Background Sarcopenia, the unintentional loss of skeletal muscle mass, is associated with poor outcomes in adult patient populations. In adults, sarcopenia is often ascertained by cross-sectional imaging of the psoas muscle area (PMA). Although children with chronic medical illnesses may be at increased risk for muscle loss because of nutritional deficiencies, physical deconditioning, endocrine anomalies, and systemic inflammation, consistent quantitative definitions for sarcopenia in children are lacking. We aimed to generate paediatric reference values for PMA at two intervertebral lumbar levels, L3-4 and L4-5. Methods In this cross-sectional study, we analysed abdominal computed tomography scans of consecutive children presenting to the emergency department. Participants were children 1-16 years who required abdominal cross-sectional imaging after paediatric trauma between January 1, 2005 and December 31, 2015 in a large Canadian quaternary care centre. Children with a documented chronic medical illness or an acute spinal trauma at presentation were excluded. Total PMA (tPMA) at levels L3-4 and L4-5 were measured in square millimetres (mm 2 ) as the sum of left and right PMA. Age-specific and sex-specific tPMA percentile curves were modelled using quantile regression. Results Computed tomography images from 779 children were included. Values of tPMA at L4-5 were significantly larger than at L3-4 at all ages, but their correlation was high for both girls (r = 0.95) and boys (r = 0.98). Amongst girls, tPMA 50th percentile values ranged from 365 to 2336 mm 2 at L3-4 and from 447 to 2704 mm 2 for L4-5. Amongst boys, 50th percentile values for tPMA ranged between 394 and 3050 mm 2 at L3-4 and from 498 to 3513 mm 2 at L4-5. Intraclass correlation coefficients were excellent at L3-4 (0.97, 95% CI 0.94 to 0.981) and L4-5 (0.99, 95% CI 0.986 to 0.995). Weight and tPMA were correlated, stratified by sex for boys (L3-4 r = 0.90; L4-5 r = 0.90) and for girls (L3-4 r = 0.87; L4-5 r = 0.87). An online application was subsequently developed to easily calculate age-specific and sex-specific z-scores and percentiles. Conclusions We provide novel paediatric age-specific and sex-specific growth curves for tPMA at intervertebral L3-4 and L4-5 levels for children between the ages of 1-16 years. Together with an online tool (https://ahrc-apps.shinyapps.io/sarcopenia/ ), these tPMA curves should serve as a reference enabling earlier identification and targeted intervention of sarcopenia in children with chronic medical conditions.

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Background and Aims Liver disease in Alagille syndrome is highly variable. Many of these patients presenting with severe cholestasis early in life improve spontaneously; 10–20% however, have progressive disease. It is currently not possible to predict long-term hepatic outcomes in Alagille syndrome. This international, multicenter study was aimed at identifying early life predictors of liver disease outcome. Methods Retrospective clinical, laboratory and radiographic data from a cohort of 144 Alagille syndrome patients, whose long-term hepatic outcomes had been determined a priori based on previously published criteria, were collected. Results Sixty-seven had mild and 77 severe hepatic outcome. Univariate analysis demonstrated that cholestasis and fibrosis on biopsy, as well as the presence of xanthomata were significantly different between the groups (p<0.05 for all). Mixed model analysis revealed that total serum bilirubin and serum cholesterol were also associated with outcome (p=0.001 and p=0.002, respectively). Graphical representation of the data revealed a change in total bilirubin levels between 12 and 24 months of age in the mild group. Recursive partitioning identified a threshold for total bilirubin of 3.8 mg/dL (65mmol/L) in that age-frame that differentiated between outcomes. A multivariable logistic regression model was developed using fibrosis, xanthomata and the total bilirubin cutoff of 3.8 mg/dL (65mmol/L), which generated an area under the ROC of 0.792. Conclusions The long-term hepatic outcomes of patients with Alagille syndrome can be predicted based on serum total bilirubin between the ages of 12–24 months combined with fibrosis on liver biopsy and presence of xanthomata on physical examination.

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Background and Aims: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis. Approach and Results: A targeted enzyme‐linked immunosorbent assay–based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL‐8, endoglin, periostin, Mac‐2–binding protein, MMP‐3, and MMP‐7) was examined in children with biliary atresia (BA; n = 187), alpha‐1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin (p = 0.04) and IL‐8 (p < 0.001) and MMP‐7 (p < 0.001) in participants with BA. The best prediction model for LSM in BA using clinical and lab measurements had an R 2 = 0.437; adding IL‐8 and MMP‐7 improved R 2 to 0.523 and 0.526 (both p < 0.0001). In participants with A1AT, CTGF and LSM were negatively correlated (p = 0.004); adding CTGF to an LSM prediction model improved R 2 from 0.524 to 0.577 (p = 0.0033). Biomarkers did not correlate with LSM in ALGS. A significant number of biomarker/lab correlations were found in participants with BA but not those with A1AT or ALGS. Conclusions: Endoglin, IL‐8, and MMP‐7 significantly correlate with increased LSM in children with BA, whereas CTGF inversely correlates with LSM in participants with A1AT; these biomarkers appear to enhance prediction of LSM beyond clinical tests. Future disease‐specific investigations of change in these biomarkers over time and as predictors of clinical outcomes will be important.

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