Inflammatory Bowel Disease Clinical Nurse Specialists (IBD-CNSs) provide essential therapeutic and emotional support services to patients with often complex disease. The ever-increasing role expectations, treatment modalities and rising patient population places significant demands on IBD-CNSs (Stansfield, 2019), many of whom enter the role soon after qualifying. Posts in the UK-based RCN IBD Nurse Facebook© page suggest stress is high amongst members. Sustaining IBD-CNSs wellbeing is essential for ensuring sustainability of services. Our aim was to explore experiences of being an IBD-CNS in the UK, in order to inform the wider dialogue around workforce and the wellbeing of specialist nurses.    

This hermeneutic phenomenological study used purposive sampling with maximum variation to recruit Band 6-8 IBD-CNSs who currently, or until recently, worked in NHS Trusts across the UK. Data were collected between July and September 2020, via online or telephone interviews. Focussing on personal perceptions, participants were invited to ‘Tell me what it means to be an IBD-CNS’ with follow-up prompts and probes as needed. Diekelmann et al’s (1989) team analysis method was used.  

Twenty-five IBD-CNSs participated [92% Female; Band 6 (n=3), Band 7 (n=10), Band 8 (n=13); 0.5–19 (mean 5.8) years in post; ex-NHS (n=4)]. Two constitutive patterns: 'Giving and receiving support', and 'Developing potential' were revealed, informed by relational themes addressing patients’ needs, service design/delivery challenges, workload, professional development opportunities, and peer support. Junior IBD-CNSs worried more about workload and learning the role, whilst senior nurses often struggled with the shift towards management responsibilities which they were expected to take on often without any managerial skills or training. The IBD-CNS role was often poorly understood by senior service managers, whose level of support varied widely. Some participants had techniques to mitigate against stressors, but there were also limited professional development opportunities especially in senior roles. 

IBD-CNSs are committed to patients, despite an often-burdensome workload. Structural, institutional, and hierarchical issues undermine confidence. Many IBD-CNSs are stressed by mixed messages of delivering an excellent service yet being criticised/under-appreciated by the system. Robust senior support structures lead to better experiences for IBD-CNSs. This work contributes to the UK and global data evidencing the need to pursue strategies which promote wellbeing of all specialist nurses. 

1. To review the literature concerning neuroendocrine proliferations in IBD

2. To look at some examples of cases of neuroendocrine tumours

3. To discuss neuroendocrine micronests/microcarcinoids

Several surgical techniques have been described aiming perianal fistula healing in CD.
In this lecture, we will discuss evidence of the following approaches: advancement flaps, LIFT, anal plug, fibrin glue injection, VAAFS, stem cells, vaccum assisted dressing among others.
There is still no superior technique aiming healing of perianal fistulas in CD.
Treatment should be individualized.

1. Diagnosis of the uncommon mimickers of IBD, which should be morphologically distinguished as treatment is totally different from IBD. The mimickers discussed are infection, drugs, vascular disorders and immune-related disorders.

The characteristic histological features of inflammatory bowel disease are a disturbed crypt architecture, basal plasmocytosis and granulomas. Numerous diseases may clinically as well morphologically mimic IBD. Hence to make a diagnosis of IBD close communication between clinicians and pathologists is essential. Mimics of IBD include SCAD (segmental colitis associated with diverticulitis), diversion colitis, infections, drugs, vascular disorders and immune disorders, of which the latter are less common. In order that the pathologist can make a distinction between these mimics, information about the clinical  history, endoscopy, imaging, microbiology, serology is required. This information as well as subtle histological features may help in this differential diagnostic process. Exclusion of these mimickers is essential as they most commonly require a totally different treatment.

An increased rate of non epithelial neoplasm in IBD is described. They could be related to inflammation or to immunosuppressive treatment. The increased risk of infection related lymphomas in IBD is debated. Concerning non epithelial neoplasm related to immunosuppressive treatment they are mainly lymphomas, skin tumours and Kaposi’s sarcomas.

