Maximizing the diagnostic information from biopsies in chronic inflammatory bowel diseases: recommendations from the Erlangen International Consensus Conference on Inflammatory Bowel Diseases and presentation of the IBD-DCA score as a proposal for a new index for histologic activity assessment in ulcerative colitis and Crohn's disease.
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SUBMITTER: Lang-Schwarz C
PROVIDER: S-EPMC7973393 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and aimsHistological scoring plays a key role in the assessment of disease activity in ulcerative colitis [UC] and is also important in Crohn´s disease [CD]. Currently, there is no common scoring available for UC and CD. We aimed to validate the Inflammatory Bowel Disease [IBD]-Distribution [D], Chronicity [C], Activity [A] score [IBD-DCA score] for histological disease activity assessment in IBD.MethodsInter- and intra-rater reliability were assessed by 16 observers on biopsy specimens from 59 patients with UC and 25 patients with CD. Construct validity and responsiveness to treatment were retrospectively evaluated in a second cohort of 30 patients.ResultsInter-rater reliability was moderate to good for the UC cohort (intraclass correlation coefficients [ICCs] = 0.645, 0.623, 0.767 for D, C, and A, respectively) and at best moderate for the CD cohort [ICC = 0.690, 0.303, 0.733 for D, C, and A, respectively]. Intra-rater agreement ranged from good to excellent in both cohorts. Correlation with the Nancy Histological Index [NHI] was moderate and strong with the Simplified Geboes Score [SGS] and a Visual Analogue Scale [VAS], respectively. Large effect sizes were obtained for all three parameters. External responsiveness analysis revealed correlated changes between IBD-DCA score and NHI, SGS and VAS.ConclusionsThe IBD-DCA score is a simple histological activity score for UC and CD, agreed and validated by a large group of IBD specialists. It provides reliable information on treatment response. Therefore, it has potential value for use in routine diagnostics as well as clinical studies.
| S-EPMC8495487 | biostudies-literature
Project description:The IBD-Character cohort (Edinburgh, Oslo, Örebro, Linköping, Zaragoza, Maastricht) included patients with inflammatory bowel diseases (IBD: Crohn's disease, ulcerative colitis) recruited at diagnosis and non-IBD controls. Paired-end RNA sequencing was used for whole blood expression profiling. Raw and normalized counts tables are provided.
2022-03-01 | E-MTAB-11349 | biostudies-arrayexpress
Project description: Not available
| S-EPMC8191823 | biostudies-literature
Project description:BackgroundInflammatory Bowel Diseases with its complexity and heterogeneity could benefit from the increased application of Artificial Intelligence in clinical management.AimTo accurately predict adverse outcomes in patients with IBD using advanced computational models in a nationally representative dataset for potential use in clinical practice.MethodsWe built a training model cohort and validated our result in a separate cohort. We used LASSO and Ridge regressions, Support Vector Machines, Random Forests and Neural Networks to balance between complexity and interpretability and analyzed their relative performances and reported the strongest predictors to the respective models. The participants in our study were patients with IBD selected from The OptumLabs® Data Warehouse (OLDW), a longitudinal, real-world data asset with de-identified administrative claims and electronic health record (EHR) data.ResultsWe included 72,178 and 69,165 patients in the training and validation set, respectively. In total, 4.1% of patients in the validation set were hospitalized, 2.9% needed IBD-related surgeries, 17% used long-term steroids and 13% of patients were initiated with biological therapy. Of the AI models we tested, the Random Forest and LASSO resulted in high accuracies (AUCs 0.70-0.92). Our artificial neural network performed similarly well in most of the models (AUCs 0.61-0.90).ConclusionsThis study demonstrates feasibility of accurately predicting adverse outcomes using complex and novel AI models on large longitudinal data sets of patients with IBD. These models could be applied for risk stratification and implementation of preemptive measures to avoid adverse outcomes in a clinical setting.
