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There is evidence that stress and psoriasis interact bidirectionally. Specifically, stress is not only induced by psoriasis, but it is also considered a precipitating factor for onset or exacerbation of the disease. Neuroendocrine alterations of the stress system have been implicated in this association.To assess the diurnal rhythm of the hypothalamic-pituitary-adrenal (HPA) axis and hair cortisol levels in patients with psoriasis compared to healthy controls, and further explore whether suggested alterations in HPA axis activity are related to anthropometric, psychological, and disease activity/severity indices.We assessed stress levels quantified by questionnaires, psoriasis severity, and stress system activity based on HPA axis biomarkers. The sample comprised 18 adult patients with exacerbation of non-pustular psoriasis compared to 18 healthy controls (18-65 years old). In particular, salivary cortisol diurnal profiles and hair cortisol concentration were evaluated in both groups. Five distinct salivary samples were collected during a day of rest and 3-cm hair segments were cut.A higher prevalence of self-reported anxiety, stress, and depressive symptoms was reported among psoriatic patients compared to healthy controls. Also, blunted salivary cortisol diurnal rhythm in psoriatic patients and a positive correlation of salivary cortisol concentration with state anxiety and psoriasis severity were revealed. No associations were shown between hair cortisol concentrations and disease presence/severity.We provide preliminary evidence that psoriasis patients may demonstrate a hypofunctional HPA axis, while our findings also suggest a complex interaction between HPA axis activity, psychosocial status and pathophysiological processes in psoriasis.

Objectives The aim of our study was to estimate the levels of mental health problems in children with celiac disease (CD) along with their parents' mental health status, to compare these levels with those of healthy controls and to investigate how these problems are affected by a gluten-free diet (GFD). Methods Our study constituted 50 patients with CD at diagnosis before the initiation of a GFD (age 8.6 ± 3.7 years, group A), 39 patients with CD on a GFD for at least 12 months (age 10.4 ± 3.4 years, group B) and 38 healthy controls (age 7.7 ± 3.8 years, group C), as well as their parents. One of the parents of each child completed the Child Behaviour Checklist (CBCL) and the Symptom Checklist 90 (SCL-90-R) to evaluate the children's and parents' mental health problems, respectively. Twenty patients in group A were reevaluated at least 12 months after initiation of a GFD (group D). Results At diagnosis, CD patients had higher scores in the CBCL for internalizing problems than healthy controls (55.7 ± 10.3 vs 47.9 ± 15.4, P = 0.007) and their parents demonstrated increased severity of mental health problems, including anxiety and depression, than the parents of healthy controls (0.72 ± 0.49 vs 0.54 ± 0.58, P = 0.013). Conclusions CD patients at diagnosis and their parents, had more mental health problems, including anxiety and depression, than healthy controls.

Prospective studies indicate that the exposure to organochlorine pesticides (OCPs) during fetal life, infancy, and early childhood may be associated with features of neurodevelopmental disorders in children. However, few studies have investigated the concentrations of serum OCPs in children with categorically diagnosed neurodevelopmental disorders. The aim of this study was to assess the concentrations and detection rates of dichlorodiphenyltrichloroethane (DDT) metabolites, hexachlorocyclohexane (HCH) isomers, cyclodienes, and methoxychlor in serum samples of children with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and specific learning disorder (SLD), all of normal intelligence, compared to typically developing controls (TD). In total, 114 schoolchildren, aged 6-13 years old, were assessed and distributed into four groups: ASD (n = 39), ADHD (n = 21), SLD (n = 32), and TD (n = 18). Each clinical group was compared to the TD group. Concentrations of serum OCPs were determined by gas chromatography and are presented as ng/g lipid. Concentrations of β-HCH, the sum of HCH isomers, and o,p'-DDD were significantly higher in ASD children: ASD vs. TD (mean ± SD): 10.5 ± 7.7 vs. 6.1 ± 4.0, (p = 0.049); 12.0 ± 10.3 vs. 6.6 ± 4.0, (p = 0.025); 7.4 ± 6.5 vs. 2.8 ± 2.3, (p = 0.0019), respectively. The detection rates of p,p'-DDT, at least one substance from DDTs detected, and the cyclodiene heptachlor epoxide, were significantly lower in the ASD group: ASD vs. TD: 12.8% vs. 38.9%, (p = 0.037); 69.2% vs. 94.4%, (p = 0.044); 10.3% vs. 38.9%, (p = 0.026), respectively. No significant differences between the ADHD or SLD groups and the TD group were observed. We demonstrated higher serum concentrations and lower detection rates of selected OCPs in ASD than TD children. Our results add to potential neurodevelopmental concerns surrounding OCPs and provide evidence of specificity in the relations between HCHs and ASD.

Context The adrenal gland undergoes substantial remodeling during the neonatal period, an essential developmental process that remains incompletely understood. With respect to control over the remodeling process and, specifically, the role of thyroid hormones (THs), no human studies have been published. The effects of both hypo- and hyperthyroidism have only been evaluated in adults, focusing on the mature adrenal. Recent studies have identified expression of the TH receptor β1 in the mouse adrenal X-zone and have demonstrated that TH administration could alter the postnatal adrenal remodeling process. Objective To address whether THs influence adrenal steroid profiles and adrenal remodeling during the neonatal period. Methods We compared the adrenal steroid profile of a naturally occurring prototype, female neonates with severe congenital hypothyroidism (CH) (n = 22, upon diagnosis of CH), with that of euthyroid neonates (n = 20). Results Significantly higher levels of adrenal steroids (17-OH-progesterone, dehydroepiandrosterone sulfate, Δ4-androstenedione, and testosterone) were measured in neonates with severe CH compared with euthyroid neonates and returned to within normal range after euthyroid state had been established on l-thyroxine replacement therapy, whereas cortisol levels did not differ. TSH values in the CH group were positively correlated with circulating adrenal steroids, whereas free T4 levels were negatively correlated with circulating adrenal steroids. Conclusions The hormonal profile of female neonates with severe CH suggests a more active adrenal fetal zone compared with control subjects. These data indirectly associate THs with the adrenal remodeling and maturation process in humans. Based on our results, we suggest that severe hypothyroidism decelerates the involution of the adrenal fetal zone that normally occurs postnatally.