The main educational objective is to know and to  be aware about the presence of this rare entities.

1. To understand the role of the IBD nurse in the surgical pathway for patients with IBD
2. To understand the role of the Stoma Care nurse for patients who have stoma formation and pouch surgery
3. Recommendations for care 

To explore the role and scope of the IBD nurse.
To emphasise the importance of the impact and perspective of IBD in our patients.
To overview the UK IBD standards and how they enhance the provision of quality of care for all patients with IBD.
To provide an overview of the N-ECCO Consensus statements and the different levels in IBD nursing.

Educational objectives:
1) To understand the various definitions of malnutrition and how they related to clinical outcomes
2) To learn the various assessment techniques for determining malnutrition, including body composition analyses
3) To learn the emerging point-of-care assessment techniques that may improve clinical assessment and monitoring of malnutrition

Summary:
Malnutrition is very common in IBD patients, but historically, attention has been mostly placed on undernutrition.  It is becoming evident that overnutrition is increasing amongst the IBD population, with similar negative impacts on clinical outcomes.  This presentation will describe various definitions of malnutrition, including protein energy malnutrition, myopenia, sacropenia, myosteatosis, visceral obesity and micronutrient deficiencies and their relevance in predicting clinical outcomes.  Identification of such forms of malnutrition, such as use of imaging for body composition analyses, BMI, bioimpedance, handgrip devices and ultrasound will also be detailed.  In clinical practice, use of BMI has limited value and does not predict poor outcomes.  Nutritional assessment should encompass both detailed body composition analysis, often through imaging that IBD patients already undergo, and cheap, quick and easily applied point-of-care techniques to assess and monitor myopenia, sarcopenia are visceral adiposity.  

1. To present and discuss the evidence that malnutrition and its various presentations are important in IBD
2. To present and discuss the various approaches for nutritional screening and assessment in routine clinical practice in patients with IBD
3. To discuss the interaction between IBD nurses and dietitians within the setting of a multidisciplinary team
3. To provide practical recommendations for use by nursing staff in routine clinical practice

Educational Objectives:
1.To have an overview of growth and pubertal development at transition in IBD 
2.To emphasize the role of food restrictions, adequacy, and beliefs in patients with IBD
3. To have an overview of body perception and eating disorders and IBD

1. To provide an overview of some of the nutrition and dietary management options for IBD
2. To highlight the role of the IBD nurse in relation to nutrition and dietary management of IBD

• •       To understand what is orofacial granulomatosis & its association with Crohn’s Disease
• •       Provide an overview of treatment options
• •       To explain the background to the Cinnamon, Benzoate free diet (CBFD)
• •       Provide an overview of how to implement CBFD
• •       Highlight some of the challenges to doing CBFD

OFG is a rare disease affecting the mouth and oral cavity. It is associated with Crohn’s disease. A significant proportion of people have a positive response to dietary treatment via the cinnamon, benzoate (& chocolate) free diet (CBFD). This talk will give an overview of OFG, its treatment options and dietary management. It will look at the evidence base for CBFD and how the diet show be implemented.

1. To understand the frequency and impact of disease symptoms in patients in remission
2. To review the impact on the quality of life
3. To discuss causes for GI symptoms and extra intestinal symptoms in IBD patients in remission
4. To provide a rational clinical approach to such symptoms.

We evaluated if integration of novel diets for donors and patients in addition to fecal transplantation (FT) could increase FT remission in refractory ulcerative colitis (UC) or have an independent effect on remission. We developed a novel diet specifically designed for the dysbiosis of UC and to decrease factors that impair goblet cells or mucous production.

This was a blinded randomized controlled pilot trial in adults with UC, defined by a simple clinical colitis activity index (SCCAI) of ≥5 and < 11 and endoscopic Mayo score 2-3, refractory to medication. Group 1 received free diet and standard FT by colonoscopy on day 1and rectal enemas from a single donor on days 2 and 14 without dietary conditioning of the donor. Group 2: FT as above but with dietary pre-conditioning of the donor for 14 days and a diet (UC Diet- UCD) for the patients after FT. Group 3 received the UC Diet alone without FT. Patients underwent a repeat endoscopy at week 8. The primary endpoint was clinical steroid free remission, defined as SCCAI <3, at week 8.

