bluuebunny/crossref_metadata_2025_split huggingface dataset:
P059 GB004 drives protective effects on immune cells and epithelial cells using human ex vivo monolayer and co-culture systems
Authors: Taylor Meadows K , Murphy S , Levesque B G , Carter L L , Salter-Cid L 
Published: May 2021

Abstract

Background
GB004 is a small molecule that stabilizes hypoxia inducible factor (HIF-1α), a key transcription factor involved in the cellular responses at the intersection of hypoxia and inflammation. GB004 induction of HIF-1a target genes improves barrier integrity and reduces barrier permeability in rodent models of colitis. Here we investigated gene expression and secretion of soluble factors elicited by GB004 treatment on immune cells and epithelial cells, human monolayer assays and immune co-culture studies to further explore its protective mechanism.

Methods
In the BioMAP human co-culture assay, cells were treated with GB004 one hour prior to stimulation and incubated for 24–168 hours. Biomarkers, cell viability and proliferation were assessed. Repligut human stem-cell-derived monolayer platforms were used to assess GB004 effects under unstimulated or TNFa stimulation conditions. Barrier integrity was assessed by Transepithelial Endothelial Electric Resistance (TEER), HIF-1a target genes were assessed in cell lysates, and tight junction formation and epithelial monolayer viability were investigated by immunofluorescence staining.

Results
GB004 demonstrated activity in 11 of 12 systems in the BioMAP human co-culture assay, which covers a range of disease-relevant immune and non-immune mechanisms under stimulation conditions. Collectively, GB004 treatment led to changes in biomarkers associated with inflammation (sTNFa, IL-8, MCP-1, CXCL11), immunomodulation (sIL-17F, sIL-17A), and tissue remodeling (collagen I, collagen IV). GB004 treatment also reduced the proliferative activity in the in vitro lymphocyte assay systems. In the human Repligut intestinal epithelium assay, GB004 significantly reduced cell death and improved barrier integrity in response to pro-inflammatory cytokines. The protective role of GB004 on barrier integrity was further supported by immunostaining experiments demonstrating that GB004 treatment protected epithelial cells from TNFa-induced cell apoptosis, improving both epithelial cell number and tight junction protein ZO-1 staining.

Conclusion
GB004 modulates key anti-inflammatory and immunomodulatory activities in human co-culture systems. Furthermore, GB004 demonstrates protective effects on human derived monolayer cultures by reducing cell death, promoting tight junction formation, and improving barrier integrity. Targeting both barrier function and local colonic inflammation represents a multi-faceted approach to treatment of inflammatory bowel disease. A phase 2 clinical study of GB004 is ongoing in patients with ulcerative colitis (NCT04556383). Sponsored by GB004, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
P081 Resolvin D2 attenuates colonic inflammation of Crohn’s disease patients
Authors: Pascoal L B , Palma B B , Chaim F H , Nogueira G , Rodrigues B L , Ayrizono M L S , Velloso L A , Leal R F 
Published: May 2021

Abstract

Background
Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Usually, the clinical management are based on sulphasalazine, corticosteroid, immunomodulators, biologics therapy and bioactive small molecules. However, new therapeutic strategies involving the inflammatory process are being proposed as the use of pro-resolution lipid mediators. This study aimed to investigate the potential therapeutical role of Resolvin D2 (RvD2) in the intestinal mucosa of CD patients and its therapeutic potential.

Methods
The study included 16 CD patients, 8 patients in remission (CDR) and 8 with active disease (CDA) and 6 healthy subjects in the control group (CTR); all were followed up in tertiary referral hospital. Blood sample and colonic biopsies were collected during colonoscopy. Disease activity was determined by the Crohn’s Disease Endoscopic Index of Severity (CDEIS). The serum blood level of RvD2 was determined by enzymatic immunosorption assay (ELISA). Intestinal biopsies were submitted to cell culture and treated with Infliximab (IFX) or RvD2. The expression of inflammatory cytokines was evaluated by real-time PCR and RvD2 levels through the ELISA. A nonparametric test was used for statistical analysis, with adopted p&lt;0.05. The study was approved by the University of Campinas research ethics committee.

