Insulin resistance surrogates and left ventricular hypertrophy in normotensive obese children.

BACKGROUND: The relationship between different surrogates of insulin resistance and left ventricular geometry in obese children is still unclear. OBJECTIVE: We sought to explore the relationship between commonly used measures of insulin sensitivity/resistance (homeostatic model assessment index, serum uric acid, and triglycerides to high-density lipoprotein cholesterol ratio) and left ventricular geometry in normotensive obese children. METHODS: In this cross-sectional study, 32 normotensive obese children were examined. Transthoracic echocardiography was used to measure left ventricular mass index and relative wall thickness. Homeostasis model assessment index, serum uric acid level, and a ratio of triglycerides to high-density lipoprotein cholesterol were used as markers of the insulin resistance. Simple and partial correlation analyses (to control for the effects of body mass index) were conducted to explore relationship between studied variables and left ventricular mass index or relative wall thickness as outcome variables. RESULTS: We found positive correlations between homeostasis model assessment index and relative wall thickness (r = 0.47, p = 0.03) which remained significant after controlling for the effect of body mass index, z-score (r = 0.48, p = 0.03). The cutoff level of homeostasis model assessment index with the optimum sensitivity (Sn) and specificity (Sp) derived from the receiver operating characteristic (ROC) curves for predicting concentric remodelling was ≥5.51 with Sn = 83.33 and Sp = 68.75. CONCLUSION: There is a positive relationship between homeostasis model assessment index and relative wall thickness of obese normotensive children which may help to distinguish at risk obese normotensive children for the development of concentric left ventricular remodelling.

First report on the nationwide prevalence of paediatric type 1 diabetes in Serbia and temporal trends of diabetes ketoacidosis at diagnosis-a multicentre study.

We aimed to collect data on all paediatric patients who were diagnosed with type 1 diabetes mellitus (T1DM) between the years 2000 and 2019 in Serbia and estimate for the first time its prevalence. Also, the trends of diabetes ketoacidosis (DKA) occurrence at the time of diagnosis are monitored. We collected and retrospectively analysed the data of patients <19 years with newly diagnosed T1DM. T1DM was diagnosed in 3134 patients (53.2% male). Total number of youth <19 years with T1DM was 1735 with prevalence of 135.25/100000 at the end of study period. T1DM was diagnosed most frequently between the ages of 5 and 11 years (42.1%). At the time of diagnosis, 35.7% presented in DKA. The incidence and severity of DKA were more significant at the youngest age (p<0.001). There were significant annual percentage increase (2.2%) in the number of new cases of DKA (p=0.007). Conclusion: This first report of nationwide prevalence of T1DM in youth shows that Serbia is among countries with high prevalence of T1DM in youth. System changes are needed in order to provide better quality of health care to these patients.

Lipid profile and left ventricular geometry pattern in obese children.

BACKGROUND: Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular and all-cause mortality. Previous studies reported conflicting results concerning the relationship between serum lipid levels and left ventricular geometry pattern. We sought to explore the relationship between standard serum lipid profile measures with left ventricular geometry pattern in obese children. PATIENTS AND METHODS: In this cross-sectional study, a total of 70 obese children were examined. Fasting blood samples were taken to measure total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TGs), glucose, and insulin. Based on these values TG/HDL ratio, BMI and HOMA index were calculated. We also measured the average 24-h ambulatory systolic blood pressure (SBP) and two-dimensional (2/D) transthoracic echocardiography was performed to determine left ventricular mass index (LVMI) and relative wall thickness (RWT). Multiple regression analyses were conducted to explore relationships between study variables and the LVMI or RWT as outcome variables. The final model with LVMI included TG/HDL ratio, BMI, 24 h-average SBP, age and sex, while for the RWT we included BMI, insulin, age and sex. RESULTS: Our study included 70 children (65.71% boys and 34.29% girls) median age (14 years, IQR = 12-16)." We demonstrated independent and positive association of TG/HDL ratio, BMI and 24 h-average SBP with LVMI (effect = 3.65, SE = 1.32, p < 0.01; effect = 34.90, SE = 6.84, p < 0.01; effect = 0.32, SE = 0.12, p < 0.01, respectively). On the other hand, in model with RWT as outcome variable, only BMI and insulin were significantly linked (BMI: effect = 13.07, SE = 5.02, p = 0.01 Insulin: effect = 2.80, SE = 0.97). CONCLUSION: Increased TG/HDL ratio in obese children is associated with the development of eccentric left ventricular hypertrophy while increased BMI and insulin were associated with concentric left ventricular hypertophy.

