bluuebunny/crossref_metadata_2025_split huggingface dataset:
N19 Understanding the emotional impact of inflammatory bowel disease: looking after nurses looking after patients
Authors: Younge L , Medcalf L , Hall A , Shaw C 
Published: January 2020

Abstract

Background
The emotional impact of inflammatory bowel disease (IBD) is well documented. Patients describe distress, anxiety, depression and relationship difficulties, (including with healthcare staff). Nurses working with IBD patients report being emotionally affected, with fears of ‘burnout’, feeling unable to respond helpfully to patients and feelings of guilt, frustration, sadness and anger. Understanding and managing the emotional impact of the work for IBD nurses is an area underrepresented in either research or nursing literature.

Methods
A collaborative project with IBD nurses and nursing and psychotherapy colleagues from the Tavistock and Portman NHS Foundation Trust developed a one-day event for IBD nurses in the UK. Attendees were self-selecting and the event was supported by Pharma. The conference had three aims: To provide an opportunity to recognise and understand the emotional impact on nurses working with IBD patients, to provide a networking opportunity, and to use information gathered before, during and after the conference to develop a clearer understanding of nurses’ experiences and needs. A pre-conference questionnaire was sent to attendees, observations were made during the conference (noting themes and dilemmas) and an evaluation form was provided.

Results
89% agreed/strongly agreed the event provided understanding of how IBD can have an emotional and psychological impact on patients. 89% agreed/strongly agreed the event provided understanding of the emotional impact on nurses working with IBD patients. Eighty-nine per cent agreed/strongly agreed the event provided understanding of ways in which the emotional impact can influence provision of care and decision making in patients with IBD. Ninety-three per cent agreed/strongly agreed the event provided them with ideas for establishing and managing reflective learning opportunities. Seventy-five per cent agreed/strongly agreed the event enabled them to identify different ways of responding to patients they work with.

Conclusion
Feedback from attendees identified a need and an expressed wish by IBD nurses to understand and explore how they are affected by their work, in relation to maintaining therapeutic and safe relationships with patients and maintaining their own well-being and job satisfaction. Learning needs relating to training in supervision, developing skills in responding to patients’ emotional states, tools for looking after one’s self and opportunities for group discussions and learning were identified. There is an opportunity to develop further learning and training events in relation to these identified needs. Further exploration of accessibility, funding and evaluation would be beneficial in identifying the impact, if any, of further training.
N26 Experiences of patients with inflammatory bowel disease (IBD) regarding faecal incontinence and the guidance received
Authors: Toivonen T T I , Helin K , Nikkola R 
Published: January 2020

Abstract

Background
Patients with inflammatory bowel disease (IBD) suffer more often than the rest of the population from faecal incontinence, which decreases their quality of life. The purpose of this study was to describe the experiences of Finnish IBD patients regarding faecal incontinence and the guidance they need and have received for faecal incontinence.

Methods
The data were collected by executing focused interviews of eleven IBD patients, who at the time of the interview were in remission. The interviewees participated in the study via the Finnish patient association Crohn ja Colitis ry. The data were analysed using an inductive content analysis.

Results
Seven participants were men and four were women. They had had IBD for an average of 2 to 40 years. Five interviewees had Crohn’s disease and six had ulcerative colitis. The extent of the faecal incontinence and its impact on quality of life were assessed by Jorge–Wexner score, which examines the frequency of solid and loose stools and intestinal gas, use of diapers or protective pads, and the patients’ perception of the impact on the quality of life. Zero points stands for complete continence and 20 points for complete incontinence. The average Wexner score among participants was 9.8 (Figure 1). The participants felt that faecal incontinence was constantly disturbing their life. They especially wished for support and information regarding diet. Fear of faecal incontinence made participants skip planned activities and isolate themselves at home. Participants tried to anticipate bowel movements and find out toilet locations in advance in order to venture out of their homes. Participants had discussed faecal incontinence with an IBD nurse and a doctor, but none had met a continence nurse. Furthermore, none of the participants had been told about potential faecal incontinence or ways to manage it. Some participants felt that diet had improved their bowel function, although health care personnel had said in their guidance that diet has no effect on faecal incontinence. Participants also felt that they would have needed information regarding the risk of faecal incontinence and wished that they had been heard regarding problems caused by faecal incontinence.

