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Introduction: Minipuberty follows different trends in boys and girls. Aim of our study was to explore timing and dynamics of minipuberty in healthy infants, analyzing urinary levels of sexual hormones. Moreover, we analyzed the association among HPG axis activity and linear growth, ano-genital distances (AGDs) in both sexes, and penile length in males., Methods: Longitudinal cohort study in healthy term infants from birth to 6 months of life. Clinical evaluation (anthropometrics and AGDs) and urine sampling were performed at 0 (T0), 3 (T3), and 6 (T6) months. Urine samples were analyzed for gonadotropins and sex hormones., Results: 165 participants were involved. The growth trend of our population was regular, as were the AGDs. Urinary hormones were correlated each other's. Specifically, in boys, the correlation coefficient between urinary FSH (uFSH) and urinary LH (uLH) decreased from T0 to T6, while between urinary Testosterone (uT) and uFSH increased. In girls, correlations between uFSH and urinary Estradiol (uE) were observed at each time point. Notably, several correlations between hormones and anthropometrics and AGDs were found; the most interesting correlation was found in males within uLH and PL (at T0 ρ: 0.323, p < 0.05 and at T3 ρ: 0.371, p < 0.01), whereas in females uFSH at T0 showed negative correlations with both length and body weight percentile at T3 (ρ: -0.505, p < 0.01 and ρ: -0.478, p < 0.01, respectively)., Conclusion: Urinary matrix has proved to be a valuable, practical, non-invasive and cheaper method for sexual hormone assessment., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Context: In the last decade the Sanger method of DNA sequencing has been replaced by next-generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM)., Objective: To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) vs 2013-2022 (NGS)., Methods: We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM + c.SIR) of the Italian dataset., Results: Fifty-five patients (50 NDM + 5 c.SIR) were identified during 2003-2012 and 49 (46 NDM + 3 c.SIR) in 2013-2022. Twenty-year incidence was 1:103 340 (NDM) and 1:1 240 082 (c.SIR) live births. Frequent NDM/c.SIR genetic defects (KCNJ11, INS, ABCC8, 6q24, INSR) were detected in 41 and 34 probands during 2003-2012 and 2013-2022, respectively. We identified a pathogenic variant in rare genes in a single proband (GATA4) (1/42 or 2.4%) during 2003-2012 and in 8 infants (RFX6, PDX1, GATA6, HNF1B, FOXP3, IL2RA, LRBA, BSCL2) during 2013-2022 (8/42 or 19%, P = .034 vs 2003-2012). Notably, among rare genes 5 were recessive. Swift and accurate genetic diagnosis led to appropriate treatment: patients with autoimmune NDM (FOXP3, IL2RA, LRBA) were subjected to bone marrow transplant; patients with pancreas agenesis/hypoplasia (RFX6, PDX1) were supplemented with pancreatic enzymes, and the individual with lipodystrophy caused by BSCL2 was started on metreleptin., Conclusion: NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and c.SIR in Italy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Thyroid function is closely linked to nutrition through the diet-gut-thyroid axis. This narrative review highlights the influence of nutritional components and micronutrients on thyroid development and function, as well as on the gut microbiota. Micronutrients such as iodine, selenium, iron, zinc, copper, magnesium, vitamin A, and vitamin B12 influence thyroid hormone synthesis and regulation throughout life. Dietary changes can alter the gut microbiota, leading not just to dysbiosis and micronutrient deficiency but also to changes in thyroid function through immunological regulation, nutrient absorption, and epigenetic changes. Nutritional imbalance can lead to thyroid dysfunction and/or disorders, such as hypothyroidism and hyperthyroidism, and possibly contribute to autoimmune thyroid diseases and thyroid cancer, yet controversial issues. Understanding these relationships is important to rationalize a balanced diet rich in essential micronutrients for maintaining thyroid health and preventing thyroid-related diseases. The synthetic comprehensive overview of current knowledge shows the importance of micronutrients and gut microbiota for thyroid function and uncovers potential gaps that require further investigation.