Standardized Map of Iodine Status in Europe.

Background: Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods: We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results: In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from -36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 µg/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 µg/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC <150 µg/L. Conclusions: We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.

Serum uric acid and left ventricular geometry pattern in obese children.

BACKGROUND: Relative importance of traditional and non-traditional components of metabolic syndrome (MetSy) as risk factors for subclinical target organ damage in obese children is still under investigation. Recent studies highlight the role of serum uric acid (SUA) as an emerging non-traditional independent risk factor which correlates with obesity, MetSy, type 2 diabetes, preclinical cardiac and extracardiac organ damage, as well as cardiovascular events. AIMS: To study the relationship between SUA and left ventricular geometry pattern in obese children with or without MetSy. PATIENTS AND METHODS: In this cross-sectional study, a total of 73 obese children, 64.4% male, and 35.6% female, with median age of 15 years (IQR = 12-16) were examined. Body mass index, glycaemia, standard lipid profile, fasting insulin level, HOMA index, serum uric acid level, 24-h average systolic blood pressure, left ventricular mass index (LVMI) and relative wall thickness (RWT) were evaluated in all children. RESULTS: LVMI in our study group was 46 g/m2.7 (IQR = 42-55) while the RWT was 37% (IQR = 31-41). Median SUA level was 341 µmol/L (IQR = 283-387). In the entire sample of children, SUA was independently associated with the RWT (coeff = 0.02, p < 0.01). In a sub-group of metabolically unhealthy children, we found no statistically significant association between SUA and LVMI nor between SUA and RWT (coeff. = 0.002, p = 0.92; coeff. = 0.01, p = 0.20, respectively). CONCLUSION: Serum uric acid is an important independent non-traditional risk factor for the development of concentric left ventricular geometry in obese children. These findings deserve further investigation to determine whether high SUA in obese children may be a therapeutic target.

Therapeutic role of methotrexate in pediatric Crohn's disease.

The main role of therapy in Crohn's disease (CD) is to achieve long-term clinical remission, and to allow for normal growth and development of children. The immunomodulatory drugs used for the maintenance of remission in CD include thiopurines (azathioprine and 6-mercaptopurine) and methotrexate (MTX). Development of hepatosplenic T-cell lymphoma in some patients with inflammatory bowel disease, treated with thiopurines only or in combination with anti-tumor necrosis factor agents, resulted in a growing interest in the therapeutic application of MTX in children suffering from CD. This review summarizes the literature on the therapeutic role of MTX in children with CD. MTX is often administered as a second-line immunomodulator, and 1-year clinical remission was reported in 25-69% of children with CD after excluding for the use of thiopurines. Initial data on MTX effectiveness in mucosal healing, and as a first-line immunomodulator in pediatric patients with CD, are promising. A definite conclusion, however, may only be made on the basis of additional research with a larger number of subjects.

Comparison of weight and length at birth of non-Roma and Roma newborn in Serbia.