Conclusion
IBD patients need guidance from health care personnel and information regarding faecal incontinence to balance their bowel function. Health care personnel taking care of IBD patients in Finland needs more training on faecal incontinence, and in addition, more guidance and criteria on when to direct a patient to a continence nurse is needed.
DOP85 The role of fibroblasts in the pathogenesis of Crohn’s disease-associated fistulas and in mesenchymal stem cell therapy
Authors: Bruckner R S , Barnhoorn M C , Mei H , Kiełbasa S M , Harrijvan T J , Hakuno S K , van der Reijden J J , van der Meulen-de Jong A E , Hawinkels L J A C 
Published: January 2020

Abstract

Background
Perianal fistulas are a severe and frequent complication in Crohn’s disease (CD) patients, significantly affecting their quality of life. High recurrence rates, incomplete fistula healing and non-responding patients make the treatment challenging. Despite some novel insights, current knowledge about the pathogenesis of fistula formation is still limited. Fibroblasts are abundantly present in CD fistulas and were recently reported to regulate Th1 cell activity in inflammatory bowel disease (IBD) (Beswick EJ et al. 2018). We hypothesised that fibroblasts act as the key drivers of fistula pathogenesis by regulating inflammatory cell recruitment.

Methods
Fibroblasts were isolated from curettage material of perianal CD fistulas, non-CD-associated fistulas, and the normal colon (obtained at surgery for colorectal cancer at least 10 cm away from the primary tumour). For all experiments, fibroblast populations were identified by qPCR and flow cytometry analysis first. Then gene expression profiling via mRNA sequencing of cultured fistula- and colon-derived fibroblasts was performed. The characterisation was complemented by flow cytometry analysis. Furthermore, the interaction of fistula-derived fibroblasts with regulatory T cells (Tregs) was studied in co-culture experiments.

Results
mRNA sequencing analysis revealed no significant differences in gene expression between perianal CD fistulas and non-CD-associated fistulas. However, comparing fistula-derived samples to fibroblasts derived from the normal colon, we found over 6000 significantly differentially expressed genes. Among the 20 most significant differentially expressed genes between CD fistulas and colon fibroblasts were genes related to epithelial-mesenchymal transition, cell migration or the NF-κB signalling pathway. Furthermore, co-culture experiments with CD fistula-derived fibroblasts, revealed increased proliferation rates of CD25+FoxP3+ Treg cells. In addition, more CD4+ T cells differentiated into Treg cells after exposure to CD fistula fibroblasts.

Conclusion
Our data indicate a pathogenic role of fibroblasts located in the fistula tract. Their gene expression profile markedly differed from fibroblasts derived from the normal part of the colon. Based on our data, there is no difference between CD-associated and non-CD-associated fistula fibroblasts. CD fistula-derived fibroblasts seem to increase both the proliferation of Treg cells, and the differentiation of CD4+ T cells into Treg cells, indicating an important immunoregulatory role of fibroblasts. Ongoing experiments should reveal which cytokines and chemokines are involved in this process.
DOP87 SUCNR1 a novel key protagonist in fistula development
Authors: Bauset C , Gisbert-Ferrandiz L , Ortiz-Masia D , Coll S , Mamie C , Scharl M , Calatayud S , Barrachina M D , Cosín-Roger J 
Published: January 2020

Abstract

Background
Intestinal fistula is a common complication in CD patients whose aetiology is still not well-characterised. It is associated with an exacerbated inflammation and epithelial-to-mesenchymal transition (EMT), a process which allows a switch from epithelial towards a fibrotic behaviour. We have recently reported that SUCNR1 mediates intestinal inflammation and fibrosis1 but its role in fistula has not yet been analysed. Therefore, we aim to analyse the role of SUCNR1 in EMT and in fistula formation.

Methods
Intestinal resections were obtained from CD and non-IBD patients. Fistula specimens were identified by the surgeons and collected from B3-CD patients. The expression of SUCNR1 and EMT markers was analysed by qPCR and the protein expression of SUCNR1 by immunohistochemistry. HT-29 cells were treated with succinate (0,0.1,0.5,1,5 mM) or TGF-β (5 ng/ml) during 48 h and transfected with SUCNR1 siRNA. Expression of EMT markers was analysed by qPCR and western blot. Intestinal fibrosis was induced in vivo using the heterotopic transplant model in WT and Sucnr1−/− mice and expression of EMT markers was analysed by qPCR and by confocal microscopy. Statistical analysis was performed with one-way ANOVA followed by Newman–Keuls test. Correlations were analysed with the Spearman’s coefficient.

Results
In intestinal resections from B3-CD patients, SUCNR1 mRNA expression was significantly increased when compared with B2-CD or non-IBD controls and it correlates positively with the mRNA expression of Snail1 and Snail2 and negatively with that of E-Cadherin. In the fistula tract, SUCNR1 is expressed in intestinal epithelial cells and lamina propria cells of the submucosa with a higher intensity in cells close to the fistula tract than in more distant areas. Succinate induced, in a dose–response manner, a significant increase in Vimentin, Snail1 and Snail2 expression and a reduction in E-cadherin expression. This effect was completely abolished when SUCNR1 was transiently knocked-down. WT-grafts 7 days after surgery exhibited: (a) an increase in gene and protein expression of SUCNR1, (b) an increase in the expression of Vimentin, Snail1 and Snail2 and a significant reduction in E-Cadherin compared with WT-grafts at day 0. Of interest, KO-grafts at day 7 failed to exhibited changes in the expression of Vimentin, Snail1, Snail2 or E-Cadherin.

