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 and aims Treatment adherence is key to the efficacy of exclusive enteral nutrition (100% EN) in active Crohn’s disease (CD), but there are no biomarkers to objectively estimate this. We explored faecal parameters as biomarkers of compliance with 100% EN, and subsequently developed and validated the Glasgow Exclusive Enteral Nutrition Index of Compliance (GENIE). Methods Healthy adults replaced all (100% EN) or part (85% EN, 50% EN, 25% EN) of their diet with a formula for 7 days. Faecal pH, water content, short chain fatty acids and branched chain fatty acids (BCFAs) were measured before (D0) and after (D7) each intervention. Optimal biomarkers and threshold values were derived using receiver operating characteristic curve analyses and machine learning to develop the GENIE. The GENIE was then validated in 30 CD children, during and after 100% EN. Results Sixty-one adults were recruited. D7 faecal pH and the ratios of BCFAs to either acetate or butyrate performed the best to differentiate between patients on 100% EN from <100% EN. Two models were generated; one including faecal metabolites (Laboratory GENIE, L-GENIE; sensitivity, specificity, and positive predictive value (PPV) of 88%, 94%, and 92%) and a second one (Clinical Genie, C-GENIE) which considers only faecal pH (sensitivity, specificity and PPV of 84%, 86% and 81%). Validation of GENIE in CD children found that C-GENIE outperformed L-GENIE, producing a sensitivity, specificity and PPV of 85%, 88% and 88%, respectively. Conclusions GENIE can help predict adherence to 100% EN and may complement current conventional dietary assessment.
Background Treatment adherence is key to the efficacy of exclusive enteral nutrition (100% EN) in active Crohn’s disease (CD), but there are currently no biomarkers to objectively support this. We explored faecal parameters as putative biomarkers of compliance with 100% EN, and subsequently developed and validated the Glasgow Exclusive enteral Nutrition Index of compliancE (GENIE). Methods Healthy adults replaced all (100% EN) or part (85% EN, 50% EN and 25% EN) of their habitual diet with a polymeric formula (Modulen IBD, Nestle©) for 7 days. Faecal pH, Bristol stool chart score, water content, short chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) were measured before (D0) and after (D7) each intervention. Faecal biomarkers and threshold values for group assignments were derived using receiver operating characteristic (ROC) curve analyses and machine learning algorithm to develop the GENIE. The GENIE was validated in 30 children with CD, during 100% EN and 4 weeks after return to normal diet. Results Sixty-one (31 females) adults (mean age [SD]: 25.9 [4.3] years) were recruited. D7 faecal pH and the ratios of BCFAs to either acetate or butyrate performed the best to differentiate between patients on 100% EN from <100% EN. A ratio of isobutyrate (IC4) to C2> 0.039 and a ratio of IC4 to C2+C4> 0.035 both produced a sensitivity, specificity, and positive predictive value (PPV) of 92%, 83% and 79%, respectively to differentiate between 100% EN vs. all other groups. A faecal pH> 8.0 produced a sensitivity, specificity and PPV of 84%, 86% and 81%, respectively. Findings using machine learning were better than those using ROC curve analysis. Two models were generated; one which includes all faecal metabolites (Laboratory GENIE, L-GENIE), and which produced a sensitivity, specificity and positive predictive value (PPV) of 88%, 94%, and 92%, respectively and a second one (Clinical GENIE, C-GENIE) which considers only faecal pH as the input data and which produced a sensitivity, specificity and PPV of 84%, 86% and 81% (Figure 1). Validation of GENIE models in children with CD found that C-GENIE outperformed L-GENIE, producing a sensitivity, specificity and PPV of 85%, 88% and 88%, respectively (Table 1). Figure 1: Glasgow Exclusive Enteral Nutrition Index of Compliance. Table 1: Results of validation of the GENIE model in children with Crohn’s disease (CD) during treatment with 100% EN and after return to unrestricted diet and compared to the development cohort of healthy adults. Conclusion GENIE can predict adherence to 100% EN in patients with CD in both the clinical and research settings. It may complement conventional dietary assessment and inform clinical decision, especially in patients who are not in remission.
