Sophie Restellini

Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding.

There exists considerable practice variation and little evidence to guide red blood cell (RBC) transfusion in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). Studies in other critically ill cohorts suggest associations between transfusions and adverse patient outcomes.

Systematic review with meta-analysis: placebo rates in induction and maintenance trials of Crohn's disease

Minimising placebo response is essential for drug development.

Co-existence of non-alcoholic fatty liver disease and inflammatory bowel disease: A review article

Emerging data have highlighted the co-existence of non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease; both of which are increasingly prevalent disorders with significant complications and impact on future health burden. Cross-section observational studies have shown widely variable prevalence rates of co-existing disease, largely due to differences in disease definition and diagnostic tools utilised in the studies. Age, obesity, insulin resistance and other metabolic conditions are common risks factors in observational studies. However, other studies have also suggested a more dominant role of inflammatory bowel disease related factors such as disease activity, duration, steroid use and prior surgical intervention, in the development of NAFLD. This suggests a potentially more complex pathogenesis and relationship between the two diseases which may be contributed by factors including altered intestinal permeability, gut dysbiosis and chronic inflammatory response. Commonly used immunomodulation agents pose potential hepatic toxicity, however no definitive evidence exist linking them to the development of hepatic steatosis, nor are there any data on the impact of therapy and prognosis in patient with co-existent diseases. Further studies are required to assess the impact and establish appropriate screening and management strategies in order to allow early identification, intervention and improve patient outcomes.

Collagen proportionate area correlates to hepatic venous pressure gradient in non-abstinent cirrhotic patients with alcoholic liver disease

AIM To explore the relationship between collagen proportionate area (CPA) and portal hypertension-related clinical manifestations in alcoholic liver disease (ALD). METHODS Retrospective study with chart review of patients with ALD adressed to our center between January 2012 and December 2013 for a transjugular liver biopsy (TJLB) and hepatic hemodynamic study. Patients were included if they met the following criteria: (1) Medical indication for a liver biopsy in the setting of ALD; (2) recent (< 15 d) clinical, radiological, endoscopic and biological data available; and (3) estimated follow-up of at least 6 mo. Liver tissue from cirrhotic subjects obtained from transjugular liver biopsies was stained with PicroSirius red and computer-assisted digital image analysis to determine fibrosis density using CPA was performed. RESULTS We included 61 patients with alcoholic ALD, subdivided in 41 active alcohol drinkers and 20 durably abstinent patients. Nine healthy liver donors served as controls. Mean CPA in patients with ALD was 7.1%, with no difference between active drinkers and abstinent patients (P = 0.17). Using a fibrosis density cutoff of 5%, we observed a positive correlation between high fibrosis density and the hepatic venous pressure gradient (HVPG) only in active drinkers (P = 0.02). At 12-mo of follow-up, in the group of active alcohol drinkers, patients reaching a composite outcome showed a higher HVPG value as compared to those who did not (18.5 mmHg vs 14.5 mmHg P < 0.04) whereas CPA values were similar (6.9% vs 11%, P = 0.23). CONCLUSION In active alcoholic ALD, CPA correlates to portal pressure but only HVPG predicts clinical events, pointing to the role of alcohol as a modulator of portal hypertension.

Polyethylene glycol versus sodium picosulfalte bowel preparation in the setting of a colorectal cancer screening program

BACKGROUND Adequate bowel preparation for colonoscopy is an important predictor of colonoscopy quality. OBJECTIVE To determine the difference in terms of effectiveness between different existing colon cleansing products in the setting of a colorectal cancer screening program. METHODS The records of consecutive patients who underwent colonoscopy at the Montreal General Hospital (Montreal, Quebec) between April 2013 and April 2014 were retrospectively extracted from a dedicated electronic digestive endoscopic institutional database. RESULTS Overall, 2867 charts of patients undergoing colonoscopy were assessed, of which 1130 colonoscopies were performed in a screening setting; patients had adequate bowel preparation in 90%. Quality of preparation was documented in only 61%. Bowel preparation was worse in patients receiving sodium picosulfate (PICO) alone compared with polyethylene glycol, in a screening setting (OR 0.3 [95% CI 0.2 to 0.6]). Regardless of the preparation type, the odds of achieving adequate quality cleansing was 6.6 for patients receiving a split-dose regimen (OR 6.6 [95% CI 2.1 to 21.1]). In multivariable analyses, clinical variables associated with inadequate bowel preparation in combined population were use of PICO, a nonsplit regimen and inpatient status. The polyp detection rate was very high (45.6%) and was correlated with withdrawal time. CONCLUSION Preparation quality needs to be more consistently included in the colonoscopy report. Split-dose regimens increased the quality of colon cleansing across all types of preparations and should be the preferred method of administration. Polyethylene glycol alone provided better bowel cleansing efficacy than PICO in a screening setting but PICO remains an alternative in association with an adjuvant.

Effect of hydrosoluble vitamin E on erythrocyte membrane lipid composition in patients with advanced cirrhosis: An open‐label pilot trial

Deficiency in vitamin E, a natural antioxidant, participates in abnormal erythrocyte membrane lipids, structural alterations and hemolysis in advanced cirrhosis. Poor absorption of fat‐soluble vitamins limits full correction of deficiency with standard formulations in cirrhosis with cholestasis. The aim of the present study was to examine safety and effects of tocofersolan, a water‐soluble derivative of vitamin E, on erythrocyte membrane lipids and anemia in patients with biopsy‐proven advanced cirrhosis, vitamin E deficiency and hemolysis.