Results
The intestinal mucosa of the CDA group showed higher levels of pro-inflammatory markers, such as, IL1β (p=0.008 and p=0.01), IL6 (p=0.002), IL23 (p=0.03) and S100A8 (p=0.004 and p=0.01), compared to CTR and CDR groups, respectively. Although serum RvD2 levels of CDA (p=0.002) and CDR (p=0.004) groups were increased when compared to the CTR group, there is no differences between CDA and CDR groups (p&gt;0.05). However, intestinal explants of the CDA group treated with RvD2 showed a significantly decrease of IL1β expression (p&lt;0.05) when compared to the non-treated biopsies in the ex vivo culture experiments, similar to what was as verified by IFX treatment (p&lt;0.05).

Conclusion
The results suggest the participation of RvD2 in the modulation of colonic inflammation associated with CD. RvD2 showed to be as effective as IFX in attenuating the pro-inflammatory response present in the intestinal mucosa of patients with CD and provide insights into pro-resolution lipid mediators approaches to modulate chronic inflammation.
P090 Risk of Rectal Cancer after Colectomy in Patients with Inflammatory Bowel Disease – A Nationwide Population-based Danish Cohort Study 1978–2018
Authors: Akimenko E , Bjerrum J T , Allin K H , Iversen A T , Jess T 
Published: May 2021

Abstract

Background
The risk of surgery remains high both among patients with ulcerative colitis (UC) and patients with Crohn’s disease (CD) with a cumulative risk of subtotal colectomy with ileostomy and diverted rectum of 7.5% after 5 years in UC and a similar risk in CD.
Ileostomy with diverted rectum after colectomy may be permanent, or the patient can undergo restorative surgery with ileo-rectal anastomosis (IRA) or ileal pouch-anal anastomosis (IPAA).
Risk of rectal cancer in this patient population remains uncertain.
We performed a nationwide population-based Danish study of rectal cancer (RC) risk after subtotal colectomy.

Methods
Through the Danish Civil Registration System, a source population of all individuals 15 years or older living in Denmark between 1978 and 2018 was retrieved. By use of the unique personal identification number given to all citizens at birth, this source population was linked to the Danish National Patient Registry (NPR) in order to identify all patients with inflammatory bowel disease (IBD). Patients with a diverted rectum, IRA or IPPA after colectomy were also identified with NPR. Cases of RC were identified in the Danish Cancer Registry. Patients with IBD were followed from the date of surgery until cancer, emigration, death or end of the study.
The risk of RC in patients with diverted rectum was assessed using Cox regression analyses, as compared to the background population as well as to subjects with IBD without subtotal colectomy.

Results
RC occurred in 42 (0.9%) of 4931 patients after subtotal colectomy with diverted rectum, compared to 209 (0.4%) of 49,251 in the matched IBD cohort with no colectomy and 941 (0.4%) of 246,550 in the matched background population.
In the IBD and subtotal colectomy population 11 (26%) of the 42 cases were in patients diagnosed with CD and 31 (74%) were in patients with UC.
The hazard ratio (HR) for RC in IBD patients with diverted rectum vs. matched IBD patients without colectomy (adjusted for IBD type and sex) was 0.80 (95% CI 0.29, 2.17) during the first 10 years of follow-up and 7.93 (95% CI 5.48, 11.48) 10 years or more after colectomy. Likewise, the HR for RC in IBD patients with diverted rectum compared to the matched background population was 0.85 (95% CI 0.32, 2.28) during the first 10 years of follow-up and 10.25 (95% CI 7.36, 14.28) 10 years or more after colectomy.

Conclusion
In our nationwide population-based cohort study covering years 1978–2018 we observed an 8 to 10-fold increased risk of RC of the diverted rectum 10 years after colectomy.These data suggest a need for developing a specific surveillance strategy for this group of IBD patients.
P113 Automatic detection of colonic ulcers and erosions in colon capsule endoscopy images using a convolutional neural network
Authors: Ribeiro T , Mascarenhas Saraiva M , Afonso J , Cardoso H , Ferreira J , Andrade P , Jorge R , Lopes S , Macedo G 
Published: May 2021

Abstract

Background
Conventional colonoscopy is gold standard for the diagnosis and monitoring of patients with suspected or known inflammatory bowel disease (IBD). Nevertheless, it is a potentially painful procedure with risk of complications, including bleeding and perforation. Colon capsule endoscopy (CCE) is a minimally invasive alternative for patients unwilling to undergo colonoscopy or when it is contraindicated or unfeasible. However, CCE produces thousands of frames and their revision is a time-consuming and monotonous task.
The detection of ulcers and erosions is paramount for the diagnosis and assessment of the activity of IBD. However, these lesions may appear in a very small number of frames, thus increasing the risk of overlooking significant lesions.
Our aim was to develop an Artificial Intelligence (AI) algorithm, based on a multilayer Convolutional Neural Network (CNN) for automatic detection of ulcers and erosions in CCE exams.

