Implementation of BSG/ACPGBI/PHE polypectomy surveillance guidelines safely reduces the burden of surveillance in a screening cohort: a virtual model study.

OBJECTIVE: To evaluate the impact of British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England (BSG/ACPGBI/PHE) 2019 polypectomy surveillance guidelines within a national faecal immunochemical test-based bowel cancer screening (BS) cohort on surveillance activity and detection of pathology by retrospective virtual application. DESIGN: A retrospective review of BS colonoscopies performed in 2015-2016 with 5 years prospective follow-up in single institution. Index colonoscopies were selected. Incomplete colonoscopies were excluded. Histology of all resected polyps was reviewed. Surveillance intervals were calculated according to BSG/ACPGBI/PHE 2019 guidelines and compared with pre-existing 'European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis' (EUQA 2013). Total number of colonoscopies deferred by virtual implementation of BSG/ACPGBI/PHE 2019 guidelines were calculated. Pathology identified on procedures that would have been deferred was reviewed. RESULTS: Total number of index BS colonoscopies performed in 2015-2016 inclusive was 890. 115 were excluded (22 no caecal intubation, 51 inadequate bowel preparation, 56 incomplete polyp clearance). N=509 colonoscopies were scheduled within a 5-year interval following index colonoscopy surveillance rounds based on EUQA guidelines. Overall, volume of surveillance was significantly reduced with retrospective application of BSG/ACPGBI/PHE 2019 guidelines (n=221, p<0.0001). No cancers were detected within the 'potentially deferred' procedures who attended for follow-up (n=330) with high-risk findings found in<10% (n=30) of colonoscopies within the BSG/ACPGBI/PHE cohort. CONCLUSION: BSG/ACPGBI/PHE 2019 guidelines safely reduce the burden of colonoscopy demand with acceptable pathology findings on deferred colonoscopies.

Reduced Serological Response to COVID-19 Booster Vaccine is Associated with Reduced B Cell Memory in Patients With Inflammatory Bowel Disease; VARIATION [VAriability in Response in IBD AgainsT SARS-COV-2 ImmunisatiON].

BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD] have an attenuated response to initial COVID-19 vaccination. We sought to characterize the impact of IBD and its treatment on responses after the third vaccine against SARS-CoV-2. METHODS: This was a prospective multicentre observational study of patients with IBD [n = 202] and healthy controls [HC, n = 92]. Serological response to vaccination was assessed by quantification of anti-spike protein [SP] immunoglobulin [Ig]G levels [anti-SPIgG] and in vitro neutralization of binding to angiotensin-converting enzyme 2 [ACE2]. Peripheral blood B-cell phenotype populations were assessed by flow cytometry. SARS-CoV-2 antigen-specific B-cell responses were assessed in ex vivo culture. RESULTS: Median anti-SP IgG post-third vaccination in our IBD cohort was significantly lower than HCs [7862 vs 19 622 AU/mL, p < 0.001] as was ACE2 binding inhibition [p < 0.001]. IBD patients previously infected with COVID-19 [30%] had similar quantitative antibody response as HCs previously infected with COVID-19 [p = 0.12]. Lowest anti-SP IgG titres and neutralization were seen in IBD patients on anti-tumour necrosis factor [anti-TNF] agents, without prior COVID-19 infection, but all IBD patients show an attenuated vaccine response compared to HCs. Patients with IBD have reduced memory B-cell populations and attenuated B-cell responses to SARS-CoV-2 antigens if not previously infected with COVID-19 [p = 0.01]. Higher anti-TNF drug levels and zinc levels <65 ng/ml were associated with significantly lower serological responses. CONCLUSIONS: Patients with IBD have an attenuated response to three doses of SARS-CoV-2 vaccine. Physicians should consider patients with higher anti-TNF drug levels and/or zinc deficiency as potentially at higher risk of attenuated response to vaccination.

Reduced Serological Response to COVID-19 Vaccines in Patients with IBD is Further Diminished by TNF Inhibitor Therapy; Early Results of the VARIATION study [VAriability in Response in IBD Against SARS-COV-2 ImmunisatiON].

BACKGROUND AND AIMS: Evidence suggests patients with inflammatory bowel disease [IBD] receiving TNF antagonists have attenuated response to vaccination against COVID-19. We sought to determine the impact of IBD and of various medications for treatment of IBD on antibody responses to vaccination against COVID-19. METHODS: Patients with IBD [n = 270] and healthy controls [HC, n = 116] were recruited prospectively, and quantitative antibody responses were assessed following COVID-19 vaccination. The impact of IBD and of medications for treatment of IBD on vaccine response rates was investigated. RESULTS: Of HC, 100% seroconverted following complete vaccination with two vaccine doses; 2% of patients with IBD failed to seroconvert. Median anti-spike protein [SP] immunoglobulin [Ig]G levels following complete vaccination in our IBD cohort was significantly lower than among HC [2613 AU/mL versus 6871 AU/mL, p ≤0.001]. A diagnosis of IBD was independently associated with lower anti-SP IgG levels [ß coefficient -0.2, p = 0.001]. Use of mRNA vaccines was independently associated with higher anti-SP IgG levels [ß coefficient 0.25, p ≤0.001]. Patients with IBD receiving TNF inhibitors had significantly lower anti-SP IgG levels [2445 AU/mL] than IBD patients not receiving TNF inhibitors [3868 AU/mL, p ≤0.001]. Patients with IBD not receiving TNF inhibitors still showed attenuated responses compared with HC [3868 AU/mL versus 8747 AU/mL, p = 0.001]. CONCLUSIONS: Patients with IBD have attenuated serological responses to SARS-CoV-2 vaccination. Use of anti-TNF therapy negatively affects anti-SP IgG levels further. Patients who do not seroconvert following vaccination are a particularly vulnerable cohort. Impaired responses to vaccination in our study highlight the importance of booster vaccination programmes for patients with IBD.

