The use of quantitative ultrasound in a tertiary-level children hospital: role in the follow-up of chronically ill patients.

PURPOSE: To evaluate the use of QUS for the bone status assessment in children cared because of a chronic disease such as: inherited metabolic disorder, kidney disease and endocrine defect and considered by the attending physician as at specific risk. METHODS: QUS outputs were calculated for each disorder and compared to: sex, age, Tanner stage, Z-score for height, weight and BMI (body mass index). RESULTS: One-hundred-sixty-eight subjects aged between 3.5 and 18 years met the inclusion criteria. The overall bone quality indexes were under the normal range in all the groups considered. Impairment of bone quality parameters was more evident in the group of patients with inherited metabolic disorders, in which 65% of patients in charge were studied by QUS. Older age and sexual development were associated with less pronounced bone quality impairment, as measured by QUS, in the vast majority of conditions. Overall, the diseases for which the prediction of outcome was the strongest were: hyperphenylalaninemia, nephrotic syndrome and insulin dependent diabetes mellitus. CONCLUSIONS: QUS is capable to provide information on skeletal status in children. Initial evaluation by QUS may allow defining patients with chronic disorders who deserve further, more invasive diagnostic studies. Inherited metabolic disorders warrant specific attention and strict monitoring for their potential effect on bone.

A Rare Case of Posterior Fossa Tumor and Central Precocious Puberty: Case Presentation and Review of the Literature.

Central precocious puberty (CPP) is a condition that causes early gonadotropin-dependent sexual development; CPP is idiopathic in girls in most cases, whereas more than 50% of boys have an identifiable etiology. We conducted a qualitative systematic review following the ENTREQ (enhancing transparency in reporting the synthesis of qualitative research) framework. A search was made in MEDLINE/Pubmed and MeSH Database using the terms "precocious puberty" AND "brain tumor" OR "posterior fossa tumor" OR "cerebellar tumor" OR "infratentorial tumor", identifying five cases of pediatric patients with infratentorial tumors and CPP and a case of cerebellar ganglioglioma without hypothalamic-pituitary-gonadal axis involvement and/or intracranial hypertension. Our work highlights the importance of a multidisciplinary approach and extensive central nervous system imaging for patients presenting with CPP in order to detect possible tumor association. Moreover, we believe that this manuscript could contribute to stimulate other research because the exact mechanism of CPP in infratentorial brain lesions has not been understood yet.

Summary of Expert Opinion on the Management of Children With Chronic Kidney Disease and Growth Failure With Human Growth Hormone.

Background: The management of children and adolescents with chronic kidney disease (CKD) and growth failure candidate for recombinant human growth hormone therapy (rhGH) is based on an appraisal of the literature established on a 2006 consensus statement and 2019 Clinical practice recommendations. The performance of these guidelines has never been tested. Aims: The objective of this study was to establish the level of adherence to international guidelines based on the 2006 consensus and the 2019 criteria that lead to the initiation of growth hormone treatment by both pediatric endocrinologists and pediatric nephrologists. Methods: A multidisciplinary team of pediatric endocrinologists and pediatric nephrologists, members of the Italian Society of Pediatric Endocrinology or of the Italian Society of Pediatric Nephrology, discussed and reviewed the main issues related to the management of pediatric patients with CKD who need treatment with rhGH. Experts developed 11 questions focusing on risk assessment and decision makings in October 2019 and a survey was sent to forty pediatric endocrinologists (n = 20) and nephrologists (n = 20) covering the whole national territory. The results were then analyzed and discussed in light of current clinical practice guidelines and recent recommendations. Results: Responses were received from 32 of the 40 invited specialists, 17 of whom were pediatric endocrinologists (42.5%) and 15 pediatric nephrologists (37.5%). Although all the centers that participated in the survey agreed to follow the clinical and biochemical diagnostic work-up and the criteria for the treatment of patients with CKD, among the Italian centers there was a wide variety of decision-making processes. Conclusions: Despite current guidelines for the management of children with CKD and growth failure, its use varies widely between centers and rhGH is prescribed in a relatively small number of patients and rarely after kidney transplantation. Several raised issues are not taken into account by international guidelines and a multidisciplinary approach with mutual collaboration between specialists will improve patient care based on their unmet needs.

Monitoring of treatment adherence with easypod™ in six Italian centers: a real-world experience.

BACKGROUND: A poor adherence to r-hGH therapy is associated to a low growth rate in patients with growth deficiency. For this reason, the choice of an objective method, such as an electronic device, for monitoring treatment adherence is very important. This retrospective study evaluated the r-hGH treatment adherence of patients with growth deficiency, monitored through the easypod™ device. METHODS: Data from 90 patients (52 males and 38 females; mean age at the end of the study: 11.9 years ±3.40) enrolled in six Italian centers, was collected from the beginning of the r-hGH therapy until the end of the study through the easypod™ device. The primary endpoint, i.e. treatment adherence, was the ratio between actual days of treatment and planned days of treatment. Secondary endpoints were: relationship between heights measured at the beginning and at the end of the study, the change of the height SDS and the growth rate. RESULTS: Data from easypod™ showed that the mean adherence was 70±13%. The mean age-adjusted growth of the patients was 28.68±13.8 cm during the treatment period of 977 days, and the 6-month growth rate for the planned period was 3.78±8.1 cm. A positive correlation between the adherence rate and the change of the height SDS value was observed (P<0.0006). CONCLUSIONS: The easypod™ device seems to be a valid tool for quickly identifying non-adherence habits, allowing physicians to implement actions focused on reinforcing the importance of treatment both for patients and caregivers.

