Search

Background The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines. Methods We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria—with no contraindications to influenza vaccination—were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 μg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine [Flucelvax Quadrivalent; Seqirus UK, Maidenhead] for those aged 18–64 years and adjuvanted trivalent influenza vaccine [Fluad; Seqirus UK, Maidenhead] for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995. Findings Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 [64·9%] of 174 vs 592 [53·3%] of 1111) or pain (69 [39·7%] vs 325 [29·3%]) at injection site, fatigue (48 [27·7%] vs 215 [19·4%]), and muscle pain (49 [28·3%] vs 237 [21·4%]). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to

Summary Background There is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes. Methods The PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov , NCT04411784 . Findings We included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes. Interpretation The COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes. Funding None.

BACKGROUND AND AIM Ustekinumab is a monoclonal antibody that targets interleukin-12/23. In Scotland, it was approved for the treatment of moderate to severe Crohn's disease in 2017. The objective of this study was to establish the real-world effectiveness and safety of ustekinumab in the treatment of Crohn's disease. METHODS We conducted a retrospective study of patients receiving ustekinumab across eight Scottish National Health Service health boards between 2017 and 2019. Inclusion criteria included a diagnosis of Crohn's disease with symptoms attributed to active disease plus objective signs of inflammation at baseline (C-reactive protein ≥ 5 mg/L or fecal calprotectin ≥ 250 μg/g or inflammation on endoscopy/magnetic resonance imaging) and completion of induction plus at least one clinical follow-up at 8 weeks. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, deep remission, and perianal fistula response. Rates of serious adverse events were described quantitatively. RESULTS Our cohort consisted of 216 patients (female sex, 37.9%; median age, 39.0 years, interquartile range [IQR] 28.8-51.8 years; disease duration, 9.9 years, IQR 6.0-16.5 years; prior biologic, 98.6%) with a median follow-up of 35.0 weeks (IQR 17.4-52.0 weeks). Twelve-month cumulative rates of clinical remission, mucosal healing, and deep remission (clinical remission plus mucosal healing) were 32.0%, 32.7%, and 19.3%, respectively. In patients with active perianal disease (n = 37), the 12-month cumulative perianal response rate was 53.1%. The serious adverse event rate was 13.6 per 100 patient-years of follow-up. CONCLUSION Ustekinumab is a safe and effective treatment for the treatment of complex Crohn's disease.

Background: Muscle–bone deficits are common in pediatric Crohn’s disease; however, few studies have assessed long-term musculoskeletal outcomes in adults with childhood-onset Crohn’s disease. This study assessed the prevalence of musculoskeletal deficits in young adults with childhood-onset Crohn’s disease compared with healthy controls. Methods: High-resolution MRI and MR spectroscopy were used to assess bone microarchitecture, cortical geometry and muscle area, and adiposity at distal femur and bone marrow adiposity (BMA) at lumbar spine. Muscle function and biomarkers of the muscle-bone unit were also assessed. Results: Twenty-seven adults with Crohn’s disease with median (range) age 23.2 years (18.0, 36.1) and 27 age and sex-matched controls were recruited. Trabecular microarchitecture, cortical geometry and BMA were not different between Crohn’s disease and controls (P > 0.05 for all). Muscle area was lower (P = 0.01) and muscle fat fraction was higher (P = 0.04) at the distal femur in Crohn’s disease compared to controls. Crohn’s disease participants had lower grip strength [-4.3 kg (95% confidence interval (CI), -6.8 to -1.8), P = 0.001] and relative muscle power [-5.0 W/kg (95% CI, -8.8 to -1.2), P = 0.01]. Crohn’s disease activity scores negatively associated with trabecular bone volume (r = -0.40, P = 0.04) and muscle area (r = -0.41, P = 0.03). Conclusion: Young adults with well-controlled Crohn’s disease managed with contemporary therapies did not display abnormal bone microarchitecture or geometry at the distal femur but exhibited muscle deficits. The observed muscle deficits may predispose to musculoskeletal morbidity in future and interventions to improve muscle mass and function warrant investigation.

Background: \ud Few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford–AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer–BioNtech, hearafter referred to as BNT).\ud \ud Methods: \ud COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY) control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130.\ud \ud Findings: \ud Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44–61) in the younger age group and 76 years (73–78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41–59) in the younger age group and 78 years (75–82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5–2·3) in the half VLA group to 32·3 (24·8–42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7–1·6) for ChAd to 3·6 (2·4–5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0–1·5) in the half VLA group to 11·5 (9·4–14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7–1·6) for half VLA to 4·7 (3·1–7·1) for m1273. The results were similar between those aged 30–69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30–69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273.\ud \ud Interpretation: \ud All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination.\ud \ud Funding: \ud UK Vaccine Taskforce and National Institute for Health Research.

PMO-21 Table 1 Oct 19 Nov 19 Dec 19 Jan 20 Feb 20 Mar 20 Apr 20 May 20 Jun 20 Jul 20 No. of tests with complete prescribing data 66 67 70 66 72 71 45 55 71 56 No. on CI % of tests 30 38 36 35 33 33 20 31 35 16 45.5% 56.7% 51.4% 53.0% 45.8% 46.5% 44.4% 56.4% 49.3% 28.6% Thiopurine specifically % of tests 24 24 26 24 22 25 17 22 27 14 36.4% 35.8% 37.1% 36.4% 30.6% 35.2% 37.8% 40.0% 38.0% 25.0% Non standard dosing % of tests 33 30 37 37 34 39 19 32 43 28 50.0% 44.8% 52.9% 56.1% 47.2% 54.9% 42.2% 58.2% 60.6% 50.0% Proactive TDM 42 50 39 42 43 48 31 34 40 31 ConclusionsOur data suggests prescribing practices remain largely static. However July 2020’s drop in CI prescribing may be an early indicator of decreased use. The small rise in non-standard dosing may be due to COVID-19 strategies employed to reduce hospital attendances and requires further review. While the nature of our data will not convey the complete COVID-19 impact, it highlights the need for stringent review of post-COVID-19 clinical practices, patient outcomes, and updated clinical guidance as our understanding of the COVID-19 impact on IBD develops.ReferencesShields S, et al. Frontline Gastroenterology Published Online First: 30 September 2020. doi: 10.1136/flgastro-2020-101563Ungaro RC, et al. Gut Published Online First: 20 October 2020. doi: 10.1136/gutjnl-2020-322539

