bluuebunny/crossref_metadata_2025_split huggingface dataset:
P095 Initial disease course in a Belgian, prospective inception cohort of patients with inflammatory bowel disease: the PANTHER cohort
Authors: Verstockt S , Glorieus E , Ukunda C , Barbaraci M , Verstockt B , Sabino J , Ferrante M , Geldof J , De Vos M , Laukens D , Cleynen I , Vandermeulen L , Lobatón T , Vermeire S 
Published: May 2021

Abstract

Background
Successful personalized treatment in inflammatory bowel disease (IBD) is critically dependent on identifying those patients at greater risk of a complicated disease course and who therefore may benefit from early advanced therapies. To this end, prospective inception cohorts integrating medical records with multi-omics data are needed. The Belgian Prognostic biobANk of paTients witH Early cRohn’s or colitis (PANTHER) was therefore initiated in 2015. We here present the initial disease course of this cohort.

Methods
The PANTHER cohort is an inception cohort of adult IBD patients from 3 Belgian, tertiary IBD referral centres. Patients are included within 3 months after diagnosis, are naïve for immunosuppressives and biologicals, and without previous IBD-related surgery. Clinical data are prospectively collected; and DNA, serum, feces and intestinal biopsies are taken at predefined time points. Patients are treated according to routine clinical management. Log-rank tests, and univariate and multivariate analyses were performed in R 3.6.2.

Results
A total of 289 newly-diagnosed IBD patients were recruited (median [IQR] follow-up of 2.9 [1.4–4.2] years), of whom 161 (56%) had Crohn’s disease (CD), 122 (42%) had ulcerative colitis, and 6 (2%) had IBD type unclassified (Table 1). Thus far, 242 of these patients (83%) are minimally at 1-year follow-up. Twenty-two patients (9%) already needed surgery (n=5 for colectomy and n=17 for ileocecal or small bowel resection) and 124 patients (51%) received biological therapy within the 1st year after diagnosis. Time series analysis showed a clear trend for increase in biological use within the 1st year after diagnosis when comparing 2015–2017 (42%) to 2018–2020 (54%) (p=0.06) (Fig.1). Being exposed to a biological within the 1st year was associated with age (OR=0.98 [95%CI: 0.96–0.99]), CD diagnosis (OR=3.7 (95% CI: 2.2–6.3) and more recent diagnosis (2018–2020 as opposed to previous years) (OR=1.2 [95% CI: 1.2–3.4]). Within CD, perianal disease was the strongest driver for early biological use (OR=4.4 [95% CI: 1.8–12.8]). Early biological exposure led to clear trends in decreased surgery rates one year later (2/99 [2%]) as compared to non-exposed patients (8/108 [7%]) (p=0.07), while hospitalization rates significantly decreased (4% versus 12%, p=0.04).

Conclusion
In this Belgian inception cohort, an increase in early biological use is observed in recent years and is associated with reduced IBD-related surgery and -hospitalization.
P131 Serum Proteomics and Intestinal Ultrasound Differentiates Fibrostenotic and Inflammatory Crohn’s Disease
Authors: Lu C , Filyk A , Mainoli B , de Almeida L , Novak K , Panaccione R , Hirota S , Dufour A 
Published: May 2021

Abstract

Background
Fibrostenotic Crohn’s disease (CD) is a challenging phenotype often leading to surgical resection. Easily accessible and cost-effective diagnostic tools are needed to advance precision medicine to manage fibrostenotic CD patients. To date, there are no biomarkers that can discriminate stricturing CD from other phenotypes. Early studies suggest that protein biomarkers identified from serum proteomics may differentiate CD subtypes. Utilizing intestinal ultrasound (IUS), which readily detects strictures, the serum of patients with and without strictures was collected for proteomic characterization.

Methods
All consecutive CD patients attending outpatient appointments received IUS, and CT (computed tomography)/MR (magnetic resonance) within 6 months of study inclusion. Strictures were defined as a fixed segment of the ileum with increased bowel wall thickness (BWT) and luminal apposition with or without prestenotic dilation. Thirty two patients with ileal strictures were matched with CD patients without strictures (inflammatory behaviour). Serum of patients were collected for quantitative shotgun proteomics using liquid chromatography and tandem-mass spectrometry (LC-MS/MS).