OBJECTIVES: Roma infants tend to be smaller and are diagnosed as SGA more often than non-Roma infants, suggesting that specific anthropometric norms for these infants may be useful. We aimed to construct population-based centile, gender-specific charts for birth weight and length for singleton Roma infants born from 35 to 42 weeks of gestation and to compare it with anthropometric data of non-Roma infants. METHODS: We analyzed data on 27,602 non-Roma (53 % males) and 2235 Roma (51 % males) singleton live infants delivered from 2006 to 2012 in South East Serbia. The LMS method was used to estimate the birth weight and length centiles. RESULTS: Roma infants were up to 12 % lighter and up to 4 % shorter than non-Roma infants. Estimated centile charts for Roma males and females were constructed showing the 3rd, 10th, 25th, 50th, 75th, 90th and 97th centiles. CONCLUSIONS: We created the separate centile charts for Roma ethnic group. The sample size was sufficient to demonstrate differences in mean birth weights and lengths of at term infants born during the study period.

The relationship between currently recommended ambulatory systolic blood pressure measures and left ventricular mass index in pediatric hypertension.

This study aims to explore the relationship between currently recommended ambulatory blood pressure (ABP) measures used to classify pediatric hypertension and left ventricular mass index (LVMI) in children with true ambulatory hypertension. We performed a cross-sectional survey among 94 children who were consecutively referred for suspected hypertension. The calculated ABP measures were average 24-h systolic blood pressure (24-h aSBP) and 24-h SBP load. The LVMI was estimated by M-mode echocardiography using Devereux's formula and indexed by height(2,7). A total of 35 children fulfilled the criteria for true ambulatory hypertension (elevated office blood pressure, 24-h SBP load >25 %, and 24-h aSBP >95th percentile). Compared with children not fulfilling these criteria, those with true ambulatory hypertension had significantly higher values of 24-h aSBP, 24-h SBP load, and LVMI, as well as body mass index (BMI; P < 0.0001). In a separate analysis of both groups, none of the examined ABP measures adjusted for age, sex, and BMI correlated with LVMI. In those with true hypertension, only BMI was significantly associated with increased LVMI (F = 9.651; P = 0.004; adjusted R (2) = 0.203). The results of our study suggest that pediatric hypertension, as determined by currently recommended ABP (SBP) measures, is not associated with subclinical end-organ damage as defined by the increased left ventricular mass. Therefore, additional factors associated with BMI increase must be considered as risk factors for the development of end-organ damage in hypertensive children.

New insights into septo-optic dysplasia.

Septo-Optic Dysplasia (SOD) is a rare disorder with postulated genetic and environmental etiology. Whilst initially considered as a very rare disease (defined as incidence of approx. 1 in 50,000 births) recent data gave a reported incidence of 1 in 10,000, with equal sex distribution. The diagnosis of SOD is predominantly a clinical one, and made with the presence of two or more features of the classic triad: 1) hypopituitarism, 2) optic nerve hypoplasia, and 3) midline brain defects, typically absence or hypoplasia of the septum pellucidum and/or corpus callosum. Hypopituitarism ranges from isolated to multiple hormone deficits, with diabetes insipidus in a minority. The condition is heterogeneous and may also manifest additional brain defects. Although homozygous mutations in the homeobox gene HESX1 have been identified in SOD, these are uncommon and genetic diagnosis can be made in only <1% of patients with autosomal recessive inheritance. Autosomal dominant inheritance has also been reported. SOX2, SOX3 and OTX2 mutations have also been identified in some forms of SOD. The aetiology of SOD is uncertain but viral infections, environmental teratogens and vascular or degenerative damage have been postulated to account for its sporadic occurrence. Other factors (endogenous or exogenous) include parental age, parity, smoking, alcohol and substance abuse, antenatal bleeding, and ethnicity. Cocaine abuse during pregnancy, which is a potent vasoconstrictor has recently been identified as a potential external cause. The phenotype of SOD is highly variable; the clinical picture may include visual impairment, short stature, obesity and sleep-wake inversion. Approximately 75-80% of patients exhibit optic nerve hypoplasia, which may be the first presenting feature. Pituitary insufficiency may evolve over time, and children with possible SOD must be kept under careful endocrine follow-up. Untreated hormonal abnormalities will further jeopardize neurodevelopment of children with SOD and could also lead to life-threatening adrenal crises. The attention should be focussed on early diagnosis and treatment and education of paediatricians how to recognize this complex disorder.