COVID-19 has dominated life in 2020 with, at the time of writing, over 4.9M global cases and >320 000 deaths. The impact has been most intensely felt in acute and critical care environments. However, with most UK elective work postponed, laboratory testing of faecal calprotectin halted due to potential risk of viral transmission and non-emergency endoscopies and surgeries cancelled, the secondary impact on chronic illnesses such as inflammatory bowel disease (IBD) is becoming apparent. Data from the Scottish Biologic Therapeutic Drug Monitoring (TDM) service shows a dramatic drop in TDM testing since the pandemic onset. April 2020 saw a 75.6% reduction in adalimumab testing and a 36.2% reduction in infliximab testing when compared with February 2020 data, a reduction coinciding with the widespread cancellation of outpatient and elective activity. It is feared that disruption to normal patterns of care and disease monitoring of biologic patients could increase the risk of disease flare and adverse clinical outcomes. Urgent changes in clinical practice have been instigated to mitigate the effects of the pandemic on routine clinical care. Further transformations are needed to maintain safe, effective, patient-centred IBD care in the future.

Background Treatment options in Inflammatory Bowel Disease (IBD) include anti-TNFα and anti-integrin biologics. Therapeutic drug monitoring (TDM) is used to support clinical decision making and improve treatment outcomes with anti-TNFα drugs infliximab and adalimumab.1,2 It is unclear if TDM can offer similar benefits with vedolizumab (VDZ) and there are no clinical guidelines for using TDM with VDZ3. The aim of this study was to identify if drug levels (DL) are associated with clinical outcomes and markers of disease activity in patients treated with VDZ. Methods All VDZ DLs performed since introduction of testing at our unit in December 2018 were retrospectively identified. Target DLs of >30 μg/ml during induction (≤14 weeks since treatment initiation (TI)) and >10 μg/ml in maintenance (>14 weeks after TI) were agreed based on available published data. Dose information, timing of DL, lab results and disease activity scores were obtained from electronic patient records and paired with the DL dose. Calprotectin was included if recorded within 3 months of DL. Patients were classified as in remission or mild, moderate or severe active disease according to partial Mayo Score for ulcerative colitis and Harvey–Bradshaw Index for Crohn’s disease. Sub-analysis was undertaken according to timing of testing in relation to TI. Results Sixty pre-dose trough VDZ levels were identified from 41 patients. Median VDZ level was 25.7 μg/ml (70). Median time from TI to first VDL DL was 36 weeks (4.6–184). No relationship was identified between VDZ levels and biochemical markers of disease (Figure 1). Fourteen (23.3%) TDM were performed during induction. 6/14(42.8%) had subtherapeutic DLs; 3 in remission, 1 mild, 2 severe disease. The remaining 8/14(57.1%) had therapeutic DL; 3 mild, 3 moderate, 1 severe disease, 1 unknown. Forty-six (76.7%) TDM were performed during maintenance. Five out of 46(10.9%) had subtherapeutic DLs; 3 remission, 1 moderate disease, 1 unknown. The remaining 41/46(89.1%) had therapeutic DLs; 16 remission, 11 mild, 10 moderate, 3 severe disease, 1 unknown. For both sub-analysis groups, no relationship between disease state and drug level was observed. Conclusion The results from this small cohort do not suggest a relationship between serum VDZ levels and clinical outcomes. Further research in larger cohorts is needed to confirm or refute these findings. References

Introduction 50% of patients with Crohn’s Disease (CD) will have surgery within the first 10 years, with 35% requiring additional surgery. The REMIND cohort linked male gender, smoking and previous resection to recurrence.1 The link between CD and deprivation is debated2, and its influence on recurrence is unknown. We aimed to define our local post-operative CD population, highlighting recurrence rates. Methods CD resections between 2008–2014 were identified from NHS Greater Glasgow & Clyde Pathology Archive. Data including gender, age at diagnosis and resection, Montreal Classification and smoking status was obtained from Electronic Patient Records. Scottish Index of Multiple Deprivation (SIMD) score was determined by postcode and was ranked 1–5 (most to least deprived). A minimum of 5 years of follow up data was collected. Type of recurrence was recorded as: 1) clinical recurrence - symptom flare requiring course of steroids or inpatient admission; 2) biochemical recurrence - faecal calprotectin >250µg/l; 3) endoscopic recurrence; or 4) surgical recurrence – the need for further CD-related surgery. Results 304 patients (59.5% female) were included. Median age at diagnosis was 29 (range 3–82 years) and at resection was 43 (range 17–85 years). 82.9% had terminal ileal, colonic, or ileocolonic involvement. Upper GI and perianal disease occurred in 17.1% and 12.8% respectively. 94% had a stricturing or penetrating phenotype. 52.9% of patients were never-smokers, 16.5% were ex-smokers and 30.6% were current smokers. 33.6% patients had a SIMD score of 1. 47% of patients had clinical recurrence and 48.7% had biochemical recurrence with 49 patients 16.1% requiring further surgery for Crohn’s disease. There were significant associations between younger age at diagnosis/resection, male sex, current smoking and biochemical, surgical and clinical recurrence respectively. There was no significant association between SIMD score and recurrence of any type. Conclusions Our data suggests rates of post-operative recurrence in line with existing published data. Risk factors for this are similar to those identified in the REMIND study1, with younger age at diagnosis/resection, male sex and smoking all associated with higher rate of recurrence. Our data suggests deprivation does not influence recurrence rates. However more work is needed to validate this in larger, prospective cohorts. References Auzolle, et al. Male gender, active smoking and previous intestinal resection are risk factors for post-operative endoscopic recurrence in Crohn’s disease: results from a prospective cohort study. Aliment Pharmacol Ther 2018 Nov;48(9):924–932 Wardle, et al. Literature review: impacts of socioeconomic status on the risk of inflammatory bowel disease and its outcomes. Bottom of Form European Journal of Gastroenterology & Hepatology 29(8):879–884.

