bluuebunny/crossref_metadata_2025_split huggingface dataset:
P054 Modulation of the Gut Microbiota-Farnesoid X Receptor Axis Improves Deoxycholic Acid-induced Intestinal Inflammation in Mice
Authors: Xu M , Shen Y , Cen M 
Published: May 2021

Abstract

Background
Inflammatory bowel disease (IBD) is associated with gut dysbiosis and dysregulation of bile acid metabolism. A high luminal content of deoxycholic acid (DCA) with consumption of a Westernized diet is implicated in the pathogenesis of IBD. The aim of the study is to explore the role of intestinal microbiota and bile acid metabolism in mice with DCA-induced intestinal inflammation.

Methods
4-week-old wild-type C57BL mice were fed with AIN-93G (control diet), AIN-93G+0.2% DCA, AIN-93G+0.2% DCA+6 weeks of fexaramine (FXR agonist), or AIN-93G+0.2% DCA+antibiotic cocktail for 24 weeks. Histopathology, Western blotting, and qPCR were performed on the intestinal tissue. Fecal microbiota was analyzed by 16S rDNA sequencing. Fecal bile acid and short-chain fatty acid (SCFA) levels were analyzed by chromatography.

Results
Gut dysbiosis and enlarged bile acid pool were observed in DCA-treated mice, accompanied by a lower farnesoid X receptor (FXR) activity in the intestine. Administration of fexaramine mitigated DCA-induced intestinal injury, restored intestinal FXR activity, activated ﬁbroblast growth factor 15, and normalized bile acid metabolism. Furthermore, fexaramine administration increased the abundance of SCFA-producing bacteria. Depletion of the commensal microbiota with antibiotics decreased the diversity of the intestinal microbiota, attenuated bile acid synthesis, and reduced intestinal inflammation induced by DCA.

Conclusion
DCA induced-intestinal inflammation is associated with alterations of gut microbiota and bile acid proﬁles. Interventions targeting the gut microbiota-FXR signaling pathway may reduce DCA-induced intestinal disease.
P063 The immunological landscape of intestinal fibrosis in Crohn’s Disease
Authors: Jacobs I , Creyns B , Dragoni G , Cremer J , Bislenghi G , D’Hoore A , Ke B J , Matteoli G , De Hertogh G , Ferrante M , Joao G S , Breynaert C , Vermeire S , Verstockt B , Vanuytsel T 
Published: May 2021

Abstract

Background
Patients with Crohn’s disease (CD) often develop strictures, necessitating surgical intervention. The immune pathways expressed in the fibrotic regions, especially in the deeper intestinal layers, are poorly characterized hence hampering therapeutic development for anti-fibrotic agents. We performed a detailed analysis of the immune cell populations in both inflammation and fibrosis in the mucosa and deeper intestinal layers in CD patients.

Methods
Patients with stricturing CD (n=25) or colorectal cancer (CRC, n=10), undergoing ileocolonic resection were included. The resection specimen of CD patients was macroscopically subdivided into fibrotic, inflammatory but not fibrotic, and unaffected regions by an IBD-experienced histopathologist. The mucosal layer was furthermore separated from the deeper intestinal layers. Immune cells were isolated, followed by flow cytometry. Quantitative real time PCR (qRT-PCR) was performed for the eosinophil chemoattractant CCL11 coding for eotaxin-1 and normalized against the housekeeping genes RPL13a and PPIA. Wilcoxon matched-pairs sign rank test was performed on paired samples while Dunn’s multiple testing was performed for unpaired comparisons.

Results
Flow cytometric analysis in CD patients showed mainly B cell enrichment in fibrotic tissue compared to the unaffected tissue, both in the mucosa (30.2% vs 20.9% of CD45+ cells, p=0.001) as in deeper layers (34.4% vs 24.1% of CD45+ cells, p=0.01) (figure 1). Mature dendritic cells (mDC), alternatively-activated macrophages and eosinophils were also enriched but in the deeper layers of the fibrotic segment compared to the mucosa (4.3% vs 3.4%, 1.07% vs 0.04% and 2.3% vs 1.5% of CD45+ cells; p = 0.02, 0.008 and 0.02) (figure 2). Moreover, increased eosinophilic presence was also shown in the unaffected CD region compared to the fibrotic area, both in deeper layers (4.0% vs 2.3% of CD45+ cells; p=0.03) as the mucosa (2.4% vs 1.5% of CD45+ cells; p=0.01) as well as in the inflamed deeper layers compared to the superficial layers (3.3% vs 2.1% of CD45+ cells, p=0.04). These data were corroborated by increased CCL11 mRNA expression, in the deeper layers of fibrotic tissue compared to the mucosa (52.3% vs 31.0%, p=0.03).

