Review of the Literature on Current Changes in the Timing of Pubertal Development and the Incomplete Forms of Early Puberty

Puberty is a sensitive period of life characterized by the appearance of secondary sex characteristics which leads to a complete sexual maturation. It physiologically starts between the age of 8 and 13 years in girls and 9 and 14 years in boys. In the last two decades, several studies have showed that start of puberty has moved up to younger ages by 12–18 months, and some of the hypotheses trying to explain this change include the role of nutritional status and obesity and the influence of extrinsic factors such as exposure to endocrine-disrupting chemicals (EDCs), as well. The hypothalamic–hypophysis–gonadal axis develops during embryogenesis, and except for a period of activation immediately after birth, remains suppressed until the onset of pubertal development. At the beginning of puberty, the pulse generator is reactivated, probably due to progressive stimulatory influences on GnRH neurons from glial signals and neurotrasmitters. Kisspeptin and its receptor play a fundamental role in this phase. Premature Pubarche/Adrenarche, Premature Thelarche, and Premature Menarche are incomplete forms of precocious pubertal development that have their origin in endocrine mechanisms that only recently have started to be understood. It is important to distinguish these forms from the complete ones in order to reassure patients and parents about the non-evolution of pubertal progression and avoid non-useful treatments with analogous LHRH

Omitting duodenal biopsy in children with suspected celiac disease and extra-intestinal symptoms

The aim of our study is to evaluate if in children with highly positive serology and HLA-DQ2/DQ8 (triple test, TT) and only extra-intestinal symptoms, it is possible to omit performing an intestinal biopsy for celiac disease (CD) diagnosis, as suggested by the new European Society for Pediatric Gastroenterology, Hepatology and Nutrition ESPGHAN guidelines

The therapeutic effects of physical treatment for patients with hereditary spastic paraplegia: a narrative review

BackgroundHereditary spastic paraplegia (HSP) encompass a variety of neurodegenerative disorders that are characterized by progressive deterioration of walking ability and a high risk for long-term disability. The management of problems associated with HSP, such as stiffness, deformity, muscle contractures, and cramping, requires strict adherence to recommended physiotherapy activity regimes. The aim of this paper is to conduct a critical narrative review of the available evidence focusing exclusively to the therapeutic advantages associated with various forms of physical therapy (PT) in the context of HSP, emphasizing the specific benefit of every distinct approach in relation to muscle relaxation, muscle strength, spasticity reduction, improvement of weakness, enhancement of balance, posture, walking ability, and overall quality of life.MethodsTo conduct a literature review, the databases PubMed, Scopus, and DOAJ (last access in June 2023) were searched.ResultsThe PubMed search returned a total of 230 articles, Scopus returned 218, and DOAJ returned no results. After screening, the final list included 7 papers on PT treatment for HSP patients.ConclusionElectrostimulation, magnetotherapy, hydrotherapy, PT, robot-assisted gait training, and balance rehabilitation have the potential to increase lower extremity strength and decrease spasticity in HSP patients

Using social robot NAO for emotional support to children at a paediatric emergency department: a randomised clinical trial

Background: Social robots have been used for improving anxiety in children in stressful clinical situations, as during painful procedures. No studies have been performed yet to assess their effect in children while waiting for emergency room consultations. Objective: To assess the impact of social robots in managing stress in children waiting for an emergency room procedure through the assessment of salivary cortisol levels. Methods: This was an open randomised clinical trial in children attending a paediatric emergency department. Children accessing the emergency room were randomised to one of three groups: 1) playing with a NAO social robot; 2) playing with a study nurse; 3) waiting with parents. All children were measured salivary cortisol levels through a swab. Salivary cortisol levels before and after the intervention were compared in the three groups. We calculated the effect size of our interventions through the Cohen's d-based effect size correlation (r). Results: A total of 109 children aged 3 to 10 years were enrolled in the study and 94 had complete data for the analyses. Salivary cortisol levels decreased significantly more in the group exposed to robot interaction than in the other two groups (r=0.75). Cortisol levels decreased more in girls (r=0.92) than boys (r=0.57). Conclusions: Social robots are efficacious in decreasing stress in children accessing the emergency room and may be considered as a tool for improving emotional perceptions of children and their families in such a critical setting. Clinicaltrial: Robot Therapy in Pediatric Emergency, NCT04627909, https://clinicaltrials.gov/ct2/show/study/NCT04627909

NUP85 as a Neurodevelopmental Gene: From Podocyte to Neuron

Pathogenic gene variants encoding nuclear pore complex (NPC) proteins were previously implicated in the pathogenesis of steroid-resistant nephrotic syndrome (SRNS). The NUP85 gene, encoding nucleoporin, is related to a very rare form of SRNS with limited genotype-phenotype information. We identified an Italian boy affected with an SRNS associated with severe neurodevelopmental impairment characterized by microcephaly, axial hypotonia, lack of achievement of motor milestones, and refractory seizures with an associated hypsarrhythmic pattern on electroencephalography. Brain magnetic resonance imaging (MRI) showed hypoplasia of the corpus callosum and a simplified gyration of the cerebral cortex. Since the age of 3 years, the boy was followed up at our Pediatric Nephrology Department for an SRNS, with a focal segmental glomerulosclerosis at renal biopsy. The boy died 32 months after SRNS onset, and a Whole-Exome Sequencing analysis revealed a novel compound heterozygous variant in NUP85 (NM_024844.5): 611T>A (p.Val204Glu), c.1904T>G (p.Leu635Arg), inherited from the father and mother, respectively. We delineated the clinical phenotypes of NUP85-related disorders, reviewed the affected individuals so far reported in the literature, and overall expanded both the phenotypic and the molecular spectrum associated with this ultra-rare genetic condition. Our study suggests a potential occurrence of severe neurological phenotypes as part of the NUP85-related clinical spectrum and highlights an important involvement of nucleoporin in brain developmental processes and neurological function