A prospective study of faecal immunochemical testing following polypectomy in a colorectal cancer screening population.

INTRODUCTION: 52% of faecal immunohistochemistry test (FIT)-positive clients in the Irish National Colorectal Cancer Screening Programme (BowelScreen) have adenomatous polyps identified at colonoscopy in round 1. Although it is known that advanced adenomas and cancers cause an elevated FIT, it is not known if small (<5 mm) adenomas cause a positive FIT. AIMS: Determine if removal of small polyps in an FIT-based colorectal cancer (CRC) screening programme is associated with a negative FIT on follow-up. METHODS: A single-centre prospective observational study of consecutive participants attending for first round screening colonoscopy who had a positive FIT (>45 µg Hb/g) as part of the Irish Colorectal Cancer Screening Programme. Subjects were consented at the time of colonoscopy and were sent a repeat FIT 4-6 weeks later. Precolonoscopy and postcolonoscopy FITs were compared and correlated with clinical findings and endoscopic intervention. RESULTS: 112 consecutive first round participants were recruited. Eight (7%) had cancer, 75 (67%) adenomatous polyps, 17 (15%) a normal colonoscopy and 12 (11%) other pathology. There was a clear difference in median FIT levels between the four groups (P=0.006). Advanced pathology (tumour or adenomatous polyp >1 cm) was associated with higher FIT than non-advanced pathology (median FIT 346 vs 89 P=0.0003). 83% (86/104) of subjects completed a follow-up FIT. Follow-up FIT remained positive in 20% (17/86). Polypectomy was associated with a reduction in FIT from a median of 100 to 5 µg Hb/g (P<0.0001). Removal of polyps >5 mm was the only factor independently associated with a negative follow-up FIT on multivariate analysis (OR 3.9 (1.3-11.9, P=0.04)). CONCLUSION: FIT is a sensitive test and levels increase with advanced colonic pathology. Polypectomy of advanced adenomas is associated with a negative follow-up FIT. However, alternative causes for a positive FIT should be considered in patients who have adenomas less than 5 mm detected or a normal colonoscopy.

CRP/Albumin Ratio: An Early Predictor of Steroid Responsiveness in Acute Severe Ulcerative Colitis.

INTRODUCTION: Identifying hospitalized patients with acute severe ulcerative colitis (ASUC) who will be refractory to corticosteroid therapy and require rescue therapy remains difficult. Hypoalbuminemia worsens with time during hospitalization and is associated with rapid clearance of and reduced response to infliximab (IFX) rescue. Early use of rescue therapy may therefore be more effective. Simple clinical and laboratory predictors of corticosteroid responsiveness would facilitate earlier use of rescue therapy. MATERIALS AND METHODS: Retrospective study of a prospectively maintained database of 3600 patients attending a single center was conducted. Patients with histologically confirmed ulcerative colitis admitted with ASUC over a 5-year period from January 2010 to December 2014 were identified. All patients initially received intravenous corticosteroids. Patient demographics were collected; C-reactive protein (CRP) and albumin levels were recorded at baseline and during admission. Receiver operating characteristic statistics were used to determine the optimal stool frequency, CRP, albumin, and CRP/albumin ratio (CAR) to predict steroid response. RESULTS: A total of 124 ASUC patients were admitted during a 5-year period. Median follow-up was 2.3 years. A total of 62 patients (50%) were steroid responsive, 55 patients (44%) received rescue IFX, 22 patients (18%) required colectomy within 30 days of admission, whereas a further 14 (11%) required colectomy during follow-up. By receiver operating characteristic statistics, day 3 CAR was a more accurate marker of steroid responsiveness than day 3 CRP or day 3 albumin alone [area under curve=0.75 (P<0.001)]. The optimal CAR to predict response to steroids on day 3 was 0.85 (sensitivity 70%, specificity 76%). When combined with D3 stool frequency, specificity improved to 83%. If at day 3, CAR was >0.85 and stool frequency was >3, the relative risk of steroid nonresponse was significantly raised at 3.9 (95% confidence interval, 2.1-7.2). CONCLUSIONS: Raised D3 CAR is an early predictor of steroid-refractory ASUC. When combined with D3 stool frequency, its predictive ability improves. In patients with predicted steroid nonresponse, early introduction of rescue IFX at this stage may be more effective, before serum albumin falls profoundly.