Serum hepcidin: Indication of its role as an "acute phase" marker in febrile children

Background: Hepcidin is classified as a type II acute phase protein; its production is a component of the innate immune response to infections. Objective. To evaluate the alterations of serum hepcidin in children during and following an acute febrile infection. Materials and methods. 22 children with fever of acute onset (< 6 hours) admitted to the 2nd Department of Pediatrics-University of Athens. Based on clinical and laboratory findings our sample formed two groups: the viral infection group (13 children) and the bacterial infection group (9 children). Hepcidin, ferritin and serum iron measurements were performed in all subjects. Results: Serum hepcidin values did not differ notably between children with viral and bacterial infection, but a significant reduction of hepcidin was noted in both groups post-infection. Conclusion: Our study provides clinical pediatric data on the role of hepcidin in the face of an acute infection. In our sample of children, hepcidin was found to rise during the acute infection and fall post-infection. © 2013 Kossiva et al.; licensee BioMed Central Ltd

Bcl-2 and caspase-9 serum levels in children and adolescents with idiopathic epilepsy and active seizures

BACKGROUND: In the present study we investigated the levels of proapoptotic caspase-9 and antiapoptotic Bcl-2 proteins in the sera of children and adolescents with idiopathic epilepsy and tried to relate the findings to the patients' clinical parameters. METHODS: This retrospective study consisted of 118 children and adolescents with idiopathic epilepsy, categorized according to type and number of seizures, duration of the disease and the control of seizures and 30 age- and sex-matched controls. The relapse of seizures was taken into consideration. RESULTS: Mean serum level between Bcl-2 and caspase-9 was significantly higher only in Bcl-2 patients, compared to controls (P≤0.0001) and (P=0.987) respectively. Significant difference in Bcl-2 level was found among the different types of focal seizures. Caspase-9 level was statistically different in patients with two or more seizures per month compared to those with one seizure per month (P=0.048). No correlation was found between Bcl-2 and caspase-9 levels and age, gender, seizure frequency, total number of seizures and the duration of epilepsy. No significant difference was found in patients with and without drug treatment. CONCLUSIONS: Bcl-2 displays an association with apoptosis and highlights the potential of being a surrogate biomarker for active seizures and epilepsy. There is a significant difference in Bcl-2 serum level among the different types of focal seizures. Proapoptotic caspase-9 cannot act as a marker of active seizures and epilepsy. Caspase-9 serum level is increased acutely in controlled cases after a single relapse

Comparing calculated LDL-C with directly measured LDL-C in healthy and in dyslipidemic children

Background LDL-C is one of the strongest markers for atherosclerosis and therapeutic decisions in children are based on its levels. Friedewald formula (FF) which is usually used for the calculation of LDL-C (cLDL-C); and Anandaraja's formula (AF) may under- or overestimate actual levels. Objective To compare cLDL-C with directly measured LDL-C (dLDL-C) as a screening tool and to evaluate dyslipidemic children. Methods The study population consisted of 1005 children, 2–18 years, 688 of whom underwent lipid screening in a regular check-up (group A); and 317 were dyslipidemic (LDL-C ≥ 130 mg/dl) (group B). A fasting serum lipid profile was assessed. LDL-C was measured using a homogenous assay and was calculated using FF and AF. Results Each method of calculating LDL-C was highly correlated to dLDL-C. Using FF, cLDL-C was lower than dLDL-C in 75.6% (group A) and in 77.3% (group B) of children; the mean difference was significant in dyslipidemic group. Moreover, in group B, 25% of children with boundary high and 12% with high dLDL-C would be misclassified. Using AF, LDL-C was higher than dLDL-C; the mean difference was significant in group A. Based on cLDL-C, 52% of group A with borderline dLDL-C and 27.5% of group B children with boundary high dLDL-C would be considered as dyslipidemic and eligible for medication respectively. Conclusions Comparing two methods of calculated LDL-C with directly measured LDL-C. FF was more accurate as a screening tool while AF was more accurate in the evaluation and follow-up of the dyslipidemic group. © 2016 The Canadian Society of Clinical Chemist

Delayed treatment of the first febrile urinary tract infection in early childhood increased the risk of renal scarring

