Histologic Severity of Nonalcoholic Fatty Liver Disease Associates with Reduced Bone Mineral Density in Children.

BACKGROUND: Lower whole body bone mineral density (BMD) has been reported in children with nonalcoholic fatty liver disease (NAFLD), but potential mediators remain uncertain. AIMS: To assess BMD at multiple skeletal sites in children with confirmed NAFLD and controls with obesity, adjusting for known determinants of BMD, and examine potential mediators. METHODS: We assessed age-, sex-, and race-specific, and height-adjusted BMD z-scores of whole body, lumbar spine, hip, femoral neck and forearm by dual-energy-x-ray absorptiometry in 79 children, 8-19 years old: 46 with biopsy-confirmed NAFLD [29 steatohepatitis (NASH)/17 fatty liver (NAFL)] and 33 controls without liver disease. We compared BMD z-scores by multivariable regression, adjusting for known BMD determinants and potential mediators (inflammatory and insulin resistance measures). RESULTS: Unadjusted mean BMD z-scores in NAFLD were similar to controls, but significantly lower in NASH vs. NAFL at all sites. After covariate adjustment, mean forearm BMD z-score was higher in NAFL (ß 0.60 ± SE 0.30, p < 0.05) and lower in NASH (ß - 0.49 ± SE 0.26, p = 0.06) vs. controls (p = 0.002 for group), with similar trends at whole body and total hip; hs-CRP negatively associated with whole body and forearm BMD z-scores (p < 0.05), while visceral fat area negatively associated with femoral neck (p < 0.05). Only three children had clinically low whole body BMD z-scores (< - 2), one per group (control, NAFL and NASH). CONCLUSIONS: NASH, but not NAFL, may be associated with increased risk of reduced BMD in children. Systemic inflammation, independent of body composition and load bearing, may mediate reduction in BMD in NASH.

Prevalence and Predictors of Compromised Bone Mineral Density in Pediatric Eosinophilic Esophagitis.

OBJECTIVES: The aim of the study was to determine whether patients with eosinophilic esophagitis (EoE) have lower bone mineral density (BMD) than expected and if bone deficits are more pronounced in subgroups of patients according to comorbidities (atopic disease and joint hypermobility) or treatments (dietary restriction, medication exposure). STUDY DESIGN: Retrospective chart review was performed to obtain clinical data, including length of diagnosis, comorbidities, and methods of treatment for patients with EoE ages 3 to 21 years who had a lumbar spine dual-energy x-ray absorptiometry scan performed between 2014 and 2017. BMD was standardized by calculation of age, sex, and race-specific z scores. RESULTS: A total of 269 patients met study criteria. The mean BMD z score (-0.55, 95% confidence interval: -0.68, -0.42) was lower than expected (P < 0.0001), and the prevalence of low BMD z score (≤-2.0) was higher than expected (8.5%, 95% confidence interval: 5.2%-11.9%, P < 0.0001). In multivariable regression models, BMD z scores were -0.27 lower among those following an elimination diet and -0.65 lower among those with any lifetime use of a proton pump inhibitor (93% of the sample). There was no association with swallowed steroid use. CONCLUSIONS: In our sample, pediatric patients with EoE had a slightly lower BMD z score compared to peers, and the prevalence of low BMD was higher than expected. Taken cautiously given the limitations of our sample, risk factors for bone deficits included any lifetime use of proton pump inhibitor and a restrictive elimination diet, but not swallowed steroid use. Larger prospective studies are needed to better characterize risk factors for low BMD to help inform screening, selection of therapies, and provide appropriate anticipatory guidance for patients with EoE.

Relative Accuracy of Bioelectrical Impedance Analysis for Assessing Body Composition in Children With Severe Obesity.

