Exabis Library

Educational objectives:
1. To understand recent epidemiology of IBD, particularly early and very early onset IBD (VEO-IBD)
2. To review the diagnostic work-up of VEO-IBD with a focus on early identification of immunodeficiency syndromes
3. To emphasise early discussion/referral with clinical immunology to identify patients most likely to benefit from transplant and reduce pre-transplant morbidity/mortality
4. To review potential future applications of genome-informed therapeutics in IBD

Elucidate factors that help to make the successful transition from the bench to research group leader.

This study aimed at comparing functional outcomes and quality of life (QoL) after transanal and transabdominal approach for ileal-pouch surgery in ulcerative colitis (UC)Ileal-pouch surgery ensures satisfactory intestinal function and QoL. The transanal ileal pouch-anal anastomisis (Ta-IPAA) has recently been developed in the effort to address the technical shortfalls of the traditional transabdominal approach (Tabd-IPAA). According to previous studies, Ta-IPAA is safe. However, functional outcomes after ta-IPAA are scarcely described. 

This is a retrospective study of consecutive UC patients who underwent IPAA from 2011 to 2017.  Only patients operated according to a modified-2 or 3 stage approach were included in the analysis. Close rectal dissection was systematically performed in Ta-IPAA as opposed to total mesorectal excision in Tabd-IPAA. Groups were compared after propensity score weighting. Functional outcomes were assessed using two functional scoring systems: the Pouch Functional Score (PFS) and the Öresland score (OS). The global quality of life scale (GQOL) was used for patients’ overall perspective on QoL. Follow-up was scheduled at 1, 3, 6, and 12 months postoperatively.

One hundred and nine patients were included. Of them, 38 patients underwent Ta-IPAA. At 12 months follow-up, mean OS and PFS were 4.6 (CI 3.2-6.0) vs 6.2 (CI 5.0-7.3), p=0.02 and 6.1 (CI 3.5-8.8) vs 7.4 (CI 5.4-9.5), p=0.32, for Ta and Tabd-IPAA, respectively. Mean GQOL score for Ta-IPAA was 82.7 (CI 75.1-90.2) vs 75.5 (69.4-81.6) for Tabd-IPAA (p=0.038).

Transanal IPAA provides better functional results and QoL scores than Tabd-IPAA in UC patients. 

Recent data havehighlighted adverse clinical outcomes in IBD patients treated with infliximab/thiopurines (IFX/THIO) upon infection with SARS-CoV-2, as well as attenuated serological responses after infection and vaccination in patients treated with IFX. To provide mechanistic insight, we explored the serological and functional anti-viral response after infection in IBD patients treated with VDZ, IFX or IFX/THIO compared to healthy controls to guide clinical decision-making regarding treatment and vaccination strategies.

Serum from 640 IBD patients attending routine infusions in Oxford and London in May to December 2020 was screened for anti-SARS-CoV-2 antibody responses by the Abbott assay. Serum from seropositive patients was compared to seropositive health care workers (Table 1). Antibody reactivity to the SARS-CoV-2 wild type strain receptor-binding domain (RBD), full-length spike, and nucleocapsid was assayed by IgG/IgA ELISA over time as well as by IgG high-throughput MSD V-PLEX ELISA at the time of seropositivity. A pseudotyped SARS-CoV-2 virus microneutralization assay was used to detect neutralising antibodies to the wild type, and an ELISA-based inhibition assay to compare differential inhibition of the wild type vs. delta variant SARS-CoV-2 RBD-ACE2 interaction.

All IBD patients showed significantly reduced IgG antibody responses compared to healthy controls for all SARS-CoV-2 antigens, using MSD V-PLEX ELISA (Figure 1). The greatest reduction in IgG response by ELISA was observed in individuals treated with IFX/THIO (p=0.00019), whereas IgG response over time declined significantly faster in the IFX treated group (p=0.019). IgA responses were significantly reduced in the IFX/THIO group compared to healthy controls (p=0.009), but not in the IFX or VDZ monotherapy group. The rate of decline in these monotherapy groups was also not significantly different to healthy controls. Functional SARS-CoV-2 neutralisation was significantly lower in all IBD patients compared to healthy controls, with the greatest reduction in patients receiving IFX/THIO (Figure 2A; p=0.00000091). The delta variant inhibition capacity was significantly reduced in 68.1% of IBD patients (30/44, Figure 2B; p=0.0005).