The degree of H19 hypomethylation in children with Silver-Russel syndrome (SRS) is not associated with the severity of phenotype and the clinical severity score (CSS).

BACKGROUND: Hypomethylation of the imprinting control region 1 (ICR 1) at the IGF2/H19 locus on 11p15 is linked to Silver-Russel syndrome (SRS). METHODS AND RESULTS: We tested the hypothesis that the severity of the phenotype in SRS patients is dependent on the clinical severity score (CSS) (1). Three SRS patients were clinically scored and their scores ranged between 12, 13 and 13. Two of the three SRS patients (66%) had hypomethylation of one allele. CONCLUSION: All three patients had high CSS. Nevertheless, only two of them had hypomethylation of one H19 allele. Interestingly, two of them had ventricular septal defects, but only one had H19 hypomethylation. All children had low birth length and weight, a classic facial phenotype, haemihypertrophy (>2.5 cm thinner left arm/leg in comparison to the right one), shorter leg, and striking thinness (BMI of >16.0). One child was operated for cryptorchidismus, and the same child had elbow contracture. Two children had scoliosis. All three children were short (-3 to 5.5 SD), and treatment with GH resulted in growth on the third percentile. Since one child had no hypomethylation and two had a lower degree of hypomethylation, the higher CSS (12, 13 and 13) was not followed by a higher degree of hypomethylation of the IGF2/H19 locus.

The therapeutic efficacy of propranolol in children with recurrent primary epistaxis.

We hypothesized that some characteristics of beta-blockers, including negative inotropic, peripheral vasoconstrictor, and antiangiogenic effects, might be potentially useful in treating children with epistaxis. From June 2010 to March 2012, a total of seven children with recurrent primary epistaxis resistant to conventional management were observed at our institution. An overall effectiveness of propranolol was noted in all seven children when given a dose of 1.5-2 mg/kg/day (divided into three doses) as a second line therapy for terminating epistaxis. Based on our first experience, we believe that propranolol could be a favorable treatment option for patients with primary epistaxis.

Hypopituitarism occurring in neonatal sepsis.

We report here a case of acquired hypopituitarism in a female neonate with Salmonella enteritidis sepsis and cystic encephalomalacia, after prolonged dopamine administration. Severe hyponatremia was suggestive of hypopituitarism development and the later was documented by hormonal status. This is the first report of infectious hypophysitis in neonatal age. The careful monitoring of pituitary function should be recommended for septic patients exposed to prolonged use of dopamine.

Determinants of atherosclerosis in children and adolescents with diabetes type 1.

INTRODUCTION: To evaluate the degree of atherosclerosis in children and adolescents with type 1 diabetes and its correlation with risk factors, traditional and other, such as anti-oxidative capacity of circulating blood and level of lipid peroxidation. MATERIAL AND METHODS: Forty children and adolescents with type 1 diabetes with mean age 13.7 years were compared with 20 age- and sex-matched healthy control subjects. Association of carotid artery intima-media thickness (cIMT) with different risk factors measured in children with type 1 diabetes was evaluated. RESULTS: Mean carotid IMT was higher in subjects with diabetes (p 〈 0.01) and was strongly associated with total cholesterol with an odds ratio of 4.08 (p = 0.016), LDL-cholesterol with an odds ratio of 2.78 (p = 0.037), length of disease with an odds ratio of 1.87 (p = 0.007) and positive family history (first- and second-degree relatives) of diabetes and early CVD (heart attack and/or stroke before the age of 60 years) with an odds ratio of 6.8 (p = 0.007). CONCLUSIONS: We found significantly increased cIMT in the diabetic patients compared to the healthy control subjects. Risk factors for the development of atherosclerosis included higher total and LDL-cholesterol, higher systolic blood pressure, positive family history of diabetes and early CVD and longer diabetes duration. In spite of the documented increased oxidative stress, we failed to establish a correlation between the oxidative stress parameters and cIMT values.