Previous studies showed that the coronavirus disease 2019 (COVID-19) lockdown imposed changes in adults’ lifestyle behaviors, however, there is limited information regarding the effects on youth. The COV-EAT study aimed to report changes in children’s and adolescents’ lifestyle habits during the first COVID-19 lockdown and explore potential associations between changes of participants’ lifestyle behaviors and body weight. An online survey among 397 children/adolescents and their parents across 63 municipalities in Greece was conducted in April–May 2020. Parents self-reported changes of their children’s lifestyle habits and body weight, as well as sociodemographic data of their family. The present study shows that during the lockdown, children’s/adolescents’ sleep duration and screen time increased, while their physical activity decreased. Their consumption of fruits and fresh fruit juices, vegetables, dairy products, pasta, sweets, total snacks, and breakfast increased, while fast-food consumption decreased. Body weight increased in 35% of children/adolescents. A multiple regression analysis showed that the body weight increase was associated with increased consumption of breakfast, salty snacks, and total snacks and with decreased physical activity. The COV-EAT study revealed changes in children’s and adolescents’ lifestyle behaviors during the first COVID-19 lockdown in Greece. Effective strategies are needed to prevent excessive body weight gain in future COVID-19 lockdowns.

BACKGROUND Aquagenic wrinkling of the palms (AWP) is an excessive and early palmar wrinkling occurring after Brief Immersion to Water (BIW), and has been reported as a frequent finding among cystic fibrosis (CF) patients. OBJECTIVES To evaluate and assess the diagnostic performance of BIW test as an initial screening tool for CF diagnosis. METHODS We measured AWP in CF patients, CF-heterozygotes (CF-het) and normal controls. The AWP parameters of palmar wrinkling, oedema, papules, pruritus and pain were assessed at 3, 7 and 11 min after a BIW test was performed for all the participants. Statistical analyses explored the progression of AWP in time for the three groups and assessed the diagnostic performance of BIW test as a diagnostic screening tool for CF. RESULTS A total of 250 individuals (100 CF patients, their 50 CF-het parents, 100 healthy controls) were included in the analysis. The average age in years (mean ± SD) was 10.4 ± 4.0 for CF, 35.9 ± 6.1 for CF-het and 10.5 ± 4.0 for controls. The rate of positives for AWP at 3 min among CF patients, CF-het and controls was 68%, 8% and 0%, respectively (P

Background Functional constipation (FC) is the most common gastrointestinal disorder of childhood and has a multifactorial etiology. We aimed to assess dietary habits in Greek children with FC compared to the general population (control group, CG). Methods This was a subgroup analysis of a school-based, cross-sectional study carried out in children 6-18 years of age, between January and June 2014, using the Rome III criteria for the diagnosis of FC. Dietary parameters, as well as socioeconomic and demographic data and their association with the likelihood of FC, were analyzed through multivariate logistic regression analysis and expressed as odds ratios (OR). Results A total of 1439 children (1218 CG, 221 FC) were included in the analysis. The final model showed that consumption of was the only dietary parameter significantly related to FC; higher frequency of consumption was inversely related to the likelihood of FC (OR: 0.98, 95% CI: 0.96, 0.99, P=0.048). Significant socioeconomic confounders with a positive association with FC were: parental educational level, victimization, physical activity and number of adults at home. Conclusions Increased frequency of fiber consumption is significantly associated with higher odds of FC irrespective of socioeconomic background and lifestyle parameters. Interventional studies are required to validate these cross-sectional observations.

Research on how children with neurodevelopmental disorders perceive, process, and interpret visual illusions (VIs) has been extensively focused on children with autism spectrum disorder providing controversial findings. In this study, we investigated the patterns of vulnerability to a wide set of VIs comprising 23 standard text book VIs and their variations in a clinical sample of children with neurodevelopmental disorders compared to typically developing children (TD). A total of 176 children, aged between 4.6 and 13.8 years old, were distributed into four groups: high-functioning autism (HFA; N = 23), attention-deficit/hyperactivity disorder (ADHD; N = 42), specific learning disorder (SLD; N = 70), and TD (N = 41). Regression models, adjusted for sex, age, and non-verbal IQ, showed that HFA was associated with greater responses accuracy than TD children to the full battery of VIs, to the cognitive illusions, to the distortions, and to both geometrical illusions of size/shape (cognitive distortions) and lightness contrast effects (physical distortions). The susceptibility of ADHD children was found attenuated for illusory contours and greater for paradoxical illusions in comparison with TD children. No significant differences were shown between the SLD group and the TD children. Our findings, which were adjusted for the same duration of visual working memory across groups, showed that there is a potential specific tendency of HFA children to failure of processing visual information in context. Contrarily, children with ADHD showed in general normal global processing such as children diagnosed with SLD.

Background/Aims The abdominal pain-related functional gastrointestinal disorders (AP-FGIDs) affect a significant proportion of the pediatric population and consist 1 of the most frequent causes for seeking medical advice. In this study, we aimed to assess the relation of dietary habits with the likelihood of AP-FGIDs. Methods This was a school-based, cross-sectional study approved by the Greek Government authorities, after obtaining informed consent by the legal representatives of the children. Diagnoses of AP-FGIDs were based on the Greek official translation of the Rome III questionnaire. Demographic, socioeconomic and dietary data were collected through self-reporting or parent-reporting questionnaires. Associations between the probability of AP-FGIDs and dietary practices were assessed after adjusting for known confounders through a multiple logistic regression analysis. Results A total of 1365 children (147 AP-FGIDs and 1218 controls, 52.4% females, mean age: 12.8 ± 2.8 years) were included. Multiple regression analysis identified the following statistically significant confounders: victimization, the presence of a person with a severe health problem at home, female sex, engaging in limited physical exercise, and living in a single adult family. Subsequently, logistic regression, adjusted for the abovementioned confounders, showed that reduced fish and increased junk food consumption were related to a higher likelihood of AP-FGIDs. Conclusions Children with AP-FGIDs report excessive junk-food and reduced fish intake compared to controls. Further studies are needed in order to clarify the nature of this observation.