| S-EPMC9515047 | biostudies-literature
Project description:IntroductionKidney disease is a well-known extraintestinal manifestation (EIM) associated with inflammatory bowel disease (IBD), with a variety of underlying etiologies. However, little is known about the overall outcomes and predictors.MethodsThis is a retrospective, observational cohort study. Patients with IBD in whom a native kidney biopsy was performed at Mayo Clinic (Rochester, MN) between 1994 and 2022, were included. Demographic, clinical, and histologic characteristics of prognostic interest were collected. The main outcomes were kidney failure, disease remission, kidney function changes at last follow-up, and death.ResultsFrom a total cohort of 318 patients, we selected a study group of 111 patients followed-up with at our institution (45 ulcerative colitis [UC] and 66 Crohn's disease [CD]), with a mean age of 48 ± 17 years (40% females). IgA nephropathy (IgAN), chronic interstitial nephritis (CIN), and acute interstitial nephritis (AIN) were the most common diagnoses (22%, 19%, 13%, respectively). Median estimated glomerular filtration rate (eGFR) at presentation was 30 ml/min per 1.73 m2 (interquartile range [IQR]: 17-54) and urinary protein-to-creatinine ratio [UPCR] 0.8 g/g (0.3-3.4), without differences between IBD types. During a median follow-up of 59 months (12-109), 29 patients (26%) reached kidney failure. By multivariable analysis, the main predictors of kidney failure were age (hazard ratio [HR]: 1.04; P = 0.002), baseline eGFR (HR: 0.94; P = 0.003) and histologic chronicity score (HR: 4.01; P < 0.001). Therapeutic management varied according to underlying etiology. Global survival (kidney failure + death) was significantly better in patients who achieved complete or partial remission, or stabilization or improvement of kidney function.ConclusionOne-fourth of patients with IBD with kidney disease may reach kidney failure, and the main determinants of this outcome is age, baseline eGFR, and degree of chronicity in kidney biopsy.
| S-EPMC10851004 | biostudies-literature
Project description:More than 200 genomic loci have been identified and validated by GWAS to be associated with IBD. However, for most of these loci, the causal gene remains unknown. The current study is aimed at uncovering the role of genes located within IBD-associated loci and endogenously expressed in the myeloid cell model THP-1 by over-expressing them in this cell lineage. The open reading frames (ORF) for 42 genes from IBD-associated loci were expressed in the THP-1 model of human monocytes using lentivirus vector for plasmid transduction. An empty vector transduced into THP-1 as control. Three biological replicates have been done for each transduction. The impact of each IBD ORFs on THP-1 transcriptome profile was analyzed using an whole RNA sequencing-based approach. This functional genomics screen showed the affected genes (upregulated and downregulated) in response to the increased expression RNA of each IBD gene (ORF) in THP-1. In order to find biological categories enriched of the affected genes, enrichment analyses have been done using the g:GOSt functional profiling tool (using Ensembl database release 98) from the online g:Profiler service.
2022-09-06 | GSE175685 | GEO
Project description:Vaccines against SARS-CoV-2 are believed to play a key role in the suppression of the COVID-19 pandemic. However, patients suffering from inflammatory bowel diseases (IBD) were excluded from SARS-CoV-2 vaccines trials. Therefore, concerns regarding vaccination efficacy and safety among those patients were raised. Overall, vaccination is well tolerated in the IBD population, and different gastroenterological societies recommend vaccinating patients with IBD at the earliest opportunity to do so. Nevertheless, very little is known about the safety of COVID-19 vaccines in special IBD populations such as pregnant and breastfeeding women or pediatric patients, and further research on this matter is crucial. The available data on vaccine efficacy are promising and show high seroconversion rates in IBD patients on different immune-modifying therapies. However, patients treated with high doses of systemic corticosteroids, infliximab or infliximab and immunomodulators may have a blunted response to the vaccination. The data on COVID-19 vaccination willingness among patients with IBD are conflicting. Nevertheless, vaccine effectiveness and safety are reported to be the most common reasons for hesitancy. This review examines the effectiveness and safety of COVID-19 vaccines and describes vaccination willingness and the reasons for potential hesitancy among patients with IBD.
