bluuebunny/crossref_metadata_2025_split huggingface dataset:
P095 PD-1 expressing T cells in patients with different types of colitis
Authors: Roosenboom B , Horjus Talabur Horje C , Smids C , Leeuwis J W , Van Koolwijk E , Groenen M , Wahab P , Van Lochem E 
Published: January 2020

Abstract

Background
Immunotherapy-related colitis is a frequent adverse event in patients with malignancies, treated with inhibitors targeting programmed death-1 (PD-1). This treatment leads to enhancement of lymphocyte activity, thereby generating antitumor T-cell activity. The role of PD-1+ T cells in the pathophysiology of different types of colitis is unclear. Therefore, we aimed to study the presence of PD-1+ T cells in inflammatory bowel disease (IBD), infectious colitis and healthy controls compared with anti-PD-1-related colitis.

Methods
We performed a prospective cohort study. Newly diagnosed patients with ulcerative colitis (UC, n = 51), Crohn’s disease (CD, n = 29), infectious colitis (n = 4), anti-PD-1-related colitis (n = 5) and healthy controls (n = 6) were included. Baseline colonic biopsy specimens were collected for immunohistochemistry identifying PD-1+ and PD-L1+ lymphocytes in the epithelium and lamina propria separately and for immunophenotyping by flow cytometry identifying PD-1+ T-cell subsets.

Results
Using immunohistochemistry, PD-1 was not present on lymphocytes in the epithelium of patients with any type of colitis, nor in healthy controls. Of all lymphocytes in the lamina propria, % PD-1 expression was 40% in UC, 5% in infectious colitis, 3% in anti-PD-1-related colitis and 0% in healthy controls. PD-L1 was expressed on lymphocytes in the epithelium and lamina propria of UC patients (12.5% and 40%) and in infectious colitis (1% and 30%), whereas in anti-PD-1-related colitis (0% and 15%) and healthy controls (0% and 15%) no PD-L1+ lymphocytes were demonstrated in the epithelium. Flowcytometry showed higher percentages of PD-1+ T cells in biopsy specimens of UC patients (25.2% (IQR 17.9–35.6)) compared with all other groups; CD patients (13.5% (5.0–25.3), p = 0.001), infectious colitis (9.8% (4.7–17.4), p = 0.005), anti-PD-1-related colitis (1.5% (1.1–2.1), p = 0.001) and healthy controls (14.3% (4.9–28.2), p = 0.08). In IBD and infectious colitis, the majority of PD-1+ T cells were CD4+ (84.8% (76.5–90.5), while in anti-PD-1-related colitis the majority of PD-1+ T cells were CD8+ (76.2% (68.5–82.1)). PD-1+ T cells in all patient groups were mainly effector T cells (CD45Ro+).

Conclusion
In patients with different types of colitis and in healthy controls, PD-1 was only expressed on T cells in the lamina propria and not in the epithelium. The percentage of PD-1+ T cells was significantly higher in patients with UC compared with patients with CD or infectious colitis and healthy controls. As expected PD-1+ T cells were nearly absent in patients with anti-PD-1-related colitis.
P099 Neutrophil gelatinase-associated lipocalin (NGAL) as biomarker in collagenous colitis
Authors: Walaas G A , Bakke I , Granlund A V , Escuderos-Hernândez C , Bruland T , Røyset E S , Thorsvik S , Münch A , Østvik A E , Sandvik A K 
Published: January 2020

Abstract

Background
Neutrophil gelatinase-associated lipocalin (NGAL) is upregulated in the intestinal epithelium in inflammatory bowel disease and is a biomarker with sensitivity and specificity comparable to calprotectin. Microscopic colitis (MC) is a common cause of chronic, watery diarrhoea and represents an inflammatory bowel disease with unknown aetiology and pathogenesis. Diagnosis depends on histological evaluation of colonic biopsies. There is a need for non-invasive diagnostic tools, and this study examines the potential of NGAL as a biomarker in collagenous colitis (CC) as one of the two main histological forms of MC.

Methods
Gene expression of colonic biopsies (n = 9/group) from active CC, budesonide treated CC in clinical remission and healthy controls (HC) was explored by RNA-sequencing analysis. An extended set of colonic biopsies (n = 17–29/group) was also examined by immunohistochemistry (IHC) and in situ hybridisation (ISH). Faecal samples from the same patient groups, in addition to samples from patients with irritable bowel disease diarrhoea (IBS-D), were assayed for NGAL and calprotectin (Calpro) by ELISA.