School bullying is increasingly recognized as an important factor affecting both individual's wellbeing and social functioning. Several studies provide evidence for the potential role of contextual factors that relate to bullying victimization such as the socioeconomic status of the parents/ family, the quality of family and home environment, the school climate, structure and ethos, and also various community characteristics. The objectives of this school-based, cross-sectional study were to report the prevalence of the perception of being bullied in a sample of Greek children and adolescents from 6 to 17 years of age and to investigate the relations among the subjective impression of bullying victimization and several sociodemographic and socioeconomic factors. We hypothesized that influences external to individual children and adolescents play a decisive role to their perception of being victimized. Bullying victimization was measured through a simple "yes/no" question, which confirmed or rejected respectively the fact that the child or adolescent has been at some time victimized in the school environment. Also, demographic and socioeconomic data about the families of children and adolescents were collected. A total of 1,588 children (51.8% females, mean age ± SD: 12.9±2.8 years) were assessed. The overall prevalence of victimization was 10.4%. Multiple logistic regression analysis on the probability of being victimized identified that living at a main urban center (Odds Ratio[OR]: 2.63, CI: 1.78-3.87, p

Background Recent studies have shown that patients with inflammatory bowel disease (IBD) are less likely to be infected with Helicobacter pylori compared with non-IBD patients. We aimed to study the prevalence of H. pylori-positive and H. pylori-negative gastritis in newly diagnosed children with IBD in comparison to those with non-IBD in Greece. Materials and Methods All children who underwent first esophagogastroduodenal endoscopy between 2002 and 2011 were retrospectively included. Four groups were studied: patients with Crohn's disease (CD), ulcerative colitis (UC), IBD unclassified (IBDU), and non-IBD individuals (non-IBD). Helicobacter pylori infection was defined by positive culture or by positive histology and CLO test. Those children with negative or not available culture and only one positive test (histology or CLO) were further evaluated by urea breath test, and the positives were also included in the infected group. Results We studied 159 patients with IBD (66 CD, 34 UC, and 59 IBDU) and 1209 patients in non-IBD individuals. Helicobacter pylori gastritis was less frequent in the IBD group (3.8% vs 13.2% in the control group, p

Crohn's disease (CD) and ulcerative colitis (UC) result in metabolic consequences. We assessed circulating leptin and adiponectin concentrations and examined their relations to glucose metabolism in children with CD and UC.Circulating morning fasting concentrations of leptin, adiponectin, glucose, and insulin were measured in 32 children with CD and 18 children with UC. Insulin resistance (IR) and β-cell function were evaluated by the updated homeostatic model assessments (HOMA2-IR and HOMA2-B).Leptin was positively related to BMI z-scores overall and in the CD and the UC subgroups (P0.001). A negative correlation between leptin and disease activity was observed in the entire population (P = 0.034) and in the UC (P = 0.03) group. None of the assessed parameters was related to adiponectin. Fourteen percent of the participants were insulin resistant (15.6% in the CD group and 11.1% in the UC group), significantly more than expected (P0.001). Leptin was associated with HOMA2-IR (overall: r = 0.29, P = 0.045). Pathway analysis suggested that, overall, disease activity and BMI significantly affect leptin, which in turn is the only correlate of HOMA2-IR.Disease activity was significantly and inversely related to leptin in children with inflammatory bowel disease (IBD). A significant proportion of the patients had increased IR, which is positively related to circulating leptin.

A strict and lifelong commitment to a gluten-free diet (GFD) remains one of the most challenging issues in children with coeliac disease. The present study aimed to record compliance rates and investigate the connection between dietary compliance and demographics, disease-related factors and parental knowledge.Parents of 90 Greek children diagnosed with coeliac disease were recruited from the outpatient gastroenterology clinic of a children's hospital in Athens, Greece. Dietary compliance and a range of demographic and clinical data were obtained from parents through a specially constructed questionnaire. Further data included parental perceived and actual knowledge about coeliac disease and GFD. Compliant and noncompliant groups were compared for measured factors and a multivariate approach was followed to elicit independent effects of compliance determinants.Overall, 44.4% of children with coeliac disease were reported to be compliant to a strict GFD. A 1-year increase in the age of the child was associated with 15% lower odds of adhering to a strict diet after adjusting for other variables (odds ratio (OR)=0.85, 95% CI: 0.75-0.96). Parental perceived knowledge was also independently and significantly associated with dietary compliance (OR=3.3, 95% CI=1.1-9.8). No statistically significant correlation emerged between dietary compliance and other clinical or demographic variables.Low compliance rates to GFD were observed in children with coeliac disease. Information based on children's age and perceived parental knowledge can be used to develop risk profiles that health care professionals can utilise to identify children likely to be noncompliant and thus adjust their counselling strategy accordingly.

Celiac disease (CD) has been associated with HLA class II heterodimers. This study aimed at determining the HLA genotypic and allelic distribution in Greek children with CD as compared with the general population.A total of 118 children with CD and 120 healthy individuals serving as controls were included in the study.Higher frequencies for HLA-DQB1*02:01 (40.25 vs. 9.58%, P0.001) and DQB1*02:02 (20.34 vs. 5.42%, P0.001) were observed in patients with CD, whereas HLA-DQB1*03:01 (16.53 vs. 30.42%, P0.001), DQB1*05:01 (0.85 vs. 10%, P0.001), and DQB1*05:02 (5.51 vs. 17.92%, P0.001) were significantly lower, as compared with the controls. DQA1*02:01 (patients with CD vs. controls: 20.76 vs. 6.67%, P0.001) and DQA1*05:01 (40.25 vs. 9.58%, P0.001) were significantly more frequent in patients. The frequencies of HLA-DQA1* 01:01, *01:02, *01:04, and *05:05 were significantly lower in patients (P0.001). The haplotype mainly associated with CD was DRB1*03-DQB1*02:01-DQA1*05:01; patients with CD vs. controls: 39.83 vs. 9.58%, P0.001. In total, 84.75% of patients carried DQ2 (vs. 21.67% in controls, P0.001), whereas 11.02% were DQ8 positive/DQ2 negative.This study confirms the existing data and provides additional evidence supporting a strong genetic predisposition for CD associated with the class II alleles DQB1*02 and DQA1*05 encoding the serological specificity DQ2.

