bluuebunny/crossref_metadata_2025_split huggingface dataset:
P051 Macrophages as a source of Notch Ligands in Crohn’s disease: implications in fibrosis
Authors: Jorge M A , Barrachina M D , Bauset C , Gisbert-Ferrándiz L , Cosin-Roger J , Coll S , Calatayud S , López-Serrano A , Ortiz-Masiá D 
Published: May 2021

Abstract

Background
Fibrosis constitute the main complications associated to Crohn’s disease (CD). Notch signalling has been implicated in lung, kidney, liver and cardiac fibrosis. Macrophages contribute to fibrosis through the release of different mediators and the pattern of secretion may vary according to their microenvironment. The aim of the present study is to analyze the role of Notch ligands derived from macrophages in the complications of CD.

Methods
We have analyzed: the mRNA expression of cytokines and Notch ligands in CD patients with fistulizing and stenting pattern, the mRNA and protein expression of macrophage markers and Notch ligands in macrophages treated with the main cytokines present in CD patients (IFNγ-, IL10-, IL4, TNFα-U937 treated cells), the mRNA expression of fibrosis markers of DLL4-HT29 treated cells. Results are expressed as fold induction (mean±SEM, n≥4). Statistical analysis was performed with one-way ANOVA followed by Newman-Keuls test. Correlations were analyzed with the Spearman coefficient.

Results
The mRNA expression of IFNγ, TNFα, IL4, IL6 and IL10 was significantly higher in intestinal samples from B2- and B3-CD patients (11.4±1.6, 6.9±1.3, 16.4±3.9, 4.1±0.4, and 5.0±1.0 respectively for B2, and 14.2±1.8, 9.6±2.6, 21.5±4.1, 6.3±1.0 and 9.2±1.7 respectively for B3) than in controls (1.0±0.09, 1.1±0.2, 1.2±0.1, 1.1±0.1 and 1.0±0.1 respectively). The mRNA expression of DLL3 and DLL4 was significantly higher in intestinal samples from B2 (6.1±1.3 and 9.3±2.4, respectively) than in B3 CD patients (4.4±1.0 and 1.8±0.7, respectively) and in controls (0.9±0.2 and 0.7±1.2 respectively). IFNγ-U937 treated cells increased significantly the mRNA expression of DLL3 and DLL4 (2,9±0,6 N=5 N=4 and 3,7±1,1 N=4, respectively) respect vehicle; IL1β increased significantly the expression of DLL4 (1,8±0,01 N=4) and TNFα increased significantly the expression of DLL3 (7,1±2,2 N=4), respect vehicle. DLL4-HT29 treated cells increased significantly fibrosis markers (VIMENTIN (4,6±0,6 N=6), α-SMA (20,9±8,2 N=6), SNAIL1 (1,8±0,4 N=6), SNAIL2 (8,3±1,3 N=6), ZEB1 (8,2±4,3 N=6) and ZEB2 (4,3±0,2 N=6), respect vehicle.

Conclusion
Macrophages may act as a source of Notch ligands who could act as fibrosis mediators in CD patients with a stenting (B2) behavior. The microenvironment rich in IFNγ could activate the fibrosis process in epithelial cells by favoring the expression of DLL4 in macrophages.
P053 Overabundance of Lactobacillus species in gut microbiota of IBD patients
Authors: Khusnutdinova D , Markelova M , Siniagina M , Boulygina E , Abdulkhakov S , Grigoryeva T 
Published: May 2021

Abstract

Background
Changes in the composition of gut microbiota, and their metabolic pathways, are important factors in the pathogenesis of inflammatory bowel disease (IBD). Many clinical trials have shown that taking probiotics based on Lactobacillus has a positive effect on patients with IBD. However, Lactobacillus should be used more carefully during the active phase of IBD, since some strains can negatively affect the pathogenesis of the disease1,2. The aim of this study was to assess the diversity of Lactobacillus species in the gut microbiome of IBD patients and healthy volunteers.