Conclusion
SUCNR1 is increased specifically in the fistula tract of B3-CD patients. It mediates EMT in intestinal epithelial cells and in a murine model of fibrosis. Hence, SUCNR1 might be a potential pharmacological target for fistula treatment.

Reference
P003 Metabolomics for improved patient stratification in inflammatory bowel disease: Characterisation of the ulcerative colitis metabolome
Authors: Diab J , Hansen T , Goll R , Stenlund H , Jensen E , Moritz T , Florholmen J , Forsdahl G 
Published: January 2020

Abstract

Background
The onset of ulcerative colitis (UC) is characterised by a dysregulated mucosal immune response triggered by several genetic and environmental factors in the context of host-microbe interaction. This complexity makes UC ideal for metabolomic studies to unravel the disease pathobiology and to improve the patient stratification strategies toward personalised medicine. This study aims to explore the mucosal metabolomic profile in treatment-naïve and deep remission UC patients, and to define the metabolic signature of UC.

Methods
Treatment-naive UC patients (n = 18), UC patients in deep remission (n = 10), and healthy volunteers (n = 14) were recruited. Mucosa biopsies were collected during colonoscopy. The UC activity and the state of deep remission were assessed by endoscopy, histology, and by measuring TNF gene expression.
Metabolomic analysis was performed by combined gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). In total, 177 metabolites from 50 metabolic pathways were identified.

Results
Multivariate data analysis revealed a distinct metabolomic profile in inflamed mucosa taken from treatment- naïve UC patients compared with non-inflamed mucosa taken from UC remission patients and healthy controls. The mucosal metabolome in UC remission patients differed to a lesser extent from the healthy controls. The most prominent metabolome changes among the study groups were in lysophosphatidylcholine, acylcarnitine, and amino acid profiles. Several metabolic pathways were perturbed, ranging from amino acid metabolism (such as tryptophan metabolism, and alanine, aspartate and glutamate metabolism) to antioxidant defence pathway (glutathione pathway). Furthermore, the pathway analysis revealed a disruption in the long-and short-chain fatty acid (LCFA and SCFA) metabolism, namely linoleic metabolism and butyrate metabolism.

Conclusion
The mucosal metabolomic profiling revealed a metabolic signature during the onset of UC, and reflected the homeostatic disturbance in the gut. The altered metabolic pathways highlight the importance of system biology approaches to identify key drivers of IBD pathogenesis which prerequisite personalised treatment.
P015 Tricellulin overexpression protects against elevated macromolecule uptake in DSS colitis mice
Authors: WEIß F , Lee I F M , Fromm A , Hu J C E , Breiderhoff T , Fromm M , Schulzke J D , Krug S M 
Published: January 2020

Abstract

Background
In Inflammatory bowel disease, intestinal homeostasis cannot be sustained due to an overreaction of the immune system and a disturbed epithelial barrier due to an impaired tight junction (TJ). At tricellular TJs (tTJs), which are formed where three cells meet, the TJ network is basolaterally expanded and forms a central tube which would be potentially large enough to allow for a paracellular passage of macromolecules. Under normal conditions, the tTJ protein tricellulin (Tric) seals the central tube against luminal uptake. However, in ulcerative colitis (UC), Tric is downregulated, resulting in increased uptake of macromolecules including antigens which may further support the inflammatory processes. Thus, we aimed to identify whether or not overexpression of Tric has a protective effect against inflammation.

Methods
We generated intestinal epithelial cell-specific overexpression of Tric in mice (B6.C-Tg(Vil-cre) Rosa26tgGFP-Tric). In Tric-overexpressing (Tric-OE) and in wild-type (wt) mice experimental colitis was induced by 3% dextran sodium sulphate (DSS) for 6 days. The effect was assessed by determining the disease activity index (DAI: weight loss, stool consistency, and stool bleeding) and the colon dimensions. Using chamber experiments were performed to determine permeabilities for ions and macromolecules of different sizes (4 and 10 kDa).

Results
No difference in weight loss was observed between wt and Tric-OE mice upon DSS treatment. However, Tric-OE mice suffered less from diarrhoea and had less bloody stools compared with wt mice resulting in a lower DAI. In addition, DSS caused a reduced colon length which was less prominent in Tric-OE mice than in wt mice. Functional analysis revealed higher permeabilities for Na+ and Cl− after DSS treatment with no significant differences between Tric-OE and wt mice. In contrast, permeabilities for macromolecules of both sizes were unchanged after DSS treatment in Tric-OE mice but elevated in wt-mice.

