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Background: Exposure–response studies have shown that higher infliximab concentrations are associated with better outcomes in inflammatory bowel disease. There is little agreement about the optimal time to measure infliximab levels in children. Objectives: We aimed to evaluate whether trough levels at week 6 or week 14 predict sustained remission. The secondary aim was to define target trough levels at weeks 6 and 14. Design: We used routinely collected electronic healthcare data of 70 anti-tumour necrosis factor naïve children with inflammatory bowel disease treated with a standard infliximab induction- and variable maintenance scheme. Methods: Trough levels and blood and faecal markers for disease activity were measured before every infliximab administration. Sustained remission was defined as the absence of symptoms and low inflammatory markers between weeks 26 and 52 after the start of infliximab therapy. Optimal infliximab levels at weeks 6 and 14 were determined using the receiver operating characteristic curve. Results: The median infliximab level at week 6 was not significantly higher in children who achieved sustained remission compared to those who did not (16.9 mg/L versus 12.0 mg/L; p = 0.058) but the median infliximab level at week 14 was significantly higher in those with sustained remission (7.7 mg/L versus 3.8 mg/L; p = 0.006). The area under the receiver operating characteristics curves at weeks 6 and 14 to predict sustained remission was 0.67 (95% CI 0.51–0.83) and 0.75 (95% CI 0.60–0.90), respectively. Target trough levels at weeks 6 and 14 were ⩾13.2 and ⩾6.9 mg/L, respectively. Conclusion: An infliximab measurement at week 14 with a target through level ⩾6.9 mg/L best predicted sustained remission.

Abstract Genome‐wide association studies in adults have identified variants in hydroxysteroid 17‐beta dehydrogenase 13 (HSD17B13) and mitochondrial amidoxime reducing component 1 (MTARC1) as protective against nonalcoholic fatty liver disease (NAFLD). We aimed to test their association with pediatric NAFLD liver histology and investigate their function using metabolomics. A total of 1450 children (729 with NAFLD, 399 with liver histology) were genotyped for rs72613567T>TA in HSD17B13, rs2642438G>A in MTARC1, and rs738409C>G in patatin‐like phospholipase domain‐containing protein 3 (PNPLA3). Genotype–histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of children. We found rs72613567T>TA in HSD17B13 to be associated with lower odds of NAFLD diagnosis (odds ratio, 0.7; 95% confidence interval, 0.6–0.9) and a lower grade of portal inflammation (p A in MTARC1 was associated with a lower grade of hepatic steatosis (p = 0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective ‐TA allele. MTARC1 levels were unaffected by genotype. Both variants were associated with down‐regulation of fibrogenic pathways. HSD17B13 perturbs plasma phosphatidylcholines and triglycerides. In silico modeling suggested p.Ala165Thr disrupts the stability and metal binding of MTARC1. Conclusion: Both HSD17B13 and MTARC1 variants are associated with less severe pediatric NAFLD. These results provide further evidence for shared genetic mechanisms between pediatric and adult NAFLD.

Abstract Background Limited physical activity (PA) and a high level of sedentary time (ST) are associated with childhood obesity and are a target for intervention. This study aimed to assess objectively measured PA and ST in Dutch children across weight categories, age groups and sex. Methods 202 children with overweight, obesity and morbid obesity (55% girls, 12 ± 3y of age, BMI z-score + 3.15 ± 0.73), referred to the Centre for Overweight Adolescents and Children’s Healthcare (COACH, Maastricht UMC+) were included. PA (total PA, light PA and moderate to vigorous PA (MVPA)) and ST were measured with the GT3X Actigraph accelerometer. Wear time validation was set to include at least four days, 480 min/day, including one weekend day. Results PA levels in children with morbid obesity were higher compared to children with obesity, also after correction for age and sex (corrected difference (B) 118 counts per minute (cpm), p = .006). ST was lower in children with morbid obesity compared to children with obesity (B − 51 min/day, p = .018). Girls performed significantly less MVPA than boys (B − 11 min/day, p

IntroductionPhysical activity (PA) plays an important role in the prevention of cardiovascular diseases, especially in children. Previous studies which investigated the role of PA and sedentary time (ST) in cardiovascular disease used different measurements and found inconsistent results. The current study used recommended standardized measures and provides an overview of PA and ST among Dutch primary school children and their associations with cardiovascular risk factors.Methods503 children (55% girls, mean age (± SD) 10 ± 1y) were included. PA (total PA, lightPA and moderate to vigorous PA (MVPA)) and ST were measured with the Actigraph GT3X accelerometer. PA in different domains was measured with the BAECKE questionnaire. Cardiovascular risk factors included BMI z-score, waist circumference, blood pressure (z-score) and estimated cardiorespiratory fitness (CRF) as measured with the 20 meter shuttle run test.ResultsChildren spent 57 ± 20 min/day (8%) on MVPA and 42% of the children reached the MVPA guideline of 60 min/day. Total PA and MVPA (h/day) were negatively associated with BMI z-score (B = -0.452, p = 0.011) and waist circumference (B = -3.553, p = 0.011) and positively associated with CRF (B = 2.527, p = ConclusionThis study used standardized measures of PA and therefore created an accurate overview of PA, ST and their associations with cardiovascular risk factors. PA and ST were associated with BMI z-score, waist circumference and CRF. The findings emphasize the importance of promoting MVPA in children, but also highlight the potential benefits of reducing ST to improve cardiovascular risk factors.Trial registrationClinicalTrials.gov NCT03440580.