α4β7 blockade is a well-established therapy in ulcerative colitis (UC), acting in part by preventing lymphocyte ingress into the mucosa. The β7 unit of the α4β7 heterodimer is shared by α_Εβ7, which is expressed on both tissue resident memory cells and γδ intra-epithelial lymphocytes (IEL). It was hypothesised that targeting both α4- and α_Εβ7 might be more efficacious; however mixed results from phase III studies of β7 blockade asks questions of the biological relevance of different α_Eβ7 expressing cells.

Colonic biopsies were obtained during endoscopy from >40 subjects. Lymphocytes were isolated using short term culture or digested from whole tissue. RNA sequencing was performed on α_Εβ7^pos and α_Εβ7^neg colonic γδ T cells from 4 donors and findings were validated by flow cytometry.

α_Εβ7 is widely expressed on TCRαβ CD8 cells and γδ IEL in both non-IBD controls and the uninflamed mucosa in UC, but its expression is significantly reduced on analogous subsets harvested from inflamed UC. On further study, the capacity of TCRαβ CD8 T cells to make TNFα and IFNγ on stimulation is similar between α_Εβ7^pos and α_Εβ7^neg cells, whereas in the γδ T cell compartment α_Εβ7^neg cells produce significantly more pro-inflammatory cytokine than their homeostatic α_Εβ7^pos counterparts. To examine the cells’ biology further, γδ T cells were isolated according to their α_Εβ7 status and RNAseq undertaken. This revealed a distinct signature with α_Εβ7^neg cells demonstrating an activated phenotype high in markers such as CD18, CD5 and lymphoid homing receptor CCR7 whereas α_Εβ7^pos cells demonstrate a homeostatic tissue-resident phenotype, expressing immune checkpoints TIGIT and CD101 and gut-homing marker CCR9. On culturing tissue from non-IBD controls in pro-inflammatory cytokines, IL-12 and IL-18, the γδ T cell compartment down-regulated α_Εβ7 and TIGIT and upregulated CD18, in part recapitulating a disease phenotype. On examining previously affected mucosa of patients who have achieved mucosal healing, α_Eβ7 expression of the γδ T cells returned to a profile resembling non-IBD controls whereas the expression levels in the inflamed mucosa remained predictably low.

This study demonstrates that α_Εβ7 expression is low in active UC but restored in mucosal healing. α_Εβ7^neg cells are proinflammatory with a distinct phenotype which may in part be recapitulated by inflammatory cytokines in vitro; whereas α_Εβ7^pos cells demonstrate a homeostatic phenotype, which may both reflect and maintain steady state barrier integrity. Hence in terms of γδ T cells, pharmacological β7 blockade has potential to interfere with the homeostatic roles of α_Εβ7 expressing cells while having little effect on a potentially pathogenic subset of tissue α_Εβ7^neg γδ cells.

Educational objectives: 

1. To understand the role of anti TNF on postoperative infectious complications
2. To review the evidence for drug levels associated with postoperative complications
   3. To understand the role of anti interleukin and anti integrins on postoperative infectious complications
   4. To understand how biologics affects staging of IPAA

1. To understand adherence in a broad perspective
2. To review existing knowledge on adherence
3. To emphasise possible predictors for low or non-adherence
4. To provide with some tools to measure adherence

Review the ACG guideline process with emphasis on pressure points and areas of improvement

Educational objectives:
1. To understand the role of IL-12 and IL-23 in the development of IBD
2. To review the pivotal UNITI and UNIFI trials
3. To review the place of ustekinumab in IBD therapy
4. To introduce specific IL-23 antibodies

Educational objectives:
1. To understand the mechanism of action of vedolizumab and other anti integrins
2. To review the key clinical data
3. To highlight studies from real world cohort and discuss the safety profile of Vedolizumab
4. To understand how to position Vedolizumab in clinical practice

Educational objectives: 1. To understand the structural and functional features of the various anti-TNF agents, including originators and biosimilars 2. To review their use in Crohn's disease (CD), ulcerative colitis (UC) and in special indications 3. To have an overview of the optimal dosing of anti-TNFs, including therapeutic dose monitoring.