Deep nasopharyngeal aspiration as a treatment option for conversion of supraventricular paroxysmal tachycardia in infants: First experiences.

OBJECTIVE: Supraventricular paroxysmal tachycardias are the most common paroxysmal rhythm disorders in childhood. Atypical clinical presentations as well as their ability to induce hemodynamic deterioration imply necessity for arrhythmia rapid termination during the first months of life. The objective of this article was to evaluate the efficiency of deep nasopharyngeal aspiration as a potential vagal maneuver for supraventricular paroxysmal tachycardias termination. DESIGN: Clinical trial. PATIENTS AND METHODS: From June 2005 to October 2009, a total of eight infants, who were admitted at our institutions and diagnosed to have supraventricular paroxysmal tachycardias, were analyzed. To terminate supraventricular paroxysmal tachycardias "diving" reflex was initially tried and in the cases of its inefficacy, deep nasopharyngeal aspiration was performed. MAIN RESULTS: Nasopharyngeal aspiration successfully converted arrhythmia in three infants (37.5%). CONCLUSIONS: Deep nasopharyngeal aspiration could be an alternative vagal maneuver for infants with supraventricular paroxysmal tachycardia.

A case of acute tuberculous pleuropneumonia in a patient with acute lymphoblastic leukemia.

Respiratory system infections are the most common complications in immunocompromised cancer patients. We here report a 14-year-old male who was admitted to the hospital because of acute pneumonia, who had been diagnosed with acute lymphoblastic leukemia (ALL) when he was 12 years old. A diagnosis of acute tuberculous pleuropneumonia was made based on clinical and radiographical findings, and Mycobacterium tuberculosis was identified by Ziehl-Neelson acid-fast stain and culture on Löwenstein-Jensen medium. Twenty months before pneumonia onset, the patient had been treated with immunosupressive therapy (ALL IC-BFM 2002 protocol).

Thymus as a target tissue of glucocorticoid action: what are the consequences of glucocorticoids thymectomy?

Glucocorticoids represent the most powerful endogenous anti-inflammatory and immunosuppressive effectors, interfering with virtually every step of immunoinflammatory responses. Glucocorticoids are often the most effective therapy in the prevention or suppression of inflammation and other immunologically mediated processes, but their use is limited by systemic side effects induced by the over-production of reactive oxygen species, causing dysregulation of physiological processes. The thymus is an organ with both endocrine and immune functions. Glucocorticoids induce thymocyte apoptosis, causing a profound reduction in thymic mass and volume and inducing hormonal thymectomy. The clinical aspects of glucocorticoid thymectomy are not under enough investigation. These unwanted systemic side effects may be the consequence of prolonged therapeutic application of glucocorticoids and prolonged or chronic activation of the hypothalamic-pituitary adrenal axis, which may lead to increased and prolonged secretion of glucocorticoids. This review will discuss the metabolic effects of glucocorticoids in the context of thymic physiology asthe primary sex hormone-responsive organ.

[Neurotoxicity during induction treatment of childhood acute lymphoblastic leukaemia--two case reports].