Conclusion
Our results suggest a role for innate immune cells in CD complicated with fibrosis. Especially in the deeper layers, eosinophils, mature dendritic cells and alternatively-activated macrophages are implicated. The eosinophilic enrichment in the deeper layers may partly be attributed to an increased eosinophil recruitment by CCL11. Our results offer opportunities for anti-fibrotic drug development in CD.
P074 Crohn’s disease clinical data standards: Adoption and implementation to promote data sharing and reuse
Authors: Owen J 
Published: May 2021

Abstract

Background
Creation and adoption of clinical data standards will transform incompatible and disparate data into universal and illuminating information, facilitating discoveries that could have invaluable impact on Crohn’s Disease clinical research. Implementation of CDISC standards deliver on the promise of FAIR data through consistent organization and analysis that allow all researchers to leverage information from studies globally.

Methods
With support from The Leona M. and Harry B. Helmsley Charitable Trust and following the CDISC consensus-based standards development process, a team of Crohn’s disease and standards development experts was created to develop clinical data standards for Crohn’s disease.The CDISC standards development process consists of five stages:

Results
Free and publicly available data standards are anticipated to be available in May 2021 in the following areas:
- Questionnaires, Ratings and Scales (including standard symptom measures, patient/investigator reported outcomes, and socio-economic measures)
- Prior and Baseline, and On-Study Treatments (including response to prior treatment)
- Disease Classification (location and phenotypic descriptions of the disease)- Endoscopy Assessments
- Cross Section Imaging Assessments (including CT, MRI and Ultrasound)
- Histopathology of Biopsy Samples
- Biomarkers of Interest for Crohn’s Disease

Conclusion
Widespread promotion of the standards for researchers to adopt and implement is of highest importance. CDISC provides complementary education courses and implementation information to assist in adoption for academic teams new to CDISC standards. Widespread adoption of the standards will bring clarity to Crohn’s Disease data and will enable the accessibility, interoperability, and reusability of data (FAIR).
P080 Burden of Disease and Cost of Illness of Inflammatory Bowel Diseases in Portugal
Authors: Magro F , Portela F , Lago P , Chagas C , Moreira F , Pereira F , Rodrigues B , Pedrosa H , Correia L 
Published: May 2021

Abstract

Background
Estimate the burden of the disease (BoD) of IBD in Portugal and quantify society’s cost of illness (CoI) associated, including direct and indirect costs. Raise awareness to IBD in Portugal and thus bringing empowerment to the patient community.

Methods
Burden of disease was assessed considering the impact in terms of DALY, estimated considering a prevalence-based model. Costs were estimated considering the societal perspective, using a prevalence-based model. Direct costs comprise hospitalizations, surgeries, medical appointments, emergency visits, pharmacological treatment, exams and transportation. Indirect costs were calculated from patient and caretaker absence, presenteeism, early retirement and premature death.
An expert panel composed by 5 Portuguese gastroenterologists and a patient reported study were conducted to support the cost analysis and fill in information gaps. The expert panel followed a two-round modified Delphi methodology. The patient reported study was conducted with 370 Portuguese IBD patients by the Portuguese Association of Inflammatory Bowel Disease (APDI).

Results
Considering a prevalence of 24,070 patients, 6,067 DALYs were estimated to be lost in Portugal due to IBD. This result reflects a total of 507 YLLs (8%) and a total of 5,560 YLDs (92%)
The total annual cost associated with IBD patients in Portugal was estimated to be €146,293,082, with an average annual cost of €6,075 per patient. This value is divided into €86,834,011 direct costs (59%) and €59,459,070 (41%) indirect costs.
Indirect costs account for 41% of IBD’s total cost. Interestingly, costs of patient work absences showed very similar values to those associated with presenteeism. This demonstrates that IBD does not manifest its impact only in isolated timepoints, but rather that it is present in the everyday lives of patients.

