Hodgkin Lymphoma in Children and Adolescents of Northern Greece: 25-Year Results and Long-term Follow-up.

Aim of this study was to evaluate the long-term therapeutic outcome and treatment-related complications in Hodgkin disease. We reviewed the medical records of 93 patients diagnosed with classic Hodgkin lymphoma, treated, and followed-up during the last 25 years. The cohort study included 49 males and 44 females with median age 11.8 years old (range: 3.95 to 17.42 y). The most common subtype was nodular sclerosis in 47/93 (50.5%). B symptoms were present in 15/93 (16.1%). From January 2009 until December 2020, 55 (59%) patients diagnosed with Hodgkin lymphoma were treated according to European Network for Pediatric Hodgkin Lymphoma (EURONET)-PHL-C1 protocol. Concerning outcome, a total of 89/93 patients are alive. Relapse occurred in 7/93. Second malignancies are reported in a total of 5 patients, 3 solid tumors (thyroid cancer, breast cancer, and osteosarcoma), and 2 acute myeloid leukemias. The overall survival and event-free survival for the whole cohort were 95.7% and 83.9%, respectively. Disease-free survival was 92.5%. Although a considerable high fraction of patients with Hodgkin disease can achieve continuous complete remission, they are at a high risk of developing long-term treatment-related complications. High curative rates as well as prevention of late effects can be achieved by implementation of individualized treatment strategies and innovative treatments.

Wolfram Syndrome 1: A Pediatrician's and Pediatric Endocrinologist's Perspective.

Wolfram syndrome 1 (WS1) is a rare autosomal recessive neurodegenerative disease caused by mutations in WFS1 and WFS2 genes that produce wolframin, a protein involved in endoplasmic reticulum calcium homeostasis and cellular apoptosis. Its main clinical features are diabetes insipidus (DI), early-onset non-autoimmune insulin-dependent diabetes mellitus (DM), gradual loss of vision due to optic atrophy (OA) and deafness (D), hence the acronym DIDMOAD. Several other features from different systems have been reported such as urinary tract, neurological, and psychiatric abnormalities. In addition, endocrine disorders that can appear during childhood and adolescence include primary gonadal atrophy and hypergonadotropic hypogonadism in males and menstrual cycle abnormalities in females. Further, anterior pituitary dysfunction with deficient GH and/or ACTH production have been described. Despite the lack of specific treatment for the disease and its poor life expectancy, early diagnosis and supportive care is important for timely identifying and adequately managing its progressive symptoms. The current narrative review focuses on the pathophysiology and the clinical features of the disease, with a special emphasis on its endocrine abnormalities that appear during childhood and adolescence. Further, therapeutic interventions that have been proven to be effective in the management of WS1 endocrine complications are discussed.

Contraceptive methods in adolescence: a narrative review of guidelines.

PURPOSE: Adolescent pregnancy, while recently in decline, remains a matter in need of addressing. Education and counselling are deemed crucial and this review aims at comparing published contraceptive guidelines, thus resolving any surrounding misconceptions. MATERIALS AND METHODS: Recently published contraception guidelines regarding adolescent pregnancy were retrieved. In particular, guidelines and recommendations from ACOG, RCOG, SOCG, AAP, CPS, NICE, CDC, and WHO were compared and reviewed based on each guideline's method of reporting. RESULTS: Three categories of contraceptive methods are available for adolescents and recommendations on their initiation should be made based on their efficacy, according to all guidelines. Therefore, long acting reversible contraceptives (LARCs) should be highly recommended as the most effective method (typical use failure rate: 0.05%), followed by short-acting hormonal contraceptives (typical use failure rate: 3-9%). The third contraceptive option includes contraceptives used in the moment of intercourse and displays the lowest effectiveness (typical use failure rate: 12-25%), mostly due to its dependence on personal consistency, however offers protection against STI transmission. CONCLUSION: Adolescents should be encouraged to initiate contraception, with LARCs being the primary choice followed by short-acting hormonal contraception. However, regardless of the chosen effective contraceptive method, the use of condom is necessary for STI prevention.

