Marked increase of final height by long-term aromatase inhibition in a boy with idiopathic short stature

Growth hormone (GH) is the most frequently used treatment in children with idiopathic short stature (ISS). Aromatase inhibitor (AI) therapy is still in an experimental state, and both final height (FH) and long-term efficacy data in ISS have not been published. We present a 14.5-year-old boy with ISS and a height of 142.7 cm [standard deviation score (SDS) -2.79]. Based on the baseline bone age (BA) of 13.5-14 years, his predicted adult height (PAH) by Bayley/Pinneau was 154 cm (SDS -3.77)-158.2 (SDS -3.15). After a 5-year letrozole monotherapy, FH was 169 cm (SDS -1.57) showing a height difference between PAH and FH from 10.8 to 15 cm. No permanent side effects of the medication have been observed. Both a transient occurrence and a spontaneous recovery of decreased bone mineral apparent density were seen, verified by dual-energy X-ray absorptiometry. Spinal magnetic resonance imaging revealed no vertebral abnormalities. AI therapy might be an effective and low-cost alternative to the use of GH. Further controlled trials should prove efficacy and safety of long-term AI therapy in boys with IS

Lipoprotein-associated phospholipase A2 activity and low-density lipoprotein subfractions after a 2-year treatment with atorvastatin in adolescents with type 1 diabetes

AbstractBackground: The objective of the study was to assess the effect of atorvastatin on inflammation markers and low-density lipoprotein (LDL) subfractions. Methods: In a prospective, randomized, double-blind pilot study involving 28 adolescents with type 1 diabetes (T1D), lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, high-sensitivity C-reactive protein (hsCRP), and subfractions of LDL were measured at baseline, after 1 year and 2 years of treatment with atorvastatin (10 mg/day) vs. placebo. Results: For the atorvastatin group, we found posttreatment reductions of Lp-PLA2 activity (p<0.001), LDL cholesterol (p=0.001), non-small dense LDL cholesterol (p<0.001), total cholesterol (p<0.001), and apolipoprotein B (apo B) (p<0.001), whereas small dense LDL cholesterol and hsCRP did not change significantly. Conclusions: In adolescents with T1D, long-term treatment with atorvastatin is safe and may reduce cardiovascular risk by significant decreases of Lp-PLA2 activity and LDL cholesterol

Decreased levels of homoarginine and asymmetric dimethylarginine in children with type 1 diabetes: associations with cardiovascular risk factors but no effect by atorvastin

Objectives: To investigate homoarginine and asymmetric dimethylarginine (ADMA) in controls compared to children with type 1 diabetes (T1D) and if homoarginine and ADMA are affected by atorvastatin. Methods: Homoarginine and ADMA levels of 28 T1D patients were compared to levels of 41 controls. In T1D patients, homoarginine and ADMA were determined at baseline, 1 year, and 2 years at daily 10 mg atorvastatin or placebo within a double-blind study. Results: At baseline, both homoarginine and ADMA were lower (p<0.001) in T1D patients compared to controls. In T1D patients, homoarginine and ADMA were not influenced by atorvastatin. Inverse correlations between homoarginine and HbA1c (p<0.001) and between ADMA and systolic blood pressure (p=0.005) and pulse pressure (p=0.003) were shown. Conclusions: Homoarginine and ADMA levels are decreased and associated with cardiovascular risk factors in children with T1D without being affected by atorvastatin

The obesity epidemic in 32,936 youth with type 1 diabetes (T1D) in the German/Austrian DPV and US T1D Exchange (T1DX) registries

Objective To examine the current extent of the obesity problem in 2 large pediatric clinical registries in the US and Europe and to examine the hypotheses that increased body mass index (BMI) z-scores (BMIz) are associated with greater hemoglobin A1c (HbA1c) and increased frequency of severe hypoglycemia in youth with type 1 diabetes (T1D). Study design International (World Health Organization) and national (Centers for Disease Control and Prevention/German Health Interview and Examination Survey for Children and Adolescents) BMI references were used to calculate BMIz in participants (age 2-<18 years and ≥1 year duration of T1D) enrolled in the T1D Exchange (n = 11 435) and the Diabetes Prospective Follow-up (n = 21 501). Associations between BMIz and HbA1c and severe hypoglycemia were assessed. Results Participants in both registries had median BMI values that were greater than international and their respective national reference values. BMIz was significantly greater in the T1D Exchange vs the Diabetes Prospective Follow-up (P < .001). After stratification by age-group, no differences in BMI between registries existed for children 2-5 years, but differences were confirmed for 6- to 9-, 10- to 13-, and 14- to 17-year age groups (all P < .001). Greater BMIz were significantly related to greater HbA1c levels and more frequent occurrence of severe hypoglycemia across the registries, although these associations may not be clinically relevant. Conclusions Excessive weight is a common problem in children with T1D in Germany and Austria and, especially, in the US. Our data suggest that obesity contributes to the challenges in achieving optimal glycemic control in children and adolescents with T1D

