Armstrong, David

Abstract Background Celiac disease (CeD) is a T-cell mediated enteropathy driven by gluten in genetically susceptible individuals. Mucosal inflammation persists for years even when treated with a gluten-free diet (GFD). Although patients may be advised to increase dietary fibre, some fibres are poorly tolerated leading, potentially, to suboptimal fibre intake and hampering dietary recommendations. Aims Our project aims to investigate whether and how the supplementation of two fibre types with distinct functional profiles affects the recovery of gluten-immunopathology in a mouse model of gluten-sensitivity. We hypothesize that: (1) HylonVII, but not inulin, accelerates mucosal recovery by increasing microbial carbolytic activity and production of short-chain fatty acids (SCFA); (2) fibre intake is decreased in CeD patients, leading to decreased SCFA production. Methods NOD-DQ8 mice were immunized to gliadin and then placed on a gluten-containing diet. Three weeks later, mice were returned to GFD supplemented with or without HylonVII or inulin to 15% total fibre, for 6, 10, or 12 weeks. Recovery from gluten-induced pathology was evaluated by counting CD3+ intraepithelial lymphocytes (IELs) in villi tips and measuring villus-to-crypt (V/C) ratios in the small intestine. Adult CeD patients (newly diagnosed n=6 and GFD-treated n=7) and healthy controls (n=5) completed a food frequency questionnaire (Victoria DQES v2) and provided fecal samples for evaluation of SCFA production. Fecal SCFA were measured with targeted single ion monitoring gas-chromatography/mass-spectrometry (Agilent) as markers of fibre metabolism. Results In gluten immunized mice, 3 weeks of wheat diet led to increased CD3+ IEL counts and decreased V/C ratios (pampersand:003C0.01), which remained abnormal after 6 weeks of GFD. Mice consuming GFD+inulin, but not HylonVII, normalized CD3+ IELs and V/C ratios, had higher fecal SCFAs (pampersand:003C0.05) (primarily acetate), and a higher carbolytic-proteolytic metabolite ratio (pampersand:003C0.05) compared with mice consuming a GFD alone for six weeks. Only 1/7 patients with CeD on GFD met the minimum recommendation for fibre intake (25 g/day, Health Canada), compared with 5/11 participants on gluten-containing diets. SCFA production was impaired in active but not in treated CeD patients (2563 vs 3744 μg/g, pampersand:003C0.01). Conclusions In gluten-immunized NOD-DQ8 mice, GFD+inulin accelerates mucosal recovery, which is associated with increased fecal SCFA. In our pilot clinical data, patients on a GFD did not meet the recommendation for fibre intake although they were capable of metabolizing fibre to produce SCFA that could facilitate mucosal recovery. Together these results suggest that CeD on GFD may benefit from increasing fibre, such as inulin, during the GFD. Funding Agencies CIHRCeliac Canada

Performance of endoscopic procedures is associated with a risk of infection from COVID-19. This risk can be reduced by the use of personal protective equipment (PPE). However, shortage of PPE has emerged as an important issue in managing the pandemic in both traditionally high and low-resource areas. A group of clinicians and researchers from thirteen countries representing low, middle, and high-income areas has developed recommendations for optimal utilization of PPE before, during, and after gastrointestinal endoscopy with particular reference to low-resource situations. We determined that there is limited flexibility with regard to the utilization of PPE between ideal and low-resource settings. Some compromises are possible, especially with regard to PPE use, during endoscopic procedures. We have, therefore, also stressed the need to prevent transmission of COVID-19 by measures other than PPE and to conserve PPE by reduction of patient volume, limiting procedures to urgent or emergent, and reducing the number of staff and trainees involved in procedures. This guidance aims to optimize utilization of PPE and protection of health care providers.

Introduction Diarrhoea is a frequent concern in the intensive care unit (ICU) and is associated with prolonged mechanical ventilation, increased length of ICU stay, skin breakdown and renal dysfunction. However, its prevalence, aetiology and prognosis in the critically ill have been poorly studied. The primary objectives of this study are to determine the incidence, risk factors and consequences of diarrhoea in critically ill adults. The secondary objectives are to estimate the incidence of Clostridium difficile- associated diarrhoea (CDAD) in ICU patients and to validate the Bristol Stool Chart and Bliss Stool Classification System characterising bowel movements in the ICU. Our primary outcome is the incidence of diarrhoea . Our secondary outcomes include: CDAD, ICU and hospital mortality and ICU and hospital length of stay. Methods and analysis This international prospective cohort study will enrol patients over 10 weeks in 12 ICUs in Canada, the USA, Poland and Saudi Arabia. We will include all patients 18 years of age and older who are admitted to the ICU for at least 24 hours and follow them daily until ICU discharge. Our primary outcome is the incidence of diarrhoea based on the WHO definition, during the ICU stay. Our secondary outcomes include: CDAD, ICU and hospital mortality and ICU and hospital length of stay. We will use logistic regression to identify factors associated with diarrhoea (as defined using WHO criteria) and the kappa statistic to measure agreement on diarrhoea rates between the WHO definition and the Bristol Stool Chart and Bliss Stool Classification System. Ethics and dissemination The protocol has been approved by the research ethics board of all participating centres. The diarrhoea interventions, consequences and epidemiology in the intensive care unit (DICE-ICU) study will generate evidence about diarrhoea and its frequency, predisposing factors and consequences, to inform critical care practice and future research. Lay summary Diarrhoea is a frequent clinical problem for hospitalised patients including those who are critically ill in the ICU. Diarrhoea can cause complications such as skin damage, dehydration and kidney problems. It is not clear how common diarrhoea is in the ICU, the factors that cause it or the best way for clinicians to assess it. The DICE-ICU study is an international prospective observational study to examine the frequency, risk factors and outcomes of diarrhoea during critical illness.