Canagliflozin and Metabolic Associated Fatty Liver Disease in Patients With Diabetes Mellitus: New Insights From CANVAS.

CONTEXT: Metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent among patients with type 2 diabetes mellitus (T2DM); however, there is still no approved pharmacological treatment. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have been suggested to beneficially modify liver-related outcomes in patients with diabetes. OBJECTIVE: We aimed to investigate the effects of the SGLT-2 inhibitor canagliflozin on liver-related outcomes in patients with advanced T2DM and high cardiovascular risk. METHODS: We performed a secondary post hoc analysis of 2 large double-blind randomized controlled trials, CANVAS (NCT01032629) and CANVAS-R (NCT01989754), which included patients with T2DM and high cardiovascular risk who were randomized to receive either canagliflozin or placebo once daily. The primary endpoint was a composite of improvement of alanine aminotransferase (ALT) levels >30% or normalization of ALT levels. Secondary endpoints included change in noninvasive tests of fibrosis and weight reduction of >10%. RESULTS: In total, 10 131 patients were included, with a median follow-up of 2.4 years (mean age 62 years; mean duration of diabetes 13.5 years; 64.2% male). Of those patients, 8967 (88.5%) had MAFLD according to hepatic steatosis index and 2599 (25.7%) exhibited elevated liver biochemistry at baseline. The primary composite endpoint occurred in 35.2% of patients receiving canagliflozin and in 26.4% with placebo (adjusted odds ratio [aOR] 1.51; 95% CI, 1.38-1.64; P < .001). Canagliflozin led to improvements in some noninvasive tests of fibrosis (NFS, APRI, FNI). Significant weight reduction of >10% (within 6 years) was achieved in 12.7% with canagliflozin compared to 4.1% with placebo (aOR 3.45; 95% CI, 2.91-4.10; P < .001). CONCLUSION: In patients with T2DM, treatment with canagliflozin vs placebo resulted in improvements in liver biochemistry and metabolism and might beneficially affect liver fibrosis.

No obesity paradox in patients with community-acquired pneumonia - secondary analysis of a randomized controlled trial.

BACKGROUND: Obesity is associated with an increased risk for several chronic conditions and mortality. However, there are data in support of beneficial outcome in acute medical conditions such as community-acquired pneumonia (CAP), termed "obesity paradox". The aim of this study was to test the association of BMI with clinical outcomes in a large randomized clinical trial of patients hospitalized with CAP. DESIGN AND METHODS: In total, 773 patients hospitalized with CAP were included in this study. Patients were stratified into four groups according to their baseline BMI (underweight <18.5, normal weight 18.5-25, overweight 25-30, and obese >30 kg/m2). The primary endpoint was time to clinical stability (TTCS). Secondary endpoints included 30-day mortality, ICU admission rate, CAP complications, and duration of antibiotic treatment. RESULTS: BMI and TTCS had a U-shaped association with shortest TTCS among patients at an overweight BMI of 28 kg/m2. In patients with obesity, there was a trend towards reduced hazards to reach clinical stability when compared to patients with normal weight (HR 0.82; 95%CI, 0.67-1.02; p = 0.07). In underweight BMI group TTCS was prolonged by 1 day (HR 0.63; 95%CI, 0.45-0.89; p = 0.008). There was no difference in mortality or ICU admission rates between BMI groups (p > 0.05). While in the underweight BMI group the total duration of antibiotic treatment was prolonged by 2.5 days (95%CI, 0.88-4.20, p = 0.003), there was no difference in patients with obesity. CONCLUSIONS: The overweight BMI group had shortest time to clinical stability. While underweight patients face adverse clinical outcomes, there is neither beneficial, nor adverse outcome in patients with obesity hospitalized for CAP. CLINICALTRIALS: gov (registration no. NCT00973154).

Acute ulceronecrotic adverse reaction to potassium hydroxide 5% solution in the treatment of molluscum contagiosum.

Molluscum contagiosum is a common childhood condition, and although it is self-limited, treatments are often prescribed. Several medications are available, but there is no consensus regarding the optimal choice in the pediatric population. We report a child who underwent potassium hydroxide 5% treatment resulting in superficial diffuse erosions caused by the inappropriate application. This underlines the importance of parent education before use of this medication with well-known caustic properties.