Introduction Treatment with exclusive enteral nutrition (EEN) offers a nutritional therapy paradigm in Crohn’s disease, with the extensive modulation of gut microbiome being its proposed mechanism of action(1). Recent studies propose variable clinical efficacy for 85% EN (Cheat EN/CEN), 50% EN (Partial EN/PEN) and 20% EN (maintenance EN/MEN), and a dose-dependent effect of EN use in CD(2–4). Therefore, this study aims to investigate the dose-dependent effect of 100%, 85%, 50%, and 20% EN on faecal microbial metabolites; and to investigate if this effect can be used as a compliance marker for EEN. Methods Healthy adults followed EEN, CEN, PEN or MEN diet for 7 days. Fresh faecal samples were collected before and after each dietary intervention. Dietary assessment was performed throughout the intervention using estimated weight food diaries. Faecal pH, Bristol Stool Chart Score (BSCS), short chain fatty acids and hydrogen sulphide were measured. Results 122 faecal samples were collected from 61 subjects. The Mean(SEM) EN intake for the 4 groups was EEN:100(0), CEN:86(0.5), PEN:50(0.4), MEN:20(0.2)% of total energy intake. The baseline levels of all faecal sample measures were no different between the 4 groups. Faecal propionate and BSCS significantly decreased only during EEN (all p≤0.03). Faecal pH significantly increased during EEN, CEN and PEN (all p Conclusions EEN and CEN extensively modulate faecal microbial metabolites. PEN induces variable effects and further analysis should investigate if this variation reflects differences in the non-EN food intake of the participants (50%). MEN had no effect on faecal microbial metabolites. Further analysis including high-throughput deep sequencing techniques will provide additional information about the dose-dependent effect of EN regimen on gut microbiome composition. 1) Quince, Am J Gastroenterol 110, 1718–1729; 2) Logan, APT 50, 664–674, 2019; 3) Gupta, IBD 19, 1374–1378, 2013; 4) Lee, IBD 21, 1786–1793, 2015

Introduction Whilst anti-TNF drugs such as adalimumab (ADL) have revolutionised the management of Inflammatory Bowel Disease treatment outcomes are not universally favourable with 30% primary non response (PNR) and 46% secondary loss of response (SLOR) rates reported1,2. Therapeutic drug monitoring (TDM) – measurement of serum drug levels (DL) and anti-drug antibodies - has become popular with clinicians who use it to optimize biologic therapy through serum DL guided dose adjustment. Conventionally TDM is based on the interpretation of trough DL, obtained by drawing a blood sample immediately prior to the next drug dose. Obtaining an ADL trough DL can be challenging as the drug is administered as a subcutaneous injection usually in the patient’s own home. The aim of this project was to determine the current use of non-trough ADL TDM in clinical practice and determine whether timing of ADL TDM in relation to next planned dose is clinically important. Methods All ADL DLs performed in 2018 in the Scottish Biologic TDM service3 were identified. DLs were included for patients in sustained clinical remission (SCR), on 40 mg every other week dosing, and if time from last dose was ≤14 days. TDM performed during induction and for PNR or SLOR were excluded, as were patients on nonstandard dosing or with missing data on dose and interval. Results were analysed by quartile according to time from the last drug dose. Results 338 DLs were included. Median DL is 8µg/ml (range Conclusion It is not necessary to use trough DLs when performing ADL TDM for individuals in SCR. This data should give clinicians the confidence to use opportunistic ADL TDM testing in a clinical setting. Further work should be undertaken on non-trough testing of ADL DLs in other clinical scenarios. Disclosure Biogen GmbH contributed funding for this research. Authors had full editorial control and approval of all content. References Ben-Horin S and Chowers. Aliment Pharmacol Ther 2011; 33: 987–995. Osterman MT, Haynes K, Delzell E, et al. Clin Gastroenterol Hepatol 2014;12:811–817. https://www.nhsggc.org.uk/media/251621/scottish-biologic-tdm-service-gastroenterology-guidance-03122018.pdf

Introduction Microscopic colitis (MC) is still perceived to be an ‘uncommon’ condition1. Despite significant impact on quality of life1, many aspects of the patient journey remain unclear. A National MC Disease Registry is being developed with the aim of gathering data on epidemiology, variations in clinical practice and patient journey. The secondary aim is to generate academic and clinical data to help create more stream-lined MC Services, improving patient care and outcomes. Methods Retrospective data was collected across 6 Scottish (2 DGHs/4 University teaching) units. Once identified from Pathology databases, further data was collected from electronic records. Results In total, 527 patients were enrolled on the registry; of whom, 54 were excluded due to incomplete information. Out of 473 patients [Collagenous colitis 328(69%), Lymphocytic colitis 127(27%), 18 unspecified (4%)] included in the analysis, 358(76%) were female, aged 20–96 (median 67) years. Watery diarrhoea (463, 98%) and abdominal pain (111, 23%) were predominant symptoms. Weight loss was noted in 115(24%). Eight (2%) patients developed complications; 2 adverse drug reactions, 1 colorectal malignancy and 3 required surgical intervention for intractable symptoms related to MC. Variations were noted in the following areas: Patient journey: Whilst 230(49%) were referred directly to Gastroenterology, 109(23%) were referred initially to Surgery– with subsequent referral to Gastroenterology following colonoscopy. This led to delay in therapy initiation in a proportion of patients. In one unit, average length of symptoms at diagnosis was 5.7 months, with an average length of 9.1 months to see Gastroenterology. Medications: There was no evidence of medication review in 121(26%) patients. Reducing-dose Budesonide was the first line treatment in 205(43%). Though 174(37%) did not require initial medical therapy; of these 18(10%) required subsequent treatment with Budesonide. There are 4(1%) patients on biologics and 4(1%) patients on immunomodulators specifically for MC– all of which were treated with budesonide first line. Follow-up: A majority, 337(71%) were followed-up in clinic, with 260(77%) later discharged. Relapse was noted in 118(25%) patients. Conclusions Initial findings from the first MC Registry in the UK demonstrate variability in referral pathway, patient journey and management. Data suggests association with alarm features and significant complications. Reference Townsend T, Campbell F, O’Toole P, et al. Microscopic colitis: diagnosis and management. Frontline Gastroenterology 2019;10(4):388–93

We present a patient with an acute kidney injury thought secondary to acute interstitial nephritis as a result of vedolizumab maintenance therapy for Crohn’s disease. This appears to be a rare but serious side effect in patients receiving this treatment which clinicians should consider in the event of renal dysfunction.