The thyroid gland regulates most of the physiological processes. Environmental factors, including climate change, pollution, nutritional changes, and exposure to chemicals, have been recognized to impact thyroid function and health. Thyroid disorders and cancer have increased in the last decade, the latter increasing by 1.1% annually, suggesting that environmental contaminants must play a role. This narrative review explores current knowledge on the relationships among environmental factors and thyroid gland anatomy and function, reporting recent data, mechanisms, and gaps through which environmental factors act. Global warming changes thyroid function, and living in both iodine-poor areas and volcanic regions can represent a threat to thyroid function and can favor cancers because of low iodine intake and exposure to heavy metals and radon. Areas with high nitrate and nitrite concentrations in water and soil also negatively affect thyroid function. Air pollution, particularly particulate matter in outdoor air, can worsen thyroid function and can be carcinogenic. Environmental exposure to endocrine-disrupting chemicals can alter thyroid function in many ways, as some chemicals can mimic and/or disrupt thyroid hormone synthesis, release, and action on target tissues, such as bisphenols, phthalates, perchlorate, and per- and poly-fluoroalkyl substances. When discussing diet and nutrition, there is recent evidence of microbiome-associated changes, and an elevated consumption of animal fat would be associated with an increased production of thyroid autoantibodies. There is some evidence of negative effects of microplastics. Finally, infectious diseases can significantly affect thyroid function; recently, lessons have been learned from the SARS-CoV-2 pandemic. Understanding how environmental factors and contaminants influence thyroid function is crucial for developing preventive strategies and policies to guarantee appropriate development and healthy metabolism in the new generations and for preventing thyroid disease and cancer in adults and the elderly. However, there are many gaps in understanding that warrant further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Street, Shulhai, Petraroli, Patianna, Donini, Giudice, Gnocchi, Masetti, Montani, Rotondo, Bernasconi, Iughetti, Esposito and Predieri.)

Glycemic abnormalities are a frequent finding in pediatric oncological patients, both during treatment and after its discontinuation. Moreover, impaired glucose tolerance (IGT), impaired fasting glycemia (IFG) and diabetes mellitus (DM) are not rarely diagnosed in non-oncological hematological diseases. To explore the current pediatric Italian approach to the diagnosis and the management of the glycemic alterations in this clinical setting and, thus, to identify and enforce current clinical needs, we submitted an online 23-items survey to all the Italian Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers, and surveys were descriptively analyzed. Thirty-nine AIEOP centers were involved in the study. In 2021, among 75278 children and adolescents affected by an oncological or a hematological disease, 1.2 and 0.65% developed DM, while IGT or IFG were widespread in 2.3 and 2.8%, respectively. The main causes of DM were the use of corticosteroids in patients with cancer and the iron overload in patients with thalassemia. Venous fasting plasma glycemia was the most used tool to detect glycemic abnormalities. The performance of oral glucose tolerance test (OGTT) was extremely limited, except when IFG occurred. Despite the diagnosis of DM, ∼45% of patients with cancer and 30% of patients with one hematological disease did not receive an appropriate treatment. In the other cases, insulin was the drug of first choice. Emerging technologies for diabetes care (glucose sensors and insulin pumps) are not largely used yet. The results of our study support the standardization of the care of the glycemic abnormalities during or after onco-hematologic diseases in the pediatric age. Despite the scarce data in pediatric literature, proper guidelines are needed.

Aims: To analyze metabolic outcomes, diabetes impact and device satisfaction in children and adolescents with type 1 diabetes in Italy who used different treatment modalities for diabetes care in a real-life context., Methods: In this multicenter, nationwide, cross-sectional study, 1464 participants were enrolled at a routine visit. The following treatment modalities were considered MDI + SMBG; MDI + CGM; Sensor Augmented Pump Therapy; predictive management of low glucose; Hybrid Closed Loop (HCL); Advanced Hybrid Closed Loop (AHCL). Health related quality of life was evaluated by the Italian version of the Diabetes Impact and Device Satisfaction Scale (DIDS) questionnaire., Results: Patients treated with AID systems were more likely to have HbA1c ≤ 6.5 %, higher percentage of time with glucose levels between 70 and 180 mg/dL, lower percentage of time with glucose levels above 180 mg/dL, higher device satisfaction, and reduced impact of diabetes. All the therapeutic modalities with respect to MDI + CGM, except for MDI + SMBG, contributed to increase the device satisfaction. HCL and AHCL respect to MDI + CGM were associated with lower diabetes impact., Conclusion: Real-life use of automated insulin delivery systems is associated with reduced type 1 diabetes impact, increased device satisfaction, and achievement of glycemic goals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Immune-checkpoint inhibitor therapy modulates the response of the immune system acting against cancer. Two pathways impacted by this kind of treatment are the CTLA4 and the PD-1/PD-L1 pathways. ICI therapy can trigger autoimmune adverse effects, known as immune-related Adverse Events (irAEs)., Areas Covered: This review focuses on irAEs which affect the endocrine system. This review elucidates the pathways used by these drugs with a focus on the hypothetical pathogenesis at their basis. In fact, the pathophysiology of irAEs concerns the possibility of an interaction between cellular autoimmunity, humoral immunity, cytokines, chemokines, and genetics. The endocrine irAEs examined are thyroid dysfunctions, immune related-hypophysitis, diabetes, peripheral adrenal insufficiency, and hypoparathyroidism., Expert Opinion: There is still much to investigate in endocrine irAES of checkpoint inhibitors. In the future, checkpoint inhibitors will be increasingly utilized therapies, and therefore it is crucial to find the proper diagnostic-therapeutic program for irAEs, especially as endocrine irAEs are nonreversible and require lifelong replacement therapies.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