Adolescent pregnancy, while recently in decline, remains a matter in need of addressing. The use of contraceptive methods such as LARCs and short-acting hormonal contraceptives should be encouraged and suggested based on effectiveness with the addition of condom for STI prevention.

Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection.

Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant pediatric inflammatory responses against SARS-CoV-2. We propose that signatures of complement missense coding SNPs associated with dysregulation could also be identified in children with multisystem inflammatory syndrome (MIS-C). We investigated 71 pediatric patients with RT-PCR validated SARS-CoV-2 hospitalized in pediatric COVID-19 care units (November 2020-March 2021) in three major groups. Seven (7) patients suffered from MIS-C (MIS-C group), 32 suffered from COVID-19 and were hospitalized (admitted group), whereas 32 suffered from COVID-19, but were sent home. All patients survived and were genotyped for variations in the C3, C5, CFB, CFD, CFH, CFHR1, CFI, CD46, CD55, MASP1, MASP2, MBL2, COLEC11, FCN1, and FCN3 genes. Upon evaluation of the missense coding SNP distribution patterns along the three study groups, we noticed similarities, but also considerably increased frequencies of the alternative pathway (AP) associated with SNPs rs12614 CFB, rs1061170, and rs1065489 CFH in the MIS-C patients. Our analysis suggests that the corresponding substitutions potentially reduce the C3b-inactivation efficiency and promote slower and weaker AP C3bBb pre-convertase assembly on virions. Under these circumstances, the complement AP opsonization capacity may be impaired, leading to compromised immune clearance and systemic inflammation in the MIS-C syndrome.

Arterial stiffness indices in children and adolescents with type 1 diabetes mellitus: A meta-analysis.

AIMS: Cardiovascular disease (CVD) represents the most frequent cause of morbidity and mortality among patients with type 1 diabetes mellitus (T1DM). Our aim was to review the evidence and conduct a meta-analysis assessing measures of arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx) in children and adolescents with T1DM compared to healthy controls. METHODS: PubMed and the Cochrane Library were searched for relevant studies published up to 10 May 2021. RESULTS: Twenty-one studies were finally included in the meta-analysis. The T1DM group had significantly higher carotid to femoral PWV levels than that of the control group (mean difference [d]: 0.53 CI: 0.35-0.71, P < 0.00001) but with a fair heterogeneity (I 2:73%). By omitting one study with marked heterogeneity, mean difference in cfPWV remained significantly increased in the T1DM group compared to the control group (mean difference [d]: 0.37 CI: 0.27-0.48, P < 0.00001) but with improved heterogeneity (I2 = 26%). Regarding Aix, the T1DM group had a significantly higher AI@75 index than that of the control group (mean difference [d]: 0.28 CI: 0.17-0.39, P < 0.00001) and with no heterogeneity (I 2 = 8%). CONCLUSIONS: Youths with T1DM show increased arterial stiffness, either as increased carotid-femoral pulse wave velocity or increased augmentation index, early in their course of life compared to healthy controls. PROSPERO REGISTRATION NUMBER: CRD42021253236.

Circulating serum and plasma levels of micro-RNA in type-1 diabetes in children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a complex metabolic disorder characterized by hyperglycaemia, with constantly increasing incidence in paediatric population. The discovery of new molecules, such as microRNAs, and their possible interactions with T1DM create novel aspects in the diagnosis of the disease. METHODS: This systematic review and meta-analysis adhered to PRISMA guidelines. MEDLINE, SCOPUS, Cochrane CENTRAL and Clinicaltrials.gov. were searched up to 20 April 2020. Inclusion criteria for individual studies were quantification of microRNAs in serum/plasma samples and study groups consisting of children and adolescents with T1DM and healthy controls. Primary outcome of the study was the qualitative expression of microRNAs between the two groups. Statistical analysis was performed with Comprehensive Meta-Analysis Software v3.0. Methodological quality of included studies was assessed using Newcastle-Ottawa scale. RESULTS: A total of 484 studies were retrieved from the initial search of the databases. These were subsequently limited to seven included studies. Seven microRNAs demonstrated contrasting expression between the two groups, with two of them showing significant overexpression in T1DM group (miR-181:95% CI: 0.429 to 1.341 P < .001, miR-210:95% CI: 0.381 to 0.852, P < .001) and one micro-RNA being significantly overexpressed in control group (miR-375:95% CI: 0.293 to 1.459, P = .003). CONCLUSION: A total of three micro-RNA molecules appeared to have a significantly different expression in T1DM patients, serving as a possible diagnostic panel of biomarkers. These findings may contribute as reference for future research to further support the use of microRNAs as a novel diagnostic tool in T1DM.

Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature.

Type-1 diabetes mellitus (T1DM) is one of the most well-defined and complex metabolic disorders, characterized by hyperglycemia, with a constantly increasing incidence in children and adolescents. While current knowledge regarding the molecules related to the pathogenesis and diagnosis of T1DM is vast, the discovery of new molecules, such as micro ribonucleic acids (micro-RNAs, miRNAs), as well as their interactions with T1DM, has spurred novel prospects in the diagnosis of the disease. This review aims at summarizing current knowledge regarding miRNAs' biosynthesis and action pathways and their role as gene expression regulators in T1DM. MiRNAs follow a complex biosynthesis pathway, including cleaving and transport from nucleus to cytoplasm. After assembly of their final form, they inhibit translation or cause messenger RNA (mRNA) degradation, resulting in the obstruction of protein synthesis. Many studies have reported miRNA involvement in T1DM pathogenesis, mainly through interference with pancreatic b-cell function, insulin production and secretion. They are also found to contribute to ß-cell destruction, as they aid in the production of autoreactive agents. Due to their elevated accumulation in various biological specimens, as well as their involvement in T1DM pathogenesis, their role as biomarkers in early preclinical T1DM diagnosis is widely hypothesized, with future studies concerning their diagnostic value deemed a necessity.

Serum Fibroblast Growth Factor 21 Levels in Children and Adolescents with Hashimoto's Thyroiditis before and after l-Thyroxin Medication: A Prospective Study.

Backgrounds and Objectives: Fibroblast growth factor 21 (FGF-21) is a complex hormone, sharing common sites of action with thyroid hormones. We investigated the association among FGF-21 levels, resting metabolic rate (RMR), and l-thyroxin (LT4) treatment in children and adolescents with Hashimoto's thyroiditis. Materials and Methods: A total of 60 youngsters with chronic autoimmune thyroiditis (AIT) (30 with subclinical hypothyroidism, 30 with euthyroidism) and 30 age and sex-matched healthy participants (5-18 years old) were enrolled in the study. Anthropometric, biochemical parameters, and RMR levels were assessed in all participants; serum FGF-21 levels were measured in the control group and the group with subclinical hypothyroidism before and six months after medication with LT4. Results: FGF-21 levels were lower in the treatment group compared with the healthy ones, but this difference was not statistically significant (p > 0.05); despite the increase in FGF-21 levels after six months of LT4 treatment, this difference was not statistically significant (p > 0.05). Free thyroxin (FT4) levels correlated well with FGF-21 levels (r = 0.399, p < 0.01), but further analysis revealed no interaction between these two variables. Both patient groups presented elevated triglyceride (TG) levels compared to controls (p < 0.05). LT4 treatment had no impact on RMR and lipid or liver or glycaemic parameters. An increase in fat mass and fat-free mass were reported, independently of FGF-21 levels. Conclusions: In youngsters with subclinical hypothyroidism due to Hashimoto's thyroiditis, the serum FGF-21 levels are not significantly lower than in healthy individuals and increase after treatment with LT4 without a statistical significance. Further studies with a large number of young patients and severe hypothyroidism are recommended to confirm our results.

DNA methylation analysis within the IL2RA gene promoter in youth with autoimmune thyroid disease.