Obesity is highly co-morbid with anxiety and/or depression in children, conditions that may further worsen the metabolic and cardiovascular risks for obese individuals. Dysregulation of the hypothalamic-pituitary-adrenal axis is involved in the pathophysiology of anxiety disorders, depression, and obesity, and diverse cortisol concentrations may be found in obese children, depending on their degree of psychological distress. The aim of this study was to examine cortisol profiles among obese children with or without symptoms of anxiety and depression. A group of 128 children (53% females; mean age ± SD: 11.2 ± 2.2 years) derived from a pediatric obesity clinic were studied. Anxiety and depressive symptomatology were assessed with appropriate instruments. Morning serum and five diurnal salivary cortisol concentrations were measured. Obese children were 3.1/2.3 times more likely to report state and trait anxiety, respectively, and 3.6 times more likely to report depressive symptoms than children of the same age group, from a contemporary Greek sample. Trait anxiety and noon salivary cortisol concentrations were significantly positively correlated (p = 0.002). Overall, salivary cortisol concentrations were increased in children with anxiety or depression symptomatology compared to obese children without any affective morbidity (p = 0.02) and to those with anxiety and depression co-morbidity (p = 0.02). In conclusion, in obese children, emotional distress expressed by symptoms of anxiety and/or depression is associated with circadian cortisol profiles reflecting a potential pathway for further morbidity. Longitudinal studies may reveal a role of cortisol in linking obesity, anxiety, and depression to the development of further psychological and physical morbidity.

Natural and vaccine-induced immunity to meningococcus C (MenC) was evaluated in asplenic adolescents and adults with β-thalassemia. At baseline 19.3% of patients and 22.8% age-matched controls had positive (>2 μg/ml) naturally acquired Men C- specific IgG antibodies; patients had a lower probability of having protective SBA compared to controls (OR=21, p=0.012). MenC conjugate vaccine (MCC) induced protective IgG concentrations in 63% of patients and 90.1% of controls. SBA increased significantly post vaccination and there were no differences between patients and controls; however patients had significantly lower IgG concentrations post vaccination compared to controls (4.52 vs 10.94 μg/ml, p

Background: With transfusions and chelation therapy, the prognosis for transfusion-dependent beta thalassaemia has changed from being fatal in early childhood to a chronic disorder with prolonged survival. Design and methods: In this historical prospective study, we present survival, causes of death and mortality ratios compared to the general population in 1044 Greek patients with transfusion-dependent beta thalassaemia. Results: At the age of 50 years, the overall survival was 65.0%, while the cardiac death–free survival was 77%. Birth cohort had a significant effect on survival (P

Cardiac Magnetic Resonance (CMR) has replaced all other surrogate measurements in the determination of transfusional cardiac iron overload in patients with thalassaemia major. We aimed to determine the diagnostic value of CMR T2* with respect to cardiac dysfunction (CD) as determined by CMR-derived left ventricular ejection fraction (LVEF). Cardiac T2* values and LVEF measured by CMR were recorded in 303 patients with thalassaemia major, at the time of their first CMR. T2* was correlated with LVEF (regression coefficient: 0·57, P 8 ms and ≤14 ms and reduced to 9·1% in patients with T2* between 14-20 ms. As the probability of CD is progressively, and not suddenly, reduced with increasing values of T2*, CMR has a limited diagnostic value for CD (Receiver operating characteristic analysis, area under the curve = 0·68). Patients with cardiac T2*≤8 ms require careful and intensive management. This risk decreases with increasing values of T2* but even in mildly loaded patients the probability of impaired LVEF is not negligible.

Objectives: Cardiac complications because of transfusional iron overload are the main cause of death in thalassaemia major. New chelators and iron monitoring methods such as cardiac magnetic resonance (CMR) became available after the year 2000. We evaluated the impact of these new management options on cardiac mortality and morbidity.

Background Linear growth restriction is a unique feature of paediatric inflammatory bowel diseases (IBD), and reduced insulin-like growth factor (IGF-1) is a major determinant of short stature. We aimed to assess factors influencing somatic height in children suffering from IBD. Materials and methods This was a retrospective, cross-sectional study conducted after approval by Institutional authorities. Anthropometric data, disease-related factors, biochemical and clinical indices of inflammation and endocrine parameters were recorded and considered as explanatory covariates. A structural equation model analysis was utilized. Somatic height was the outcome of interest, and possible associations of explanatory covariates directly or through the mediation effect of IGF-1 were assessed. Results Systemic inflammation, as expressed by high-sensitivity intereukin-6 (IL-6), and nutritional status described by body mass index (BMI) were the pathways that significantly affected stature through the mediation effect of IGF-1. Cortisol showed a direct, positive and independent of IGF-1 association with height. Conclusions Insulin-like growth factor-1 is a key player in the process that results in impaired linear growth. Malnutrition and systemic inflammation have a restrictive action on growth by reducing circulating IGF-1. The positive relation of serum cortisol to height could correspond to suppressed pituitary-adrenal axis due to long-term use of glucocorticoids.

Varicella-zoster virus vaccine has diminished the consequences of chicken pox in terms of health and economical burden. The increasing number of doses administered worldwide has revealed rare but important adverse effects that had not occurred during clinical trials. We report here the case of an immunocompetent 3½-year-old girl who developed encephalitis and herpes zoster opthalmicus 20 months after her immunization with varicella-zoster virus vaccine. Molecular analysis confirmed the vaccine strain as the causative agent. After an intravenous course with acyclovir, the child made a full recovery with no neurologic sequelae.

