Novel transcriptomic panel identifies histologically active eosinophilic oesophagitis.

BACKGROUND AND AIMS: Eosinophilic oesophagitis (EoE) is characterised by symptoms of esophageal dysfunction and oesinophil tissue infiltration. The EoE Diagnostic Panel (EDP) can distinguish between active and non-active EoE using a set of 77 genes. Recently, the existence of distinct EoE variants featuring symptoms similar to EoE, such as oesophageal dysfunction but lacking eosinophil infiltration, had been determined. METHODS: We used oesophageal biopsies from patients with histologically active (n=10) and non-active EoE (n=9) as well as from healthy oesophageal controls (n=5) participating in the Swiss Eosinophilic Esophagitis Cohort Study (SEECS) and analysed the gene expression profile in these biopsies by total RNA-sequencing (RNA-seq). Moreover, we employed the publicly accessible RNA-seq dataset (series GSE148381) as reported by Greuter et al, encompassing a comprehensive genomic profile of patients presenting with EoE variants. RESULTS: A novel, diagnostic gene expression panel that can effectively distinguish patients with histologically active conventional EoE from patients with EoE in histological remission and control individuals, and from three newly discovered EoE variants was identified. Histologically Active EoE Diagnostic Panel (HAEDP) consists of 53 genes that were identified based on differential expression between histologically active EoE, histological remission and controls (p≤0.05). By combining the HAEDP with EDP, we expanded our knowledge about factors that may contribute to the inflammation in EoE and improved our understanding of the underlying mechanisms of the disease. Conversely, we suggested a compact group of genes common to both HAEDP and EDP to create a reliable diagnostic tool that might enhance the accuracy of EoE diagnosis. CONCLUSION: We identified a novel set of 53 dysregulated genes that are closely associated with the histological inflammatory activity of EoE. In combination with EDP, our new panel might be a valuable tool for the accurate diagnosis of patients with EoE as well as for monitoring their disease course.

Microbiota Therapy in Inflammatory Bowel Disease.

Background: In both Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD) the immune reaction is - at least partially - directed against components of the luminal microbiota of the gut. These immune responses as well as other factors contribute to a phenomenon frequently described as "dysbiosis" meaning an alteration of the composition of the colonic microbiota. To improve the dysbiosis and to restore the normal composition of the colonic microbiota, fecal microbiota transplantation (FMT) has been tested as a therapeutic option to induce and maintain remission in IBD patients. Summary: This review will first discuss changes in the composition of the intestinal microbiota found in IBD patients and second the therapeutic potential of microbiological interventions for the treatment of these patients. FMT has been studied in several clinical trials in both, CD and UC. Reported results and subsequent meta-analyses indicate that FMT may be effective to induce remission in UC. However, the optimal route of FMT, the necessary number of administrations and the question whether life bacteria of freshly prepared stool is more effective than frozen are still unclear. Concepts associated with an optimization of FMT such as the "super donor concept" or the "consortia-approach" will be discussed to illustrate open questions and difficulties associated with microbiota therapy in IBD. Key Messages: The microbiota composition in IBD patients shows significant alterations compared to healthy individuals termed as "dysbiosis". FMT and other therapeutic approaches to modify the microbiota composition have been studied in clinical trials in recent years. Efficacy has been shown in UC; however, many questions with respect to the optimization of microbiota therapy remain to be answered.

Specific antibiotics increases the risk of flare-ups in patients with inflammatory bowel disease - results from a Danish nationwide population-based nested case-control study.

INTRODUCTION: IBD patients have a relapsing-remitting disease course, and amongst environmental factors that aggravate the disease course, common drugs aside from NSAIDs are not studied in detail. While the microbiome is considered to play a significant role on the disease course the impact of antibiotics is poorly understood. This study investigated the potential impact of different classes of antibiotics on course of disease in IBD using the Danish National Patient Registry. METHODS: Danish IBD patients were studied using two nested case-control cohorts exploring associations between antibiotic types and IBD flare-ups, defined as IBD-related hospitalizations and/or high-dose systemic steroid exposure. Multivariate logistic regression and eXtreme Gradient Boosted decision tree (GBDT) machine learning methods evaluated antibiotic risks. RESULTS: Two cohorts with 15,636 and 5,178 patients were analysed for risk of hospitalisation and course of steroids, respectively.The risk of a flare-up was significantly increased with antecedent exposure to quinolones (ATC:J01M. OR:3.04-3.82), antimycotics (ATC:J02A. OR:1.50-2.30), agents against amoebiasis and protozoal infections (ATC:P01A. OR: 1.95-3.18), intestinal anti-infectives (ATC:A07A. OR:2.09-2.32) and beta-lactam antibiotics (ATC:J01C. OR:1.36).The GBDT models achieved an AUC between 0.71-0.85 for predicting flare-ups, with the same above-mentioned antibiotics being in the 10 most important variables. CONCLUSION: We found distinctive antibiotics to be significantly associated with an increased risk of IBD flare-ups. Our findings are corroborated by our GBDT machine learning models. Healthcare providers should be aware about the deleterious potential of specific antibiotic groups in patients with IBD only using these agents in a restrictive manner or preferentially consider alternative antibiotic groups.

Diagnostic Accuracy of Different Soluble fms-Like Tyrosine Kinase 1 and Placental Growth Factor Cut-Off Values in the Assessment of Preterm and Term Preeclampsia: A Gestational Age Matched Case-Control Study.

Introduction: The objective was to investigate the diagnostic accuracy of different thresholds of the soluble vascular endothelial growth factor receptor-1 (sFlt-1) and the placental growth factor (PlGF) in preterm (≤37 weeks) and term (>37 weeks) preeclampsia (PE). Materials and Methods: A nested case-control study was performed from a high-risk Swiss cohort. Only blood samples on the day of PE diagnosis were included. The primary outcome was to verify the diagnosis using the recently proposed cut-off values for PE (sFlt-1:PlGF ratio of ≥85 in ≤ 34 weeks or ≥110 in >34 weeks), and the gestational age dependent centiles. Results: Thirty-four women with preterm PE were matched with 64 controls and 25 women with term PE with 45 controls. The test performance of the sFlt-1:PlGF ratio in preterm PE was very good (AUROCC of 0.95). The sFlt-1:PlGF ratio could adequately predict adverse fetal or neonatal outcome. In term PE, sFlt-1 alone showed a slightly better diagnostic accuracy with an AUROCC of 0.84. Almost all women with a sFlt-1:PlGF ratio above threshold delivered during the following week. Discussion: In pregnant women with high risk of developing PE, the sFlt-1:PlGF ratio and sFlt-1 levels help clinicians to confirm the diagnosis of imminent preterm PE and can additionally be used to rule out PE at term.