BACKGROUND: Alpha-subunit of the interleukin-2 receptor (IL2RA) is involved in the regulation of T-cell function and has been related to autoimmune thyroid disease (AITD). Although the exact mechanisms are not fully understood, promoter methylation might account for differences in gene expression. The aim of this study was to investigate whether there are differences in the percentage of DNA methylation within the IL2RA gene promoter in young patients with AITD. MATERIALS AND METHODS: In a cross-sectional design, the presence of DNA methylation in the IL2RA gene promoter was quantified, by real-time PCR and melting curve analysis, in modified genomic DNA isolated from blood samples of a total of 149 children and adolescents with AITD, including patients with Hashimoto thyroiditis (ΗΤ) (n = 60), Graves' disease (GD) (n = 9), concurrent diagnosis of HT and type 1 diabetes (T1DM + HT) (n = 25), and healthy controls (n = 55). RESULTS: The percentage of DNA methylation in the IL2RA gene promoter was significantly decreased in patients with GD (26.0 ± 4.2%) but not in those with HT (36.3 ± 1.4%) in comparison with controls (41.3 ± 1.5%). CONCLUSIONS: The observed DNA hypomethylation in the IL2RA gene promoter in patients with GD might be related to its increased expression, thus contributing to the etiopathogenesis of GD in childhood and adolescence.

De novo Unbalanced 1;22 Translocation with 22q11 Deletion Syndrome.

This report describes a newborn girl presenting with some of the common features of DiGeorge syndrome/velocardiofacial syndrome (DGS/VCFS), including hypocalcemia, atrial septal defect, and aortic stenosis. Several genetic tests were carried out to determine the origin of the clinical phenotype. MLPA was initially performed followed by aCGH, cytogenetic analysis, and FISH. Cytogenetic analysis of the proband's parents was also done. MLPA revealed a deletion in 22q11.1q11.2 spanning from the cat eye syndrome region to the most commonly deleted region in DGS/VCFS patients. The size of the deletion as defined by aCGH was 3.2 Mb. The karyotype of the proband was 45,XX,der(1)t(1;22)(p36.3;q11.2)dn,-22, the karyotypes of the parents were normal. FISH analysis showed that the 22q11 deletion occurred in the der(1). No loss or gain of chromosomal material was evident for chromosome 1, as confirmed by MLPA, aCGH, and FISH. Unbalanced translocations resulting in DGS are relatively rare, with limited reports in the literature. To our knowledge, this is the second case involving chromosome 1 and the first one with breakpoints in 1p36 and 22q11.2. This case also emphasizes the importance of combining diagnostic methods to better understand a given genetic abnormality.

l-selenomethionine supplementation in children and adolescents with autoimmune thyroiditis: A randomized double-blind placebo-controlled clinical trial.

WHAT IS KNOWN AND OBJECTIVE: Although a beneficial effect of selenium (Se) administration has been proposed in adults with autoimmune thyroiditis (AT), there is a paucity of similar data in children and adolescents. The purpose of the study was to investigate whether administration of a high dose of organic Se (200 µg daily as l-selenomethionine) has an effect on antithyroid antibody titres in children and adolescents with AT. METHODS: Seventy-one (71) children and adolescents, with a mean age of 11.3 ± 0.3 years (range 4.5-17.8), diagnosed with AT (antibodies against thyroid peroxidase [anti-TPO] and/or thyroglobulin [anti-Tg] ≥60 IU/mL, euthyroidism or treated hypothyroidism and goitre in thyroid gland ultrasonography) were randomized to receive 200 µg l-selenomethionine or placebo daily for 6 months. Blood samples were drawn for measurement of serum fT4, TSH, anti-TPO and anti-Tg levels, and thyroid gland ultrasonography was performed at the entry to the study and after 6 months of treatment. RESULTS AND DISCUSSION: At the end of the study, a statistically significantly higher reduction in anti-Tg levels was observed in the Se group compared to the placebo group (Δ: -70.9 ± 22.1 vs -6.7 ± 60.6 IU/mL, P = 0.021). Although anti-TPO levels were also decreased in the Se group, this change was not statistically different from that of the control group (Δ: -116.2 ± 68.4 vs +262.8 ± 255.5 IU/mL, P = 0.219). No significant difference in thyroid gland volume was observed between the two study groups (P > 0.05). WHAT IS NEW AND CONCLUSION: In this original study, organic Se supplementation appears to reduce anti-Tg levels in children and adolescents with AT.