Conclusion
It is essential to discuss the relationship between the burden of disease and its cost, especially when discussing a clinical condition with an increasing incidence rate in an ageing population as it is in Portugal. Due to the need to generate further data and evidence regarding IBD, this study provides the first comprehensive insight at a national level considering all the dimensions of disease burden. The results presented will raise social-economic awareness of IBD, allow for the definition of disease management strategies and support prioritization on resource allocation, especially considering the availability of new treatment approaches. Moreover, this study will set the basis for the thorough assessment of the real burden of IBD in the Portuguese healthcare system and society overall.
P122 Machine learning for prediction of intra-abdominal abscesses in patients with Crohn’s disease visiting the emergency department
Authors: Levartovsky A , Barash Y , Ben-Horin S , Ungar B , Klang E , Soffer S , Amitai M M , Kopylov U 
Published: May 2021

Abstract

Background
Intra-abdominal abscess is an important clinical complication of Crohn’s disease (CD), which can be diagnosed using computed tomography (CT) or magnetic resonance imaging (MRI). However, a high index of clinical suspicion is needed to diagnose an abscess as abdominal imaging is not routinely used during hospital admission. This study aimed to identify clinical predictors of an intra-abdominal abscess among hospitalized patients with CD.

Methods
We created an electronic data repository of all patients with CD who visited the emergency department (ED) of our tertiary medical center between 2012 and 2018. Data included tabular demographic and clinical variables, as well as CT and MRI imaging outcomes. We searched the data repository for the presence of an abscess on abdominal imaging within seven days from the ED visit. Machine learning models were trained to predict the presence of an abscess. A logistic regression model was compared to a random forest model. The area under the receiver operator curve (AUC) was used as a metric. To establish statistical significance, bootstrapping of 100 experiments with random 80/20 training/testing splits was performed. We included only patients who were hospitalized due to complaints that can be attributed to CD exacerbation. Patients presenting within 30 days from an abdominal surgery were excluded.

Results
Overall, 1556 patients with CD visited the ED, of those 555 patients with a CD exacerbation. Of them, 339 patients were hospitalized and underwent abdominal imaging within 7 days from the ED visit. Forty-two patients (12.1%) were diagnosed with an abscess on abdominal imaging. The average length of the abscess was 32 mm (IQR 21.5, 43.5), mainly in the mesentery adjacent to the small bowel (38.1%). On multivariate analysis, high CRP values (64.97 mg/L, aOR 14.42 [95% CI 4.93–42.13]), high platelet count (322.5 K/microL, aOR 4.01 [95% CI 1.97–8.15]), leukocytosis (10.55 K/microL, aOR 3.83 [95% CI 1.71–8.56]) and higher heart rate (over 87.5 beats per minute, aOR 2.58 [95% CI 1.22–5.46]) were independently associated with an intra-abdominal abscess. Overall, random forest and logistic regression showed similar performance. The random forest model showed an AUC of 0.824±0.065 with eight features (CRP, Hemoglobin, WBC, age, current biologic medical treatment, BUN, current immunomodulatory medical treatment, gender).

Conclusion
In our large tertiary center cohort, the machine-learning model identified features associated with the presentation of an intra-abdominal abscess. Such a decision support tool may assist in triaging CD patients for imaging to exclude this potentially life-threatening complication.
P135 Proximal Extension of lower rectal Ulcerative Proctitis
Authors: Yokoo T , Yoshikawa S , Masuda T , Terauchi S , Uchida H , Nakao T , Yamaoka K , Inagaki M , Okamoto K , Shibata Y , Higashio T , Inatsugi N 
Published: May 2021

Abstract

Background
Previous studies have shown proximal extension (PE) rate of ulcerative proctitis (UP) is approximately 50%. This rate teach us the importance of treating UP adequately. Basically, we have to treat them with topical 5-ASA. But in clinical practice, we sometimes experience the case whose inflammation remain endoscopically, even though the symptoms have been relieved. Should we strengthen our treatment at this situation, especially inflammation at lower rectum? We aimed to know PE rate of lower rectal UP and optimize the treatment.

Methods
We retrospectively investigated the medical charts of patients with UP from 2010 to 2020 at Kenseikai Nara Coloproctology Center. We excluded the patients with UP shrinking from left-sided or pancolitis as a result of the treatment. The cases with missing value were excluded too. Variables of interest included gender, onset age, disease location, initial mayo endoscopic subscore (MES) and treatment, and the time to PE. To compare the cohorts we used Fisher’s exact test and Mann-Whitney test. Proximal extension free survival (PEFS) was calculated using the Kaplan-Meier method.