Aim: This study evaluated the controversial relationship between the duration of fever before treatment initiation (FBT) for a febrile urinary tract infection (UTI), with renal scarring based on dimercaptosuccinic acid scintigraphy (DMSA) findings. Methods: The inpatient records of 148 children under two years of age with a first episode of febrile UTI were analysed. Acute and repeat DMSA findings, and clinical and laboratory parameters were evaluated. Results: Acute DMSA showed that 76 of the 148 children with a febrile UTI had renal lesions: 20 were mild, and 56 were moderate or severe. Repeat DMSA showed renal scarring in 34 patients. The only factors associated with the development of renal scars in the repeat DMSA were FBT of more than 72 hours, the presence and severity of vesicoureteral reflux and increased procalcitonin levels and absolute neutrophil counts. Multiple regression analysis showed that an FBT above 72 hours was the only significant factor that predicted renal scars. Conclusion: Delay in treatment initiation of 72 hours or more was a risk factor for permanent renal scars after the first episode of febrile UTI. Other associated factors were increased procalcitonin and absolute neutrophil count on admission and the presence and severity of vesicouretal reflux. ©2016 Foundation Acta Pædiatrica. Published by John Wiley & Sons Lt

Diabetic neuropathy in children and adolescents with type 1 diabetes mellitus: Diagnosis, pathogenesis, and associated genetic markers

Diabetic neuropathy (DN) is a common long-term complication of type 1 (T1D) and type 2 (T2D) diabetes mellitus, with significant morbidity and mortality. DN is defined as impaired function of the autonomic and/or peripheral nervous system, often subclinical, particularly in children and adolescents with T1D. Nerve conduction studies (NCS) and skin biopsies are considered gold-standard methods in the assessment of DN. Multiple environmental and genetic factors are involved in the pathogenesis of DN. Specifically, the role of metabolic control and glycemic variability is of paramount importance. A number of recently identified genes, including the AKR1B1, VEGF, MTHFR, APOE, and ACE genes, contribute significantly in the pathogenesis of DN. These genes may serve as biomarkers to predict future DN development or treatment response. In addition, they may serve as the basis for the development of new medications or gene therapy. In this review, the diagnostic evaluation, pathogenesis, and associated genetic markers of DN in children and adolescents with T1D are presented and discussed. © 2019 John Wiley & Sons, Ltd

Increased levels of Dickkopf-1 are indicative of Wnt/beta-catenin downregulation and lower osteoblast signaling in children and adolescents with type 1 diabetes mellitus, contributing to lower bone mineral density

Higher levels of Dickkopf-1, which is an inhibitor of Wnt/beta-catenin bone metabolic pathway, could be indicative of downregulated Wnt system, with possible lower osteoblast activation and higher osteoclast signaling in type 1 diabetes mellitus children and adolescents. Dickkopf-1 could significantly contribute to diabetes osteopathy. Increased fracture risk and elevated Dickkopf-1 levels, which is an inhibitor of Wnt/beta-catenin bone metabolic pathway, have been documented in adult patients with type 2 diabetes mellitus (T2D), while no relevant data exist on childhood type 1 diabetes (T1D). Our aim was to study plasma Dickkopf-1 distribution in children and adolescents with T1D and to correlate Dickkopf-1 with metabolic bone markers and bone mineral density (BMD). We evaluated 40 children and adolescents with T1D (mean +/- SD age 13.04 +/- 3.53 years, T1D duration 5.15 +/- 3.33 years) and 40 healthy age-matched and gender-matched controls (age 12.99 +/- 3.3 years). Dickkopf-1 and bone metabolic markers were measured, while total body and lumbar spine BMD were evaluated with dual-energy X-ray absorptiometry (DXA). Dickkopf-1 demonstrated a Gaussian distribution, with higher levels in T1D patients (13.56 +/- 5.34 vs 11.35 +/- 3.76 pmol/L, p = 0.024). Higher values were found in boys and in prepubertal children. Dickkopf-1 correlated positively with osteoprotegerin and fasting glucose in patients, while positive correlation with sclerostin and total soluble receptor activator of nuclear factor-kappaB ligand (s-RANKL) was found in controls. Positive correlations with C-telopeptide cross-links (CTX), osteocalcin, alkaline phosphatase, phosphate, and insulin-like growth factor 1 (IGF1) were documented in both groups. Lumbar spine Z-score was positively associated with Dickkopf-1 in controls, while a negative trend was found in patients. Higher levels of Dickkopf-1 could indicate a downregulated Wnt/beta-catenin system with possible lower osteoblast activation and higher osteoclast signaling in T1D children and adolescents. Dickkopf-1 could possibly be a significant contributor of T1D osteopathy. Future therapies could focus on Wnt/beta-catenin metabolic pathway

Quantiferon-Cytomegalovirus assay: A potentially useful tool in the evaluation of CMV-specific CD8+ T-cell reconstitution in pediatric hematopoietic stem cell transplant patients