Musculoskeletal deficits are among the most commonly reported extra-intestinal manifestations and complications of inflammatory bowel disease (IBD), especially in those with Crohn’s disease. The adverse effects of IBD on bone and muscle are multifactorial, including the direct effects of underlying inflammatory disease processes, nutritional deficits, and therapeutic effects. These factors also indirectly impact bone and muscle by interfering with regulatory pathways. Resultantly, individuals with IBD are at increased risk of osteoporosis and sarcopenia and associated musculoskeletal morbidity. In paediatric IBD, these factors may contribute to suboptimal bone and muscle accrual. This review evaluates the main pathogenic factors associated with musculoskeletal deficits in children and adults with IBD and summarises the current literature and understanding of the musculoskeletal phenotype in these patients.

Background Treatment with exclusive enteral nutrition (EEN) offers a nutritional therapy paradigm in Crohn’s disease, with the extensive modulation of gut microbiome being its proposed mechanism of action (1). Recent studies propose variable clinical efficacy for 85% EN (Cheat EN/CEN), 50% EN (Partial EN/PEN) and 20% EN (maintenance EN/MEN), and a dose-dependent effect of EN use in CD (2–5). Therefore, this study aims to investigate the dose-dependent effect of 100%, 85%, 50%, and 20% EN on faecal microbial metabolites; and to investigate if this effect can be used as a compliance marker for EEN. Methods Healthy adults followed EEN, CEN, PEN or MEN diet for 7 days. Fresh faecal samples were collected before and after each dietary intervention Dietary assessment was performed throughout the intervention using estimated weight food diaries. Faecal pH, water content, Bristol Stool Chart Score, short-chain fatty acids and hydrogen sulphide were measured. Results A total of 122 faecal samples were collected from 61 subjects. The Mean(SEM) EN intake for the four groups was EEN: 100(0), CEN: 85.6(0.5), PEN: 50.1(0.4), MEN: 19.9(0.2) % of total energy intake. The baseline levels of all faecal sample measures were no different between the four groups. Faecal water content, propionic acid and Bristol Stool Chart Score significantly decreased only during EEN (all p≤0.03). Faecal pH significantly increased during EEN, CEN and PEN (all p < 0.001), but not during MEN (p = 0.728). Faecal pH post-intervention was highest for EEN, followed by CEN and PEN [Mean(SEM), EEN: 8.2(0.1); CEN: 7.8(0.2); PEN: 7.3(0.1), all pairwise p ≤ 0.002]. The faecal concentration of hydrogen sulphide, acetic and butyric acid significantly decreased following both EEN and CEN groups (all p ≤ 0.009). The concentration of acetic acid post-EEN was significantly lower than the concentration post CEN [Mean(SEM), EEN: 173(10); CEN: 261(24) μmol/g, p = 0.001]. Hydrogen sulphide and butyric acid concentrations post EEN and post CEN were unchanged (p = 0.337, p = 0.141). Conclusion EEN extensively modulates faecal microbial metabolites and CEN induces similar effects. PEN induces variable effects and further analysis should investigate if variation in responses reflects differences in the non-EN food intake of the participants (50%). MEN had no effect on faecal microbial metabolites. Further analysis including high-throughput deep sequencing techniques will provide additional information about the dose-dependent effect of EN regimen on gut microbiome composition. References 1. Quince et al., Am J Gastroenterol, 110:1718–1729. 2. Logan et al., Aliment Pharmacol Ther, 2019;50:664–674. 3. Gupta et al., IBD, 2013;19:1374–1378. 4. Duncan et al., BMC Gastroenterol, 2014;14:50. 5. Lee et al., IBD, 2015;21:1786–1793.

Introduction Biosimilar infliximab (BI) has been widely adopted in to clinical practice since launch in 2015. Switching patients with Inflammatory Bowel Disease (IBD) from originator infliximab (OI) to BI was endorsed by the BSG and ECCO despite a lack of data on the long-term implications of this strategy. Infliximab discontinuation (ID) occurs in 20–40% patients per annum. It is unclear whether switching to BI affects ID rates. This study assessed long-term outcomes after a managed BI switch programme. Methods Individuals with Crohn’s disease (CD) and Ulcerative Colitis (UC) who were changed from OI to BI in a switch programme in Dec 2016 were reviewed via electronic patient records. Demographics and pre-switch disease characteristics were recorded. Pre-switch medications and laboratory data were collected. Changes to BI dose/frequency at switch and during follow-up were recorded along with other changes to IBD medications. Post-switch durability of clinical response was evaluated. Rates of IBD related steroid use, hospitalisation and surgery were gathered. Incidence of adverse events was determined. Potential pre-switch indicators of future ID were explored. Results 76 individuals considered to be clinically responding to OI were entered in to the BI switch programme. 2 patients had OI stopped prior to 1st dose BI based on clinical assessment and Therapeutic Drug Monitoring (TDM) results. 74 people were switched from OI to BI. At time of switch 38 (51%) were prescribed an immunomodulator. 52/74 (70%) were on 5 mg/kg 8 weekly treatment, the rest on higher doses. 48/74 had a pre-switch FC, 32 (67%) FC 2 years post switch, 54/74 (73%) remained on BI with sustained clinical response. ID was observed in 20 (27%); 11 (55%) now on another biologic, 8 (40%) biologic free. 33/54 remaining on BI had treatment escalation at time of or subsequent to switch. There was 1 non-treatment/IBD related death. 1 infusion reaction adverse event was observed. There were 6 IBD related surgeries, 4 unplanned hospital admissions and 12 required steroids for IBD flare. Evaluation of data identified no pre-switch factors associated with ID. Conclusions Over 2 years of follow-up clinical response was maintained in the majority of individuals following BI switch. Rates of ID were lower than historically reported in non-switched patient cohorts. BI switching appears to be a safe and effective intervention.