Background There is increasing recognition of ‘holistic’ wellbeing as a key target in the management of IBD. Patient-reported outcomes (PROs) capture the impact of IBD on social, emotional and general wellbeing. Recently, regulatory bodies such as FDA/EMA mandates the study of PROs in interventional clinical trials. However, the role of PROs has never been investigated as a potential end-point in translational scientific research in IBD Methods CUCQ32 is a 32-question form that captures well-being of IBD patients including aspects of fatigue/anxiety/sexual/emotional health – score range from 0-272 (↑score correlating with worse quality QoL). We prospectively captured CUCQ32-PROs in our on-going MUSIC (Cohort 1) and GI-DAMPs (Cohort 2) IBD biomarker studies (www.musicstudy.uk) based in Edinburgh, Glasgow and Dundee (2018-present, ~total n=700 patients recruited). MUSIC is a prospective 12-month longitudinal study (over 5 time points) following active IBD patients in response to current drug treatment whilst GI-DAMPs is a cross-sectional study across IBD disease activity at one-time point. CUCQ32-PROs has been recorded since 2021 with 163 data-points captured. CUCQ32 were filled independently by patients. Results In IBD, CUCQ32-PROs scores were high with medians of 113 (IQR of 67.5-152.2) and 132 (IQR of 91-179) in Cohorts 1 and 2 respectively. In MUSIC Cohort 1, CUCQ32 decreased in response to treatment 113→62→58→45→30 over 3-monthly intervals. CUCQ32 scores are significantly correlated to clinical indices of disease activity, SCCAI for UC (Cohort 1, p=0.003/Cohort 2, p<0.001) and HBI for CD (Cohort 1, p<0.001/Cohort 2, p<0.001). Of interest, no correlation was observed with CRP and faecal calprotectin. Notably, although overall CUCQ32 scores associated with active disease, those deemed in ‘clinical remission’ continue to have high score (median 154 vs. 87 respectively, p=0.06). High CUCQ32 scores were observed even in those achieving complete mucosal healing (defined as either endoscopic SESCD or UCEIS score of 0) from longitudinal prospective endoscopic follow-up; median decrease from 116 (baseline) to 55 (6-months SESCD/UCEIS =0), paired data available in n=14 patients. There is no statistical correlation with endoscopic mucosal healing (p=0.6; in 34 patients). Conclusion Although patient wellbeing improved with medical treatment in IBD and PROs are correlated with clinical indices of IBD activity, high CUCQ32 (thereby poor quality of life) scores were observed in traditional categorisation of ‘clinical remission’. This suggests a far-reaching impact of IBD beyond gut-related signs/symptoms. Our current work incorporates PROs into our scientific biomarker studies and molecular analyses) and will be the first in IBD, to our knowledge.
Aim The impact of appendicectomy on the natural history of ulcerative colitis (UC) is unclear. We aimed to assess our cohort of patients with UC to examine the incidence of appendicectomy and association with disease severity. We also examined association of social deprivation with disease severity. Method Patients with UC in the health board region were identified by the Gastroenterology consultants. These were divided into moderate-severe (defined as current biologic therapy) and mild-moderate disease (no or 5-ASA therapy only). Two cohorts were sex-matched on a 1:1 basis. Demographic data was identified by review of the patients’ Electronic Patient Record (EPR) and the Scottish Index of Multiple Deprivation 2020. The EPR was reviewed for evidence of previous appendicectomy. Results A total of 664 patients were identified: 328 mild-moderate and 336 moderate-severe. 145 patients (44%) in the mild-moderate group and 145 patients (43%) in the moderate-severe group were female. The majority of patients had left-sided disease. There were no significant differences in smoking status. Rates of appendicectomy in the moderate to severe group were double that of the mild to moderate group (8 v 4; p= .25). Mild-moderate disease was associated with increased social deprivation (X2 (2, N = 664) = 10.60, p = .03) (Fig. 3). Conclusions There were double the number of appendicectomies in the mild-moderate cohort, however the relationship between severity and previous appendicectomy was not significant. Disease severity appears to be negatively associated with social deprivation. Further collaborative work across Scotland is planned.
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
Background Intravenous (IV) infliximab (IFX) monotherapy is associated with significant loss of response. Therapeutic drug monitoring shows an association with low serum trough drug levels and development of anti-IFX antibodies. Combination therapy with immunomodulators is not always possible, and IFX dose escalation leads to higher drug costs and time pressure on infusion units. Both approaches have raised heightened patient safety concerns due to the Covid-19 pandemic. Subcutaneous (SC) IFX pharmacokinetics lead to improved drug trough levels, which could lead to better clinical outcomes. Methods The NHS Greater Glasgow and Clyde biologics database was used to identify selected patients currently treated with IV IFX for IBD for suitability for SC switch. Patients were contacted to allow informed choice to opt in or out of switch. Baseline clinical data was collected, and patients were reviewed at week 8 and week 24 for assessment of clinical disease activity scores, IFX trough levels/anti-drug antibody levels, and faecal calprotectin. Patient experience outcomes were assessed using a quality of life questionnaire (CUCQ-8). Results 31 patients consented to switch; F:M = 17:14. The majority of patients (16) had Crohn’s disease, with 13 with UC and 2 IBDU. Mean duration of disease was 9.1 years and duration of prior IV therapy was 3.3 years. 28 patients were reviewed at week 8 and 24 at week 24. At week 24, 71% of patients were in clinical remission (Harvey-Bradshaw index score <5 or partial Mayo score <2), 96% had CRP <5 mg/Land 87% had FCP <250µg/g. 21% of patients had subtherapeutic IFX trough levels at baseline, all had increased by week 8 and there were no subtherapeutic levels measured by week 24. One patient had detectable antibodies at week 24, compared with 9 patients at baseline. Three patients required oral steroid therapy during the 24-week follow up period. There were no hospital admissions, significant infections or adverse reactions within the cohort. 15 patients submitted CUCQ-8 scores, of these 7 patients’ scores had worsened at week 8 but by week 24 13/15 were stable or improved compared to baseline. Conclusion Switching from IV to SC infliximab is welcomed by most patients. The efficacy, tolerability, increased drug level and safety which has previously been demonstrated is reproduced in our cohort. This study is the first to explore patient experience outcomes. The finding of initial worsening of the CUCQ-8 score, but overall improvement by week 24 opens further opportunity for engaging patient involvement in switch programmes.
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