Clinical and molecular characterization of a second family with the 12q14 microdeletion syndrome and review of the literature.

The 12q14 microdeletion syndrome is a rare condition characterized by low birth weight, failure to thrive, short stature, learning disabilities, and osteopoikilosis. To date, 20 cases of 12q14 deletion have been reported in the literature, displaying both phenotypic than genetic variability. We report on three familial cases, a mother and two brothers, with severe short stature. The mother and elder brother presented with osteopoikilosis while the younger brother had severe short stature and developmental delay. SNP array analysis revealed a 1.9 Mb heterozygous 12q14.2q14.3 deletion in all three patients encompassing 14 genes and 3 miRNAs. In addition, the younger brother carried a paternal 11q13.4 duplication including the SHANK2 gene. This latter patient was investigated for developmental delay and did not show osteopoikilosis, confirming the role of age in the clinical presentation of this condition. To the best of our knowledge, this is the second family described with the syndrome. Comparing the clinical and molecular data of our patients with those previously reported we performed a detailed genotype-phenotype correlation confirming the association between growth retardation and osteopoikilosis when the rearrangement includes both LEMD3 and HMGA2 genes. In addition, we suggest the XPOT, TBK1, WIF1 genes as candidates for the clinical features observed in our patients and discuss for the first time the possible involvement of some microRNAs, when deleted, in the etiology of the phenotypes in 12q14 microdeletion syndrome patients. We expect the interpretation of our findings to be useful both from a molecular point of view and for genetic counseling.

The Interplay among BMI z-Score, Peer Victmization, and Self-Concept in Outpatient Children and Adolescents with Overweight or Obesity.

BACKGROUND: Research has provided evidence that obesity is associated with peer victimization and low levels of self-concept. No study has examined the relationship between BMI z-score, self-concept in multiple domains, and peer victimization. METHODS: The aim of the research was to investigate the interplay between BMI z-score, self-concept in multiple domains (physical, athletic, social), and peer victimization, testing direct, mediated, and moderated associations. Eighty hundred fifteen outpatient children and adolescents were consecutively recruited in 14 hospitals distributed over the Italian country. The sample consisted of 419 males and 396 females; mean age 10.91 ± 1.97 years (range 6-14 years) and mean BMI z-score 1.85 ± 0.74 (range -0.97 ± 3.27). Peer victimization and self-concept were assessed with a revised Olweus Bully/Victim Questionnaire and with the Self-Perception Profile for Children. A structural equation model approach was used to determine the associations among variables, testing two competing models. RESULTS: In both models, path analysis revealed that BMI z-score was directly associated with peer victimization and self-concept in multiple domains. In the first model, peer victimization mediated the relationship between BMI-score and self-concept, whereas in the alternative model, self-concept mediated the relationship between BMI z-score and peer victimization. Interaction analyses revealed that social competence moderated the relationship between BMI z-score and peer victimization and that peer victimization moderated the relationship between BMI z-score and physical appearance. CONCLUSIONS: Higher levels of BMI z-score are a risk factor for peer victimization and poor self-concept. When high levels of BMI z-score are associated with a negative self-concept, the risk of victimization increases. Preventive and supportive interventions are needed to avoid negative consequences on quality of life in children and adolescents with obesity.

Bullying and Victimization in Overweight and Obese Outpatient Children and Adolescents: An Italian Multicentric Study.

OBJECTIVE: Being overweight or obese is one of the most common reasons that children and adolescents are teased at school. We carried out a study in order to investigate: i) the relation between weight status and school bullying and ii) the relation between weight status categories and types of victimization and bullying in an outpatient sample of Italian children and adolescents with different degrees of overweight from minimal overweight up to severe obesity. PARTICIPANTS/METHODS: Nine-hundred-forty-seven outpatient children and adolescents (age range 6.0-14.0 years) were recruited in 14 hospitals distributed over the country of Italy. The participants were classified as normal-weight (N = 129), overweight (N = 126), moderately obese (N = 568), and severely obese (N = 124). The nature and extent of verbal, physical and relational bullying and victimization were assessed with an adapted version of the revised Olweus bully-victim questionnaire. Each participant was coded as bully, victim, bully-victim, or not involved. RESULTS: Normal-weight and overweight participants were less involved in bullying than obese participants; severely obese males were more involved in the double role of bully and victim. Severely obese children and adolescents suffered not only from verbal victimization but also from physical victimization and exclusion from group activities. Weight status categories were not directly related to bullying behaviour; however severely obese males perpetrated more bullying behaviour compared to severely obese females. CONCLUSIONS: Obesity and bullying among children and adolescents are of ongoing concern worldwide and may be closely related. Common strategies of intervention are needed to cope with these two social health challenges.