Results
Sixty-five patients were recruited. Mean age was 42 years old, the ratio of males to females was 1.17. The number of lower rectal UP patients at first examination was 24. We observed MES 1 inflammation for 30 patients, and MES 2 for 35. Median follow-up duration was 73.5 months. PE occurred in 34 patients: 28 patients had left-sided colitis and 6 had pancolitis. Fifty-four patients were medicated and other 11 patients were just observed. Among the patients medicated, 23 patients were took only topical drugs, 18 were took only oral drugs and other 13 were took both. We couldn’t find any relationships between initial medication and PE rate. The multivariate analysis revealed that having peri-appendiceal red patch and lower rectal UP were reduce the risk of PE. MES was not related to PE (table 1).
PEFS at 1 year, 2 year are 81%, 81% for lower rectal UP (Rb group), and 66%, 61% for the patients having the disease beyond middle Houston’s valve (Not-Rb group), though we couldn’t find significant difference (Fig.1). Among 34 patients having PE, we used biologics for only five patients and got their inflammation under control.

Conclusion
Patients with lower rectal UP is less likely to extent their disease location. There’s no difference between the route of treatment and PE rate, but it’s important to carefully check PE within first one year.
P151 Validation of the MaRIA Score in pediatric patients
Authors: Palomino Pérez L M , Velasco Rodríguez-Belvis M , Sirvent Cerdá S I , Vazquez Gómez J A , Muñoz Codoceo R A 
Published: May 2021

Abstract

Background
To validate the Magnetic Resonance Index of Activity (MaRIA Score) in the pediatric population and determine if it would be possible to monitor inflammatory bowel disease (IBD) without invasive tests in some cases.

Methods
A cross-sectional and descriptive study of paediatric patients with previously diagnosed or suspected IBD who underwent upper endoscopy (EGD) and colonoscopy, blood tests, stool analysis and MR Enterography (MRE) in a 15 days range, from October 2018 to February 2020. The clinical and endoscopic situation were assessed with the activity indices PUCAI/PCDAI/shPCDAI and the activity scores UCEIS/Mayo/SES-CD respectively, according to the underlying pathologies. We considered analytical remission as FC&lt; 250 mcg/g, ERS&lt; 20 mm and CRP&lt; 1 mg/dl. The MRE results were assessed with the MaRIA Score, that is validated for adults.

Results
Amongst 21 patients, 12 (57%) were males. 12 patients had Crohn ́s disease (CD) (57%), 3 had ulcerative colitis (UC) (14%), 6 had IBD unclassified (IBDu) (28%). The mean age at diagnosis was 14.2 ± 0.7 and the progression time of the disease was 3.9 ± 0.6 years. A total of 16 patients showed clinical remission (76%), 6 of them (28%) also had endoscopic and histological remission. Eight patients were receiving biological treatment (38%). The measured acute phase reactants (APR) were: CRP 0.9 ± 0.5 mg/dl, ESR 13.7 ± 2.6 mm, α1 acid glycoprotein 95.5 ± 1.1 mg/dl and fecal calprotectin (FC) of 1154.3 ± 254.8 mcg/g. Rotavirus, adenovirus, Clostridium difficile toxin analysis and stool culture were performed in 14 patients, all of them negative.
The MaRIA Score values were 54.3 ± 53.3, being 0 in 11 cases. We found no differences between the MaRIA Score and the analytical remission. We found a significant correlation between the MaRIA Score and the PUCAI value (p &lt; 0.05), but not with other clinical scores. Patients in clinical remission showed a tendency to have a lower MaRIA Scores, but these differences were not statistically significant (p = 0.09). The MaRIA Score showed lower values for those with endoscopic and histological remission (p &lt; 0.05), All the patients with MaRIA Score&gt; 0 were CD except one, diagnosed with UC. Out of the 15 patients with endoscopic/histological involvement, 10 presented a MaRIA Score&gt; 0. Five of the 11 patients (45%) in whom the MaRIA Score was 0 did not have endoscopic and histological remission, only one of them had a diagnosis of CD.

Conclusion
The MaRIA Score was significantly correlated with endoscopic scores in pediatric IBD patients, especially in CD. However, based on the results of this study, the MRE should not replace the EGD and colonoscopy in order to thoroughly evaluate the disease activity.
P159 Patients with Inflammatory Bowel Disease Present with Lower Trabecular Bone Scores
Authors: Yarur A , Alexandra B , Beniwal-Patel P , Stein D , Nunez L , Berens B , Shaina S , Parakkal D , Shaker J , Jenna S 
Published: May 2021

Abstract

Background
Patients with inflammatory bowel diseases (IBD) have lower bone mineral density (BMD). However, BMD does not reflect bone micro-structure/geometry, nor indicates the intrinsic properties of bone tissue. The trabecular bone score (TBS) delivers an indirect measurement of bone microarchitecture and predicts fracture risk independent of bone density. The aim of this study was to assess if patients with IBD present with lower TBS vs a healthy control (HC) population and to identify variables associated with lower TBS.