Results
The NGAL gene, LCN2, was significantly upregulated in active CC vs. HC (log2 2.694, fold change 6.471) adjusted p-value 0.005) and in pairs of active CC vs. treated CC LCN2 was significantly downregulated (log2 0.345, fold change −1.536), adjusted p-value 0.04). Both immunohistochemical staining and in situ hybridisation identified increased NGAL expression localised to the mucosal epithelial cells in active CC, compared with an almost absent and scarce expression in HC and treated CC, respectively. There were great individual differences in faecal concentrations of NGAL particularly in the active CC group, but the NGAL concentrations were significantly increased compared with HC, IBS-D and treated CC.

Conclusion
NGAL is upregulated and located mainly to the colonic epithelium of active CC and reduced in clinical remission after budesonide treatment. This is also reflected in the faecal concentrations. We propose NGAL as a valuable biomarker in evaluating the inflammatory activity related to CC and a potential faecal biomarker discriminating CC from IBS-D.
P105 Glutathione S-transferase theta 1 protects against colitis through goblet cell differentiation via interleukin-22
Authors: Kim J H , Ahn J B , Kim D H , Kim S , Ma H W , Che X , Seo D H , Kim T I , Kim W H , Cheon J H , Kim S W 
Published: January 2020

Abstract

Background
The enzyme glutathione S-transferase theta 1 (GSTT1) is involved in detoxifying chemicals, including reactive oxygen species (ROS). Oxidative stress plays a key role in the pathogenesis of inflammatory bowel disease (IBD). Although mutation of the GSTT1 gene increases IBD susceptibility, the underlying mechanisms remain unexplained.

Methods
The Gstt1 gene was intrarectally or intraperitoneally delivered to mice with dextran sodium sulphate (DSS)-induced colitis. The GSTT1 gene was knocked down or knocked out using short interfering RNA or genome editing, respectively. Protein and mRNA expression and differentiation of goblet cells were evaluated.

Results
We identified decreased expression of GSTT1 in inflamed tissues from IBD patients and mice compared with their control counterparts, respectively. We also noted attenuation of colitis through gene transfer of Gstt1 to DSS-treated mice via the interleukin-22 (IL-22) pathway. GSTT1 was differently regulated by pathogens and host immune responses. Down-regulation of GSTT1 reduced innate defence responses and goblet cell differentiation. The GSTT1 mutation in intestinal epithelial cells as well as IBD patients diminished its dimerisation, which was connected to insufficient phosphorylation of signal transducer and activator of transcription 3 and p38/mitogen-activated protein kinase by their common activator, IL-22.

Conclusion
GSTT1 ameliorated IL-22 in colitis in a dependent manner and contributed as a modulator of goblet cells through sensing pathogens and host immune responses. Its mutations are linked to chronic intestinal inflammation due to its insufficient dimerisation. Our results provide new insights into GSTT1 mutations and their functional consequences in IBDs.
P109 Construction of a suite of computable biological network models focused on inflammatory bowel disease
Authors: Ruiz Castro P A , Yepiskoposyan H , Szostak J , Talikka M , Hoeng J 
Published: January 2020

Abstract

Background
Inﬂammatory bowel diseases (IBDs) are chronic relapsing inflammatory disorders that result from an inappropriate inflammatory response to the enteric microbiota in a genetically susceptible host. Because the molecular mechanisms of IBD have been the subject of intensive exploration, we assembled the available information into a suite of comprehensive causal biological network models, which offer a better visualisation and understanding of the processes underlying IBD.

Methods
Biological expression language (BEL), which represents biological findings in a computable form was used for scientific text curation. The curated BEL statements were compiled using the OpenBEL framework 3.0.0. Cytoscape was used to visualise and analyse network properties. The network perturbation amplitude methodology was used to score the network models with transcriptomic data from public data repositories.