Results
64 patients in the stricture group had a significantly greater mean ileal bowel wall thickness (7.5 mm) compared to the inflammatory group (4.5mm, p = 0.02). A distinct and statistically significant protein signature was discovered between both patient populations. In the stricture group: plexin-A2, CD5 antigen-like protein, neogenin and dystonin were found, while in the non-strictured patients, matrix metalloproteinase 16, C-reactive protein, vinculin and apolipoprotein C-III were detected. Using Metascape and STRING-db, gene ontology and reactome pathway analyses, we identified enrichment of B cell differentiation and muscle contraction in the stricture patients, whereas in the non-stricture group, an enrichment for high-density lipoprotein remodeling, innate immune system and calcium ion transport were found.

Conclusion
We identified a unique protein signature that could robustly distinguish CD strictures from inflammatory phenotypes. This innovative diagnostic preliminary protein panel will be further expanded and validated in inflammatory and fibrostenotic CD populations, potentially allowing for future clinical decision optimization.
P140 Predicting Non-Responsiveness to Iron Therapy in Anaemic Children with Inflammatory Bowel Disease
Authors: Bevers N , Aliu A , Rezazadeh Ardabili A , Winkens B , Raijkmakers M , van de Vijver E , Swinkels D , Pierik M , van Rheenen P 
Published: May 2021

Abstract

Background
Anaemia negatively impacts physical fitness and quality-of-life, and therapy is aimed at normalization of haemoglobin (Hb) levels. In the majority of patients with inflammatory bowel disease (IBD) anaemia has a mixed aetiology resulting from chronic inflammation and iron deficiency. A considerable proportion of patients will fail to respond to iron therapy, but it has been difficult to identify non-responders at baseline with currently used iron indicators. Hepcidin is a peptide hormone involved in iron homeostasis. Upregulation leads to decreased iron availability, whereas downregulation facilitates iron absorption and release from macrophages to allow for erythropoiesis.
We evaluated commonly used iron indicators (ferritin and transferrin saturation [TSAT]) and emerging biomarkers (soluble transferrin receptor [sTfR] and hepcidin levels) at baseline to predict non-responsiveness to iron therapy in anaemic children with IBD.

Methods
We performed a prospective multi-centre cohort study among patients with IBD and anaemia (defined as Hb &gt; 2 standard deviations (SD) below the reference mean according to WHO cut-offs). We assessed iron indicators, sTfR, and hepcidin at baseline and again one month after the initiation of oral or intravenous iron therapy. Therapy was given according to international guidelines. Primary outcome was based on the change of Hb z-score (one month after treatment vs baseline) divided by baseline SD, where non-responsiveness was defined as a standardised change score of less than 1. Hepcidin was expressed as z-score to allow correction for age and gender. Baseline data of ferritin and TSAT were used to construct a basic logistic regression model. Hepcidin and/or sTfR were then added to the basic prediction model (models [M] 1–3). Optimal sensitivity and specificity were identified using the Youden’s J Index.

Results
Of 40 anaemic IBD patients (mean age 12.8 years; mean Hb z-score -3.1 SD), sixteen (40%) were non-responsive to iron therapy one month after initiation. The basic prediction model yielded an area under the curve (AUC) of 0.69. Figure 1 shows that adding sTfR, hepcidin or both to the model increased the AUC to 0.78 (M1), 0.82 (M2), and 0.90 (M3), respectively. For model 3, sensitivity and specificity at the optimal cut-off value were 94% and 71%, respectively.