Age, maturation and serum lipid parameters: findings from the German Health Survey for Children and Adolescents

Background Recommendations on preventive lipid screening among children and adolescents remain controversial. The aim of the study was to assess age and puberty-related changes in serum lipids, including total cholesterol (TC), and high-density (HDL-C) and non-high-density lipoprotein cholesterol (Non-HDL-C). Methods Using cross-sectional data from the National Health Interview and Examination Survey for Children and Adolescents in Germany (KiGGS 2003–2006; N = 13,676; 1–17 years), changes in distributions of serum lipids were visualized according to sex, age and maturation. Youth aged 10–17 years were classified as prepubescent, early/mid-puberty, and mature/advanced puberty. Multiple linear regressions were used to quantify the impact of pubertal stage on serum lipid levels, adjusted for potential confounding factors. Results Among children 1–9 years mean serum lipid measures increased with age, with higher mean TC and Non-HDL-C among girls than boys. Among children 10–17 years, advanced pubertal stage was independently related to lower lipid measures. Adjusted mean TC, HDL-C and Non-HDL-C was 19.4, 5.9 and 13.6 mg/dL lower among mature/advanced puberty compared to prepubescent boys and 11.0, 4.0 and 7.0 mg/dL lower in mature/advanced puberty compared to prepubescent girls. Conclusions Lipid concentrations undergo considerable and sex-specific changes during physical growth and sexual maturation and significantly differ between pubertal stages. Screening recommendations need to consider the fluctuations of serum lipids during growth and sexual maturation.Peer Reviewe

Ruxolitinib Controls Lymphoproliferation and Diabetes in a STAT3-GOF Patient

Anesthesia care providers and anesthesia decision support tools use mathematical pharmacokinetic models to control delivery and especially removal of anesthetics from the patient's body. However, these models are not able to reflect alterations in pharmacokinetics of volatile anesthetics caused by obesity. The primary aim of this study was to refine those models for obese patients. To investigate the effects of obesity on the elimination of desflurane, isoflurane and sevoflurane for various anesthesia durations, the Gas Man® computer simulation software was used. Four different models simulating patients with weights of 70 kg, 100 kg, 125 kg and 150 kg were constructed by increasing fat weight to the standard 70 kg model. For each modelled patient condition, the vaporizer was set to reach quickly and then maintain an alveolar concentration of 1.0 minimum alveolar concentration (MAC). Subsequently, the circuit was switched to an open (non-rebreathing) circuit model, the inspiratory anesthetic concentration was set to 0 and the time to the anesthetic decrements by 67% (awakening times), 90% (recovery times) and 95% (resolution times) in the vessel-rich tissue compartment including highly perfused tissue of the central nervous system were determined. Awakening times did not differ greatly between the simulation models. After volatile anesthesia with sevoflurane and isoflurane, awakening times were lower in the more obese simulation models. With increasing obesity, recovery and resolution times were higher. The additional adipose tissue in obese simulation models did not prolong awakening times and thus may act more like a sink for volatile anesthetics. The results of these simulations should be validated by comparing the elimination of volatile anesthetics in obese patients with data from our simulation models

Synergistic effects of elevated systolic blood pressure and hypercholesterolemia on carotid intima-media thickness in children and adolescents

This study aimed to investigate the synergistic effects of elevated systolic blood pressure (SBP) and hypercholesterolemia on carotid intima-media thickness (cIMT). For this study, 60 children with hypercholesterolemia and 40 healthy control children were divided into four subgroups: hypercholesterolemic children with normal (>90th percentile) or elevated (<or= 90th percentile) SBP and control children with normal or elevated SBP. The highest mean and maximal cIMT values were found in the hypercholesterolemic children with elevated SBP and were significantly different from those of all the other groups. The synergistic effects of elevated SBP and hypercholesterolemia lead to a significant increase in cIMT as a subclinical sign of early atherosclerosis

Hyperpyrexia resulting in encephalopathy in a 14-month-old patient with cblC disease

Cobalamin C (cblC) defect, the most common inborn error of cobalamin metabolism, is a multisystem disorder usually presenting with progressive neurological, haematological and ophthalmological signs. We report on a cblC patient diagnosed in the newborn age who developed nearly normal during the first year of life. During an upper respiratory tract infection with severe hyperpyrexia at the age of 14months he developed an acute encephalopathic crisis resulting in severe mental retardation and marked internal and external cerebral atrophy. Hyperacute encephalopathic crises have not been observed so far in patients with cblC defect. It remains unclear, if this association is incidental or if the underlying metabolic defect may have predisposed the brain tissue to hyperpyrexia-induced damage