Results
The IBD network model suite consists of four independent models that represent signalling pathways contributing to biological processes involved in IBD. In the ‘wound healing’ model, fibroblast growth factor and thymosin β-4-associated signalling pathways emerged as the main routes leading to epithelial cell proliferation and thus to wound repair. Phosphoinositide 3-kinases and carcinoembryonic antigen-related cell adhesion molecule-associated pathways were identified in the ‘bacterial colonisation’ model as the primary pathways modulating bacterial adhesion and internalisation. In the ‘immunity’ model, nuclear factor-κB and myeloid differentiation primary response 88 emerged as the main contributors to immune responses. In the ‘epithelial barrier defence’ model, tumour necrosis factor- and interleukin 1-associated signalling cascades were the main routes leading to tight junction disruption and thereby, to increased permeability in the intestinal epithelium. The scoring of publicly available transcriptomic data sets onto these network models demonstrates that the IBD models capture the perturbation in each dataset accurately.

Conclusion
This work is a continuation of our approach using computational biological network models and mathematical algorithms in order to interpret high-throughput molecular datasets. The IBD network model suite can provide better mechanistic insights of the transcriptional changes in IBD and constitutes a valuable tool in personalised medicine to further understand molecular heterogeneity and individual drug responses in IBD.
P118 A comprehensive evaluation of mucosal redness in patients with ulcerative colitis by linked colour imaging
Authors: Uchiyama K , Kubota M , Azuma Y , Yasuda R , Shun T , Takagi T , Naito Y , Yoshito I 
Published: January 2020

Abstract

Background
Mucosal healing is important for the patients of ulcerative colitis (UC) to avoid clinical relapse and developing colitic cancer. Though Mayo endoscopic subscore (MES) has been widely used to evaluate mucosal healing of UC patients, it is not enough to predict relapse. We have reported the new endoscopic evaluation by linked colour imaging (LCI) that enhances mucosal redness and can predict relapse with more precision compared with MES1). However, the diagnosis in both MES and LCI depends on the local lesion and it has not been established the comprehensive evaluation because mucosal redness is not clearly recognised by white light image. In the present study, we examined the comprehensive evaluation of mucosal redness in the patients of UC by LCI and investigate the relation with long-term prognosis.

Methods
All examinations were carried out with an EG-L590WR endoscope and a LASEREO endoscopic system (FUJIFILM Co., Tokyo, Japan) including 47 UC patients (pan colitis type) with clinically remission (Under 4 of Lichtiger CAI score). Each part of the large intestine (ascending colon, transverse colon, descending colon, sigmoid colon and rectum) was observed with LCI and WLI (white light image), and the area of redness (regardless of strength) was evaluated. The score was marked 0, 1, 2 and 3, in case of the area of redness is 0%, &lt;50%, 50% or higher and 100%, respectively. The score of each part was totalled (total redness score), and the relapse rate for 1 year after the endoscopy was investigated. Relapse of ulcerative colitis was defined as the need for more aggressive medication for ulcerative colitis due to aggravation or clinical symptoms, or aggravation of endoscopic findings.

Results
The relapse ratio was 19.1% (9/47 cases). The average of total redness score by LCI was 4.02 ± 2.25 and total redness score by WLI was 3.11 ± 2.5. The average of total redness score by LCI in the patients with no relapse group was 3.94 ± 2.21, on the other hand, with relapse group was 4.33 ± 2.23 (p = 0.0354). However, total redness score measured by WLI showed no statistical difference between no relapse group and relapse (p = 0.278).

Conclusion
A comprehensive evaluation of mucosal redness using LCI is useful approach to predict relapse for UC patients with clinical remission.
P143 Gastrointestinal ultrasound is an accurate marker for endoscopic activity in Crohn’s disease
Authors: Sævik F , Gilja O H , Nylund K 
Published: January 2020

Abstract

Background
Treatment goals for Crohn’s disease (CD) have changed from symptom control to objective endpoints, preferably endoscopic remission. However, as the relative invasiveness of ileocolonoscopy limits repeated examinations, a surrogate marker of endoscopic remission is needed. Gastrointestinal ultrasound (GIUS) is accurate in detecting CD, and we aimed to explore its ability to distinguish between patients with active disease from patients in remission.

Methods
One hundred and forty-five CD patients scheduled for ileocolonoscopy were prospectively included. The endoscopic disease activity was quantified using the Simple Endoscopic Score for Crohn’s disease (SES-CD), and endoscopic remission was strictly defined as SES-CD=0. Ultrasound remission was defined as wall thickness &lt;3 mm (&lt;4 mm in the rectum). Additionally, SES-CD was compared with colour Doppler, Harvey Bradshaw’s index (HBI), C-reactive protein (CRP) and calprotectin. Twenty-three patients were examined by two investigators for interobserver assessment.

