have waived many social activities as going out with friends, holidays or cinema. More than 50% wished they had more psychological support as well as more information about the disease and the way they could help their relatives. The main factors associated with a higher psychological impact were the following: Female sex (OR 2.23; 95%CI 1.51–3.28; p&lt;0.0001), parental status (OR 2.29; 95%CI 1.28–4.11; P&lt;0.0001), IBD duration &lt;5 years (OR 1.72; 95%CI 1.11–2.66; P=0.005) and the lack of information about the disease (OR 0.59; 95%CI 0.39–0.88; P=0.01).

Conclusion
IBD had an important impact on PCs’ QOL at personal and social levels. A psychological support and an appropriate information about the disease and the help they can provide to their relatives are essential to reduce the burden of IBD on their daily life.
P134 Are hepatic steatosis predictive scores still useful to predict metabolic associated fatty liver disease (MAFLD) in Crohn’s disease patients?
Authors: Capela T , Macedo Silva V , Freitas M , Cúrdia Gonçalves T , Magalhães J 
Published: January 2022

Abstract

Background
Crohn’s disease (CD) patients have a higher risk of nonalcoholic fatty liver disease (NAFLD) compared with the general population. There are many NAFLD predictive scores, including Hepatic Steatosis Index (HSI), Fatty Liver Index (FLI) and the Clinical Prediction Tool for NAFLD in Crohn’s Disease (CPN-CD), a recently validated score specifically developed for CD patients. However, it is not known whether these scores are useful in predicting metabolic associated fatty liver disease (MAFLD) in CD patients.
Our aim was analyze and compare the performances of CPN-CD, Hepatic Steatosis Index (HSI) and Fatty Liver Index (FLI) in identifying CD patients with MAFLD.

Methods
Retrospective cohort study which consecutively included all adult CD patients submitted to transient elastography (TE) from January to December 2020. Patients’ demographic, clinical and biochemical data were recorded. MAFLD criteria were assessed and hepatic steatosis (HS) was defined by a controlled attenuation parameter (CAP) &gt;248 dB/m using TE. CPN-CD, HSI, and FLI were calculated, their accuracy for the prediction of MAFLD was evaluated through a receiver-operating characteristic (ROC) curve and their areas under the ROC curve (AUROC) were compared.

Results
Of 103 CD patients, 56 (54.4%) were female with a mean age of 38.2±11.5 years. Body mass index &gt;25, type 2 diabetes mellitus, dyslipidemia and arterial hypertension were present in 53 (51.5%), 4 (3.9%), 27 (26.2%) and 9 patients (8.7%), respectively. HS was identified in 50 patients (48.5%), of which 44 (88%) fulfilled MAFLD criteria. Median HSI was 38.9 (IQR 7.2) and mean FLI and CPN-CD were 36.7±27.7 and -0.5±1.5, respectively. FLI (AUROC, 0.919; 95% confidence interval, 95% IC, 0.866–0.972), HSI (AUROC, 0.850; 95% CI, 0.775–0.925) and CPN-CD (AUROC, 0.809; 95% CI, 0.722–0.896) had excellent discrimination in predicting MAFLD. FLI performance was significantly higher than CPN-CD (P=0.01) but not significantly different from HSI (P=0.06). Additionality, HSI performance was not significantly different from CPN-CD (P=0.81).

Conclusion
The FLI, HSI and CPN-CD scores can accurately identify MAFLD in CD patients, allowing the selection of those in whom hepatic steatosis and metabolic risk factors assessment may be particularly beneficial.