Unsedated transnasal endoscopy:a safe, well-tolerated and accurate alternative to standard diagnostic peroral endoscopy

Diagnostic unsedated transnasal endoscopy (uTNE) has been proven to be a safe and well-tolerated procedure. Although its utilization in the United Kingdom (UK) is increasing, it is currently available in only a few centers. Through consideration of recent studies, we aimed to perform an updated review of the technological advances in uTNE, consider their impact on diagnostic accuracy, and to determine the role of uTNE in the COVID-19 era. Current literature has shown that the diagnostic accuracy of uTNE for identification of esophageal pathology is equivalent to conventional esophagogastroduodenoscopy (cEGD). Concerns regarding suction and biopsy size have been addressed by the introduction of TNE scopes with working channels of 2.4 mm. Advances in imaging have improved detection of early gastric cancers. The procedure is associated with less cardiac stress and reduced aerosol production; when combined with no need for sedation and improved rates of patient turnover, uTNE is an efficient and safe alternative to cEGD in the COVID-19 era. We conclude that advances in technology have improved the diagnostic accuracy of uTNE to the point where it could be considered the first line diagnostic endoscopic investigation in the majority of patients. It could also play a central role in the recovery of diagnostic endoscopic services during the COVID-19 pandemic

How to Apply for and Secure EU Funding for Collaborative IBD Research Projects.

peer reviewedThe European Union offers opportunities for high-level of funding of collaborative European research. Calls are regularly published: after the end of the FP7 funding programme the new round of Horizon 2020 calls started in 2015. Several topics are relevant to inflammatory bowel disease (IBD) challenges, including chronic disease management, biomarker discovery and new treatments developments. The aim of this Viewpoint article is to describe the new Horizon 2020 instrument and the project submission procedures, and to highlight these through the description of tips and tricks, taking advantage of four examples of successful projects in the field of IBD: the SADEL, IBD-BIOM, IBD Character and BIOCYCLE projects

Genome-Wide Methylation Profiling in 229 Patients With Crohn's Disease Requiring Intestinal Resection: Epigenetic Analysis of the Trial of Prevention of Post-operative Crohn's Disease (TOPPIC).

Background &amp; Aims: DNA methylation alterations may provide important insights into gene-environment interaction in cancer, aging, and complex diseases, such as inflammatory bowel disease (IBD). We aim first to determine whether the circulating DNA methylome in patients requiring surgery may predict Crohn's disease (CD) recurrence following intestinal resection; and second to compare the circulating methylome seen in patients with established CD with that we had reported in a series of inception cohorts. Methods: TOPPIC was a placebo-controlled, randomized controlled trial of 6-mercaptopurine at 29 UK centers in patients with CD undergoing ileocolic resection between 2008 and 2012. Genomic DNA was extracted from whole blood samples from 229 of the 240 patients taken before intestinal surgery and analyzed using 450KHumanMethylation and Infinium Omni Express Exome arrays (Illumina, San Diego, CA). Coprimary objectives were to determine whether methylation alterations may predict clinical disease recurrence; and to assess whether the epigenetic alterations previously reported in newly diagnosed IBD were present in the patients with CD recruited into the TOPPIC study. Differential methylation and variance analysis was performed comparing patients with and without clinical evidence of recurrence. Secondary analyses included investigation of methylation associations with smoking, genotype (MeQTLs), and chronologic age. Validation of our previously published case-control observation of the methylome was performed using historical control data (CD, n = 123; Control, n = 198). Results: CD recurrence in patients following surgery is associated with 5 differentially methylated positions (Holm P &lt;.05), including probes mapping to WHSC1 (P = 4.1 × 10 -9, Holm P =.002) and EFNA3 (P = 4.9 × 10 -8, Holm P =.02). Five differentially variable positions are demonstrated in the group of patients with evidence of disease recurrence including a probe mapping to MAD1L1 (P = 6.4 × 10 -5). DNA methylation clock analyses demonstrated significant age acceleration in CD compared with control subjects (GrimAge + 2 years; 95% confidence interval, 1.2–2.7 years), with some evidence for accelerated aging in patients with CD with disease recurrence following surgery (GrimAge +1.04 years; 95% confidence interval, -0.04 to 2.22). Significant methylation differences between CD cases and control subjects were seen by comparing this cohort in conjunction with previously published control data, including validation of our previously described differentially methylated positions (RPS6KA2 P = 1.2 × 10 -19, SBNO2 = 1.2 × 10 -11) and regions (TXK [false discovery rate, P = 3.6 × 10 -14], WRAP73 [false discovery rate, P = 1.9 × 10 -9], VMP1 [false discovery rate, P = 1.7 × 10 -7], and ITGB2 [false discovery rate, P = 1.4 × 10 -7]). Conclusions: We demonstrate differential methylation and differentially variable methylation in patients developing clinical recurrence within 3 years of surgery. Moreover, we report replication of the CD-associated methylome, previously characterized only in adult and pediatric inception cohorts, in patients with medically refractory disease needing surgery.</p