Fifty-one of the 96 planned patients were enrolled. The mean age was 40.4 ±12.5 years, 28/51(54.9%) had failed a biologic, 15/40 (29.4%) were on steroids at enrolment.  Remission week 8 in Group 1 was 2/17(11.8%), Group 2 was 4/19 (21.1%), and 6/15 (40%) Group 3 (NS).  Endoscopic remission was present in Group 1: 2/17(12%), Group 2: 3/19(16%) and 4/15 (27%) Group 3. Mucosal healing (Mayo 0) was achieved only in Group 3 (3/15, 20%) vs. 0/36 patients receiving FT (P=0.022). Exacerbation of disease occurred in 3/17 (17.6%) Group1, 4/19 (21.1%) Group 2, and 1/15 (6.7%) Group 3 (NS). The study was stopped for futility by a safety monitoring board.

Fecal transplantation was not effective in this UC cohort. A UC Diet alone appeared to achieve higher clinical remission (40%) and mucosal healing than single donor FT with or without diet in mild to moderate UC failing medical therapy. This diet should be investigated further in a RCT specifically designed for the UCD. This study was supported by an ECCO Pioneer grant

Background

We studied the efficacy and safety of ustekinumab (UST) vs adalimumab (ADA) through 1 year in biologic-naïve patients (pts) with moderate-to-severe Crohn's disease.

Methods

SEAVUE was a multicenter, randomized, blinded, parallel-group, active-controlled study in adults with CD Activity Index (CDAI) scores ≥220/≤450. Biologic-naïve pts failing/intolerant to conventional therapy with any size ulcer on baseline (BL) ileocolonoscopy were eligible. Pts were randomized 1:1 to UST (⁓6mg/kg IV at BL then 90mg SC every 8 weeks [Ws]) or ADA (160/80mg SC at BL/W2, then 40mg SC every 2 Ws) per US-approved regimens (no dose modifications). Primary endpoint was clinical remission at W52 (CDAI <150). Major secondary endpoints were corticosteroid-free remission, clinical response (≥100-point CDAI decrease from BL), remission in pt-reported CDAI components (PRO-2 symptom remission: abdominal pain mean daily score ≤1 and stool frequency mean daily score ≤3), and endoscopic remission (SES-CD score ≤3/0 for pts with BL score=3) at W52 and clinical remission at W16.

Results

386 pts were randomized to UST or ADA. BL demographics and disease characteristics were balanced between groups and indicative of pts with early, moderate-to-severe CD (median CD duration, 2.58 years; CDAI, 289.5; SES-CD, 8.0). At W52, 65% of UST-treated and 61% of ADA-treated pts achieved clinical remission (Δ=4.0%; 95% CI, -5.5%, 13.5%; p=0.417). Major secondary endpoints, including endoscopic remission, were similar between groups (Table 1), as were remission rates at assessment points through W52. Some other secondary endpoints showed numerical (not statistical) differences between UST and ADA (Table 1). Key safety events are summarized in Table 2. Among UST-treated and ADA-treated pts, 34.0% and 40.5% had infections, 2.6% and 7.2% had serious adverse events (AEs) of worsening CD, and 6.3% and 11.3% had AEs that led to discontinuation (DC) of study drug, respectively. One ADA-treated pt had active pulmonary TB. Injection-site reactions associated with active treatment occurred in 1.0% of UST-treated and 10.3% of ADA-treated pts. Overall, 15.2% of UST-treated and 23.6% of ADA-treated pts DC before W52. Reasons for DC were primarily lack of efficacy (UST, 2.1% vs ADA, 5.1%), AEs (UST, 5.7% vs ADA, 10.7%), and withdrawal of consent (UST, 5.8% vs ADA, 5.1%). Time to treatment DC was longer with UST vs ADA (post hoc analysis).