Methods
In the study, 62 stool samples from healthy people, 31 from patients with Crohn’s disease (CD), and 34 - ulcerative colitis (UC) in active phase were analyzed. DNA was isolated using the QIAamp Fast DNA Stool Mini Kit (Qiagen, USA) following with shotgun metagenomic sequencing the NextSeq 500 (project #0671-2020-0058). Bioinformatic analysis was performed with the MetaPhlAn2 package.

Results
An increased relative abundance of Lactobacillus was found in patients with IBD (3.2% ± 6.6% in CD and 1.6% ± 2.8 in UC) compared to healthy individuals (0.3% ± 1.2%, p&lt;0.05).
In the control group, Lactobacillus were absent in 41% of samples and 1–5 species were found in 58% of samples. Most CD and UC patients are characterized by the presence of 3 to 5 species of Lactobacillus (38% and 31%, respectively). For 23% of CD patients and 26% of UC patients, 6 to 9 types of Lactobacillus were found. Some patients with IBD have more than 10 different types of Lactobacillus in the gut microbiota (Fig.1).
The intestinal microbiota in IBD patients is characterized by an increased abundance of several species: L. salivarius, L. gasseri, L. mucosae, as well as L. casei paracasei in patients with CD and L. vaginalis in patients with UC (Fig.2).

Conclusion
The composition of the intestinal microbiota of IBD patients differs significantly in terms of Lactobacillus proportion and species diversity. Overabundance of five Lactobacillus species could be associated with the active phase of IBD.

References
P067 The effect of a probiotic mix on mucosal healing and fibrotic responses in healthy colonic subepithelial myofibroblasts
Authors: Tarapatzi G , Filidou E , Kandilogiannakis L , Arvanitidis K , Vradelis S , Kotzampassi K , Kolios G 
Published: May 2021

Abstract

Background
Various probiotic strains play a positive role in Inflammatory Bowel Disease and might support mucosal healing. Colonic Subepithelial Myofibroblasts (SEMFs) have a pivotal role in mucosal healing and fibrosis, by migrating to the trauma region and secreting collagen. Our study aimed to investigate whether different strains of probiotics can affect the migration capacity and the fibrotic phenotype of SEMFs isolated from healthy individuals.

Methods
The probiotic mix of Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis and Saccharomyces boulardii was reconstituted in SEMFs culture medium, they were identified by Gram staining and their viability was assessed by Trypan Blue staining. Primary SEMFs were isolated from colonic biopsies from healthy individuals, and stimulated with 102, 104 or 108 cfu/ml of the mix for 6h or 48h; in 6h total RNA was collected and mRNA expression of collagen type I, III, fibronectin, tissue factor (TF) and α-SMA was measured by quantitative PCR, and in 48h their effect on migration rate through the Wound Healing Assay and collagen secretion via Sircol was assessed.

Results
Trypan Blue confirmed that the majority of the probiotic mix was alive, and all three bacterial strains and the yeast were stained Gram positive. Stimulation of SEMFs with the probiotic mix resulted in different effects depending on its concentration; 102 cfu/ml downregulated protein collagen secretion (3.4μg/ml, IQR: 2.7–5.0, p&lt;0.01 vs control 6.3μg/ml, IQR: 5.2–6.7) and α-SMA mRNA production (0.7-fold, IQR: 0.7–0.8, p&lt;0.01), 104 cfu/ml upregulated the Fibronectin mRNA expression (1.6-fold, IQR: 1.2–1.8, p&lt;0.0001) and 108 cfu/ml downregulated collagen type I (0.2-fold, IQR: 0.1–0.8, p&lt;0.01) and III mRNAs (0.3-fold, IQR: 0.1–0.8, p&lt;0.01). In addition, all three concentrations resulted in the overall upregulation of TF mRNA expression. Regarding the effect of the probiotic mix on SEMFs migration capacity, 104 cfu/ml of the probiotic mix resulted in increased migration rate by 133.8% (IQR: 102.8–150.2, p&lt;0.01) after 24h, while the use of 102 cfu/ml and 108 cfu/ml decreased it by 58.2% (IQR: 34.8–79.7, p&lt;0.01) and by 46.8% (IQR: 34.3–72.1, p&lt;0.01) respectively.