Introduction Therapeutic drug and antibody monitoring (TDM) of infliximab (IFX) is used with increasing regularity as a tool to optimize outcomes in inflammatory bowel disease (IBD). Trough levels (TL) of 2–8 mcg/ml are recommended during maintenance IFX treatment. The introduction of biosimilar infliximab (BI) in 2015 lead to widespread switching of patients from originator infliximab (OI) to BI. The value of TDM when switching to BI has not been defined. This study aimed to assess the impact of TDM testing before and after a managed switch to BI. Methods Individuals with IBD treated with OI and demonstrating a satisfactory response to treatment, were entered in to BI switch programme in Dec 2016. Pre-switch information was provided to patients, virtual or face to face clinical assessment was undertaken and it was recommended that all patients had pre-switch TDM performed. After switching patients returned to routine clinical care. Further TDM was performed at clinician discretion with recommendation to follow published TDM testing guidance.1 Virtual review of all patients was undertaken 2 years post-switch. Demographics, pre and post switch TDM data, OI and BI dosing regimens and other IBD related medications were recorded along with clinical outcome data. Comparative analysis of pre-switch and most contemporary TDM results was performed. Results 76 individuals considered to be clinically responding to OI were entered in to the BI switch programme. 70/76 (92%) had TDM at Of 69/74 with pre-switch TDM, 32/69 (46%) had subtherapeutic TLs ( 58/74 (78%) had TDM testing in the 2 years after switch (median no. tests 2; range 1 – 5) at which point 54/74 (73%) remained on BI with sustained clinical response. 49 out of 54 still on BI had both pre and post switch TDM with results demonstrating a statistically significant increase in mean TLs (2.1 vs 6.3 mcg/ml; p Conclusions High rates of sustained clinical response were observed to occur following a BI switch supported by the use of pre and post switch TDM. TDM dose escalation resulted in a statistically significant increase in TLs, this may account for the rates of continued clinical response Reference Papamichael K. Frontline Gastroenterol. 2016 Oct;7(4):289–300.

Background & Aims Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn’s disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. Methods This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn’s disease with objective evidence of active inflammation at baseline (Harvey–Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan–Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. Results Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn’s disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26–52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn’s disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. Conclusions Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn’s disease.

Background:Anti-tumour necrosis factor α (anti-TNFα) drugs infliximab (IFX) and adalimumab (ADL) are effective treatments for several rheumatic diseases. Therapeutic drug level and anti-drug antibody monitoring (TDM) has emerged as a useful tool for optimising drug effectiveness, by identifying individuals who may benefit from dose or treatment frequency adjustment, or have secondary drug failure due to immunogenicity.Objectives:Ensuring safe and effective use of biologic medicines has been identified as a key priority for NHS Scotland. Inequity and inconsistency of access to TDM across the nation was recognised as a barrier to delivering best practice and so a nationally commissioned TDM service was proposed in January 2018 to support clinical practice, providing universal access to TDM for services treating inflammatory diseases across Scotland. Data collection and analysis of results regarding usage and clinical impact of the service were identified as key outcome measures to assess service success and sustainability.Methods:A service webpage was developed to provide guidance on testing strategies and interpretation of TDM results (1). An automated search of clinical data and test results recorded within the clinical biochemistry electronic results management system was conducted to identify all TDM tests performed between 01/01/2018 and 31/12/2018. Descriptive analysis outcomes included the number of samples received, processed, overall testing population, service utilisation by Health Board, number and results of TDM tests performed per patient. TDM results were interpreted according to published guidance on the service webpage and comparison was made with previously published data (2).Results:3609 specimens were received for testing, from 13 of the 14 Scottish Health Boards. 3561 drug level (DL) tests were performed; 1786IFX, 1775 ADL. 2717 total antidrug anti-body (TABT) tests and 681 free antidrug anti-body tests (FABT) were performed according to service protocol. 2791 individuals had one or more TDM tests during the 12-month period, of whom 541 were tested twice or more (range 2-5).Table 1.IFX & ADL DL, TABT and FABT results by category as defined in service guidance (AU/ml = Arbitrary Units/ml)]INFLIXIMABADALIMUMABDrug level by categorySupratherapeutic DL > 8mcg/ml546 (30.6%)708 (39.9%)Supratherapeutic DL > 10 mcg/mlTherapeutic DL ≥3738 (41.3%)636 (35.8%)Therapeutic DL ≥5Sub-therapeutic DL < 3mcg/ml502 (28.1%)431 (24.3%)Sub-therapeutic DL < 5 mcg/mlTABT by categoryNegative (791 (54.2%)905 (71.9%)Negative (Positive (>10 AU/ml)668 (45.8%)353 (28.1%)Positive (>10 AU/ml)FABT by categoryNegative (< 5AU/ml)376 (82.8%)176 (77.6%)Negative (Positive (> 5 AU/ml)78 (17.2%)51 (22.4%)Positive (>10 AU/ml)Conclusion:TDM has been enthusiastically embraced. It is estimated that > 50% of individuals treated with IFX or ADL have been tested at least once in the first year. DL results were found to be similar to previously published data, as were rates of antibody positivity. The large volume of data generated by the service may provide additional evidence regarding the utility of TDM in predicting clinical response. Next steps are to conduct a comparative effectiveness analysis where proactive vs reactive TDM testing strategies will be compared, with the primary outcome measure being the proportions of patients with secondary loss of response.References:[1]Scottish Biologic therapeutic Drug Monitoring Servicehttps://www.nhsggc.org.uk/about-us/professional-support-sites/biochemistry/biological-therapy-monitoring/[2]Jani, M. Et al (2015), Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis. Arthritis & Rheumatology, 67: 2011-2019. doi:10.1002/art.39169Acknowledgments:Biogen GmbH contributed partial funding for this research. Authors had full editorial control and approval of all contentDisclosure of Interests:Jonathan MacDonald: None declared, Martin Perry Grant/research support from: Grifols, Abbvie, Sandoz unrestricted educational grant, Consultant of: Abbvie, Gilead, Celltrion Advisory Board, Speakers bureau: Sandoz, Peter Galloway: None declared, John-Paul Seenan: None declared, Alan Dunlop: None declared