Therapeutic Drug Monitoring With Ustekinumab and Vedolizumab in Inflammatory Bowel Disease

In patients with Crohns disease (CD) and ulcerative colitis (UC), the use of therapeutic drug monitoring (TDM) with TNF-α antagonists has led to a personalized approach to optimize treatment and has been shown to be cost-effective. The utility of this TDM-based personalized approach for novel biologic agents, which target different inflammatory pathways, is unclear. Commercial assays for ustekinumab (UST) and vedolizumab (VDZ) are available, but there is little available guidance for clinicians regarding the use of TDM with these drugs. Although there is limited evidence for definitive threshold concentrations for UST and VDZ, this review highlights the available literature on the pharmacokinetics of these medications, the association of clinical and endoscopic outcomes with drug concentrations, and the clinical utility of TDM to guide treatment decisions.

Therapeutic Drug Monitoring Guides the Management of Crohn’s Patients with Secondary Loss of Response to Adalimumab

Background Managing loss of response (LOR) in Crohns disase (CD) patients remains challenging. Compelling evidence supports therapeutic drug monitoring (TDM) to guide management in patients on infliximab, but data for other biologics are less robust. We aimed to asses if empiric dose escalation led to improved clinical outcome in addition to TDM-guided optimization in CD patients with LOR to adalimumab (ADA). Methods Retrospective chart review of patients followed between 2014 and 2016 at McGill IBD Center with index TDM for LOR to ADA was performed. Primary outcomes were composite remission at 3, 6, and 12 months in those with empiric adjustments versus TDM-guided optimization. Results There were 104 patients (54.8% men) who were included in the study. Of this group, 81 patients (77.9%) had serum level (SL) ≥5µg/ml at index TDM with a median value of 12µg/ml (IQR 6.1-16.5). There were 10 patients (9.6%) who had undetectable SL with high anti-ADA antibodies and 48 (46.2%) received empiric escalation. TDM led to change in treatment in 58 patients (55.8%). Among them, 28 (48.3%) had discontinued ADA, 12 (21.7%) had addition of immunomodulator or steroid, and 18 (31%) had ADA dose escalation. Empiric dose escalation before TDM-based optimization was not associated with improved outcomes at 3, 6, and 12 months, irrespective of SL levels. Clear SL cutoff associated with composite remission was not identified. Conclusions Our data do not support empiric dose adjustment beyond that based on the result of the TDM in patients with LOR to ADA. TDM limits unnecessary dose escalation and provides appropriate treatment strategy without compromising clinical outcomes. 10.1093/ibd/izy044_video1izy044.video15768828880001.

Screening for Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Diseases: A Cohort Study Using Transient Elastography

Background Inflammatory bowel disease (IBD) patients may be at risk for nonalcoholic fatty liver disease (NAFLD) due to chronic inflammation, hepatotoxic drugs, and alteration of the gut microbiota. Prospective data using accurate diagnostic methods are lacking. Methods We prospectively investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography (TE) with associated controlled attenuation parameter (CAP) in IBD patients as part of a routine screening program. NAFLD was defined as CAP ≥248 dB/m. Significant liver fibrosis (stage 2 or higher out of 4) was defined as TE measurement ≥7.0 kPa. Predictors of NAFLD and significant liver fibrosis were determined by logistic regression analysis. Results A total of 384 patients (mean age 42.4 years, 45.0% male, 64.6% with Crohns disease) with no significant alcohol intake were included. Prevalence of NAFLD and significant liver fibrosis was 32.8% and 12.2%, respectively. Independent predictors of NAFLD were older age (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.15-1.82), higher body mass index (BMI; aOR, 1.31; 95% CI, 1.20-1.42) and higher triglycerides (aOR, 1.45; 95% CI, 1.01-2.09). Significant liver fibrosis was independently predicted by older age (aOR, 1.38; 95% CI, 1.12-1.64) and higher BMI (aOR, 1.14; 95% CI, 1.07-1.23). Extrahepatic diseases were more common in IBD patients with NAFLD compared with those without, namely chronic kidney disease (10.3 vs 2.3%; P < 0.001) and cardiovascular diseases (11.3 vs 4.7%; P = 0.02). Conclusions NAFLD diagnosed by TE with CAP is a frequent comorbidity in IBD patients and is associated with extrahepatic diseases. Noninvasive screening strategies could help early diagnosis and initiation of interventions, including weight loss, correction of dyslipidemia, and linkage to care. 10.1093/ibd/izy200_video1izy200.video15794817619001.

Systematic review and meta-analysis of colon cleansing preparations in patients with inflammatory bowel disease

AIM To performed a systematic review and meta-analysis to determine any possible differences in terms of effectiveness, safety and tolerability between existing colon-cleansing products in patients with inflammatory bowel disease. METHODS Systematic searches were performed (January 1980-September 2016) using MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge for randomized trials assessing preparations with or without adjuvants, given in split and non-split dosing, and in high (> 3 L) or low-volume (2 L or less) regimens. Bowel cleansing quality was the primary outcome. Secondary outcomes included patient willingness-to-repeat the procedure and side effects/complications. RESULTS Out of 439 citations, 4 trials fulfilled our inclusion criteria (n = 449 patients). One trial assessed the impact of adding simethicone to polyethylene glycol (PEG) 4 L with no effect on bowel cleansing quality, but a better tolerance. Another trial compared senna to castor oil, again without any differences in term of bowel cleansing. Two trials compared the efficacy of PEG high-volume vs PEG low-volume associated to an adjuvant in split-dose regimens: PEG low-dose efficacy was not different to PEG high-dose; OR = 0.84 (0.37-1.92). A higher proportion of patients were willing to repeat low-volume preparations vs high-volume; OR = 5.11 (1.31-20.0). CONCLUSION In inflammatory bowel disease population, PEG low-volume regimen seems not inferior to PEG high-volume to clean the colon, and yields improved willingness-to-repeat. Further additional research is urgently required to compare contemporary products in this population.