Right Or Left in COLonoscopy (ROLCOL)? A Randomized Controlled Trial of Right- versus Left-Sided Starting Position in Colonoscopy.

OBJECTIVES: Colonoscopy is technically challenging and can cause discomfort for patients. We aimed to test whether right-sided starting position for colonoscopy would result in shorter procedure time and greater patient comfort when compared with conventional left-sided starting position. METHODS: We conducted a randomized controlled trial in which patients were randomized to begin in either the right- (RL) or conventional left-lateral (LL) position. One hundred and sixty-three adult patients undergoing scheduled colonoscopy were stratified by age, gender, body mass index, and experience of the endoscopist. Patients were then randomized 1:1 in permuted blocks. The primary outcome measure was time to cecal intubation and secondary outcome measures included patient comfort that was evaluated by visual analog comfort scale. RESULTS: Median time to reach the cecum was quicker when colonoscopy began with patients positioned RL rather than LL (P=0.0078). Moreover, patients found RL more comfortable than LL (P=0.02). Multiple linear regression confirmed starting position in colonoscopy as an independent determinant of time to reach the cecum (P=0.007). Women and those who had previously undergone abdominal surgery gained the greatest benefit from right-sided positioning (RL vs. LL: 498 vs. 824 s; P=0.03 and 498 vs. 797 s; P=0.006, respectively). CONCLUSIONS: Our study reveals that right-sided positioning at the start of colonoscopy results in more comfortable and quicker procedures. Of the factors identified by multiple linear regression to independently have an impact on time to reach the cecum, only starting position is modifiable. Right-sided starting position may therefore be of benefit in colonoscopy, in particular for women and patients who have previously undergone abdominal surgery.

IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH): a study protocol for a multicentre, randomised, placebo-controlled trial to explore the potential benefits of canakinumab in the treatment of alcoholic hepatitis.

BACKGROUND: Alcohol consumption causes a spectrum of liver abnormalities and leads to over 3 million deaths per year. Alcoholic hepatitis (AH) is a florid presentation of alcoholic liver disease characterized by liver failure in the context of recent and heavy alcohol consumption. The aim of this study is to explore the potential benefits of the IL-1ß antibody, canakinumab, in the treatment of AH. METHODS: This is a multicentre, double-blind, randomised placebo-controlled trial. Participants will be diagnosed with AH using clinical criteria. Liver biopsy will then confirm that all histological features of AH are present. Up to 58 participants will be recruited into two groups from 15 centres in the UK. Patients will receive an infusion of Canakinumab or matched placebo by random 1:1 allocation. The primary outcome is the difference between groups in the proportion of patients demonstrating histological improvement and will compare histological appearances at baseline with appearances at 28 days to assign a category of "improved" or "not improved". Patients with evidence of ongoing disease activity will receive a second infusion of canakinumab or placebo. Participants will be followed up for 90 days. Secondary outcomes include mortality and change in MELD score at 90 days. DISCUSSION: This phase II study will explore the benefits of the IL-1ß antibody, canakinumab, in the treatment of AH to provide proof of concept that inhibition of IL-1ß signalling may improve histology and survival for patients with AH. TRIAL REGISTRATION: EudraCT 2017-003724-79 . Prospectively registered on 13 April 2018.

Obesity in acute alcoholic hepatitis increases morbidity and mortality.

BACKGROUND: Alcohol and obesity synergise to increase the risk of liver-related mortality. We examined the influence of adiposity on clinical outcomes in alcoholic hepatitis (AH) and the underlying inflammatory crosstalk between adipose tissue (AT) and the liver. METHODS: A cohort of 233 patients with AH from the UK and USA provided data to analyse the effects of obesity in AH. Body mass index was corrected for the severity of ascites, termed cBMI. Inflammatory and metabolic profiling was undertaken by proteome analysis of human serum samples. The effect of alcohol on adipose tissue and CXCL11 expression was studied in 3 T3-derived adipocytes and in mice using the high-fat diet-plus-binge ethanol model. FINDINGS: Obesity was common amongst patients with AH, seen in 19% of individuals. Obesity (HR 2.22, 95%CI 1.1-4.3, p = .022) and underweight (HR 2.38, 1.00-5.6, p = .049) were independently associated with mortality at 3 months. Proteome analysis demonstrated multiple metabolic and inflammatory factors differentially expressed in obese AH verse lean AH, with CXCL11 being the most elevated factor in obese AH. In vitro analysis of cultured adipocytes and in vivo analysis of mouse models showed that alcohol induced CXCL11 expression in AT, but not in liver. INTERPRETATION: Obesity is common in AH and associated with a greater than two-fold increase in short-term mortality. Obese AH is associated with a different inflammatory phenotype, with the greatest elevation in CXCL11. These data confirm that adiposity is clinically important in acute alcohol-related liver disease and illustrate the adipose-liver inflammatory axis in AH. FUND: This work was supported in part by an EASL Sheila Sherlock Physician Scientist Fellowship. The funder played no role in gathering or analysing data or writing the manuscript. This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.