Background 50% of patients with Crohn’s disease (CD) will have surgery within the first 10 years, with 35% requiring additional surgery in the following decade. The REMIND cohort-linked male gender, smoking and previous resection to recurrence1. The link between CD and deprivation is debated, while its influence on recurrence is unknown. We aimed to define our local post-operative CD population, highlighting recurrence rates and associated risk factors. Methods CD resections between 2008 and 2014 were identified from NHS Greater Glasgow and Clyde Pathology Archive. Data including gender, age at diagnosis/resection, Montreal classification and smoking status was obtained from the Electronic Patient Record (EPR). Scottish Index of Multiple Deprivation (SIMD) score was determined by postcode and was ranked 1–5 (most to least deprived). Five years of follow-up data were collected. The type of recurrence was recorded as clinical recurrence - symptom flare requiring a course of steroids or inpatient admission; biochemical recurrence—faecal calprotectin >250 µg/l; endoscopic recurrence; or surgical recurrence—the need for further Crohn’s disease-related surgery. Results 304 patients (59.5% female) were included. Median age at diagnosis was 29 (range 3–82 years) and at resection was 43 (range 17–85 years). 52.9% of patients were never-smokers, 16.5% were ex-smokers and 30.6% were current smokers. 33.6% of patients had a SIMD score of 1. Eighty-two per cent had ileal, colonic or ileocolonic involvement. 46.7% of patients had clinical recurrence, 48.7% biochemical recurrence and 31.6% endoscopic recurrence. 15.8% required further surgery for CD. For clinical recurrence, younger age at diagnosis (p = 0.012, and younger age at resection (p = 0.002) were significant determinants. Gender, smoking and SIMD were not significantly associated with recurrence. Chemical recurrence showed similar associations. Similarly, for surgical recurrence, younger age at diagnosis (p = 0.030, and younger age at resection (p = 0.003) were significant determinants. Male gender was the only risk factor for endoscopic recurrence (OR=1.88, 95% CI: 1.13–3.08). Conclusion Our data suggest rates of post-operative recurrence in line with published data. Risk factors were similar to those identified in the REMIND study, with younger age at diagnosis/resection associated with higher rates of recurrence. Our data suggest sociodemographic deprivation does not influence recurrence rates; however,, more work is needed to validate this. References

Introduction The GEMINI trials and an increasing body of real-world data have demonstrated the effectiveness and safety of vedolizumab (VDZ) in IBD. However, there is limited available data about its effect on hospitalisations and steroid use. Our aim was to address this in a large real-world cohort of IBD patients from across Scotland. Methods A multicenter retrospective cohort analysis of medical records was performed across 7 Scottish healthcare trusts. Primary outcomes were hospitalisation rates and overall steroid use in patients remaining on VDZ. Secondary outcomes were safety and intention to treat steroid free remission rates in patients with active disease. All data were prospectively collected as part of routine clinical care. Baseline demographics, clinical scores (HBI or Partial Mayo), faecal calprotectin (FC), endoscopy and radiology at 3, 6 and 12 months was recorded where available. Active disease was defined as endoscopic or radiographic evidence of disease or FC >200 mcg/g. Clinical remission was defined as HBI Results 340 (137 UC and 203 CD) patients were included in the primary analysis with a median follow-up of 9.4 months. Hospitalisation rates per patient-year were 0.60, 0.67, 0.36 and 0.16 at baseline, 3, 6 and 12 months of treatment respectively. Total number of hospitalisations reduced by 52.5% from 204 (12 months prior to VDZ) to 97 (12 months after VDZ). Proportion of patients on concomitant steroids reduced from 39.7% to 16.7% (n=332), 8.1% (n=270), 9.3% (n=194) at 3, 6 and 12 months respectively. In patients with active CD (n=153, 75.4%) steroid free clinical and steroid free biochemical remission rates were; 54.4% and 30.2% at 3 months; 47.7% and 32.1% at 6 months; 28.6% and 33.9% at 12 months. In patients with active UC (n=112, 81.8%) steroid free clinical and steroid free biochemical remission rates were; 57.4% and 40.9% at 3 months; 51.6% and 39.1% at 6 months; 37.5% and 41.2% at 12 months. Our cohort received >2066 VDZ infusions, 2 (0.6%) patients developed infusion reactions, 9 (2.6%) patients developed serious infections and 17 (5.0%) serious adverse events. Conclusions VDZ is associated with reduced hospitalisation and steroid use over 1 year. Steroid free remission rates and safety profile is in keeping with the published literature.

Introduction There is evidence that biosimilar infliximab (BSI) has comparable efficacy and safety to originator infliximab (OI) and is significantly cheaper. ECCO guidelines suggest therapeutic drug monitoring (TDM) can help determine whether infliximab (IFX) should be continued or dose-adjusted during maintenance treatment of inflammatory bowel disease (IBD). Method Our unit developed a switch programme in order to take advantage of the cost savings associated with BSI. We identified patients established on OI as IBD maintenance therapy (n=76). Our IBD nurses counselled patients, gained their consent to switch from OI to BSI, and obtained IFX TDM samples. We audited the usefulness of IFX TDM and whether concomitant immunomodulation (IM) or pretreatment with hydrocortisone were associated with lower rates of antibodies to infliximab (ATI). Results 3 patients were excluded as their trough levels of IFX (TLI) were felt inaccurate due to the timing of the test. 73 were included: 16 (21.9%) had therapeutic TLI (3–7 µg/mL), 3 (4.12%) had high TLI (>7 µg/mL), 37 (50.68%) had low TLI (0.8–2.9 µg/ml) and 17 (23.3%) had TLI IFX TDM changed management in 46 (63%) patients: IFX was dose-optimised in 24 (32.9%) patients and discontinued in 14 (19.2%) others (7 were started on adalimumab or vedolizumab, and 7 stopped biological therapy altogether). 8 (10.9%) patients were re-staged with a view to stopping IFX. No changes were made in 27 (37%) patients: 16 (21.9%) had optimal TLI, 4 (5.5%) were in remission with only marginally suboptimal TLI and no ATI, and 7 (9.6%) had not yet had their IFX TDM reviewed by the MDT. Only one patient did not consent to switching from OI to BSI. 93.5% of patients continuing on IFX were switched from OI to BSI. All patients received some form of co-treatment in an attempt to reduce the development of ATI (table 1). Despite this, 41 (53.9%) patients had ATI. The mean duration of IFX therapy was 34.3 months overall, 33 months in those with ATI, and 35.8 months in those without ATI. Conclusion A switch programme facilitates cost savings, and is acceptable to patients if the rationale is properly explained. IFX TDM altered management in 63% of our patients and therefore should be incorporated in switch programmes. More than half of patients had ATI. This may be explained by the fact that patients had been on IFX for a prolonged time. In our cohort it appears that concomitant IM was better at preventing ATI than pretreatment with hydrocortisone. Disclosure of Interest None Declared

Menetrier disease is a rare disease characterised by hyperplasia of the gastric epithelium and large gastric folds. We present a case of a 58-year-old woman who was referred with iron deficiency anaemia, with a family history of a sibling who had undergone gastrectomy for presumed gastric malignancy. Endoscopy showed prominent gastric mucosal folds and biopsies showed hyperplastic gastric mucosa, with prominent foveolar hyperplasia suggestive of Menetrier disease. Further information about her brother’s diagnosis was sought, and it was found that his pathology after gastrectomy showed diffuse glandular hyperplasia also in keeping with Menetrier disease. Adult familial Menetrier disease has so far been a rarity in the literature—review elicits five previous cases of this presentation in siblings.