Results
102 had active disease and 43 patients were in remission. GIUS yielded a sensitivity of 92.2% and specificity of 86% for wall thickness and sensitivity 66.7% and specificity 97.7% for colour Doppler. For HBI sensitivity was 34.3% and specificity 88.4%, CRP sensitivity 35.7% and specificity 82.9% and calprotectin sensitivity 55.9 % and specificity 82.1%. The interobserver analysis revealed excellent agreement (k=0.90).

Conclusion
GIUS has a high sensitivity for detecting endoscopic activity, but poorer specificity. In a hospital cohort of patients with Crohn’s disease, the number of invasive procedures could be reduced by reserving ileocolonoscopy for patients with a normal ultrasound for identification of patients in remission.
P149 Ulcerative colitis patients with high calprotectin levels should undergo endoscopy within 7 days for therapeutic decision
Authors: Kim J O , Jeon S R , Park H , Kim H G , Ko B M , Park S 
Published: January 2020

Abstract

Background
Fecal calprotectin (FC) has considered as a useful surrogate marker to predict which patients with ulcerative colitis (UC) are in endoscopic activity. FC has to be collected at the time of endoscopy for more accurate correlation between FC and endoscopic disease activity. In real practice, however, both tests cannot be easy to perform at the same time. Therefore, the aim of this study was to evaluate the optimal time interval for the correlation between FC and endoscopic disease activity in UC patients.

Methods
We analysed retrospectively 103 cases (79 patients) that was performed FC measurement and endoscopy within 3 months. FC quantitative tests was defined as normal (&lt;100 μg/g), mild (100–200, 100–250 or 100–300 μg/g), and moderate to severe activity (&gt;200, &gt; 250, or &gt; 300 μg/g). Endoscopic activity was graded using the Mayo endoscopic subscore (MES). After assessing concordance between FC level and MES, we use the youden index method to estimate the optimal time interval between both tests using the receiver operator curves (ROCs).

Results
Among 79 UC patients, 64.5% (51/79) were male. The mean FC level was 673.6 ± 1054 μg/g. The mean interval between FC measurement and endoscopy was 13.8 ± 22.7 days. FC levels and MES were positively correlated (r = 0.473, p &lt; 0.001). Using a ROC curve with a cut off value of FC 200 μg/g, the optimal cut-off of the time interval for separation of non-correlation and correlation between FC level and MES was 7 days with a sensitivity of 74.4% and a specificity of 50.0% (AUC 0.6032; 95% CI 0.4779–0.6896). Similarly, using ROC curves with a cut off value of FC 250 or 300 μg/g as a standard for dividing mild and moderate, the optimal cut-off of the time interval were all 5.5 days (FC 250, sensitivity 71.7%, specificity 49.1, AUC 0.5862, 95% CI 0.4728–0.6884; FC 300, sensitivity 69.6%, specificity 47.4, AUC 0.5549, 95% CI 0.4668–0.6513).

Conclusion
FC level within 7 days could reflect endoscopic disease activity in patients with UC. In patients with high-level FC more than 200 μg/g, endoscopic evaluation for therapeutic decision making should be performed within a maximum of 7 days.
P150 Risk of hepatitis flare in patients with previous hepatitis B virus exposure amongst inflammatory bowel disease patients: results from a territory-wide Hong Kong IBD Registry study
Authors: Mak J W Y , Yip T C F , Lam H M , Cheng T Y , Wong S H , Chan F K L , Ng S C , Wong V W S , Wong G L H 
Published: January 2020

Abstract

Background
Biological therapies, thiopurines and steroid are commonly used in the treatment of inflammatory bowel disease (IBD) and may cause hepatitis B virus (HBV) reactivation. However, their exact risk of hepatitis B flare in patients with previous HBV exposure is poorly defined. We aim to study the risk of hepatitis flare in IBD patients with previous HBV exposure.