Conclusion

Both UST and ADA were highly effective in this population of biologic-naïve pts. Rates of clinical remission at W52 were not statistically significantly different between treatment groups. DC rates were numerically lower for UST. Safety results were consistent with prior experience for both treatments.

Anti-TNF drugs increase the risk of serious respiratory infections and impair protective immunity following pneumococcal, influenza, and viral hepatitis vaccinations. Therefore, we sought to determine whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses following SARS-CoV-2 infection.

CLARITY IBD is a multicentre, prospective observational cohort study. Antibody responses in participants treated with infliximab were compared to a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22nd September and 23rd December 2020.  Nucleocapsid anti-SARS-CoV2 antibodies were measured using the Roche Elecsys assay. Clinical data and serum were collected every 8 weeks. Durability was defined as nonreduction in antibody level by at least 50% from baseline.

At baseline, rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab- than vedolizumab-treated patients (3.4% [161/4685], vs 6.0% [134/2250], p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; odds ratio [OR] 0.66 [95% CI 0.51-0.87], p=0.0027) and immunomodulator use (OR 0.70 [95% CI 0.53-0.92], p=0.012) were independently associated with lower seropositivity (Fig 1). In patients with confirmed SARS-CoV-2 infection seroconversion was observed in fewer infliximab- than vedolizumab-treated patients (48% [39/81], vs 83% [30/36], p=0.00044) and the magnitude of anti-SARS-CoV2 reactivity was lower (median 0.8 cut off index (COI) [0.2-5.6] vs 37.0 [15.2-76.1], p<0.0001). An initial increase in anti-SARS-Cov2 antibody reactivity was observed four weeks after a positive PCR test, in vedolizumab-(47.2 COI [IQR 24.1 - 113.0] vs 14.5 COI [IQR 0.4 – 30.7], p=0.0079), but not infliximab-treated patients (0.7 COI [IQR 0.2 - 7.5] vs 1.1 COI [IQR 0.4 - 4.5], p=0.70) (Fig 2). Antibody responses after an initial positive reading were also less durable in infliximab-treated patients (hazard ratio 5.15 [95%CI 2.95-9.00]; Fig 3), but durability was not influenced by immunomodulator use.

Seroprevalence, seroconversion in PCR-confirmed cases, and the magnitude and durability of anti-SARS-CoV2 antibodies were reduced in infliximab- compared with vedolizumab-treated patients. Serological testing and virus surveillance should be considered in patients treated with anti-TNF drugs to detect suboptimal vaccine responses, persistent infection, and viral evolution to inform public health policy.

Prior data have suggested that 5-aminosalicylates (5-ASA) may be associated with an increased risk of severe COVID-19 among inflammatory bowel disease (IBD) patients. We aimed to evaluate the association of 5-ASA with severe COVID-19 in a large cohort of IBD patients.

We analyzed data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, a large, international database of IBD patients with confirmed COVID-19. The primary outcome was severe COVID-19, defined as intensive care unit admission, ventilator use, and/or death. Hospitalization due to COVID-19 was a secondary outcome. We performed multivariable regression modeling with a generalized estimating equation accounting for country as a random effect to analyze the association of 5-ASA with severe COVID-19. Models a priori included age, sex, race, disease phenotype (CD or UC/IBD-U), corticosteroid use, azathioprine/6-mercaptopurine use, TNF antagonist use, disease activity by physician global assessment, number of comorbidities, and days from SECURE-IBD inception to reporting. We constructed three models examining 5-ASA use as binary covariate using 1) all patients, 2) only patients on any biologic, and 3) only patients on TNF antagonists.

