Colonic cytomegalovirus DNA detection by polymerase chain reaction does not influence outcomes in inflammatory bowel disease and immunosuppressed cohorts.

BACKGROUND AND AIM: Cytomegalovirus (CMV) colitis is associated with negative outcomes in inflammatory bowel disease (IBD) and immunosuppressed cohorts and therefore requires timely recognition for appropriate management. We aimed to evaluate the diagnostic tools for CMV colitis and their associations with clinical outcomes. METHODS: A retrospective cohort study of patients in a metropolitan health service with colonic samples analysed for CMV between 2012 and 2022, stratified into IBD and non-IBD groups, was performed. The main outcome measures were the prevalence of positive and negative results for each CMV test, as well as need for colectomy, use of antiviral and hospital length of stay. RESULTS: Five hundred eighty-two biopsies from 418 patients were included; the median age was 36 years (interquartile range, 24-52 years) and 223 (53.3%) were men. Four hundred sixty-one (79.2%) biopsies were from patients with IBD and 121 (20.8%) were from those without IBD. There were similar proportions of positive CMV histology (IBD 5.9% and non-IBD 7.4%) and tissue CMV polymerase chain reaction (PCR) in the two groups (IBD 5.6% and non-IBD 5.0%), but within each group, results were discordant. Positive CMV histology was significantly associated with need for colectomy in the IBD group, while positive tissue CMV PCR was not. Positive CMV histology, and tissue and serum CMV PCR were all significantly associated with antiviral use. Positive serum CMV PCR was significantly associated with colectomy. CONCLUSIONS: Histopathology remains the most predictive tool in assessing CMV colitis, while qualitative tissue CMV PCR was found to have limited utility. Quantitative serum CMV PCR may be useful but requires further evaluation.

Immunomodulator use does not prevent first loss of response to anti-tumour necrosis factor alpha therapy in inflammatory bowel disease: long-term outcomes in a real-world cohort.

BACKGROUND: Recent prospective studies suggest combination therapy with immunomodulators improves efficacy, but long-term data is limited. AIM: To assess whether anti-tumour necrosis factor alpha (anti-TNF) monotherapy was associated with earlier loss of response (LOR) than combination therapy in a real-world cohort with long-term follow up. METHODS: A retrospective audit was conducted of inflammatory bowel disease patients receiving anti-TNF therapy in a tertiary centre and specialist private practices. All patients with accurate data for anti-TNF commencement and adequate correspondence to determine end-points were included. Outcomes measured included time to first LOR, causes and biochemical parameters. RESULTS: Two hundred and twenty-four patients were identified; 139 (62.1%) on combination therapy and 85 (37.9%) on monotherapy. Forty-five percent of patients had LOR during follow up until a maximum of 8.5 years; 59.4% on combination therapy and 40.6% on monotherapy (P = 0.533). The median time to LOR was not different between groups; 1069 days for combination therapy and 1489 days for monotherapy (P = 0.533). There was no difference in time to LOR between patients treated with different combination regimens or different anti-TNF agents. CONCLUSION: In this large cohort of patients in a real-world setting, patients treated with anti-TNF monotherapy had similar rates of LOR as patients on anti-TNF combination therapy, at both short- and long-term follow up.

Time-Restricted Fasting Improves Liver Steatosis in Non-Alcoholic Fatty Liver Disease-A Single Blinded Crossover Trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with visceral adiposity. We assessed the effectiveness of time-restricted fasting (TRF) for 16 h daily without calorie restrictions compared to standard care (SC; diet and lifestyle advice) in improving visceral adiposity and steatosis via controlled attenuation parameter (CAP). METHODS: In a prospective single-blind randomized controlled trial, 32 participants with NAFLD were randomly assigned to TRF or SC for 12 weeks. The secondary endpoints were changes in liver stiffness, anthropometry, blood pressure, and other metabolic factors. RESULTS: Twenty-eight participants completed the first arm of the study (TRF = 14, SC = 14), with 23 completing the crossover arm (TRF = 10, SC = 13). The baseline demographics were similar between the groups. Intermittent fasting caused a significant decrease in hepatic steatosis (p = 0.038), weight (p = 0.005), waist circumference (p = 0.001), and BMI (p = 0.005) compared to standard care. Intermittent fasting also resulted in additional within-group changes that were not seen in the standard care intervention. CONCLUSION: TRF offers superior improvements in patients with NAFLD, improving steatosis, weight, and waist circumference despite a lack of change in overall caloric intake. Time-restricted fasting should be considered as a primary weight loss intervention in the context of NAFLD. TRIAL REGISTRATION: ACTRN12613000935730.

Weight and Body Composition Compartments do Not Predict Therapeutic Thiopurine Metabolite Levels in Inflammatory Bowel Disease.

OBJECTIVES: Thiopurine drugs are the most commonly used steroid-sparing therapies in moderate-to-severe inflammatory bowel disease (IBD). Their complex metabolism and their narrow therapeutic windows means that optimal dosing is difficult. However, weight-based dosing is the norm. Similar antimetabolites are dosed by body composition parameters. In IBD, treatment response and toxicity has been shown to correlate with thiopurine metabolite levels. We sought to determine whether weight or body composition parameters predicted therapeutic 6-thioguanine nucleotide (6TGN) or toxic 6-methylmercaptopurine (6MMP) levels. METHODS: This single-center retrospective cohort study identified 66 IBD patients who had body composition analysis and thiopurine metabolite levels tested. Statistical analysis was performed using Spearman correlation, Kruskal-Wallis, Mann-Whitney, and unpaired t tests and receiver-operator operating characteristic curves. A P value of <0.05 was considered significant. RESULTS: No correlation was identified between 6TGN and any body composition parameters, absolute drug dose or drug dose/kg of fat mass, fat-free mass (FFM), subcutaneous adipose tissue area, or visceral adipose tissue area. However, 6MMP correlated with azathioprine dose, thiopurine dose/kg of body weight, and with several body composition parameters. CONCLUSIONS: No relationship was found between therapeutic metabolite levels and weight or body composition compartments. Higher thiopurine doses, especially in relation to FFM, are associated with higher levels of potentially hepatotoxic 6MMP and shunting toward this metabolite. Conventional weight-based dosing to attain therapeutic metabolite levels appears unreliable and may be replaced by metabolite level testing.

Marantic endocarditis presenting as recurrent arterial embolisation.

Marantic endocarditis is a non-infective cause of valvular masses. It is most commonly associated with advanced malignancy. We report a case of rapidly progressive marantic endocarditis, complicated by valve destruction and recurrent systemic embolisation, in a patient whose cancer was occult.