Exabis Library

Educational objectives
To discuss the evidence for somatic mutation in the IBD affected colonic epithelium
To consider mechanisms mutagenesis
To discuss evidence for selection pressures on mutations and their implications for cancer risk and inflammation

1. To identify the areas where standardisation of IBD pathology reporting is achievable and the areas requiring improvement. 
2. To recognise the importance of a multidiscipinary approach and good communication.
3. To consider the development of a consistent approach to the assessment and description of IBD histology.
4. To be aware of the diversity of approaches to the assessment of histological acitvity. 
4. To explore the ideal ways in which to construct the summary and conclusion of an IBD pathology report.
5. To be aware of the existence and value of guidelines and datasets in pathology generally and in IBD pathology in particular.  

Four randomized controlled trials studying faecal microbiota transplantation (FMT) in active UC patients showed variable success rates. The efficacy of FMT appears to be influenced by various factors including donor- and procedure-specific characteristics. We hypothesized that the outcome of FMT in patients with active UC could be improved by donor preselection on microbiota level, by using a strict anaerobic approach, and by repeated FMT administration.

The RESTORE-UC trial (NCT03110289) was a national, multi-centric double-blind, sham-controlled randomized trial. Active UC patients (Total Mayo score 4-10 with endoscopic sub-score ≥2) were randomly allocated (1:1) to receive 4 anaerobic-prepared superdonor (S) FMT or autologous (A) FMT (Figure 1) by permutated blocks (2 and 4) and stratified for weight, concomitant steroid use, and therapy refractoriness.
S-FMTs were selected after a rigorous screening excluding samples with Bacteroides2 enterotype, high abundances of Fusobacterium, Escherichia coli and Veillonella and the lowest microbial loads (Q1).
A futility analysis after 66% (n=72) of inclusions was planned per protocol including a modified intention-to-treat (mITT) analysis using non-responder imputation (NRI) for patients receiving at least one FMT. The primary endpoint was steroid-free clinical remission (Total Mayo ≤ 2, with no sub-score >1) at week 8.

Between March 2017-2021, 72 patients signed the ICF and 66 were randomly allocated to S-FMT (n=30) or A-FMT (n=36) and received at least one FMT. In the S-FMT and the A-FMT resp. 4 and 5 patients terminated the trial early due to worsening of colitis (4 in both arms) or FMT enema intolerance (1 A-FMT). They were included in the mITT analysis using NRI (Fig. 2). Both study arms were matched for baseline characteristics (Table 1), yet a trend (p= 0.066) towards higher concomitant biological use in the S-FMT arm was observed.
After 66% of intended inclusions, the primary endpoint was reached in 3/30 (10%) S-FMT and 5/31 (13.9%) patients randomized to A-FMT (p=0.72).
As the predefined minimum difference between both treatment arms was not attained, the study was stopped due to futility. The full set of endpoints are summarized in Table 2.Of note, no patients on concomitant biologicals reached the primary endpoint.
There were 2 serious adverse events in the A-FMT arm: dysuria requiring hospitalization and worsening of UC requiring colectomy.

In this double-blind sham-controlled trial comparing repeated administrations of anaerobic-prepared S-FMT with A-FMT in patients with active UC, no significant difference in steroid-free remission rates at week 8 were observed. The FMT procedure was generally well tolerated, and no new safety signals were observed.

Optimization and standardization of imaging reporting is currently an unmet need and would facilitate the comparison between different reports and communication between the different specialties involved in IBD. The current presentation summarizes results of a consensus guideline that has been developed by members of ECCO, IBUS and ESGAR. The consensus group identified standardized parameters and suggests how to report and how to characterize findings of cross-sectional imaging that encompasses MRI, CT, IUS, endoanal ultrasonography [EAUS] and transperineal ultrasonography [PUS] in IBD. These methods are used for diagnosis, assessment of disease activity and severity, and to detect complications and monitor disease course. Mural and extramural disease manifestations beyond the reach of the endoscope can be visualized and determined by cross sectional imaging.

The core elements of the presentation will describe the imaging parameters of assessment of disease activity and severity as well as intra- and extramural complications of IBD in a standardized manner. The presentation will suggest vital data for each reporting type, and proposes possible strategies to optimize and standardize reporting quality of cross-sectional imaging in IBD. Similarities and differences in reporting between MRI/CT and IUS will be identified and addressed. Practical examples will be provided on how to standardize reporting of individual cases in daily clinical practice.

Educational objectives:
•Synthesis and structure
•Mechanism of action
•Effects on inflammatory and immune processes
•Pharmacology  and formulations
•Efficacy of steroids as anti-inflammatory agents in inflammatory bowel diseases (IBD)
•Safety and complications

Educational objectives:
•Synthesis and structure
•Mechanism of action
•Effects on inflammatory and immune processes
•Pharmacology  and formulations
•Efficacy of steroids as anti-inflammatory agents in inflammatory bowel diseases (IBD)
•Safety and complications