Background & Aims In the West, a substantial proportion of subjects with adenocarcinoma of the gastric cardia and gastroesophageal junction have no history of reflux. We studied the gastroesophageal junction in asymptomatic volunteers with normal and large waist circumferences (WCs) to determine if central obesity is associated with abnormalities that might predispose individuals to adenocarcinoma. Methods We performed a study of 24 healthy, Helicobacter pylori –negative volunteers with a small WC and 27 with a large WC. Abdominal fat was quantified by magnetic resonance imaging. Jumbo biopsy specimens were taken across the squamocolumnar junction (SCJ). High-resolution pH-metry (12 sensors) and manometry (36 sensors) were performed in upright and supine subjects before and after a meal; the SCJ was visualized fluoroscopically. Results The cardiac mucosa was significantly longer in the large WC group (2.5 vs 1.75 mm; P = .008); its length correlated with intra-abdominal (R = 0.35; P = .045) and total abdominal (R = 0.37; P = .034) fat. The SCJ was closer to the upper border of the lower esophageal sphincter (LES) in subjects with a large WC (2.77 vs 3.54 cm; P = .02). There was no evidence of excessive reflux 5 cm above the LES in either group. Gastric acidity extended more proximally within the LES in the large WC group, compared with the upper border (2.65 vs 4.1 cm; P = .027) and peak LES pressure (0.1 cm proximal vs 2.1 cm distal; P = .007). The large WC group had shortening of the LES, attributable to loss of the distal component (total LES length, 3 vs 4.5 cm; P = .043). Conclusions Central obesity is associated with intrasphincteric extension of gastric acid and cardiac mucosal lengthening. The latter might arise through metaplasia of the most distal esophageal squamous epithelium and this process might predispose individuals to adenocarcinoma.

Acid reflux produces troublesome symptoms (heartburn) and complications including esophagitis, Barrett's esophagus, and adenocarcinoma. Reflux occurs due to excessive and inappropriate relaxation of the lower esophageal sphincter. An important mediator of this is nitric oxide, high concentrations of which are generated within the lumen when swallowed saliva meets gastric acid. Saliva contains nitrite, derived from the enterosalivary recirculation of dietary nitrate, which is reduced to nitric oxide by gastric acid. The aim of this study was to investigate whether salivary nitrite contributes to dysfunction of the lower esophageal sphincter.In 20 volunteers, studies of gastro-esophageal function were performed on four separate days, following consumption of a standardized meal, with saliva nitrite concentrations modified differently each day by intra-oral nitrite infusion.The infusions produced an appropriate range in saliva nitrite concentrations, from below to well above the physiological range. The standardized meal induced expected physiological changes in gastro-esophageal function confirming the recordings were sensitive and robust. Esophageal acid exposure (primary outcome) was similar on each study day. Secondary outcomes, including number and duration of reflux events, rate of transient lower esophageal sphincter relaxations, lower esophageal sphincter pressure and rate of gastric emptying were also unaffected by variations in saliva nitrite concentration.Nitrite in swallowed saliva does not modify gastro-esophageal junction function or predispose to gastro-esophageal reflux. The wide range in saliva nitrite concentrations, the sensitivity of the physiological recordings and the number of subjects studied make it very unlikely that an effect has been missed.

Introduction Most pathology of the upper gastrointestinal tract now occurs close to the gastro-oesophageal squamo-columnar junction (SCJ). Studying the pathophysiology of this region even using high resolution pH, impedance and manometry is unreliable due to constant movement with respiration, swallowing and transient lower oesophageal sphincter relaxations. Aims and methods A technique is reported allowing continuous real-time monitoring of the position of the SCJ. It involves endoscopically clipping a magnet (2mm×1mm) to the SCJ and monitoring its position relative to a probe in the oesophago-gastric lumen. The latter has 26 Hall-Effect sensors mounted at 5mm spacing on a circuit board within a silicone tube. Results Bench studies : The recorded position of the magnet along the length of the probe was compared with its actual position. Accuracy was related to the distance between magnet and probe, orientation of the magnet relative to the probe and whether the magnet was anterior, posterior or lateral to the probe. Including all possible orientations of the magnet at or nearer than 10mm from the probe, the median accuracy along the length of probe was 2.4mm (IQR 2.1mm). The proportion of all possible orientations within 10mm of the probe giving an accuracy of ±10mm was 88.9%. In vivo studies : With simultaneous fluoroscopy, eight healthy subjects were asked to perform normal breathing, deep breathing, water swallows and finally advancement and retraction of probe over a 12cm segment. The position recorded by fluoroscopy and probe at each second interval were compared. The correlation co-efficient for all 224 position readings was 0.96 (95% CI: 0.89–0.96). No significant interference was observed when the probe was tested alongside high resolution pH and manometry. Conclusion Used in conjunction with high resolution pH, impedance and manometry, this technique will allow for the first time detailed studies at the squamo-columnar junction.