INTRODUCTION: During chemotherapy of acute lymphoblastic leukaemia (ALL), children sometimes exhibit neurological disturbances. Chemiotherapeutic regimens include methotrexate, administered either intravenously or via intrathecal route. Although multiple drugs are used in addition to methotrexate, the acute neurotoxicity reported in patients is usually attributed to methotrexate. The acute neurotoxicity usually results in stroke-like symptoms such as aphasia, weakness, sensory deficits, ataxia and seizures. OUTLINE OF CASES: From 2002 until January 2008, 32 children with ALL were diagnosed and treated at the Children's Hospital in Nis. The patients' age ranged from 1.5 to 16 years. They were treated in accordance with the protocol ALL IC-BFM 2002 (ALL Intercontinental Berlin Frankfurt Münster 2002). Two of the patients (6.25%) exhibited neurotoxicity. After the occurrence of neurological symptoms, the patients were ophthalmologically and neurologically examined. In addition, the magnetic resonance (MR) imaging, computerized tomography and electroencephalography were applied. The paper presents two patients, aged 9 and 15 years respectively, who exhibited acute neurotoxicity--methotrexate encephalopathy during ALL treatment. Both patients had tonic-clonic seizures and neurological symptoms in the course of the induction therapy. Neurotoxicity occurred 7 days after the third, and 3 days after the fourth intrathecal methotrexate therapy. MR images confirmed multi-focal morphological changes of brain density in one of the patients, while the other patient had normal CT reading. Even though the development significantly differed, the changes were reversible in both patients. CONCLUSION: The neurotoxicity in patients with ALL can be combined with significant structural changes of the brain, but also morphological changes can be absent. Several questions concerning aetiology and treatment of neurological events are raised.

Orexitropic signaling proteins in obese children.

Adipose tissue is not only the main organ for energy storage, but it also has endocrine properties, producing "adipokines" responsible for energy homeostasis, insulin sensitivity, and inflammation. Leptin, produced by adipocytes, is the key hormone in appetite regulation and suppression of orexigenic, hypothalamic neuropeptide Y (NPY). We wanted to establish and compare levels of leptin and NPY in different obesity types in childhood, and to investigate their correlations with auxological parameters. Twenty-one obese children (seven girls and 14 boys), divided into two groups, were compared with 14 controls. The mean age of the study group was 10.81 +/- 3.69 years and the mean puberty stage was 2.21. The mean body mass index (BMI) was 32.80 kg/m2 (range 23.30-47.02) and the mean overweight 30.73 kg (range 8.00-74.00). The mean leptin level was higher in boys and in the group with central obesity, but was not significant. Leptin/NPY ratio and leptin/BMI ratio was also higher in the central obesity group and there was a more significant difference compared with controls. We found significant correlation of the leptin level with body mass (BM), body mass excess (BME), and BMI (p < 0.05). The mean leptin level in obese children was very high (36.39 ng/ml). Leptin and NPY levels showed inverse values in two different obesity types. Results are suggestive for leptin resistance rather than leptin deficiency in our group of obese children. Orexitropic signaling proteins correlated significantly with auxological parameters. Determination of the leptin and NPY concentrations provided evidence that obesity represents disease with neuroendocrine dysfunction and high leptin/NPY ratio, which could be a useful marker for central obesity.

Heart rate variability in children with idiopathic ventricular tachycardia.

Idiopathic ventricular tachycardia (IVT) is a rare arrhythmia in children. A great deal of uncertainty and numerous questions still remain regarding the extent of investigation, therapy, and long-term prognosis for children with IVT. The existence of subclinical cardiac disease, as well as of autonomic dysfunction in patients with ventricular arrhythmias, has been well documented. A number of experimental and clinical studies have suggested that imbalances within the cardiac autonomic system's activity may be crucial in the generation of ventricular tachycardia, irrespective of the presence of cardiovascular pathological substrate. Heart rate variability (HRV) analysis provides a useful method for measuring the autonomic activity. This study evaluates HRV in children with IVT. The study included 31 children with ventricular arrhythmia who were divided into two groups: (1) patients with frequent ventricular extrasystoles (VES) and (2) patients with IVT. The control group comprised 23 healthy children without pathological findings on 24-h ECG Holter. Twenty-four-hour ambulatory electrocardiography recordings were obtained, and the time-domain variables were calculated. HRV was compared to age-related normal values. It was observed that the overall heart rate variability is diminished in children with IVT. We recommend HRV analysis of any child with IVT. Quantification of the autonomic nervous system activity using time domain analyses may be a helpful diagnostic tool in the clinical assessment and initial evaluation of these children.