Conclusion
This study provides evidence that the probiotic strains L. plantarum, L. acidophillus, B. lactis and S. boulardii remain viable in SEMFs’ culture medium and have the ability to interact with and alter the behavior of SEMFs. Moreover, the effect of the probiotic mix on SEMFs fibrotic phenotype is dependent of the concentration of the probiotics used. Further preclinical research is needed in order to identify the effect of each strain, as well as the suitable dose and combinations in various pathological conditions.
P101 Fecal calprotectin is increased among patients with pouchitis and increases with increasing endoscopic subscores: Real-world data from a prospectively collected database
Authors: Ollech J , Bannon L , Maharshak N , Tulchinsky H , Yanai H , Dotan I 
Published: May 2021

Abstract

Background
An accurate and non-invasive surrogate marker of inflammation is needed for managing patients after Ileal pouch-anal anastomosis (IPAA). In this study, we evaluate the performance of fecal calprotectin (FC) in patients with ulcerative colitis (UC) who underwent IPAA and were assessed with clinical, endoscopic, and histologic examination of the pouch.

Methods
Medical records of patients who underwent IPAA with J-pouch formation registered in a prospectively collected database at the Tel Aviv Sourasky Medical Center, Israel, were evaluated. Clinical, endoscopic, histologic, and laboratory data were extracted. Each pouch evaluation was regarded separately. Pouchitis was defined as a Pouchitis Disease Activity Score (PDAI) of ≥7 (maximum score: 18).

Results
One hundred and fifty-six patients underwent 296 unique pouch evaluations. Fifty-two percent of patients were male, the median age at the time of evaluation was 43 years (IQR 35–58), and the median pouch age from the closure of the ileostomy was 10 years (IQR 2.5–15). The median [IQR] FC values were significantly lower in patients without pouchitis than in patients with pouchitis (208 [96–478] vs. 550 [250–1051] ug/g, p&lt;0.0001). Mean FC values were lower in patients with lower endoscopic and histologic scores when compared to higher scores, with a significant linear trend for higher FC levels with increasing endoscopic and histologic disease activity. FC performed better than CRP as a predictor of pouchitis. A FC of over 400 ug/g had over 80% specificity for predicting significant endoscopic disease.

Conclusion
FC levels increase among patients with pouchitis and increase with increasing endoscopic and histologic inflammation. A FC of over 400 ug/g had good discriminative ability as a predictor of significant endoscopic disease. We suggest that in patients with symptoms of pouchitis and an FC level above 400 ug/g, antibiotic treatment can be initiated without awaiting pouchoscopy. Further research is needed to define FC concentrations more precisely among various outcome measures of interest in these patients.
P162 Microscopic inflammation in limited Ulcerative Colitis at diagnosis: can a single histological feature predict prognosis?
Authors: Revés J , Frias Gomes C , Ellul P , Callé C , Almeida A , Burisch J , Buhagiar T , Attard A , Lo B , Ungaro R , Morão B , Gouveia C , Branco J , Rodrigues J , Teixeira C , Castro F , Nunes G , Brito M , Antunes M , Torres J , Borralho P 
Published: May 2021

Abstract

Background
Histological assessment is becoming increasingly important in the management of Ulcerative Colitis (UC). The Nancy index (NI), a recently developed and validated score, has been shown to accurately represent histological inflammation and to correlate with prognosis. However, it is a composite score, involving the analysis of more than one histological feature, which may limit its applicability. Our aim was to evaluate if a single component of the NI could individually predict prognosis in limited UC (E1 and E2) patients.

Methods
Multi-centre retrospective cohort study of newly diagnosed, treatment-naïve proctitis and left-sided ulcerative colitis patients. Biopsies from inflamed rectal mucosa were reviewed by two pathologists. Histological features from the NI were selected for analysis, including presence of ulcers, acute inflammatory infiltrate (with separate evaluation of neutrophils in lamina propria and epithelium) and chronic inflammatory infiltrate. Mucin depletion and basal plasmacytosis were also evaluated. The primary outcome was a composite outcome intended to evaluate disease-related complications, including proximal disease extension, need for hospitalisation or colectomy. Survival analysis, including univariate and multivariate Cox-regression analysis was performed.