OBJECTIVES: The accuracy of different bioelectrical impedance analysis (BIA) devices for assessing body composition in children with obesity is unclear. We determined the relative accuracy of 2 BIA devices compared to dual x-ray absorptiometry (DXA) in obese and severely obese children. METHODS: We measured body composition in a cross-sectional study of 78 obese children by a handheld single frequency tetrapolar BIA device (Omron), a stationary multifrequency octopolar BIA device (InBody 370) and DXA. Intermethod agreement was assessed by intraclass correlations, paired t tests, and Bland-Altman analyses. RESULTS: Participants (37% female, age 14.8 ±â€Š2.7 years) had mean (±standard deviation) body mass index of 36.7 ±â€Š7.5 kg/m, body fat percentage of 46.4% ±â€Š5.2%, and appendicular lean mass of 22.5 ±â€Š6.0 kg by DXA. Intraclass correlations with DXA for body fat percentage were 0.39 and 0.87 for single frequency tetrapolar and multifrequency octopolar BIA devices, respectively. The single frequency tetrapolar BIA underestimated body fat percentage by 5.5% ±â€Š2.9% (P < 0.0001). Differences between the multifrequency octopolar BIA and DXA for body fat percentage (-1.1% ±â€Š2.8%) and appendicular lean mass (-0.3 ±â€Š1.4 kg) were small, and 95% limits of agreement were approximately ±5%. CONCLUSIONS: BIA machines vary in relative accuracy in measuring body composition in children who are obese and severely obese. The multifrequency octopolar BIA device accurately estimated body fat percentage and appendicular lean mass relative to DXA and has the advantage of point of care performance.

Interlaboratory agreement of coccidioidomycosis enzyme immunoassay from two different manufacturers.

Coccidioidomycosis, a fungal infection endemic to the Southwestern United States, is challenging to diagnose. The coccidioidomycosis enzyme immunoassay (EIA) test is the least expensive and simplest to perform to detect coccidioidomycosis antibodies in the serum. Concerns regarding falsely positive immunoglobulin (Ig) M EIA test results have led to questions about the agreement of commercially available EIA test kits among laboratories. We sought to evaluate the laboratory agreement of the EIA test at three laboratories using both IMMY and Meridian EIA test kits. Sensitivity and specificity of EIA IgM and IgG were calculated as secondary outcomes. The percent agreement of the EIA IgM and IgG test results among all three laboratories was 90% and 89% for IMMY test kits, respectively, and 67% and 80.5% for Meridian test kits, respectively. Agreement between IgM and IgG combined test results was 85.5% and 70.5%, for IMMY and Meridian, respectively. Combined IgM and IgG assays demonstrated a sensitivity of 68% (62.7%-76%) and a specificity of 99.3% (98%-100%) [IMMY] and a sensitivity of 72.4% (57.3%-87.3%) and a specificity of 91.3% (74%-100%) [Meridian]. In summary, results from the IMMY EIA test kit agreed more often across laboratories than Meridian EIA results, especially for the IgM assay. Isolated positive IgM EIA results using the Meridian test kit should be interpreted with caution and consideration of clinical information and test methodology. Further study of the sensitivity and specificity of coccidioidomycosis EIA test kits is warranted.

Predictive biomarkers for acute gallstone pancreatitis in the pediatric population.

BACKGROUND: Early biomarkers for diagnosis of gallstone pancreatitis (GP) in pediatrics have not been well studied. Reliably differentiating GP from other causes of acute pancreatitis (AP) would allow for early diagnosis and prompt management. We sought to assess biomarkers and clinical variables for early GP diagnosis from a prospectively-enrolled registry of pediatric patients presenting with first AP episode. METHODS: Cross-sectional analysis of a prospective acute pancreatitis registry of children enrolled from March 2013 through October 2016 was performed. Fisher's exact test and Wilcoxon rank sum test were used to compare demographic and clinical variables between GP and non-GP groups. A multivariable logistic regression model was derived, and receiver operating characteristic (ROC) curve was built using stepwise selection. RESULTS: 114 subjects were enrolled (21 with GP, 93 as non-GP). Median was statistically higher for GP patients in lipase values X upper limit of normal (ULN) on admission, weight percentile for age, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase. By multivariable analysis, significant predictors were ALT and Lipase xULN. A model built using these two variables for prediction of GP identified an AUROC of 0.85. At a predictive probability of 0.35, the model had an 80% sensitivity, 93% specificity, 76% positive predictive value and 95% negative predictive value. CONCLUSIONS: We have developed a model for predicting GP in children that could help guide clinical management of AP patients. Future studies are needed to validate use of laboratory findings and clinical variables in evaluation of gallstone etiology in pediatric AP patients.