Reticulocyte indices are easy to obtain, low cost parameters and have gained interest in the field of diagnosing anaemias of childhood.We assessed distribution, age and gender variation, relation to indices of iron metabolism and diagnostic performance of reticulocyte haemoglobin content (CHr), percentage of microcytic reticulocytes (micro_r), percentage of hypochromic reticulocytes (hypo_r), and percentage of reticulocytes with low CHr (low_CHr) in 386 pre-school children classified in four groups: healthy, iron deficiency (ID), iron deficiency anaemia (IDA), and beta-thalassaemia carriers (beta-thal).Age had a positive effect in CHr (Spearman's rho = 0.21) and a negative effect in hypo_r (Spearman's rho = -0.2) in healthy children. CHr and low_CHr were related to ferritin in the IDA group (Spearman's rho 0.55 and -0.53, respectively). In the beta-thal group, HbA(2) is strongly related to all reticulocyte indices. micro_r and CHr performed best in discriminating between IDA and beta-thal heterozygosity (ROC analysis, area under the curve (AUC): 0.76 and 0.74, respectively). CHr achieved the best AUC (0.58) in identifying ID among children without anaemia.Age, IDA and beta-thal significantly affect reticulocyte indices. CHr and micro_r may have a role as screening tools in discriminating between IDA and beta-thal heterozygosity.

Cardiac and endocrine disorders are common sequelae of iron overload in transfused thalassaemia patients. Combined chelation with desferrioxamine (DFO) and deferiprone (DFP) is well tolerated and produces an additive/synergistic effect superior to either drug alone. 52 thalassaemia major patients were transitioned from DFO to combined chelation with DFO and DFP. Serum ferritin, cardiac and hepatic iron levels were monitored regularly for up to 7 years, as were cardiac and endocrine function. Patients' iron load normalized, as judged by ferritin and cardiac and hepatic magnetic resonance imaging findings. In all 12 patients receiving treatment for cardiac dysfunction, symptoms reversed following combined chelation, enabling nine patients to discontinue heart medications. In the 39 patients with abnormal glucose metabolism, 44% normalized. In 18 requiring thyroxine supplementation for hypothyroidism, 10 were able to discontinue, and four reduced their thyroxine dose. In 14 hypogonadal males on testosterone therapy, seven stopped treatment. Of the 19 females, who were hypogonadal on DFO monotherapy, six were able to conceive. Moreover, no patients developed de novo cardiac or endocrine complications. These results suggest that intensive combined chelation normalized patients' iron load and thereby prevented and reversed cardiac and multiple endocrine complications associated with transfusion iron overload.

Background: Cardiac complications are the leading cause of death in thalassaemic patients (TM) worldwide. Improved management protocols including new chelators and imaging have reduced cardiac-related deaths but also require more advanced analytical methods to reflect temporal fluctuations in mortality risk. Objectives: To evaluate time patterns of risk of cardiac death in TM patients according to birth cohort, gender and degree of haemosiderosis and to apply new flexible methods of analysis that may allow assessment of trends in risks as affected by innovations in management. Design and methods: Cardiac-free survival and time trend of the risk of cardiac-related death were assessed in 648 transfusion-depended thalassaemic patients (48.3% females) managed in a single unit located in Athens, Greece. Patients were classified according to birth cohort (prior or after 1/1/1975) and according to the severity of haemosiderosis (mild, moderate and severe) as estimated by the mean ferritin levels during the last 5 yr of follow-up. Results: The median time of observation was 27.8 yr and 84 cardiac deaths were recorded. A parametric analysis predicted a non-monotonous time pattern for the cardiac risk with an initial increasing phase until the fourth decade of life followed by a drop off in deaths. Women have 23% longer life expectancy than men (P = 0.010) while patients born after 1975 die of heart complications at an older age compared to those born prior to 1975 (time ratio = 1.34, P = 0.003). Patients with mild and moderate haemosiderosis lived 89% (P

Pediatric obesity commonly co-exists with emotional and behavioral disorders, while disturbed cortisol concentrations have been reported in both obese and chronically stressed individuals with anxiety and/or depression. We investigated the prevalence of internalizing and externalizing problems, reported by both parents and children, in a clinical population of obese children (OC) compared to normal-weight children. We examined the role of cortisol as a potential mediator between obesity and such problems.We compared 110 obese with 31 normal-weight children. The Greek version of the child behavior checklist (CBCL) and the youth self-report (YSR) were used and salivary cortisol was determined serially five times a day.T-scores of internalizing problems (anxiety/depression, social withdrawal, somatic complains) reported by both children (49.3±12.3 vs. 43.2±9.1) and mothers (60.6±11.3 vs. 50.6±10.4) were significantly higher (p=0.03 and p0.001, respectively) in the obese than in the lean children. Externalizing problems (delinquency, rule-breaking behaviors) reported only by mothers were significantly higher in the OC (57.2 ±10.5 vs. 48.2±13.3, p=0.003). The cortisol area under the curve (AUC) was significantly smaller (p=0.03) in the OC than in the controls; however, a cortisol correlation with internalizing/externalizing symptoms was not observed.There is a high prevalence of internalizing and externalizing problems in a clinical population of OC. A mediation effect of cortisol in the relation between internalizing/externalizing problems and obesity could not be supported.