Figure 1: Receiver operating characteristic (ROC) curves representing the accuracy of iron therapy non-responsiveness. AUC, area under the curve; CI, confidence interval

Conclusion
Based on prediction quality of the models, triaging with a strategy that involves baseline ferritin, TSAT, sTfR, and hepcidin is preferred to assess non-responsiveness to iron therapy in anaemic children with IBD.
P149 Application of revised Pediatric Inflammatory Bowel Disease (PIBD) classes criteria to the Korean PIBD patients
Authors: Shin M , Lim J G , Kim M S , Moon S Y , Hahn J W , Kim D H , Moon J S , Ko J S 
Published: May 2021

Abstract

Background
In 2017, Porto group of ESPGHAN published the PIBD classes criteria, a diagnostic classification criteria for PIBD by conducting multi-center study, and the revised PIBD classes criteria were released in 2020 after multi-center verification. Consisting of 19 items classified into a total of 3 classes, this criteria classifies PIBD into UC, atypical UC, CD, and IBD-U through an algorithm. The purpose of this study is to examine the appropriateness of diagnosis and criteria by applying the revised PIBD classes-criteria for PIBD patients diagnosed in a certified tertiary hospital.

Methods
Among 156 new patients aged 1–18 years old diagnosed with PIBD at Seoul National University Children’s Hospital from January 1, 2014 to August 18, 2020, 102 patients who had no underlying disease, did not administer drugs that affect the immune system, whose key items of PIBD class criteria (upper and lower gastrointestinal endoscopy, gastrointestinal imaging, pathology, etc.) and basic demographic characteristics were verified were analyzed retrospectively through electronic medical records.

Results
Of the 102 PIBD patients, 85 (83%) were initially diagnosed with CD, 15 (15%) with UC, and 2 (2%) with IBD-U by clinicians. Of the 102 patients, 69 (68%) were male, and the age of first diagnosis was 11.5±3.7 years. After applying the revised PIBD classes criteria, the diagnosis was changed to CD for 2 IBD-U patients, IBD-U for 7 UC patients, and CD for 1 UC patient. Finally, the diagnosis was changed to 86 (84%) CD, 8 (8%) UC and 7 (7%) IBD-U. The two patients whose diagnosis was changed from IBD-U to CD satisfied the items of Class 1, so the diagnosis was changed. All 7 patients whose diagnosis changed from UC to IBD-U did not satisfy all the items of Class 1, but most of the items ‘Focal active colitis on histology in more than one biopsy’ (6/7) and ‘Focal enhanced gastritis on histology’ (7/7) of class 3 criteria were satisfied, and the diagnosis has changed.

Conclusion
As a result of applying the PIBD class criteria, there was no significant change in the diagnosis of CD, but the diagnosis of UC decreased by 73% and the diagnosis of IBD-U increased by 5 times. In this study group, the positive rates of items ‘Fistulising disease’, ‘‘Thickened jejunal or ileal bowel loops on radiology or other evidence of significant small bowel inflammation on capsule endoscopy’, ‘Focal active colitis on histology in more than one biopsy’ and ‘Focal enhanced gastritis on histology’ tended to be significantly higher than those of the previous study. So, Further validation and confirmation are needed.
P157 Microbiome Analysis Reveals That Ralstonia is Responsible for Decreased Renal Function in Patients with Ulcerative Colitis
Authors: Kim J M , Rim J H , Kim D H , Kim H Y , Choi S K , Kim D Y , Choi Y J , Yu S , Gee H Y , Cheon J H 
Published: May 2021

Abstract

Background
Inflammatory bowel diseases (IBDs), such as ulcerative colitis (UC), are characterized by a disturbance of the normal gut microbiota and contribute to the development of chronic kidney disease (CKD). The incidence of CKD is higher in individuals with UC, but the causal link is unknown. Therefore, we investigated the role of gut microbiota in decreasing renal function in patients with UC

Methods
We performed 16S ribosomal DNA sequencing using ileocecal mucosal samples from nine individuals with UC and CKD (UC+CKD), 29 individuals with UC only, and 12 healthy controls. We also analyzed the operational taxonomic units, microbial diversity, and correlation with renal function. Co-culture assay using kidney organoids and Caco-2 cells was performed.

Figure 1. The taxonomic composition of the gut microbiota of the study population and comparison of the 10 most abundant genera and species in the UC + CKD, UC, and control groups.