Methods
This prospective cohort study included patients with active Crohn’s disease (CD) or ulcerative colitis (UC) and a matched HC group. Patients with ostomies, short gut or known endocrine co-morbidities associated with low BMD, patients with osteoporosis on pharmacologic therapy were excluded. L1-L4 TBS and BMD parameters were determined by dual-energy X-ray absorptiometry (DXA) using a GE Lunar iDXA scan and TBS iNsight™ and GE enCORE™. Other collected variables included demographics, disease phenotype, laboratories (25-OH vitamin D [25OHD] and parathyroid hormone levels [PTH]), disease activity (c-reactive protein [CRP], simple endoscopic score [SES-CD] in CD, and endoscopic Mayo score [EMS] in UC). IBD severity was stratified based on endoscopy: mild (EMS=1 in UC or SES-CD=3–6), moderate (EMS=2 or SES-CD=7–15) and severe (EMS=3 or SES-CD&gt;15). The primary outcome was the L1-L4 TBS. Secondary outcomes were left total and neck femoral BMD and the L1-L4 region BMD.

Results
A total of 141 patients were included (115 IBD and 26 HC). Patients with IBD had significantly lower TBS, femoral and L1-L4 BMD and Z-Scores when compared to controls (Figure 1). Endoscopic disease activity was not associated with TBS (Figure 2) or total/neck femur and L1-L4 BMD and Z-scores (p&gt;0.05 for all). When stratifying levels by 25OHD quartiles, patients with 25OHD ≥28 ng/mL (the highest 50th percentile of the study population) had significantly higher TBS Z-scores when compared to those with 25OHD ≤28 ng/mL (0.3 [-0.2 – 1.1] vs -0.1 [-1.1 – 0.5], p=0.002). No associations were seen between TBS Z-scores and use of steroids, gender, type of IBD (UC vs CD), smoking status or when comparing females 50 years or older vs the rest of the group (p&gt;0.05 for all). Moreover, there were no differences in TBS between patients who did or did not engage in resistance exercises (p=0.22) and/or regular aerobic exercises (RAPA ≥6) (p=0.84).

Conclusion
Patients with IBD present with lower TBS Z-scores when compared to HC and there is no correlation with disease activity. The only variable associated with lower TBS was a 25OHD &lt;28 ng/mL. Further studies looking at the implications of these findings are warranted.

FIGURE 1

FIGURE 2
P194 Alexithymia traits are associated with symptom severity and disease activity in IBD patients
Authors: Vinni E , Karaivazoglou K , Lourida T , Kalogeropoulou M , Tourkochristou E , Tsounis E , Lampropoulou E , Theocharis G , Thomopoulos K , Gourzis P , Triantos C 
Published: May 2021

Abstract

Background
Alexithymic traits are quite prevalent in patients with inflammatory bowel diseases (IBD) and have been linked with a heightened psychological burden including anxiety, depression, somatization and obsessive-compulsive symptoms. However, there are limited data regarding the association of alexithymia with gastrointestinal symptom severity and disease activity.

Methods
The current study was conducted at the Division of Gastroenterology of the University Hospital of Patras, in Greece with the collaboration of the Department of Psychiatry. Adult IBD outpatients and healthy controls were enrolled to the study. Alexithymic traits were assessed with the Toronto Alexithymia Scale (TAS-20). Disease activity was assessed with the calculation of the Truelove-Witts Index for ulcerative colitis (UC) patients and the Harvey-Bradsaw Index for Crohn’s disease (CD) patients.

Results
57 IBD patients and 50 healthy controls entered the study. 26 (45.6%) IBD patients reported clinically significant alexithymia traits. In addition, IBD patients faced increased difficulties in emotional expression (p=0.024) and reported increased overall alexithymic traits (p=0.033) compared to healthy controls. Moreover, we detected a borderline tendency of IBD patients to exhibit more disturbances in emotional recognition (p=0.067) compared to the control group. Difficulties in emotional recognition were significantly correlated with the presence of nausea (p=0.031), belly pain (p=0.015) and bloating (p=0.018), while overall alexithymic traits were strongly associated with the presence of nausea (p=0.008). Finally, increased disease activity was significantly associated with a higher total alexithymia score in Crohn’s disease (p=0.037) and ulcerative colitis (p=0.047) patients.

Conclusion
IBD patients report increased alexithymic traits which are associated with more severe gastrointestinal symptomatology and increased disease activity.