ObJEctIVE: childhood obesity and the Metabolic syndrome (Mets) are associated with an increased risk for early onset endothelial dysfunction and atherosclerosis. Placental growth factor (PlGF), a member of the vascular endothelial growth factor family, plays an important role in atherosclerosis by stimulating angiogenesis and atherogenic migration of monocytes/ macrophages into the arterial wall. the aim of this study was to investigate differences in circulating PlGF concentrations between children with obesity/metabolic syndrome and non-obese children. We have previously shown increased high-sensitivity troponin (hs-tnt) concentrations in children with Mets from the same cohort. DEsIGN: Fifty-seven obese (49 without and 8 with Mets) and 25 non-obese children (controls) were assessed at the childhood Obesity clinic of our Department. Obesity was defined using the IOtF criteria. Mets was defined based on the IDF criteria. PlGF was measured using electrochemiluminescence methodology. rEsULts: Mean PIGF concentrations of obese children were significantly higher (p=0.048) compared with those of the controls. Analysis of the three groups, the οbese (without MetS), the MetS and the control, demonstrated a significant difference in PlGF concentrations (p=0.035). subgroup analysis revealed increased PlGF concentrations in children with the Mets compared to the controls (p=0.009). troponin had a significant positive correlation with PlGF overall (p=0.003) and in the obese group (p=0.046). cONcLUsIONs: Increased serum concentrations of PlGF, a biomarker of angiogenesis, are found in obese children with the Mets compared to non-obese controls, whereas PlGF correlated positively with troponin. Longitudinal studies may reveal the prognostic role of this biomarker in the progression of atherosclerosis in obese children with the Mets.

AIM To assess the impact of disease characteristics on the quality of life (QOL) in children with inflammatory bowel diseases (IBD). METHODS This was a cross-sectional study conducted at the First Department of Pediatrics of the University of Athens at the "Aghia Sophia" Children's Hospital. Children diagnosed with Crohn's disease (CD) or ulcerative colitis (UC), who were followed as outpatients or during a hospitalization, participated, after informed consent was obtained from their legal representative. QOL was assessed by the IMPACT-III questionnaire. Demographic data and disease characteristics were also collected. Statistical analyses included parametric (Student's t-test and Pearson's r) and non-parametric (Mann-Whitney test, Fisher's test and Spearman's rho) procedures. RESULTS Ninety-nine patients (UC: 37, 73.0% females, CD: 62, 51.6% females), aged 12.8 ± 2.6 years were included. Overall, as well as, sub-domain scores did not differ between UC and CD (overall score: 73.9 ± 13.3 vs 77.5 ± 11.2, respectively, P = 0.16). In the entire sample, total score was related to physician's global assessment (PGA, patients classified as "mild/moderate" active disease had, on average, 14.8 ± 2.7 points lower total scores compared to those "in remission", P < 0.001) and age at IMPACT completion (Pearson's r = 0.29, P = 0.05). Disease activity assessed by the indices Pediatric Ulcerative Colitis activity index, Pediatric Crohn's disease activity index or PGA was significantly associated with all subdomains scores. Presence of extraintestinal manifestations had a negative impact on emotional and social functioning domains. CONCLUSION Disease activity is the main correlate of QOL in children with IBD, underlining the importance of achieving and sustaining clinical remission.

Objectives Beta thalassaemia major (β-TM) and sickle-cell disease (SCD) are severe haemogobinopathies requiring life-lasting, advanced medical management. In the Mediterranean region, both conditions occur with high frequency. We assessed the efficacy of the National Program for the Prevention of Haemoglobinopathies in Greece during the last 30 yrs. Methods Data of affected births between 01/01/1980 and 31/12/2009 were collected in a nationwide scale, and expected vs. observed rates of new births were calculated and compared. In a subpopulation of affected births of Greek origin, the causes for occurrence of the new affected birth were also collected and analysed. Results Overall, the reduction in new cases was 81.1% and 84.6% for β-TM and SCD, respectively. For β-TM, a constant declining trend was recorded over the 30-yr period, whereas for SCD, a transient reversal was observed in the mid-1990s probably due to the significant influx of immigrants of African origin. Programme failure was 2.2 times more common among new β-TM births of Greek origin compared to new SCD cases (P

Microvillus inclusion disease (MVID), a rare severe congenital enteropathy characterized by intracytoplasmic microvillous inclusions and variable brush border atrophy on intestinal epithelial cells histology, is associated with defective synthesis or abnormal function of the motor protein myosin Vb encoded by the MYO5B gene. Although MYO5B gene is expressed in all epithelial tissues, it is unclear so far whether organs other than intestine are affected in MVID patients. We report a case of an infant with MVID who presented liver dysfunction, hematuria, and Pneumocystis jiroveci pneumonia during the course of the disease. It is discussed whether extraintestinal manifestations in this patient are secondary consequences of MVID or might be features of the disease associated with altered MYO5B function. Conclusions: MVID is classically included in the differential diagnosis of congenital diarrhea of secretory type. Recent advances in our knowledge regarding the role of myosin Vb in the pathophysiology of MVID is expected to clarify the clinical spectrum of the disease and the possible primary involvement of organs other than intestine.

Focally enhanced gastritis (FEG) has been suggested as a diagnostic marker for patients with Crohn's disease. In this study we evaluated the prevalence of FEG in children with inflammatory bowel diseases (IBD) and assessed the ability of FEG to distinguish IBD from non-IBD patients.A retrospective study of the children who underwent esophagogastroduodenal endoscopy (EGD) during 2004-2011 was performed, after excluding individuals with H. pylori infection and celiac disease. Two groups were studied: patients with IBD (IBD group, n=185) and non-IBD patients who underwent endoscopy of the upper gastrointestinal tract for various abdominal complaints (non-IBD group, n=684). Relation of FEG to age and gender was also assessed.FEG was found significantly more frequently among children with IBD (35.7% vs 3.4%, respectively, p0.001). Children with FEG were 15.4 times more likely to have IBD than to belong in the non-IBD group. All types of IBD had significantly higher frequencies of FEG compared to non-IBD individuals (Crohn's disease: 54.1%, ulcerative colitis: 21.6%, IBD unclassified: 18.4%, all three comparisons with the non-IBD group: p-values0.001). FEG positivity was more common in females compared to males with Crohn's disease and ulcerative colitis and in children younger than 2 years in the IBD-unspecified group. FEG achieved a sensitivity of 35.7% and specificity of 96.6% in distinguishing between IBD from non-IBD patients.FEG has significantly higher prevalence in children with IBD, particularly Crohn's disease and can be a valuable supporting finding in cases of indefinite diagnosis.