Results
Bacterial species diversity was significantly decreased in the UC+CKD group compared to that in the other groups based on Shannon and inverse Simpson indexes. At the genus level, Ralstonia had significantly greater abundance in the UC+CKD and UC groups compared to the control group. At the species level, unclassified Ralstonia species and Citrobacter portucalensis showed higher abundance in the UC+CKD group compared to the other groups. The relative abundance of Ralstonia showed a negative correlation with the estimated glomerular filtration rate (eGFR), but a positive correlation with the serum uric acid level. Ralstonia pickettii represented a negative correlation with eGFR, and induced damaging changes to kidney organoids in co-culture assay.

Figure 2. The correlation between the relative abundance of Ralstonia with renal function (indicated by eGFR) and serum uric acid level. Effects of Ralstonia pickettii on Caco-2 cells and kidney organoids. (A) mRNA expression of pro-inflammatory cytokine genes in Caco-2 cells treated with and without Ralstonia pickettii, reflecting the inflammation seen in ulcerative colitis.

Conclusion
Gut microbial community profiles of the UC+CKD group are different from those of the UC group. Furthermore, Ralstonia pickettii contributes in decreasing renal function in patients with UC.
P206 Paediatric Genital Crohn’s Disease: Presentation and Treatment, a combined case series
Authors: Sethuraman A , Kontaki E , Gaynor E , Jones K , Cherian A , Zamvar V , Kiparissi F 
Published: May 2021

Abstract

Background
Metastatic Crohn’s Disease (MCD) affecting the genitalia is a rare condition, characterised by granulomatous inflammation of the genital tract. Only few paediatric cases have been described in the literature with a female preponderance. Paucity of literature is noted with regards to treatment and outcome.

Methods: Aim
To describe the clinical presentation, associated features, and response to treatment in a cohort of paediatric patients diagnosed as genital metastatic Crohn’s disease (MCD).

Methods
All cases of paediatric genital MCD were retrospectively collected from two centres at Great Ormond Street Hospital for Children and Leeds Children’s Hospital for the past 20 years (January 2001 to January 2021). Medical history, symptoms at presentation, histological characteristics, results of investigations and response to treatment were reviewed.

Results
A total of 12 patients (7 male and 5 female) were diagnosed with genital MCD. The mean age at presentation of genital MCD symptoms was 8.9 years of age (1.5–14 years). Generalised swelling of the genital region was the most common presentation. 5/12 (42%) children had luminal Crohn’s disease (CD) before development of Genital MCD whereas 4/12 (33%) children developed luminal CD after Genital MCD presentation. 3/12 (25%) children after evaluation were found to have only Genital MCD with no luminal pathology of CD. Genital MCD was the first presentation of Crohn’s disease in 7/12 children (58.3%) in our cohort. 6/12(50%) children were seen to have perianal disease. All children were extensively investigated endoscopically and radiologically. Genital biopsy was done in 6/12(50%) patients showing non caseating granulomatous inflammation. 11/12 patients received dual therapy at some point in their treatment with azathioprine and infliximab. Switch of infliximab to adalimumab was seen in 7/12 (58.3%) patients mostly in view of escalating treatment to control luminal CD. Initiation of treatment since first symptoms of genital MCD appeared to be prolonged, perhaps due to delay in diagnosis via referral pathways from local paediatrician via urologist to paediatric gastroenterologist. Improvement of genital MCD was seen in most children with dual therapy of azathioprine and infliximab.

Conclusion
Genital MCD can be the first presentation of Crohn’s disease and may not be associated with GI symptoms or luminal CD. All children with MCD do benefit from histological as well as radiological and endoscopic evaluation. Formal MDT discussions with the urologist, radiologist and gastroenterologist may help in early diagnosis and treatment. A retrospective multi-centre case reviews will help to identify the prevalence of genital MCD in children and also help develop a national pathway.
P237 Prevalence of dysplasia and colorectal cancer in Ulcerative Colitis patients from a referral center in Latin America
Authors: Junior R S F , Carvalho M F , Silva J C , Barros L L , Azevedo M F C , Carlos A D S , Oba J , Hashimoto C L , Cançado E L R , Damiao A O M C , Sipahi A M 
Published: May 2021

Abstract

Background
Ulcerative colitis (UC) is a chronic inflammatory disease characterized by relapsing and remitting course of bloody diarrhea. UC patients are at higher risk of dysplasia and colorectal cancer (CRC) when compared to the general population, especially those with primary sclerosing cholangitis (PSC), long-standing disease and active inflammation. The aim of this study was to determine the prevalence of dysplasia and CRC in a large cohort of UC patients in Latin America.