Improved Outcomes with an Outpatient Multidisciplinary Intensive Feeding Therapy Program Compared with Weekly Feeding Therapy to Reduce Enteral Tube Feeding Dependence in Medically Complex Young Children.

PURPOSE OF REVIEW: The prevalence of feeding disorders in medically complex children is estimated to be as high as 80%. Enteral tube nutrition (ETN) is commonly used for nutritional support in children with feeding disorders. Adverse consequences of ETN include medical complications, psychosocial problems, and higher healthcare costs. We used a retrospective cohort controlled study design to compare outcomes of our outpatient multidisciplinary intensive feeding therapy (IFT) program to our traditional therapy (TT) of single-discipline, once weekly feeding therapy to reduce ETN dependence in medically complex young children. RECENT FINDINGS: Children in the IFT cohort experienced a median reduction in ETN dependence of 49% (34.5-58.5%) compared with a median reduction of 0% (0-25%) for TT (p > 0.0001). Almost half of the IFT cohort no longer required ETN by the conclusion of the 5-week program. Medically complex young children (median age 26 months) successfully reduce or eliminate ETN in an outpatient multidisciplinary intensive feeding program.

The Challenges of Diagnosing and Following Wilson Disease in the Presence of Proteinuria.

The coexistence of Wilson disease with Alport syndrome has not previously been reported. The diagnosis of Wilson disease and its ongoing monitoring is challenging when associated with an underlying renal disease such as Alport syndrome. Proteinuria can lead to low ceruloplasmin since it is among serum proteins inappropriately filtered by the damaged glomerulus, and can also lead to increased urinary loss of heavy metals such as zinc and copper. Elevated transaminases may be attributed to dyslipidemia or drug induced hepatotoxicity. The accurate diagnosis of Wilson disease is essential for targeted therapy and improved prognosis. We describe a patient with a diagnosis of Alport syndrome who has had chronic elevation of transaminases eventually diagnosed with Wilson disease based on liver histology and genetics.

A history of recurrent positive selection at the toll-like receptor 5 in primates.

Many genes involved in immunity evolve rapidly. It remains unclear, however, to what extent pattern-recognition receptors (PRRs) of the innate immune system in vertebrates are subject to recurrent positive selection imposed by pathogens, as suggested by studies in Drosophila, or whether they are evolutionarily constrained. Here, we show that Toll-like receptor 5 (TLR5), a member of the Toll-like receptor family of innate immunity genes that responds to bacterial flagellin, has undergone a history of adaptive evolution in primates. We have identified specific residues that have changed multiple times, sometimes in parallel in primates, and are thus likely candidates for selection. Most of these changes map to the extracellular leucine-rich repeats involved in pathogen recognition, and some are likely to have an effect on protein function due to the radical nature of the amino acid substitutions that are involved. These findings suggest that vertebrate PRRs might show similar patterns of evolution to Drosophila PRRs, in spite of the acquisition of the more complex and specific vertebrate adaptive immune system. At shorter timescales, however, we found no evidence of adaptive evolution in either humans or chimpanzees. In fact, we found that one mutation that abolishes TLR5 function is present at high frequencies in many human populations. Patterns of variation indicate that this mutation is not young, and its high frequency suggests some functional redundancy for this PRR in humans.