Conclusion
Tric-overexpression prevents the epithelial barrier from elevated paracellular uptake of macromolecules during DSS colitis without affecting ion permeability. This protects against DSS colitis as indicated by less affected clinical and structural outcome parameters, most likely via a reduction in a load of immunologically active macromolecules in the subepithelium.
P023 Identification of regulated mechanistic pathways and genes to protect intestinal barrier injury by larazotide acetate in an IBD microenvironment
Authors: Jin Y , Madan J , Radha B K , Anthony B 
Published: January 2020

Abstract

Background
Inflammatory bowel disease (IBD) is due to a combination of factors, including genetics, mucosal barrier dysfunction and dysregulated immune responses. Recently, it has been appreciated that IBD is associated with profound tissue anoxia. Tight junctions (TJs) located at the apical lateral region of adjacent intestinal epithelial cells are largely responsible for regulating the intestinal mucosal barrier. Larazotide acetate (LA, Innovate Biopharmaceuticals, Inc., Raleigh, NC) is a synthetic, eight amino acid peptide that is known to act as a TJ regulator capable of closing ‘leaky’ interepithelial junctions. Presently, LA is being studied in Phase 3 clinical trials for the treatment of celiac disease. Based on prior work in our lab, we hypothesised that LA would protect the TJ barrier in an anoxic injury IBD model associated with upregulation of TJ-associated signalling pathways.

Methods
C2BBe1 (Caco-2 brush border expressing) monolayers were treated apically with LA and were subjected to anoxia for 2 h followed by reoxygenation with 21% O2. Barrier function was assessed by measuring transepithelial electrical resistance (TEER) during anoxic injury and recovery. TJ proteins and cytoskeleton protein F-actin were assessed by western blotting and immunofluorescence microscopy. Then, next-generation RNA sequencing was employed to assess cellular regulatory pathways.

Results
Pre-treatment of anoxic injured C2BBe1cells with 10 mM LA significantly increased TEER as compared with untreated anoxic injured cells. The TJ protein occludin and ZO-1 were disrupted in anoxia-injured monolayer. Alternatively, treatment with 10 mM LA prevented disruption of TJ proteins during anoxic injury. Gene ontology annotation revealed a number of critical signalling pathways that were differentially expressed in cells treated with LA, including biological processes involved in establishment of cell polarity, molecular functions that regulate junctional structures, and cellular components associated with epithelial repair (cell leading edge, ruffle and apical junctional complex). Furthermore, Ras/Rho GTPase binding and protein serine/threonine kinase activity were differentially expressed in cells treated with LA. Additionally, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed enrichment of target genes for ‘cell cycle,’ ‘adherens junction’ and ‘Wnt signalling pathways’.

Conclusion
The results of the present study provide novel insights into the molecular mechanism of action of LA on the protection of TJ integrity in anoxic injury, an IBD microenvironment and the potential for a more broad use in important digestive diseases such as IBD.
P025 Evaluation of endoplasmic reticulum stress in intestinal mucosa from patients with Crohn’s disease
Authors: Rodrigues B , Pascoal L B , Coope A , Ayrizono M L S , Camargo M G , Velloso L A , Fagundes J J , Leal R F 
Published: January 2020

Abstract

Background
The endoplasmic reticulum (ER) is responsible for the synthesis and processing of secretory and membrane proteins. In some cases, proteins cannot reach their final conformation and they remain unfolded in the ER lumen. The accumulation of unfolded proteins leads to a state of stress in the ER (ER stress) that is considered toxic to the cells. As a result, cells may respond by driving the proteins to degradation, pausing the transcription process, or even inducing apoptosis.1 ER stress has recently been linked to the exacerbation of the inflammatory process in the pathogenesis of Crohn’s disease (CD).2 Therefore, our aim was to evaluate the effect of a chemical inhibitor on the activation of ER stress pathways and its modulation of pro-inflammatory cytokines.

Methods
After approval of a local Ethics Committee, biopsies of intestinal mucosa were collected by colonoscopy from patients with CD (CD group) and from patients without inflammatory bowel diseases (control group). Explant culture was performed to evaluate the occurrence of ER stress and was treated with a chemical ER stress inhibitor. Non-parametric tests were performed for statistical analysis adopting p &lt; 0.05 as significant value.

Results
Samples were collected from 10 patients with active CD (CDEIS ≥5) and six control patients. After cell culture, a significant difference was observed in the activation of the main ER stress pathway in the CD group when compared with control group. After treatment with a chemical inhibitor, there was significant decrease in the expression of genes responsible for the activation of ER stress. In addition, a decrease in the expression of inflammatory cytokines was observed after treatment.

Conclusion
The use of a chemical inhibitor has been shown to be effective in significantly decreasing the activation of ER stress and to modulate the inflammation in CD. The activation of the main ER stress pathways may contribute to the inflammatory process in CD, and its blockade suggests a potential new target in the treatment of CD.

References