Chylomicron retention disease (CRD), or Anderson disease, is a rare, hereditary cause of fat malabsorption. It is one of the familial hypocholesterolaemia syndromes, along with homozygous hypobetalipoproteinaemia (HBL) and abetalipoproteinaemia (ABL). We report clinical, laboratory and histological data as well as molecular DNA analysis in the case of a 4-month-old boy with failure to thrive and steatorrhea who was diagnosed with CRD. His mother's first cousin, who was diagnosed as hypobetalipoproteinaemia 30 years ago, was also reviewed and his diagnosis was revised to CRD. Both patients were treated with a low fat diet and supplementation with fat-soluble vitamins resulting in significant improvement. In conclusion, CRD is a well-defined cause of fat malabsorption and can be distinguished from other forms of familial hypocholesterolaemia because of its specific lipid profile.

With transfusions and chelation therapy, the prognosis for transfusion-dependent beta thalassaemia has changed from being fatal in early childhood to a chronic disorder with prolonged survival. In this historical prospective study, we present survival, causes of death and mortality ratios compared to the general population in 1044 Greek patients with transfusion-dependent beta thalassaemia. At the age of 50years, the overall survival was 65.0%, while the cardiac death-free survival was 77%. Birth cohort had a significant effect on survival (P0.001) with a negative trend towards past decades. The standardised mortality ratio (standardised for sex and ages 20-40years) compared to the general population improved significantly from 28.9 in 1990-1999 to 13.5 in 2000-2008, while the standardised cardiac mortality ratio reduced from 322.9 to 106.6, respectively. Survival in thalassaemia has dramatically improved over the last twenty years but mortality remains significantly increased, compared to the general population.

Purpose: To evaluate whether the introduction of magnetic resonance imaging (MRI) in the management of thalassemia major (TM) patients has affected the risk of cardiac death. Materials and Methods: In all, 804 TM patients from two large reference units were included and the risk of dying of cardiac causes, before and after their first MRI, was assessed by a Cox proportional hazards model with time-dependent covariates. Results: Adding information from MRI reduced the risk of cardiac death from 6.0 deaths/1000 patient-years to 3.9 deaths/1000 patient-years (P = 0.22). The risk of cardiac death before having an MRI study was 82% higher compared to the risk observed after the first MRI. Conclusion: MRI has become a vital component of ongoing management and seems to have a beneficial effect on cardiac mortality in TM. J. Magn. Reson. Imaging 2011;. © 2011 Wiley-Liss, Inc.

Objectives: Cardiac complications because of transfusional iron overload are the main cause of death in thalassaemia major. New chelators and iron monitoring methods such as cardiac magnetic resonance (CMR) became available after the year 2000. We evaluated the impact of these new management options on cardiac mortality and morbidity. Methods: The risk of cardiac death during 1990–1999 and 2000–2008 was compared. Furthermore, after 1999, morbidity, mortality and reversal of heart failure were evaluated according to chelation regime: desferrioxamine (DFO), deferiprone (DFP) and combination therapy of DFO and DFP. We also present preliminary results for deferasirox (DFX), a new oral chelator. Results: Three hundred and fifty-four patients were included in the de novo cardiac event evaluation, while 86 were included in the improvement component. The annual risk of cardiac death in patients aged between 20–30 and 30–40 reduced from 1.52% to 0.67% and 1.87% to 0.56%, respectively, before and after the year 2000. The risk for a de novo cardiac event for DFO was 9.1 times greater than that of DFP and 23.6 than with the combination of DFP and DFO. For DFX, there was one cardiac event over 269 patient-years. The risk of cardiac death was 9.5 per 1000 patient-years for DFO, 2.5 on DFP, 1.4 on combination. In the DFX group no cardiac deaths were recorded. The odds of improvement were 8.5 times greater with DFP and 6.1 with combination therapy compared to DFO. Conclusions: The new chelation regimes, together with CMR have contributed significantly to the reduction in cardiac morbidity and mortality in patients with thalassaemia major.

We have given a general description of the chelation therapy prescribed. With combination therapy it would be too complicated and not necessarily of clinical value to describe all the changes in either the dose of desferrioxamine (DFO) or the frequency of its weekly infusions. Obviously, when patients do reduce their hepatic iron to normal levels, adjustments to the frequency and dosage of DFO are made. We have indicated that what is important in patients is the individual tailoring of their chelation therapy. Drs Kolnagou and Kontoghiorghes commented: ‘the rate for achieving normalization of the body iron store range levels using the deferiprone (L1)/DFO combination could be

Varicella-zoster virus vaccine has diminished the consequences of chicken pox in terms of health and economical burden. The increasing number of doses administered worldwide has revealed rare but important adverse effects that had not occurred during clinical trials. We report here the case of an immunocompetent 3(1/2)-year-old girl who developed encephalitis and herpes zoster opthalmicus 20 months after her immunization with varicella-zoster virus vaccine. Molecular analysis confirmed the vaccine strain as the causative agent. After an intravenous course with acyclovir, the child made a full recovery with no neurologic sequelae.

Background Available iron chelation regimes in thalassaemia may achieve different changes in cardiac and hepatic iron as assessed by MR. The aim of this study was to assess the efficacy of four available iron chelator regimes in 232 thalassaemia major patients by assessing the rate of change in repeated measurements of cardiac and hepatic MR. Results For the heart, deferiprone and the combination of deferiprone and deferoxamine significantly reduced cardiac iron at all levels of iron loading. As patients were on deferasirox for a shorter time, a second analysis ("Initial interval analysis") assessing the change between the first two recorded MR results for both cardiac and hepatic iron (minimum interval 12 months) was made. Combination therapy achieved the most rapid fall in cardiac iron load at all levels and deferiprone alone was significantly effective with moderate and mild iron load. In the liver, deferasirox effected significant falls in iron load and combination therapy resulted in the most rapid decline. Conclusion With the knowledge of the efficacy of the different available regimes and the specific iron load in the heart and the liver, appropriate tailoring of chelation therapy should allow clearance of iron. Combination therapy is best in reducing both cardiac and hepatic iron, while monotherapy with deferiprone or deferasirox are effective in the heart and liver respectively. The outcomes of this study may be useful to physicians as to the chelation they should prescribe according to the levels of iron load found in the heart and liver by MR.