Osteoprotegerin increases parallel to insulin resistance in obese adolescents.

Purpose/Aim of the Study: Osteoprotegerin (OPG) is an α tumor necrosis factor receptor superfamily glucoprotein that acts as a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL), exerting an antiresoptive bone effect. It was recently shown that OPG/RANKL axis is activated during vascular calcification, contributing to atherosclerotic lesions formation. Additionally, OPG levels are charachterized as an independent risk factor for overall vascular mortality in obese adults. We aimed to investigate OPG levels in children/adolescents with obesity and explore possible relations with obesity-related insulin resistance (IR). MATERIAL AND METHODS: A total of 160 participants (85 obese) were enrolled. Participants with obesity underwent an oral glucose tolerance test. IR was evaluated according to the homeostasis model assessment-insulin resistance index. Serum OPG levels were determined. RESULTS: OPG levels did not differ significantly between obese subjects and controls in the total sample (p = 0.133). However, in the adolescents' subgroup, serum OPG levels were significantly increased in obesity (p = 0.019). After stratifying participants according to their IR status, only subjects with both obesity and IR exhibited increased OPG levels compared to controls (p < 0.001). Factor analysis further associated OPG levels variation to insulin levels variation and to IR. CONCLUSIONS: Obese individuals demonstrate increased serum OPG levels during puberty. Obesity per se is not the potent factor for this increase; indeed, IR accompanying obesity seems to exert a fundamental role in OPG upregulation.

Malnutrition in Hospitalized Pediatric Patients: Assessment, Prevalence, and Association to Adverse Outcomes.

Malnutrition is a frequent finding in pediatric health care settings in the form of undernutrition or excess body weight. Its increasing prevalence and impact on overall health status, which is reflected in the adverse outcomes, renders imperative the application of commonly accepted and evidence-based practices and tools by health care providers. Nutrition risk screening on admission and nutrition status evaluation are key points during clinical management of hospitalized pediatric patients, in order to prevent health deterioration that can lead to serious complications and growth consequences. In addition, anthropometric data based on commonly accepted universal growth standards can give accurate results for nutrition status. Both nutrition risk screening and nutrition status assessment are techniques that should be routinely implemented, based on commonly accepted growth standards and methodology, and linked to clinical outcomes. The aim of the present review was to address the issue of hospital malnutrition in pediatric settings in terms of prevalence, outline nutrition status evaluation and nutrition screening process using different criteria and available tools, and present its relationship with outcome measures. Key teaching points • Malnutrition-underweight or excess body weight-is a frequent imbalance in pediatric settings that affects physical growth and results in undesirable clinical outcomes. • Anthropometry interpretation through growth charts and nutrition screening are cornerstones for the assessment of malnutrition.To date no commonly accepted anthropometric criteria or nutrition screening tools are used in hospitalized pediatric patients. • Commonly accepted nutrition status and screening processes based on the World Health Organization's growth standards can contribute to the overall hospital nutrition care of pediatric patients.

Supplementation with long chain polyunsaturated fatty acids (LCPUFA) to breastfeeding mothers for improving child growth and development.