5,174patients were included with 212 (4.1%) severe COVID-19 events. At the time of COVID-19 infection, 1,504 patients were taking 5-ASA. 5-ASA patients were older (mean age 44 vs. 38.3 years, p<0.001), more likely to have UC (70.7% vs. 27.7%, p<0.001), less likely to be in remission (49.6% vs. 57.2%, p<0.001), and more likely to have at least one comorbidity (33.6% vs. 26.7%, p<0.001) compared to patients not on 5-ASA. 3,325 patients were on any biologic and 2,216 were on a TNF antagonist. Among all patients, 5-ASA was not associated with severe COVID-19 (adjusted OR [aOR] 1.14, 95% confidence interval [CI] 0.86-1.52) (Table 1). Prior associations of age, comorbidities, TNF antagonists, and corticosteroids with severe COVID-19 were similar to prior analyses (Table 1). In analyses restricting to those on any biologic or only TNF antagonists, there was also no significant association between 5-ASA and severe COVID-19 (aOR 0.76, 95% CI 0.38-1.50 and aOR 0.99, 95% CI 0.43-2.32, respectively). Use of 5-ASA was not associated with risk of COVID-19 related hospitalization in any analysis.

In an analysis of updated data from the SECURE-IBD registry, 5-ASA use was not associated with worse outcomes among IBD patients with COVID-19.

Evaluation of endoscopic disease severity is a key component in the management of ulcerative colitis (UC) patients.  However, endoscopic assessment suffers from substantial intra- and interobserver variation, up to 75 %, thereby limiting the reliability of individual assessments. Our aim was to develop an artificial intelligence (AI) model capable of distinguishing active from healed mucosa as well as to differentiate different levels of endoscopic disease activity.

1484 unique endoscopic images from 467 patients were extracted for classification. Two experts classified all images independent of each other according to the Mayo endoscopic subscore (MES). In case of disagreement, a third expert classified the images.

Different convolutional neural network architectures were implied in the development of the AI model. Five-fold cross-validation was employed to select the best model. Unseen test data were used for evaluation.

The final model was evaluated on its performance for distinguishing MES 0 from 1–3, MES 0–1 (i.e. mucosal healing) from 2–3, and distinguish between all MES.

The accuracy, sensitivity, specificity, positive and negative predictive value, and Cohen’s Kappa were used to evaluate the final models.

Our final model achieved at the most difficult task (distinguishing between all 4 categories of MES) a mean accuracy of 0.82, mean AUC of 0.99, test accuracy of 0.84, a sensitivity of 0.88, and a specificity of 0.81 and a weighted Cohens Kappa of 0.83 (p<0.001 compared to the experts).

The results from the other tasks are shown in table 1.

We propose a new standardised way of evaluating endoscopic images from UC patients for both clinical and academic purposes. The proposed AI model demonstrated a very good capability of distinguishing between all 4 MES levels of activity. This will optimize and unify the evaluation of the disease severity measured by the Mayo endoscopic subscore across all centres and hospitals no matter the level of medical expertise.

Treating beyond endoscopic remission, aiming for histological remission, has shown to reduce relapse and hospitalization rates in patients with ulcerative colitis (UC). However, very little is known on how histological remission associates with patient reported outcomes (PROMs).

PROMs (Simple clinical colitis activity index [SCCAI], IBD disk and Visual Analogue Scales [VAS]) were prospectively collected through a digital questionnaire in all patients with UC undergoing colonoscopy between July 21^st 2020-Jan 21^st 2021. Mayo endoscopic sub score and UCEIS were determined, as well as the Nancy histologic index (NHI) of the most affected area. Endoscopic remission was defined as Mayo endoscopic sub score 0 and UCEIS 0; histologic remission as NHI 0, absence of active inflammation as NHI ≤ 1. PRO2 remission was defined as stool frequency ≤ 1 (absolute stool frequency ≤ 3 OR 1-2 stools more than usual) and rectal bleeding score of 0.