Methods
A total of 24 CCE exams (PillCam COLON 2®) performed at a single centre between 2010–2020 were analysed. From these exams, 3 635 frames of the colonic mucosa were extracted, 770 containing colonic ulcers or erosions and 2 865 showing normal colonic mucosa. These images were used for construction of training (80% of the frames) and validation (20% of the frames) datasets. For automatic identification of these lesions, these images were inputted in a CNN model with transfer learning. The output provided by the CNN (Figure 1) was compared to the classification provided by a consensus of specialists. Performance marks included sensitivity, specificity, positive and negative predictive values, accuracy and area under the receiving operator characteristics curve (AUROC).

Results
After the optimization of the neural architecture of the CNN, our model automatically detected colonic ulcers and erosions with a sensitivity of 90.3%, specificity of 98.8% and an accuracy of 97.0% (Figure 2). The AUROC was 0.99 (Figure 3). The mean processing time for the validation dataset was 11s (approximately 66 frames/s).

Conclusion
We developed a CNN model which demonstrated high levels of efficiency for the automatic detection of ulcers and erosions in CCE images. Our study lays the foundations for the development of effective AI tools for application to CCE exams. These systems may enhance the diagnostic accuracy and reading efficiency of CCE, thus expanding the role of minimally-invasive colonic exploration in the management of IBD patients.
P116 Development of a new patient-reported outcome measure for patients with complex cryptoglandular fistulas
Authors: McCurdy J , Crooks P , Gwaltney C , Krupnick R , Cadogan K A , Gonzalez S , Karki C 
Published: May 2021

Abstract

Background
Complex cryptoglandular fistulas (CCF) arise from infected anal glands and are often associated with substantial morbidity and healthcare utilization. Standarized patient-reported outcome measures (PROMs) for CCF are lacking. Thus, we aimed to develop a disease-specific PROM to assess the burden of symptoms and their impact on daily life in patients with CCF.

Methods
To develop a conceptual model, a targeted literature review was conducted to identify symptoms and impacts on daily life associated with CCF. Existing PROMs relating to anal fistulas were also sought. Semi-structured interviews with colorectal surgeons (n=5) assessed clinical perspectives on patient experience of CCF. A draft item pool was developed based on the refined conceptual model and using the Quality of Life in Patients with Anal Fistula Questionnaire as a reference. The tool was refined through concept elicitation interviews on the symptoms and impacts of CCF, and cognitive debriefing on the interpretation, understanding and response to each item. Interviews were conducted until concept saturation was achieved and patient feedback suggested no further refinements were required.

Results
The literature review identified discharge, pain, faecal incontinence and bleeding as the most prevalent symptoms, and embarrassment as the most prevalent impact on daily life. Results from surgeon interviews were then used to revise the initial conceptual model. Twenty US adults (60% female; mean age, 49 years) with clinically confirmed CCF participated in interviews (four waves of n=5). Patients identified 10 salient symptoms and 11 salient impacts on daily life (salient defined as mention by ≥50% of patients and mean disturbance rating ≥5 on a 10-point scale). The final conceptual model included the main symptoms and treatment-related effects, and impacts on daily life. The draft item pool was refined, resulting in a final PROM consisting of 14 items (covering frequency and severity) relating to symptom domains – discharge, incontinence, pain, irritation, odour, abscess – and 6 items relating to health-related quality of life domains – functional, physical, psychological, social health. The PROM features a 7-day recall period, with responses mostly given on a 5-point verbal rating scale. Cognitive debriefing confirmed that the PROM was clear, easy to understand and relevant to patients’ experiences.