Efficacy and safety of growth hormone treatment in children with short stature: the Italian cohort of the GeNeSIS clinical study

Purpose: We examined auxological changes in growth hormone (GH)-treated children in Italy using data from the Italian cohort of the multinational observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) of pediatric patients requiring GH treatment. Methods: We studied 711 children (median baseline age 9.6 years). Diagnosis associated with short stature was as determined by the investigator. Height standard deviation score (SDS) was evaluated yearly until final or near-final height (n = 78). Adverse events were assessed in all GH-treated patients. Results: The diagnosis resulting in GH treatment was GH deficiency (GHD) in 85.5 % of patients, followed by Turner syndrome (TS 6.6 %). Median starting GH dose was higher in patients with TS (0.30 mg/kg/week) than patients with GHD (0.23 mg/kg/week). Median (interquartile range) GH treatment duration was 2.6 (0.6\u20133.7) years. Mean (95 % confidence interval) final height SDS gain was 2.00 (1.27\u20132.73) for patients with organic GHD (n = 18) and 1.19 (0.97\u20131.40) for patients with idiopathic GHD (n = 41), but lower for patients with TS, 0.37 ( 120.03 to 0.77, n = 13). Final height SDS was > 122 for 94 % of organic GHD, 88 % of idiopathic GHD and 62 % of TS patients. Mean age at GH start was lower for organic GHD patients, and treatment duration was longer than for other groups, resulting in greater mean final height gain. GH-related adverse events occurred mainly in patients diagnosed with idiopathic GHD. Conclusions: Data from the Italian cohort of GeNeSIS showed auxological changes and safety of GH therapy consistent with results from international surveillance databases

Endocrine features of Prader-Willi syndrome: a narrative review focusing on genotype-phenotype correlation

Prader-Willi syndrome (PWS) is a complex genetic disorder caused by three different types of molecular genetic abnormalities. The most common defect is a deletion on the paternal 15q11-q13 chromosome, which is seen in about 60% of individuals. The next most common abnormality is maternal disomy 15, found in around 35% of cases, and a defect in the imprinting center that controls the activity of certain genes on chromosome 15, seen in 1-3% of cases. Individuals with PWS typically experience issues with the hypothalamic-pituitary axis, leading to excessive hunger (hyperphagia), severe obesity, various endocrine disorders, and intellectual disability. Differences in physical and behavioral characteristics between patients with PWS due to deletion versus those with maternal disomy are discussed in literature. Patients with maternal disomy tend to have more frequent neurodevelopmental problems, such as autistic traits and behavioral issues, and generally have higher IQ levels compared to those with deletion of the critical PWS region. This has led us to review the pertinent literature to investigate the possibility of establishing connections between the genetic abnormalities and the endocrine disorders experienced by PWS patients, in order to develop more targeted diagnostic and treatment protocols. In this review, we will review the current state of clinical studies focusing on endocrine disorders in individuals with PWS patients, with a specific focus on the various genetic causes. We will look at topics such as neonatal anthropometry, thyroid issues, adrenal problems, hypogonadism, bone metabolism abnormalities, metabolic syndrome resulting from severe obesity caused by hyperphagia, deficiencies in the GH/IGF-1 axis, and the corresponding responses to treatment

Possible effects of an early diagnosis and treatment in patients with growth hormone deficiency: the state of art

Abstract Growth hormone deficiency (GHD) is a relatively uncommon and heterogeneous endocrine disorder presenting in childhood with short stature. However, during the neonatal period, the metabolic effects of GHD may to require prompt replacement therapy to avoid possible life-threatening complications. An increasing amount of data suggests the importance of an early diagnosis and treatment of GHD because of its auxological, metabolic, and neurodevelopmental features with respect to the patients diagnosed and treated later in life. The available results show favourable auxological outcomes for patients with GHD diagnosed and treated with r-hGH early in life compared with those from patients with GHD who do not receive this early diagnosis and treatment. Because delayed referral for GHD diagnosis and treatment is still frequent, these results highlight the need for more attention in the diagnosis and treatment of GHD. Despite these very encouraging data regarding metabolic and neurodevelopmental features, further studies are needed to better characterize these findings. Overall, the importance of early diagnosis and treatment of GHD needs to be addressed

The Effects of the Ukrainian Conflict on Oncological Care: The Latest State of the Art

Background: The COVID-19 pandemic has dramatically affected all aspects of the patient’s pathway to cancer diagnosis and subsequent treatment. Our main objective was to evaluate the status of cancer trials in Ukraine as of September 2022. Methods: Initially, we examined with a narrative review the state of breast, colorectal, and cervical cancer population-based screening. Subsequently, we assessed each trial status for the years 2021 and 2022. Results: Estimates of participation in breast and cervical cancer screening are different from region to region. Moreover, regarding cervical cancer screening, extremely different participation estimates were reported: 73% in 2003 vs. <10% 2020. Our data show that from 2014 to 2020, despite the pandemic, cancer trials in Ukraine significantly increased from 27 to 44. In 2021 no trials were completed; in fact, we observed that out of 41 trials, 8 were active not recruiting, 33 were recruiting, and 0 were completed or terminated. In 2022 in Ukraine, for oncological pathologies, only 3 trials were registered, while in 2021, 41 trials were registered. The suspension of trials regarded above all concern hematological tissue (66.7%) and the genitourinary tract (60%). Conclusions: Our work has highlighted how the areas most affected by the conflict present criticalities in oncological care