Serum Calprotectin - A novel diagnostic and prognostic marker in Inflammatory Bowel Diseases

OBJECTIVES: There is an unmet need for novel blood-based biomarkers that offer timely and accurate diagnostic and prognostic testing in inflammatory bowel diseases (IBD). We aimed to investigate the diagnostic and prognostic utility of serum calprotectin (SC) in IBD. METHODS: A total of 171 patients (n=96 IBD, n=75 non-IBD) were prospectively recruited. A multi-biomarker model was derived using multivariable logistic regression analysis. Cox proportional hazards model was derived to assess the contribution of each variable to disease outcomes. RESULTS: SC correlated strongly with current biomarkers, including fecal calprotectin (FC) (n=50, ρ=0.50, P=1.6 × 10−4). SC was the strongest individual predictor of IBD diagnosis (odds ratio (OR): 9.37 (95% confidence interval (CI): 2.82–34.68), P=4.00 × 10−4) compared with other markers (C-reactive protein (CRP): OR 8.52 (95% CI: 2.75–28.63), P=2.80 × 10−4); albumin: OR 6.12 (95% CI: 1.82–22.16), P=0.004). In a subset of 50 patients with paired SC and FC, the area under receiver operating characteristic discriminating IBD from controls was better for FC than for SC (0.99, (95% CI 0.87–1.00) and 0.87 (95% CI:0.78–0.97), respectively; P=0.01). At follow-up (median 342 days; interquartile range: 88–563), SC predicted treatment escalation and/or surgery in IBD (hazard ratio (HR) 2.7, 95% CI: 1.1–4.9), in particular Crohn’s disease (CD) (HR 4.2, 95% CI 1.2–15.3). A model incorporating SC and either CRP or albumin has a positive likelihood ratio of 24.14 for IBD. At 1 year, our prognostic model can predict treatment escalation in IBD in 65% of cases (95% CI: 43–79%) and 80% (95% CI: 31–94%) in CD if ≥2 blood marker criteria are met. CONCLUSIONS: A diagnostic and prognostic model that combines SC and other blood-based biomarkers accurately predicts the inflammatory burden in IBD and has the potential to predict disease and its outcomes. Our data warrant further detailed exploration and validation in large multicenter cohorts

Altered DNA methylation within DNMT3A, AHRR, LTA/TNF loci mediates the effect of smoking on inflammatory bowel disease

This work aims to investigate how smoking exerts effect on the development of inflammatory bowel disease (IBD). A prospective cohort study and a Mendelian randomization study are first conducted to evaluate the association between smoking behaviors, smoking-related DNA methylation and the risks of Crohn's disease (CD) and ulcerative colitis (UC). We then perform both genome-wide methylation analysis and co-localization analysis to validate the observed associations. Compared to never smoking, current and previous smoking habits are associated with increased CD (P = 7.09 × 10-10) and UC (P -16) risk, respectively. DNA methylation alteration at cg17742416 [DNMT3A] is linked to both CD (P = 7.30 × 10-8) and UC (P = 1.04 × 10-4) risk, while cg03599224 [LTA/TNF] is associated with CD risk (P = 1.91 × 10-6), and cg14647125 [AHRR] and cg23916896 [AHRR] are linked to UC risk (P = 0.001 and 0.002, respectively). Our study identifies biological mechanisms and pathways involved in the effects of smoking on the pathogenesis of IBD