Soluble transferrin receptors have gained interest in the field of diagnosing anemias. Reference ranges differ according to the method used for the quantification of sTfR. We aim to explore the distributional properties and diagnostic performance of sTfR in pre-school healthy children as well as in children with beta-thalassemia carriers, iron deficiency with normal hematological phenotype (ID) and iron deficiency anemia (IDA). Circulating sTfR as well as biochemical and hematological indices were determined in 521 pre-school children and four groups (normal children, beta-thalassemia traits, ID and IDA) were formed. Diagnostic performance and distribution of sTfR according to age and in relation to several parameters were evaluated in every group. Three hundred eighty one children (261 normal, 60 beta-thalassemia traits, 44 ID and 16 IDA) aged 1-6 years were included. We found that distribution of sTfR differed significantly among the four groups (Kruskal Wallis p0.001) with children in the normal group exhibiting lower concentrations compared to all other. A negative correlation between sTfR and age occurred in the normal (beta=-0.12, p0.001) and the ID groups (beta=-0.13, p=0.035). In the beta-thal and IDA groups sTfR is correlated to HbA(2) (beta=0.34, p=0.001) and ferritin (Spearman's rho=-0.6, p=0.014) respectively. An area under the curve equal to 0.63 was achieved by sTfR in distinguishing between normal and ID children. Sensitivity and specificity were 70.5% and 50% respectively at a cut-off of 2.5 mg/l. Levels of sTfR are negatively correlated to age in pre-school children while dyserythropoietic procedures like beta-thal, ID, and IDA significantly affect them. These findings indicated that the accuracy of sTfR in diagnosing ID from normal children is limited. Standardization will allow the use of formulas that combine sTfR and ferritin which are of greater diagnostic value than sTfR alone.

Abstract 2110 An important goal in iron chelation is preventing tissue iron overload by maintaining low levels of plasma non-transferrin bound iron (NTBI). This is important in periods between chelator administration, when the plasma iron might surpass not only transferrin- but also chelator-iron binding capacities, thereby raising plasma NTBI and exposing cells to infiltrating forms of iron. We aimed to assess the ability of different chelation protocols to maintain patients free of the redox active and chelatable component of NTBI referred to as labile plasma iron (LPI) and the correlation between LPI and eLPI (equivalent to NTBI including mobilizable and chelated iron) with respect to compliance. Patients & Methods: 49 TMps (23 M, 26 F, mean age 35.5±11 years were included. Patients received deferoxamine (DFO)=8–40 (mg/kg) and/or deferiprone (DFP)=74–100 and/or deferasirox (DFX)=7.6–25 for >3 years. Blood samples were drawn at trough levels (12 hr for DFP & 24 hr for DFO and/or DFX) and at peak plasma levels of chelator (2 hrs post DFP and/or DFX p/o). LPI and eLPI were determined with the FeROS™ assay (Aferrix, Israel). Stata 11.0 was used for statistical analysis. The numbers of patients receiving a particular regime were adequate for comparison in the two combination regimes that included deferiprone. Results: 28/49 (57%) of TMps had normal basal LPI ( The same trends were confirmed by analysis of the probability of increasing eLPI, reducing LPI and normalizing LPI. No differences were observed in the proportion of patients who increased their baseline eLPI between the two regimes (p>0.05). In contrast, patients on DFP+DFO were 11.0 times more likely to reduce their baseline LPI levels compared to DFP+DFX (exact logistic regression, odds ratio (OR)=11.0, 95% ci: 1.05 - +∞, p=0.045). Similarly, patients treated with DFP+DFO were 14.7 times more likely to normalize their baseline LPI levels compared to DFP+DFX (exact logistic regression, OR =14.7, 95% ci: 1.0 - +∞, p=0.05). Discussion: The DFP+DFO combination seems to be superior to DFP+DFX in reducing LPI despite the lower compliance with the former. As the DFP is in both regimes our results indicate that the DFP is more efficient in combination with DFO than with DFX. The concept of having chelator present in the circulation at all times is logical as it would protect from the infiltrating forms of iron and is attainable with the present repertoire of chelators. This preliminary study suggests that the measurement of LPI provides a convenient and immediate index of chelation efficacy, adequacy of doses of chelator prescribed, and patient compliance. Repeating such measurements every 3 months should be useful in guiding patient management. Disclosures: Berdoukas: Apopharma: Consultancy. Cabantchik:Aferrix: Consultancy.

Background Azathioprine (AZA) and 6-mercaptopurine (6MP) are used in the treatment of pediatric inflammatory bowel disease (IBD). Genetic variations in thiopurine S-methyltranfarase (TPMT) gene have been correlated with enzyme activity and with the occurrence of adverse events to AZA and 6MP. The aim of the present study was to examine the sensitivity and specificity of TPMT genotyping for TPMT enzymatic activity, reducing harm from thiopurine by pretesting, and the association of thiopurine toxicity with TPMT status in children with IBD. Methods TPMT red blood cell (RBC) activity was measured by using a radiochemical method and genotype was determined for the TPMT alleles *2, *3A, *3B and *3C in 108 thiopurinetreated pediatric IBD patients with a mean age of 11.3 years (range 3-16). Results Significant TPMT activity differences between wild-type and heterozygous and homozygous mutated subjects were observed. We divided TPMT activity into three categories according to frequency distribution: low (16.67%), intermediate (25.92%) and high (57.41%). The whole population included a total of 77.78% of homozygous wild-type subjects, 15.74% heterozygous variants, 1.85% homozygous variants and five (4.63%) compound heterozygous variant TPMT*3B/*3C. The overall concordance rate between TPMT genotypes and phenotypes was 88.2%. Seven carriers of at least one variant allele and low or intermediate TPMT activity developed adverse effects.