Pediatric HSCT recipients are at high risk for CMV reactivation due to their immature immune system and therapy following transplantation. Reconstitution of CMV-specific T-cell immunity is associated with control and protection against CMV. The clinical utility of monitoring CMV-specific CMI to predict CMV viremia in pediatric HSCT patients using the Quantiferon-CMV (QIAGEN®) test was investigated prospectively. Thirty-seven pediatric allogeneic HSCT recipients were enrolled from 3/2010-6/2012. CMV viremia was detected via weekly real-time PCR. The Quantiferon-CMV test was conducted pretransplant, early after transplantation, 30, 90, 180, 270, and 360 days post-transplantation. The incidence of CMV viremia was 51% (19/37) with half of the episodes within ≤30 days post-transplant. Fifteen patients showed CMV-specific immunity (average of 82 days). The cumulative incidence of CMV reactivation in patients who developed CMV-specific immunity was lower than those who did not (15% vs 53%; P =.023). The ROC statistical analysis showed that the AUC was 0.725 in predicting viremia, for Quantiferon-CMV test. In this cohort, the Quantiferon-CMV assay was a valuable method for identifying pediatric HSCT patients at high risk for CMV viremia, suggesting potential clinical utility to individualize patient's management post-transplant. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Lt

The prevalence of early subclinical somatic neuropathy in children and adolescents with Type 1 diabetes mellitus and its association with the persistence of autoantibodies to glutamic acid decarboxylase (GAD) and islet antigen-2 (IA-2)

Aim: To evaluate the prevalence of early somatic neuropathy in children and adolescents with Type 1 diabetes mellitus (Type 1 DM) and its association with the presence of glutamic acid decarboxylase and islet antigen-2 autoantibodies (GADA and IA-2A). Methods: A cross-sectional study was conducted in a hospital-based cohort of pediatric Type 1 DM patients (n = 85, mean(±SD) age: 13.5 ± 3.4 years, mean(±SD) disease duration 5.5 ± 3.4 years). Peripheral neuropathy was assessed with nerve conduction studies (NCS). GADA and IA-2A titers were measured with radioligand assays. Results: Among the study population, 34.1% had at least one abnormal electrophysiological parameter, although predominantly asymptomatic. The highest rates of abnormality were detected in sensory peroneal nerve (25.9%) followed by sural nerve (15.3%). Affected patients were not different in terms of age, diabetes duration or glycaemic control. Among the participants, 62.4% had positive GADA, 58.8% positive IA-2A and 42.4% double antibody positivity. Abnormal NCS correlated neither with GADA nor with IA-2A levels or positivity. However lower sensory nerve action potential in the peroneal nerve, indicative of early axonal dysfunction, was observed in patients with GADA or IA-2A positivity. Absence of both antibodies was associated with better action potentials in all the examined nerves of the lower limbs. Conclusions: Impaired indices of subclinical peripheral primarily sensory neuropathy were present among one third of Type 1 DM children and adolescents, with no impact of diabetes duration or glycaemic control. GADA and IA-2A seem to be involved in the development of axonal degeneration, in a pathway which remains to be identified. © 2016

Plant sterols-enriched diet decreases small, dense LDL-cholesterol levels in children with hypercholesterolemia: A prospective study

Background: Small dense low density lipoprotein-cholesterol (sdLDL-C) molecules are more atherogenic compared with large buoyant ones. Phytosterols-enriched diets are effective in decreasing total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) concentrations in hyperlipidemic children without significant adverse effects. Limited data on the impact of such a diet on sdLDL-C levels is available in adults while there are no reports concerning children. The purpose of this study is to prospectively evaluate the effect of the daily consumption of 2 g of plant sterols on sdLDL-C levels in children with hypercholesterolemia. Methods. Fifty-nine children, 25 with LDL-C ≥ 3.4 mmol/l (130 mg/dl) and 34 with LDL-C < 3.4 mmol/l, aged 4.5-15.9 years, were included in the study. A yogurt-drink enriched with 2 g of plant sterols was added to the daily diet of hypercholesterolemic children and 6-12 months later lipid profiles were reassessed. Direct quantitative methods were used to measure LDL-C and sdLDL-C levels. Results: The consumption of plant sterols reduced sdLDL-C significantly (p < 0.001), but levels remained higher compared with controls (p < 0.001). TC, LDL-C, non high density lipoprotein-cholesterol (NonHDL-C) and apolipoprotein B (ApoB) levels also decreased significantly (p < 0.05). The median reduction of sdLDL-C and LDL-C was 16.6% and 13%, respectively. These variables decreased >10% in sixteen children (64%), independently from baseline levels, sex, age and body mass index (BMI). High density lipoprotein-cholesterol (HDL-C), lipoprotein a [Lp(a)], and triglycerides (TGs) levels remained unaffected. Conclusions: Plant sterols decrease sdLDL-C significantly and may be beneficial for children with hypercholesterolemia. © 2014 Garoufi et al.; licensee BioMed Central Ltd