Conclusion
The 20-item CCF questionnaire (CCFQ-20) is a new PROM that has been developed and tested for content validity, following expert guidance and regulatory best practices. It addresses a comprehensive set of salient symptoms and impacts experienced by patients with CCF. Psychometric testing is required to fully evaluate this PROM.
Sponsor: Takeda Pharmaceuticals USA, Inc.
P130 Adhesions are not always the enemy: pouch volvulus
Authors: Dionigi B , Lavaryk O , Lightner A , Holubar S , Hull T 
Published: May 2021

Abstract

Background
Proctocolectomy with ileal pouch anal anastomosis (IPAA) was introduced over 40 years ago, prior to the era of laparoscopy. Minimally invasive surgery (MIS) techniques have been applied to pelvic pouch surgery. One advantage of MIS is the reduction in adhesion-related complications. The lack of adhesions may result in different complications. When the pouch is not adherent in the pelvis, pouch volvulus can occur around the mesenteric axis. The aim of this study was to describe our experience with pelvic pouch volvulus.

Methods
Our prospectively maintained pelvic pouch registry and our enterprise wide electronic medical record were queried for keyword combinations of “pouch volvulus” between 1994 and 2020. Pouch volvulus was defined as torsion of the ileal pouch on its mesenteric axis or around small bowel maintaining the proper orientation of the ileo-anal anastomosis. Patients with pouches constructed with twisted mesenteric axis from ill-aligned anastomoses were excluded. Data for these patients was collected from the pouch registry and additional chart review.

Results
We identified 17 patients with pouch volvulus; of these, 11 patients did not meet our selection criteria and were excluded. Of the 6 patients (5 female; median age 25) with true volvulus, the diagnosis at IPAA was ulcerative colitis (n=5) and Lynch syndrome with a rectal cancer. All pelvic pouches were constructed with MIS techniques, including standard laparoscopy (n=4) and single incision laparoscopic technique (n=2). All 6 patients presented with diffuse abdominal pain and abdominal distention. The average time from pouch construction to pouch volvulus was 2.5 years (range: 5.2 – 97.5 months). Computed tomography with or without rectal contrast was the initial diagnostic test in 4/6 with findings highly suspicious for pouch volvulus. Surgery was performed urgently in 5/6 of patients; all 6 had open surgery. At reoperation, all had minimal adhesions and a gap between the pouch mesentery and the retroperitoneum. Interventions included pouch-pexy (n=3), closure of gap between pouch and sacrum (n=2), and pouch excision and ileostomy (n=1). At a median of 9 months (IQR: 4–97) of follow up, pouch survival was 83%; functional outcomes included mild fecal incontinence (n=1) and paradox requiring intermittent pouch intubation for stool evacuation (n=1).

Conclusion
Pelvic pouches constructed by minimally invasive techniques may be at risk for pouch volvulus due to minimal adhesions. Surgeons should have a high index of suspicion for patients with unexplained abdominal pain, distension, and other obstructive symptoms. Cross-sectional imaging with rectal contrast, may help clarify the diagnosis. Immediate surgical care can allow for pouch salvage.
P156 Translation into Spanish, adaptation and validation of the “IBD- control”, a short validated English PRO (patients reported outcomes) questionnaire: the EII-Control
Authors: Vicente Lidon R , García S , Corsino P , Boudet J M , Sierra E M , García P , Sanz P , Gomollón F 
Published: May 2021

Abstract

Background
The measure of patient reported outcomes (PROM) in inflammatory bowel disease (IBD) clinical practice, is hardly to use as it lacks a simple and valid tool. There is a short, generic and validated English questionnaire for this purpose: the IBD Control. Its validation and application in other IBD populations is necessary and would support its practical use. Our purpose is to translate into Spanish, adapt and validate the “IBD- control” in our ambit and culture, in order to have a useful measure for clinical practice.

Methods
The IBD-control was translated into Spanish, demonstrating its understandability, content, validity and acceptability for patients, generating the EII-Control instrument. Subsequently, the EII-Control was prospectively validated, using current psychometric standards. At the baseline visit, consecutive patients completed the EII-Control, the short form of IBD quality of life (QOL) questionnaire (CVEII-9), the generic QOL instrument (EQ-5D), the hospital anxiety and depression scale (HDA and HDS), the fatigue questionnaire (FSS), as well as a clinical assessment, blind to the questionnaires (global clinical rating, Harvey-Bradshaw indice or simple index of clinical activity of colitis (SSCAI) and treatment outcome). A subgroup of patients repeated the assessment on a second visit within the study period. The usefulness of summary scales of the IBD-Control, was also analyzed (EII-Control-8 and EII-control-VAS).