Methods
This study was a retrospective analysis of all UC patients registered and followed-up in our outpatient clinic between January 2010 and September 2020. The diagnosis was confirmed by clinical, endoscopic, histopathological, and radiologic findings according to current guidelines. CRC was confirmed by one or more experienced pathologists. Medical records were abstracted for the data: demographic characteristics; duration, extent, and treatment of UC; dysplasia and cancer.

Results
In total, 560 patients with UC were identified. Of all cases, 364 (64.8%) had pancolitis, 115 (20.5%) had left side colitis and 81 (14.4%) were diagnosed with proctitis. There was a slight predominance of female, 331 (59.1%). The mean age at inclusion was 48 years. Among these patients 11.2% had concomitant PSC. Aminosalicylates were the most common treatment in 70% of our cohort, whereas 40% were treated with immunobiologics at any time during UC course. The length of the disease was between 10 to 20 years in 42% of cases and from 20 to 30 years in 17% of them. In our analysis the prevalence of dysplasia was 21%. Five of them were of high grade, which occurred in whom the length of the disease was between 10 to 20 years. In the majority of cases dysplasia was related to the inflammatory burden of UC (75.2%) and 37 patients were diagnosed with sporadic dysplasia. Seven cases (1.25%) of colorectal cancer were found (median time from UC diagnosis to CRC = 18 years), which two of these patients had concomitant PSC. All UC-CRC patients had extensive colitis.

Conclusion
Recent studies have suggested that the risk of CRC in UC population has decreased during the last decades due to tight control treatment and adequate endoscopic surveillance. In Latin America data on the prevalence and prognosis of UC-CRC patients are scarce. Herein we report the frequency of UC-related dysplasia and UC-CRC in Brazil over a period of 10 years. Our results revealed higher prevalence rates when compared to underdeveloped countries, such as India and China. Longer disease duration and extensive colitis were identified as important risk factors for developing CRC in accordance with the literature. Further research is warranted to better identify ethnical and environmental risk factors in this population.
P247 Carotid Plaque Assessment reclassifies patients with Inflammatory Bowel Disease into Very-High Cardiovascular Risk
Authors: Hernandez Camba A , Carrillo-Palau M , Ramos L , Hernández Alvarez-Buylla N , Alonso-Abreu I , Hernández A , Vela M , Arranz L , Hernández-Guerra M , González-Gay M A , Ferraz- Amaro I 
Published: May 2021

Abstract

Background
The addition of carotid ultrasound into cardiovascular (CV) risk scores has been found to be effective in identifying patients with chronic inflammatory diseases at high-CV risk. We aimed to determine if its use would facilitate the reclassification of patients with inflammatory bowel disease (IBD) into the very high-CV-risk category and whether this may be related to disease features.

Methods
Multicenter cross-sectional study encompassing 186 IBD patients and 175 controls. Systematic Coronary Risk Evaluation (SCORE), disease activity measurements, and the presence of carotid plaques by ultrasonography were assessed. Reclassification was compared between patients and controls. A multivariable regression analysis was performed to evaluate if the risk of reclassification could be explained by disease-related features and to assess the influence of traditional CV risk factors on this reclassification.

Results
After evaluation of carotid ultrasound, a significantly higher frequency of reclassification was found in patients with IBD compared to controls (35% vs. 24%, p=0.030). When this analysis was performed only on subjects included in the SCORE low-CV-risk category, 21% IBD patients compared to 11% controls (p = 0.034) were reclassified into the very high-CV-risk category. Disease related data, including disease activity, were not associated with reclassification after fully multivariable regression analysis. Traditional CV risk factors showed a similar influence over reclassification in patients and controls. However, LDL-cholesterol disclosed a higher effect in controls compared to patients (beta coef. 1.03[95%CI 1.02–1.04] vs. 1.01[95%CI 1.00–1.02], interaction p=0.035) after adjustment for confounders.

Conclusion
Carotid plaque assessment is useful to identify high-CV risk IBD patients.