The proximal cardia region of the stomach has a high incidence of inflammation, metaplasia and neoplasia. It demonstrates less acid buffering following meals than the more distal stomach. Novel high definition pHmetry was employed to investigate acidity at the cardia under fasting conditions and in response to a meal.15 healthy subjects were studied. A custom-made 12-electrode pH catheter was clipped at the squamocolumnar junction with four electrodes recording proximal to and eight distal to the squamocolumnar junction. The most distal pH electrode was located at the catheter tip, and nine electrodes in the region of the squamocolumnar junction were 11 mm apart.The electrode situated in the cardia 5.5 mm distal to the squamocolumnar junction differed from all other intragastric electrodes during fasting in recording minimal acidity (pH4 = 2.2%) while all other intragastric electrodes recorded high intragastric acidity (pH4 =or39%) (p0.05). The cardia also differed from the rest of the stomach, showing a marked increase in acidity in response to the meal (from 2.2% fasting to 58.4% at 60-70 min after the meal; p0.05) while the electrodes distal to the cardia all showed a marked decrease in acidity (p0.05). These changes in acidity at the cardia following the meal caused the gastric acidity to extend 10 mm closer to the squamocolumnar junction.Whereas the rest of the stomach shows a marked fall in acidity on ingesting a meal, the cardia paradoxically increases in acidity to become the most acidic region throughout the postprandial period.

Acid reflux and its associated symptoms occur most frequently following the ingestion of a meal. This observation presented a dilemma as intragastric pH is at its least acidic following eating due to the buffering effect of the food. However, the observation by Fletcher et al that the proximal cardia region of the stomach escapes the buffering effect of the meal provided a rational explanation for the acidic nature of the postprandial refluxate.1 The zone of high acidity detected in the proximal stomach after a meal has been termed the acid pocket. The presence of the acid pocket has been confirmed by a substantial number of investigators and by a variety of different investigative techniques. The latter have included pH pull-through,2–4 multiple static pH electrodes3 and single photon emission CT (SPECT) of the stomach following intravenous injection of [99MTc]pertechnetate which is secreted by the acid-secreting cells of the gastric mucosa.5 It had been suggested that the acid pocket might represent only a film of acid lining the proximal stomach without any significant volume.6 In the current issue of Gut ( see page 441 ) Beaumont et al placed a catheter at the anatomical site of the acid pocket and aspirated 50–70 ml of gastric juice pH 1.7–2.5 during the postprandial period.7 They were also able to show that the SPECT imaging of …

Introduction The position of the squamo-columnar (SC) junction is constantly changing and this precludes accurate monitoring of acid exposure of the most distal oesophagus. The authors have developed a novel probe to allow continuous monitoring of the SC junction location. The method involves endoscopically clipping a small magnet (2 mm diameter and 1 mm thick) to the SC junction and monitoring its position relative to the probe comprising 26 Hall Effect sensors mounted at 5 mm spacing on a circuit board contained within a silastic tube (diameter 3.2 mm). The aim of the current study was to assess the accuracy of the system on the bench. Methods The accuracy was determined by comparing the recorded position of the magnet along the length of the probe with its actual position along the probe. This was assessed with the magnet in various rotations and orientations both anterior and posterior to the probe and various distances away from the probe. As the conductive property of Hall Effect sensors is dependent on temperature, bench studies were performed to assess effects of rising temperature on the system9s accuracy. The potential electro-magnetic interference of the locator probe with multi-channels pH probe (Synectics, UK) and solid state high resolution manometer (Synmed, UK) was also investigated. Results The accuracy was related to the distance between magnet and probe, orientation of the field of the magnet relative to the probe and whether the magnet was positioned anterior, posterior or lateral to the probe. Greatest accuracy was with the magnet anterior to the probe and its magnetic field perpendicular to the length of probe with position errors of ±2.3, ±2.9, ±2.7 mm at 5, 10 and 15 mm distance from the probe respectively. The poorest accuracy was with the magnet lateral to the probe and its magnetic field horizontal to the line of the probe, with position errors of ±2.3, ±7.1, ±7.9 mm at 5, 10 and 15 mm distance from the probe respectively. Over 95% of all studied orientations, an accuracy of less than ±10 mm was achieved up to a distance of 15 mm between the magnet and the probe. Increase in temperature from 20°C to 37°C did not affect accuracy of the system even though it reduces the magnetic field strength. The manometer had a minor impact on the system9s accuracy due to metallic properties of its sensors but no interference was seen with the pH probe. Conclusion This technique should allow monitoring of the location of the SC junction to an accuracy greater than that of currently available high resolution manometry or multiple pH sensor devices.

Introduction The gastric cardia is an important site of pathology with a high incidence of inflammation, metaplasia and neoplasia. However the area is poorly understood and cardia mucosa may itself be pathological. Previous autopsy studies show a near absence of cardia epithelium in neonates and an increase in length with age. Aims: To1 investigate whether parietal cell density in the columnar mucosa at the squamocolumnar junction (SCJ) changes with age and2 determine the association of parietal cell density with distal oesophageal acid exposure. Methods 25 healthy volunteers (14 males, 5 Helicobacter pylori positive) were studied. Biopsies were taken from the macroscopic SCJ, 1 cm distal to the SCJ, gastric body and antrum. Biopsies were embedded in paraffin and 5-micron sections cut for immunohistochemistry. Parietal cells were stained and visualised using a standardised monoclonal anti-H+/K+ATPase antibody. Slides were digitally scanned and uploaded onto a slide server. An image analysis programme was used to quantify parietal cell density expressed as intracellular positive pixels. The average parietal cell density in a minimum of four sections of columnar mucosa per slide was reported as the percentage of the total cells per section. In 20 subjects pH studies were performed before and after a standardised meal. Acid exposure was calculated as per cent time pH Results There was a significant negative correlation between age and parietal cell density in the columnar mucosa at the level of the SCJ (R=−0.530, p=0.008). There was no significant correlation between age and parietal cell density 1 cm distal to the SCJ (R=0.153, p=0.5), in the gastric body (R=0.386, p=0.08) or antrum (R=0.117, p=0.6). In the HP negative subgroup, parietal cell density at the SCJ of volunteers under 30 years old was significantly greater than those aged 30 years and over (6.8% vs 0.4%, p=0.05). In contrast, gastric body parietal cell density was lower in the younger group (30.0% vs 34.5%, p=0.019). There was no significant correlation between distal oesophageal acid exposure and parietal cell density at the SCJ (R=0.223, p=0.3). Conclusion Parietal cell density decreases with age in the columnar mucosa at the SCJ. This effect appears to be localised to the SCJ and is not seen 1 cm distal to this or within the stomach. There was no correlation between parietal cell density and acid exposure. These results support cardiac mucosa being acquired and due to mechanisms other than traditional gastro-oesophageal reflux.