Anti-TNF were the first biological therapies available in IBD as well as in other immune-inflammatory disorders such as rheumatoid arthritis, spondyloarthritis and psoriasis. These agents can induce and maintain remission of CD and UC. They are also used in refractory pouchitis and microscopic colitis. Infliximab and adalimumab are approved in CD and UC, while certolizumab pegol is only approved for CD in some jurisdictions but not EU, and golimumab is approved for UC only. Biosimilars of infliximab and adalimumab are now available with all the indications of their originators. Data accumulate to support similar activity in both diseases, but some individual differences may be observed. Anti-TNF agents are increasingly used during pregnancy and for the treatment of extraintestinal manifestations of IBD.  Infliximab remains the best studied biological agent in IBD. The possibility of iv administration at high doses makes it the favored agent in fulminant colitis, fistulizing CD and in pyoderma gangrenosum. As all biological agents, anti-TNFS can induce anti-drug antibodies that represent the main cause of loss of response to these therapies. Continuous dosing beyond induction, combination therapy and premedication with hydrocortisone reduce this risk. Therapeutic dose monitoring and antibody detection are now available for all anti-TNF agents, the proactive use of which improves treatment outcome and preserves long-term response. Based on data with infliximab, anti-TNF may decrease immune response to SARS-CoV-2 infection and may decrease vaccine response. 

A discussion between a guidelines methodologist and a clinician regarding (potential) limitations of GRADE methodology and whether OCEBM still has a place in clinical guidelines.

Educational objectives:
1) A recap of strengths and challenges of using GRADE methodology
2) Discussion of the role of Oxford levels of evidence in clinical guidelines
3) Critical thought regarding how evidence based guidelines are developed

This is a tandem talk between Joana Torres and Stefanos Bonovas on clinical practice guidelines' potential benefits and harms.

Educational objectives

Understand how to assess safety of a drug in real life practice

Understand the differences between small molecules and biologics

Understand how IBD drugs can be classified according to their safety profile

Understand how to improve IBD drug safety

Summary

Biologics differ from small molecules by many aspects, among which the chemistry, their degradation and their mechanism of action. These aspects may directly influence safety. Safety of a drug is itself difficult to quantify and qualify. The safety profile depends on the available data, strongly depending also on the time of apparition of the drug on the market and its widespread use. Most of the comparative data on safety generated through network meta-analyses or head to head trials correspond to relatively short duration of use of the drug and relatively small population compared to what would be needed to really assess safety. Therefore no or only minor differences are disclosed by these studies. If we adopt a pragmatic classification of side effects, we could classify them into mild-moderate intolerance, cumulative toxicity, major side effects that can be prevented or treated, major side effects that can hardly be prevented or treated, serious adverse events potentially lethal. When analysing the safety profiles of currently available drugs according to such classification, we find both small molecules and biologics with all these kinds of side effects. Therefore, if we can currently consider that some drugs are associated with lower or higher safety concerns, there is no difference between biologics and small molecules, the mechanism of action being sometimes closer between one small molecule and one biologic than between two biologics. Instead of safer drug or beside safer drug, we should maybe mainly aim at a safer use of these drugs.

Educational objectives
1) To understand the limitation of current endoscopic scoring systems and why artificial intelligence may help 
2) To understand the basic principles of developing artificial intelligence with its potential and limitations
3) To understand how artificial intelligence may influence patient management in the future

Educational objectives:
1/ To understand the limitation of human interpretation of endoscopic images
2/ To review the rational and goals for implementing artificial intellegence in image processing
3/ To understand the different types of artificial intelligence applications in image processing
4/ To have an overview of the future potential application of artificial intelligence in IBD endoscopy

This talk discusses the importance of sex and body image in relation to IBD and surgery. We will consider how disease and surgery affect all aspects of sex, and crucially we will examine how conversations about sex should be managed.

Educational Objectives:
1. To understand how IBD can affect patients' body image and sexual pleasure

2. To consider how clinicians feel about discussing sex and address our own anxieties

3. To develop techniques and confidence in discussing sex in clinical consultations

4. To appreciate when sex should be discussed, particularly around surgery

To discuss the possibilities for achieving a 'cure' from surgical intervention in both Crohn's Disease and Ulcerative Colitis

To discuss the definition of a 'cure' in this context 

Crohns:
To explore which patients with Crohn's disease may be at low risk of recurrence post-surgery and who may achieve a cure in the medium or long-term

To refine the role of withdrawing post-operative medical therapy in Crohn's to achieve disease- and medication-free survival

To explore emerging evidence and novel biomarkers to help stratify patients who may achieve excellent post-surgery results

Ulcerative Colitis:
To discuss the emerging potential for appendicectomy to treat/cure UC

To explore resectional and reconstructive options in UC and discuss whether these offer a 'cure' for patients 

IBD cannot be cured with the currently available forms of medical therapy. However, therapeutic options can be significantly improved using an artificial intelligence-based approach that takes into consideration and integrates all omics components of the disease.

•To review the available evidence on pre-clinical studies
•To propose a common terminology for the preclinical period of disease
•To discuss important research question on the field