BACKGROUND: Long chain polyunsaturated fatty acids (LCPUFA), especially docosahexaenoic acid (DHA), are the most abundant fatty acids in the brain and are necessary for growth and maturation of an infant's brain and retina. LCPUFAs are named "essential" because they cannot be synthesised efficiently by the human body and come from maternal diet. It remains controversial whether LCPUFA supplementation to breastfeeding mothers is beneficial for the development of their infants. OBJECTIVES: To assess the effectiveness and safety of supplementation with LCPUFA in breastfeeding mothers in the cognitive and physical development of their infants as well as safety for the mother and infant. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 August 2014), CENTRAL (Cochrane Library 2014, Issue 8), PubMed (1966 to August 2014), EMBASE (1974 to August 2014), LILACS (1982 to August 2014), Google Scholar (August 2014) and reference lists of published narrative and systematic reviews. SELECTION CRITERIA: Randomised controlled trials or cluster-randomised controlled trials evaluating the effects of LCPUFA supplementation on breastfeeding mothers (including the pregnancy period) and their infants. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and trial quality, performed data extraction and evaluated data accuracy. MAIN RESULTS: We included eight randomised controlled trials involving 1567 women. All the studies were performed in high-income countries. The longest follow-up was seven years.We report the results from the longest follow-up time point from included studies. Overall, there was moderate quality evidence as assessed using the GRADE approach from these studies for the following outcomes measured beyond 24 months age of children: language development and child weight. There was low-quality evidence for the outcomes: Intelligence or solving problems ability, psychomotor development, child attention, and child visual acuity.We found no significant difference in children's neurodevelopment at long-term follow-up beyond 24 months: language development (standardised mean difference (SMD) -0.27, 95% confidence interval (CI) -0.56 to 0.02; two trials, 187 participants); intelligence or problem-solving ability (three trials, 238 participants; SMD 0.00, 95% CI -0.36 to 0.36); psychomotor development (SMD -0.11, 95% CI -0.48 to 0.26; one trial, 113 participants); motor development (SMD -0.23, 95% CI -0.60 to 0.14; one trial, 115 participants), or in general movements (risk ratio, RR, 1.12, 95% CI 0.58 to 2.14; one trial, 77 participants; at 12 weeks of life). However, child attention scores were better at five years of age in the group of children whose mothers had received supplementation with fatty acids (mean difference (MD) 4.70, 95% CI 1.30 to 8.10; one study, 110 participants)). In working memory and inhibitory control, we found no significant difference (MD -0.02 95% CI -0.07 to 0.03 one trial, 63 participants); the neurological optimality score did not present any difference (P value: 0.55).For child visual acuity, there was no significant difference (SMD 0.33, 95% CI -0.04 to 0.71; one trial, 111 participants).For growth, there were no significant differences in length (MD -0.39 cm, 95% CI -1.37 to 0.60; four trials, 441 participants), weight (MD 0.13 kg, 95% CI -0.49 to 0.74; four trials, 441 participants), and head circumference (MD 0.15 cm, 95% CI -0.27 to 0.58; three trials, 298 participants). Child fat mass and fat mass distribution did not differ between the intervention and control group (MD 2.10, 95% CI -0.48 to 4.68; one trial, 115 participants, MD -0.50, 95% CI -1.69 to 0.69; one trial, 165 participants, respectively).One study (117 infants) reported a significant difference in infant allergy at short-term follow-up (risk ratio (RR) 0.13, 95% CI 0.02 to 0.95), but not at medium-term follow-up (RR 0.52, 95% CI 0.17 to 1.59).We found no significant difference in two trials evaluating postpartum depression. Data were not possible to be pooled due to differences in the describing of the outcome. One study (89 women) did not find any significant difference between the LCPUFA supplementation and the control group at four weeks postpartum (MD 1.00, 95%CI -1.72 to 3.72).No adverse effects were reported. AUTHORS' CONCLUSIONS: Based on the available evidence, LCPUFA supplementation did not appear to improve children's neurodevelopment, visual acuity or growth. In child attention at five years of age, weak evidence was found (one study) favouring the supplementation. Currently, there is inconclusive evidence to support or refute the practice of giving LCPUFA supplementation to breastfeeding mothers in order to improve neurodevelopment or visual acuity.

Polythelia: simple atavistic remnant or a suspicious clinical sign for investigation?