Results
A total of 91 patients were included (56.0% males, mean age 44±17 years, median follow-up 44 months [2–328]). Overall, 64.8% of the patients had proctitis (E1) and 35.2% left-sided colitis (E2). The most frequent histological features were the presence of chronic inflammatory infiltrate (93.4%), mucin depletion (81.3%) and basal plasmacytosis (78.0%). During the follow-up, 22.0% presented a disease-related complication. The NI was not able to predict prognosis (HR 3.09, 95% CI 0.71–13.36, p=0.132). In univariate analysis, the presence of neutrophils in the epithelium in more than 50% of the crypts was marginally significant for the primary outcome (HR 2.51, 95% CI 0.99–6.36, p=0.05). In multivariate analysis, after adjusting for gender, age at diagnosis, disease extent (E1 vs E2), Mayo endoscopic score (&lt; 2 vs ≥ 2) and clinical severity at diagnosis (mild vs moderate to severe UC) this single component of the score was associated with the primary outcome (aHR 3.36, 95% IC 1.21–9.31, p=0.02). No other histological feature was able to individually predict prognosis (p&gt;0.05).

Conclusion
The presence of neutrophils in the epithelium in more than 50% of the crypts in endoscopically inflamed mucosa at diagnosis was associated with higher disease complications in limited UC patients. The evaluation of a single feature could facilitate the use of histology in the prediction of prognosis in UC. Our results need to be prospectively validated.
P190 Ileo-caecal Crohn’s Disease; medical or surgical management. Cost and outcomes
Authors: Charan M , Maclaren L , Bryant C , Wade K , Johnson H , McLaughlin S 
Published: May 2021

Abstract

Background
An ileo-caecectomy is known to be an effective treatment for Crohn’s disease limited to the terminal ileum that can lead to a long term remission. ECCO guidelines recommend that patients with active inflammation should be treated medically. However the LIR!C trial suggested there are QOL benefits and reduced costs to performing primary surgery.

Methods
We aimed to compare the outcomes of patients treated with primary medical treatment to primary surgery for patients with Crohn’s disease limited to the terminal ileum. We reviewed our database to identify all these patients and analysed outcome data.

Results
49 patients were identified:
Mean age was 50 yrs (range 22 - 93). 23 were male.
Mean length of follow-up was 96 months (range 3 - 404).
1st line treatment was: medical; 33 (67.3%), surgery; 16 (32.6%).
Outcomes after medical treatment: 27 of 33 patients failed primary medical treatment, they required surgery at a mean of 38 months (range 1–900) after initiating medical treatment.
Colonoscopy after surgery to assess for disease recurrence: Colonoscopic assessment or calprotectin post was undertaken ileo-caecectomy in 4 of 16 patients at a mean of 6.2 months (range 1–10) who underwent primary surgery; and in 25 of 27 patients who underwent surgery following failure of medical treatment.
Outcomes after surgery: 4 of 16 patients who had primary surgical treatment had endoscopic recurrence, requiring medical treatment after a mean of 4.4 months (range 0–10). 8 of 27 patients who had surgery post-failure of medical treatment developed disease recurrence, requiring medical treatment after a mean of 40 months (range 7–136)
Bile acid malabsorption (BAM): BAM occurred after surgery in 10 of 43 patients. No medically managed patient developed BAM.

Conclusion
These data suggest that in our population the vast majority of patients with ileo-caecal Crohn’s disease will fail medical treatment and require surgery. 25% of those who undergo surgery will develop BAM (requiring medication), and 40% of those treated surgically will require immunosuppressant treatment in the medium term.
These outcomes should be discussed with patients so that they appreciate that ileo-caecectomy is unlikely to lead to long term drug free treatment, and medical treatment is unlikely to lead to the avoidance of surgery. From a health-economics point of view it could be argued there is little point in offering primary medical therapy and ileo-caecectomy should be the initial treatment of choice for patients with limited ileo-caecal Crohn’s disease.
Unfortunately endoscopic/calprotectin assessment following primary surgery was often not performed in the majority of patients, and changes in our local practice need to be undertaken to correct this.
P202 De novo Inflamatory Bowel Disease after solid organ transplantation
Authors: Luque Carmona A M , Rojas Feria M , De la Cruz Ramirez M D , Trigo Salado C , Herrera Justiniano J M , Leo Carnerero E 
Published: May 2021

Abstract

Background
The aim of this study was to determine the disease phenotype, evolution and therapeutic needs of de novo inflammatory bowel disease (IBD) in transplanted patients.