Results
249 patients completed the baseline surveys (Crohn’s disease, n = 177; ulcerative colitis, n = 71 and indeterminate colitis, n = 1) and 101 repeated the same assessment on a second routine visit. Internal consistency: Cronbach’s for EII-control 0.83 with strong correlation between EII-Control-8 and EII-Control-VAS subscales (r = 0.5). Reproducibility: intraclass correlation = 0.70 for EII-Control and 0.61 for EII-Control-VAS. Construct validity: moderate to strong correlations between EII-Control versus activity, anxiety, depression, fatigue or quality of life indices Discriminant validity: (mean scores of the instruments for remission, mild, moderate or severe): p &lt;0.001. Sensitivity to change: same response in effect size and mean differences as CCVEII-9. Sensitivity and specificity at cut-off 14 of 0.696 and 0.903 respectively to determine the quiescent state.

Conclusion
The EII-Control is a rapid, reliable, valid and sensitive instrument to measure the overall control of the disease from the perspective of the patient in spanish culture. Its simplicity, ease of use, and generic applicability make it a candidate for supporting routine care, including telemedicine, and also to use in clinical research.
P200 Celiac disease (CD) and CHRONIC INFLAMMATORY BOWEL DISEASE (IBD) association
Authors: Hmimass S , Benelbarhdadi I , Lagdali N , Borahma M , Ajana F Z 
Published: May 2021

Abstract

Background
Association Celiac disease (CD) and CHRONIC INFLAMMATORY BOWEL DISEASE (IBD) is rare. the aim of the study is to determine the frequency as well as the anatomical and evolutionary characteristics of this association.

Methods
This is a retrospective descriptive and analytical study of 10 patients between 2005 and 2020. The diagnosis of CD was established after careful clinical examination and questioning, on the determination of specific auto antibodies against transglutaminase type Ig A and endomysium and on the histological study of duodenal biopsies showing a IEL&gt; 30%. And that of IBD was based on a range of clinical, endoscopic, histological and radiological arguments

Results
10 cases of association CD and IBD were diagnosed in a cohort of 267 CD, 960 Crohn’s disease and 520 Haemorrhagic rectocolitis. The frequency of association was 3.7% in the cohort of CD, 0.9% In the Crohn’s disease cohort and 0.2% in the cohort of Haemorrhagic rectocolitis. Predominantly female, 80% female and 20% male. The diagnosis of CD preceded that of Crohn’s disease in 80% (n=8), with an average delay of 32 months (12–72 months). All patients were put on a gluten-free diet (GFD). Despite good therapeutic compliance for at least 18 months, the evolution was marked by the persistence of anaemic syndrome and dysenteric syndrome in six cases (60%), diarrhoea and colic-type abdominal pain in four cases (40%). And an occurrence of rectorragie, anaemic syndrome and dysenteric syndrome in two cases (20%). In front of the persistence of symptoms, we first eliminated a resistance to GFD. Then an upper and lower digestive, radiological and histological endoscopic assessment concluded that there was an isolated colonic crohn’s disease in five (50%) of the patients; gastric and colonic in three (30%). 60% (n=6) of the patients had luminal and stenotic involvement in two patients. The diagnosis of IBD preceded that of celiac disease in 20% (n=2), one patient had luminal colonic Crohn’s disease and one patient had left Haemorrhagic rectocolitis. The diagnosis of CD was clinically retained by the appearance of an associated anemic syndrome in one case with atypical abdominal pain, and with dysenteric syndrome in the other case. Serologically, one was positive for anti transglutaminase type Ig A and the other was seronegative. Histologically, both patients had a IEL &gt;30% with subtotal atrophy. The evolution was favourable on the GFD, which was always followed up alongside the treatment of IBD, with good clinical and endoscopic improvement

Conclusion
The association between CD and IBD is possible, albeit rare. It is necessary to think about the search for it whenever there is a persistence or appearance of other evocative symptoms despite good therapeutic compliance.