Supernumerary nipples (or polythelia) usually appear along the embryonic milk lines or in other sites including the back, thigh, vulva, neck etc. The frequency of polythelia ranges from 0.2% to 5.6%. Despite the plethora of published cases concerning its association with other congenital malformations or syndromes with different patterns of inheritance, polythelia still remains a controversial and theoretical issue. Although most reports describe a link between supernumerary nipples and kidney/urinary tract anomalies, a potential relationship with other congenital anomalies or malignancies has also been speculated. Additionally, polythelia has been associated with genodermatoses, thus being related with an increased malignant potential, as well as with an increased risk for solid tumors such as renal adenocarcinoma, testicular cancer, prostate cancer, and urinary bladder carcinoma. The fact that the Scaramanga (ska) mutant mice presented with ectopic breast tissue imply that misregulation of the neuregulin-3 signaling pathway may be critical in the occurrence of polythelia. This is an attempt to review existing literature in order to (a) draw reliable conclusions whether polythelia is a manifestation of simple atavism or may be associated with concomitant severe conditions needing further investigation and/or management, (b) elucidate its aetiology and (c) establish appropriate clinical and laboratory approach.

Genital Abnormalities and Growth Retardation as Early Signs of Dilated Cardiomyopathy with Ataxia Syndrome.

Dilated cardiomyopathy with ataxia syndrome is a rare mitochondrial disease caused by autosomal recessive mutations in the DNAJC19 gene. The disease has been described in detail in the Canadian Hutterite population, but a few sporadic cases with de novo mutations have been published worldwide. We describe a homozygous pathogenic variant in the DNAJC19 gene, diagnosed in Northern Greece, presenting with genital anomalies, growth failure, cardiomyopathy, and ataxia, but without increased urinary 3-methylglutaconic acid and additional presence of vitamin D disorders, hypercalciuria, and osteopenia. This case not only expands the clinical characteristics of 3-methylglutaconic aciduria type V (MGCA5) but also highlights the power of genetic analysis for detecting a diagnosis when the metabolic screen is negative.

Evaluation of Health-Related Quality of Life in Adolescents With Obesity: A Randomized Qualitative Study Among Healthcare Professionals.

Adolescent obesity constitutes a disorder with physical and psychosocial implications. Childhood and adolescent obesity rates are constantly increasing worldwide. Since adolescent obesity is a chronic disease, which is part of noncommunicative degenerative diseases, its holistic approach decisively includes the assessment of its impact on quality of life. The use of the tools Pediatric Quality of Life Inventory 4.0 (PedsQL4.0) and The Impact of Weight on Quality of Life for Kids (IWQOL-Kids), the familiarity of health professionals with them, their applicability, and relevance in clinical practice, are a cornerstone in the promotion of health services in adolescent obesity. The present randomized qualitative study aimed to highlight the attitudes and preferences of pediatricians on the assessment of health-related quality of life (HRQoL), among obese adolescents. The sample consists of 120 pediatricians, randomly selected from the totality of municipality-registered pediatricians (Municipality of Thessaloniki, Greece) who were interviewed in a semi-structured way, regarding their attitudes in the assessment of health-related quality of life, as measured by the PedsQL4.0 and IWQOL-Kids tools. The interviews revealed that most participants gained insight into the HRQoL assessment process during the present study interview with the researchers. Only eight (n=8/120) participants were familiar with the explored tools, PedsQL4.0 and IWQOL-KIDS. The remaining sample (n=112/120) was unfamiliar with both the two questionnaires and their content as well. Among the referred barriers to the usage of the tools, lack of time was stated as the pivotal factor hindering the implementation of the tools in clinical practice. There was no consensus on the preferred questionnaire among the participating healthcare professionals. All participants stated that the use of one or both questionnaires would have added significant value to the support and care of adolescents with obesity. Tools assessing HRQoL present low familiarity among pediatricians in real-world data. Focus on the engagement of the healthcare providers in the evaluation of obesity-related quality of life is unequivocal, in order to improve health care status in adolescents with obesity.

Evaluation of the possible impact of the fear of hypoglycemia on diabetes management in children and adolescents with type 1 diabetes mellitus and their parents: a cross-sectional study.