Fifty-six paired assessments were collected in 48 unique patients (Table 1), with a histologic, endoscopic and PRO-2 remission rate of 23.2%, 28.6% and 38.2% respectively. Patients with histologic remission or absence of histologic inflammation had a significantly lower overall IBD disability (p=0.007, p=0.003) and disease activity score (p=0.003, p<0.001), as compared to patients without. In line, NHI correlated with the overall IBD disk (r=0.40, p=0.002) and SCCAI score (r=0.50, p<0.001). Many individual components of both scores (abdominal pain, arthralgia, impact on education and work/interpersonal interactions/sexual function, regulation of defecation, blood loss, general wellbeing, joint pain, numbers of stools during night/day, urgency) differed significantly between patients with and without histologic remission. VAS scores assessing general wellbeing (r=0.33, p=0.01), impact on daily activities (r=0.41, p=0.002), UC-related symptoms (r=0.42, p=0.001) and worries (r=0.40, p=0.002) correlated with histology.  Quartile analysis of the overall IBD disk and SCCAI scores confirmed the highest likelihood for histologic remission in patients with the lowest scores (Q1-Q2 vs Q3-Q4 39.3% vs 7.1%, p=0.01; 40.0% vs 9.7%, p=0.01) (Figure 1). Nevertheless, the overall accuracy of the IBD disk (0.75) or SCCAI score (0.76) for histologic remission is lower (p<0.05) than the accuracy of the Mayo endoscopic (0.90) or UCEIS (0.90) score.

Table 1 : Baseline features

In patients with UC, PROMs for disability and clinical disease activity reflect histologic disease activity and should therefore be further explored in (trial) endpoint discussions. However, they cannot fully replace endoscopic and histologic findings, and should be considered complementary.

Biologics are being used increasingly in the treatment of Inflammatory Bowel Disease. However, up to 40% of patients do not respond to biologics. Therefore, methods to predict response are imperative. We aimed to identify novel genes and pathways predictive of anti-TNF response in patients with Ulcerative Colitis (UC) undergoing electronic chromoendoscopy and probe confocal laser endomicroscopy (pCLE). We further evaluated the ex-vivo binding of fluorescent labelled biologics as markers of response

26 UC patients starting anti-TNF therapy as standard of care were recruited. Pre-treatment colonoscopy, with electronic chromoendoscopy and pCLE (Cellvizio, Mauna Kea) by injecting intravenous fluorescein (2.5-5mls), was performed to assess disease activity. Targeted biopsies were taken for fluorescein isothiocyanate (FITC)-labelled infliximab staining and RNA extraction and gene expression analysis. Ex vivo labelling was evaluated by an automated analysis: after a first pre-processing step to remove biases, the labelled regions were identified using statistical multi-level thresholding, and evaluated as area and intensity. To assess response, the same endoscopic procedure was repeated at week 12-14 after anti-TNF. cDNA libraries were prepared using QIAseq UPX 3’Transcriptome reagents and sequenced. Normalised gene expressions were obtained through the CLC Genomics Workbench. Differentially expressed genes (DEGs) (FDR-corrected P-value<0.05) were determined using the Limma package and PLS-DA modelling performed to calculate their importance (VIP score). Functionally related genes were identified and classified using DAVID tools. Strongest indicators of response were predicted by Random Forest area under the curve (AUC) analysis in this cohort and a similar validation cohort

At baseline increased binding of the labelled biologic was associated with a higher likelihood of response to treatment  (AUROC81%, accuracy77%, PPV100%, NPV63%). 342 DEGs (75 up-regulated, 267 down-regulated) distinguished responders from non-responders, 76 fell within enriched pathways. Pathways related to inflammation, chemotaxis, TGF-beta signalling, extracellular matrix and carbohydrate metabolism were reduced and cell-cell adhesion increased in responders pre-treatment. Among the 37 genes with VIP>1, CRIP2, CXCL6,EMILIN1,GADD45B, LAMA4 and MAPKAPK2 were upregulated in non-responders pre-treatment and were good predictors of response (AUROC>0.7) in this cohort and validation cohort

A higher mucosal binding of the biologics before treatment was observed in anti-TNF responders. Responsive UC patients have a less inflamed and fibrotic state pre-treatment. Chemotactic pathways, involving CXCL6 may be novel targets to treat non-responders