Methods
A retrospective single center study that included all patients who developed IBD after solid organ transplantation in a tertiary hospital. Data collected included transplant-related variables, IBD phenotype, course of the disease and its treatment. A control group of non-transplanted IBD patients was randomly selected.

Results
We included 17 post-transplanted IBD patients and 57 non-transplanted IBD patients. Post-trasplanted patients were older at diagnosis, had greater colonic involvement, with an inflammatory behaviour, absence of perianal involvement and extraintestinal manifestations compared to control group (Table 1).
The most common immunosuppression regimen was tacrolimus+mycophenolate mofetil (MMF)+prednisone and the most frequent change after diagnosis was the switch of MMF for azathioprine. De novo IBD patients required less biological therapy than the control group (11.8 vs 42.1% p 0.02) and none required surgical intervention compared to 35.1% in the control group (p 0.002).
Multivariate analysis carried out on the total population showed that active smoking, perianal disease and extraintestinal manifestations were associated with a greater need for biologics, while the only factor that influenced surgical risk was stricturing and penetrating behaviour of Crohn′s disease.

Conclusion
De novo IBD after solid organ transplantation has a favorable course, predominating the inflammatory behaviour and requiring less biological therapy and surgical interventions. The absence of extraintestinal manifestations and perianal disease stands out.
P248 Assessment of health-related quality of life of paediatric Inflammatory Bowel Disease patients through the IMPACT-III questionnaire
Authors: Vázquez Gómez J A , Velasco Rodríguez-Belvís M , Palomino Pérez L M , Sánchez Llorente P , Aguilar Ladrón de Guevara C , Muñoz Codoceo R A 
Published: May 2021

Abstract

Background
Health-related quality of life (HRQOL) is a multi-dimensional concept used to examine the impact of health status on their global well-being. The IMPACT-III is a 35-item questionnaire specifically designed to evaluate the quality of life of patients with paediatric Inflammatory Bowel Disease (pIBD). This questionnaire had its origin in 1999 in Canada (Otley et al.) and, since then, it has been adapted to many languages.
The objective of this study was to assess the quality of life of pIBD patients using the IMPACT-III questionnaire and to identify specific needs according to the patient’s profile.

Methods
An observational, descriptive, and retrospective study was carried out in November 2020, including the pIBD patients undergoing follow-up in a tertiary hospital that have previously completed the IMPACT-III questionnaire. Epidemiological and clinical data were anonymously retrieved from the electronic medical records. We established three blocks of IMPACT-III items according to physical, emotional and social well-being, or to the perception of body image. The results of each block and totals were compared according to gender, age, diagnosis, time of evolution, activity and treatment.
To make the comparison, the Mann-Whitney U test for independent samples for 2 groups and the Kruskal-Wallis test for 3 or more independent groups were used. The statistical analysis was performed using SPSS software and the results were considered statistically significant when reaching a bilateral critical level (p) ≤ 0.05, with a 95% confidence interval.

Results
We included a total of 40 patients. There were no significant differences according to gender, type of IBD or type of treatment. The group of adolescents obtained a higher score in the body image block (p = 0.009). Patients with over two years of evolution of the disease obtained statistically significantly higher scores in the physical well-being block (p = 0.027). In patients who filled out the questionnaire during a flare, the scores on questions of physical well-being (p = 0.007), emotional and social (p = 0.037), as well as total (p = 0.012) were significantly higher. Overall, 31 patients (77.5%) answered that IBD had negatively affected their family.

Conclusion
Our data suggest that patients with a longer evolution time, adolescents and patients suffering an active flare seem to report a worst HRQOL. Patients with the mentioned characteristics constitute a vulnerable population with special care needs that should be addressed from an interdisciplinary point of view. Despite the limitations of the retrospective design and the scarce number of patients, our results indicate that family-centered care should be a priority.