IFX/THIO is associated with significantly lower IgA and IgG responses, and with impaired functional SARS-CoV-2 neutralising antibody capacity, compared to healthy individuals. Whilst IgG and neutralisation responses are reduced in each group of IBD patients, these findings were most pronounced in the combination treatment group. As neutralising antibody responses are associated with protection, this observation may impact on decision-making regarding treatment and vaccination/antiviral strategies.

Recent data havehighlighted adverse clinical outcomes in IBD patients treated with infliximab/thiopurines (IFX/THIO) upon infection with SARS-CoV-2, as well as attenuated serological responses after infection and vaccination in patients treated with IFX. To provide mechanistic insight, we explored the serological and functional anti-viral response after infection in IBD patients treated with VDZ, IFX or IFX/THIO compared to healthy controls to guide clinical decision-making regarding treatment and vaccination strategies.

Serum from 640 IBD patients attending routine infusions in Oxford and London in May to December 2020 was screened for anti-SARS-CoV-2 antibody responses by the Abbott assay. Serum from seropositive patients was compared to seropositive health care workers (Table 1). Antibody reactivity to the SARS-CoV-2 wild type strain receptor-binding domain (RBD), full-length spike, and nucleocapsid was assayed by IgG/IgA ELISA over time as well as by IgG high-throughput MSD V-PLEX ELISA at the time of seropositivity. A pseudotyped SARS-CoV-2 virus microneutralization assay was used to detect neutralising antibodies to the wild type, and an ELISA-based inhibition assay to compare differential inhibition of the wild type vs. delta variant SARS-CoV-2 RBD-ACE2 interaction.

All IBD patients showed significantly reduced IgG antibody responses compared to healthy controls for all SARS-CoV-2 antigens, using MSD V-PLEX ELISA (Figure 1). The greatest reduction in IgG response by ELISA was observed in individuals treated with IFX/THIO (p=0.00019), whereas IgG response over time declined significantly faster in the IFX treated group (p=0.019). IgA responses were significantly reduced in the IFX/THIO group compared to healthy controls (p=0.009), but not in the IFX or VDZ monotherapy group. The rate of decline in these monotherapy groups was also not significantly different to healthy controls. Functional SARS-CoV-2 neutralisation was significantly lower in all IBD patients compared to healthy controls, with the greatest reduction in patients receiving IFX/THIO (Figure 2A; p=0.00000091). The delta variant inhibition capacity was significantly reduced in 68.1% of IBD patients (30/44, Figure 2B; p=0.0005).

IFX/THIO is associated with significantly lower IgA and IgG responses, and with impaired functional SARS-CoV-2 neutralising antibody capacity, compared to healthy individuals. Whilst IgG and neutralisation responses are reduced in each group of IBD patients, these findings were most pronounced in the combination treatment group. As neutralising antibody responses are associated with protection, this observation may impact on decision-making regarding treatment and vaccination/antiviral strategies.

Educational objectives:

1. To understand the research in the missing links in the pathophysiology of IBD
2. To understand the need for increased quality of care in IBD and the impact on long term outcomes
3. To review the need for personalized medicine and the requirement from a research perspective

Understand the clinical features of IBD
Recognise the endoscopic findings in IBD
Review the potential treatments for IBD

In this lecture, I will discuss the essential ingredients to doing excellent research which the prerequisite to getting your work published in the best journals, such as the Journal of Crohn's and Colitis. I will also give an overview of how to pick the right journal and review the processes that editors use to select what to publish.

Educational objectives
1. To learn the essential ingredients for good research
2. To understand how to target your work to the best journal
3. To understand how your paper is evaluated by editors using the peer review process