| S-EPMC9104993 | biostudies-literature
Project description:Cytomegalovirus (CMV) infects approximately 40% of adults in France and persists lifelong as a latent agent in different organs, including gut. A close relationship is observed between inflammation that favors viral expression and viral replication that exacerbates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBDs), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation and T helper cell (TH) 2 cytokines, together with immunomodulatory drugs used for controlling flare-ups, favor viral reactivation within the gut, which, in turn, increases mucosal inflammation, impairs corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in the case of CMV colitis), and enhances the risk for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during inflammatory bowel diseases (IBD) and underlines the interest of using ganciclovir for treating flare-ups associated to CMV colitis in UC patients.
| S-EPMC7409252 | biostudies-literature
Project description:Background and aimOne of the most impacted regions by the pandemic globally, Latin America is facing socioeconomic and health-care challenges that can potentially affect disease outcomes. Recent data suggest that inflammatory bowel disease (IBD) patients do not have an increased risk of the development of COVID-19 complications. However, the impact of COVID-19 on IBD patients living in least developed areas remains to be fully elucidated. This study aims to describe the outcomes of IBD patients diagnosed with COVID-19 in countries from Latin America based on data from the SECURE-IBD registry.MethodsPatients from Latin America enrolled in the SECURE-IBD registry were included. Descriptive analyses were used to summarize clinical and sociodemographic characteristics. The studied outcomes were (i) a composite of need for intensive care unit admission, ventilator use, and/or death (primary outcome) and (ii) a composite of any hospitalization and/or death (secondary outcome). Multivariable regression was used to identify risk factors of severe COVID-19.ResultsDuring the study period, 230 cases (Crohn's disease: n = 115, ulcerative colitis: n = 114, IBD-unclassified [IBD-U]: n = 1) were reported to the SECURE-IBD database from 13 different countries. Primary outcome was observed in 17 (7.4%) patients, and the case fatality rate was 1.7%. In the adjusted multivariable model, the use of systemic corticosteroids (odds ratio [OR] 10.97; 95% confidence interval [CI]: 3.44-34.99) was significantly associated with the primary outcome. Older age (OR 1.03; 95% CI: 1.00-1.05), systemic corticosteroids (OR 9.33; 95% CI: 3.84-22.63), and the concomitant presence of one (OR 2.14; 95% CI: 0.89-5.15) or two (OR 10.67; 95% CI: 1.74-65.72) comorbidities were associated with the outcome of hospitalization or death.ConclusionInflammatory bowel disease patients with COVID-19 in Latin America appear to have similar outcomes to the overall global data. Risk factors of severe COVID-19 are similar to prior reports.
| S-EPMC8447321 | biostudies-literature
Project description:Recently, mesenchymal stem/stromal cells (MSCs) therapy has become an emerging therapeutic modality for the treatment of inflammatory bowel disease (IBD), given their immunoregulatory and pro-survival attributes. MSCs alleviate dysregulated inflammatory responses through the secretion of a myriad of anti-inflammatory mediators, such as interleukin 10 (IL-10), transforming growth factor-β (TGFβ), prostaglandin E2 (PGE2), tumor necrosis factor-stimulated gene-6 (TSG-6), etc. Indeed, MSC treatment of IBD is largely carried out through local microcirculation construction, colonization and repair, and immunomodulation, thus alleviating diseases severity. The clinical therapeutic efficacy relies on to the marked secretion of various secretory molecules from viable MSCs via paracrine mechanisms that are required for gut immuno-microbiota regulation and the proliferation and differentiation of surrounding cells like intestinal epithelial cells (IECs) and intestinal stem cells (ISCs). For example, MSCs can induce IECs proliferation and upregulate the expression of tight junction (TJs)-associated protein, ensuring intestinal barrier integrity. Concerning the encouraging results derived from animal studies, various clinical trials are conducted or ongoing to address the safety and efficacy of MSCs administration in IBD patients. Although the safety and short-term efficacy of MSCs administration have been evinced, the long-term efficacy of MSCs transplantation has not yet been verified. Herein, we have emphasized the illumination of the therapeutic capacity of MSCs therapy, including naïve MSCs, preconditioned MSCs, and also MSCs-derived exosomes, to alleviate IBD severity in experimental models. Also, a brief overview of published clinical trials in IBD patients has been delivered.
| S-EPMC9881387 | biostudies-literature