PURPOSE: Hypoglycemia represents a significant source of anxiety for children with type 1 diabetes mellitus (T1DM) and their caretakers. Fear of hypoglycemia (FoH) was measured in children and adolescents with T1DM as well as in their parents using an established research instrument, the Hypoglycemia Fear Survey (HFS). METHODS: This is a two-center, cross-sectional study involving 100 children and adolescents aged 6-18 years old diagnosed with T1DM. One parent of each child also participated in the study. The participants, who were recruited from two different pediatric endocrine outpatient clinics, were asked to complete the translated Greek version of the HFS, which includes one version for children (C-HFS) and one for parents (P-HFS). The association of the questionnaire responses with subjects' characteristics, such as current age, age at diagnosis, duration of diabetes, HbA1c levels, and mode of diabetes treatment were assessed. RESULTS: Parents exhibited significantly higher mean HFS scores than their children. No significant correlation was found between the P-HFS or the C-HFS scores and the age of the children, duration of diabetes, HbA1c, or mode of treatment. CONCLUSION: The finding that parents experience higher levels of FoH compared to their children emphasizes the importance of healthcare providers to screen parental FoH and focus on approaches to support them in order to reduce their psychological burden, thus optimizing children's diabetes management.

miRNAs as predictive biomarkers of response to treatment in pediatric patients with acute lymphoblastic leukemia.

MicroRNAs (miRNAs/miRs) are promising prognostic biomarkers in pediatric acute lymphoblastic leukemia (ALL). The present study aimed to identify miRNAs that could serve as prognostic biomarkers or as novel therapeutic targets in ALL. The expression levels of 84 miRNAs were assessed in the bone marrow aspirates of 10 pediatric patients with newly diagnosed ALL at diagnosis and on day 33 of induction of the ALL Intercontinental Berlin-Frankfurt-Münster 2009 protocol, and associations with established prognostic factors were evaluated. The levels at diagnosis of 25 miRNAs were associated with ≥2 prognostic factors. Higher expression levels of let-7c-5p, miR-106b-5p, miR-26a-5p, miR-155-5p, miR-191-5p, miR-30b-5p and miR-31-5p were significantly associated with a good prednisone response. The expression levels of miR-125b-5p, miR-150-5p and miR-99a-5p were significantly higher in standard- or intermediate-risk patients compared with those in high-risk patients (P=0.017, P=0.033 and P=0.017, respectively), as well as in those with a complete response at the end of induction (P=0.044 for all three miRNAs). The change in expression levels between diagnosis and the end of induction differed significantly between risk groups for three miRNAs: miR-206, miR-210 and miR-99a (P=0.033, P=0.047 and P=0.008, respectively), with the post induction levels of miR-206 increased in high-risk patients, whilst miR-210 and miR-99a levels were increased in intermediate/standard risk patients. Therefore, miRNAs that could be integrated into the risk stratification of pediatric ALL after further evaluation in larger patient cohorts were identified.

Thyroidectomy in children and adolescents: a systematic review.

Background: Thyroid surgery in pediatric population is not as common as that in adults, although they share the same indications, techniques and complications. This review aims to evaluate the surgical management of thyroid disease in patients under 18 years old. Methods: We conducted a bibliographic search in the international literature. Data from the identified studies such as demographics, indication for surgery, type of procedure, complications and length of hospital stay were recorded. A retrospective review study of all patients under 18 years old who underwent thyroidectomy was performed. Results: We included 37 retrospective studies and a total of 12,728 patients. Thyroidectomy was more common in female patients and the mean age was approximately 14 years old. The leading indication for surgery was benign thyroid pathology. Due to the surgical treatments' safety and effectiveness in young patients, total and subtotal thyroidectomy, whether for malignancies or benign diseases, is becoming more popular today. The most often occurring complication of pediatric thyroid surgery is hypoparathyroidism. Despite the high likelihood of recurrence of pediatric malignancies, overall survival rates of pediatric thyroid cancer are excellent. Conclusions: Thyroidectomy performed by high-volume thyroid surgeons in children and adolescents is considered an efficient and safe method of treatment of thyroid disease.