Methods
Patients were identified from a territory-wide Hong Kong IBD Registry. IBD patients who were negative for HBsAg and received biological therapies or thiopurines or steroids from 1 January 2000 to 30 June 2019 were included. Patients who were positive for total antibody to hepatitis B core antigen (anti-HBc) and/or hepatitis B surface antigen (anti-HBs) were defined to have previous HBV exposure. Primary endpoint was development of hepatitis flare (alanine Aminotransferase [ALT) &gt;80U/L).

Results
Total 369 patients fulfilled the inclusion criteria and were classified into three groups: anti-HBs positive only (n = 246); anti-HBs and anti-HBc positive (n = 78) and anti-HBc positive only (n = 45). Median follow-up duration was 60 months (Interquartile range: 32.7–60 months). Seventy-six IBD patients (20.6%) developed hepatitis flare. Cumulative incidence of hepatitis flare were 13.2%, 18.3% and 22% at 12 months, 36 months and 60 months respectively. Use of thiopurine [adjusted hazard ratio (aHR) 2.56; 95% Confidence Interval (CI) 1.54 – 4.26, p &lt; 0.001]and ever exposure to steroid [aHR 2.73; 95% CI 1.30–5.72; p = 0.008] were risk factors for hepatitis flare after adjustment of baseline ALT level. The use of biological therapy was not associated with risk of hepatitis flare [aHR 1.79; 95% CI 0.79–3.99; p = 0.14]. Ever exposure to steroid was associated with increased risk of hepatitis flare irrespective of the peak dose (&lt;20mg prednisolone daily, 20-40mg daily or &gt;40mg daily) [aHR: 2.34–4.18]. Fifteen patients (4.1%) developed severe icteric hepatitis flare (ALT &gt; 120U/L and bilirubin &gt;38 mmol/L). Cumulative incidence of severe icteric hepatitis flare were 2.7%, 7.2% and 8.4% at 12 months, 36 months and 60 months respectively.

Conclusion
Amongst IBD patients with previous HBV exposure who were treated with biological therapy, thiopurines or steroid, 20.6% developed hepatitis flare. The use of thiopurine and ever exposure to steroid were risk factors for hepatitis flare. The use of biological therapy was not associated with risk of hepatitis flare.
P153 Fertility rate in women with IBD is decreased compared with general population: first multicentre survey in the Czech Republic
Authors: Duricova D , Bortlik M , Kratka Z , Slaba L , Kovarova T , Lukas M , Pfeiferova M 
Published: January 2020

Abstract

Background
Several previous studies reported negative impact of inflammatory bowel disease (IBD) on reproductive plans and fertility rate. The aim of our study was to investigate for the first time reproductive plans and fertility rate among Czech women with IBD.

Methods
Between March and August 2019 consecutive women with IBD (age 18–55 years) from 22 centres across the whole Czech Republic were anonymously surveyed during their visit of gastroenterology centre using predefined questionnaire. The questionnaire was created by physicians of participating centres and commented by members of Patient organisation. The questionnaire was divided into 5 domains focused on patient’s demographics, details on IBD and treatment, gynaecologic history, reproductive issue and patients’ knowledge on this topic. The fertility rate was calculated as mean number of children per woman with known number of children and compared with data from the general Czech population.

Results
The questionnaire was filled-in by 501 women (median age 33 years; 67% with Crohn’s disease) of whom 287 (57%) already had ≥ 1 child (median 2 children; 40% born before IBD diagnosis). Up to 56% women (281) confessed having ever fear of infertility due to IBD and 27% (137) reported that the disease influenced (mainly negatively) their earlier reproductive plans with regard to decision not to have children, to have fewer children, or another timing of the pregnancy then previously wished. The total fertility rate in our study group was lower compared with the general population with 0.99 live births/IBD women vs. 1.69 live births/woman in Czech population. The pattern of decreased fertility among IBD females was observed in all age-specific categories (Table 1). No significant difference in fertility rate between women with Crohn’s disease and ulcerative colitis was found (0.97 vs. 1.08, p = 0.51). Of the childless women, 67% planned to have offsprings in future, 16% were yet to decide and 16% did not want any children. Of those not planning infants, 58% reported IBD to be the primary cause, with the most frequent reason being fear of IBD heritability (29%) and worsening of IBD during pregnancy (26%).

Conclusion
Fertility rate in women with IBD in our survey was decreased compared with the general population of women in the Czech Republic. The negative impact of IBD seemed to contribute most to this finding.