This Position Statement updates the different components of the therapy of obesity (lifestyle intervention, drugs, and surgery) in children and adolescents, previously reported in the consensus position statement on pediatric obesity of the Italian Society of Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics. Lifestyle intervention is the first step of treatment. In children older than 12 years, pharmacotherapy is the second step, and bariatric surgery is the third one, in selected cases. Novelties are available in the field of the medical treatment of obesity. In particular, new drugs demonstrated their efficacy and safety and have been approved in adolescents. Moreover, several randomized control trials with other drugs are in process and it is likely that some of them will become available in the future. The increase of the portfolio of treatment options for obesity in children and adolescents is promising for a more effective treatment of this disorder., (© 2023. The Author(s).)

Background: Phthalates are non-persistent chemicals largely used as plasticizers and considered ubiquitous pollutants with endocrine disrupting activity. The exposure during sensible temporal windows as pregnancy and early childhood, may influence physiological neurodevelopment., Aims and Scope: The aim of this study is to analyze the relationship between the urinary levels of phthalate metabolites in newborn and infants and the global development measured by the Griffiths Scales of Children Development (GSCD) at six months., Methods: Longitudinal cohort study in healthy Italian term newborn and their mothers from birth to the first 6 months of life. Urine samples were collected at respectively 0 (T0), 3 (T3), 6 (T6) months, and around the delivery for mothers. Urine samples were analyzed for a total of 7 major phthalate metabolites of 5 of the most commonly used phthalates. At six months of age a global child development assessment using the third edition of the Griffith Scales of Child Development (GSCD III) was performed in 104 participants., Results: In a total of 387 urine samples, the seven metabolites analyzed appeared widespread and were detected in most of the urine samples collected at any time of sampling (66-100%). At six months most of the Developmental Quotients (DQs) falls in average range, except for the subscale B, which presents a DQ median score of 87 (85-95). Adjusted linear regressions between DQs and urinary phthalate metabolite concentrations in mothers at T0 and in infants at T0, T3 and T6 identified several negative associations both for infants' and mothers especially for DEHP and MBzP. Moreover, once stratified by children's sex, negative associations were found in boys while positive in girls., Conclusions: Phthalates exposure is widespread, especially for not regulated compounds. Urinary phthalate metabolites were found to be associated to GSCD III scores, showing inverse association with higher phthalate levels related to lower development scores. Our data suggested differences related to the child's sex., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lucaccioni, Palandri, Passini, Trevisani, Calandra Buonaura, Bertoncelli, Talucci, Ferrari, Ferrari, Predieri, Facchinetti, Iughetti and Righi.)

Metabolic syndrome (MetS) is defined by a cluster of several cardio-metabolic risk factors, specifically visceral obesity, hypertension, dyslipidemia, and impaired glucose metabolism, which together increase risks of developing future cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D). This article is a narrative review of the literature and a summary of the main observations, conclusions, and perspectives raised in the literature and the study projects of the Working Group of Childhood Obesity (WGChO) of the Italian Society of Paediatric Endocrinology and Diabetology (ISPED) on MetS in childhood obesity. Although there is an agreement on the distinctive features of MetS, no international diagnostic criteria in a pediatric population exist. Moreover, to date, the prevalence of MetS in childhood is not certain and thus the true value of diagnosis of MetS in youth as well as its clinical implications, is unclear. The aim of this narrative review is to summarize the pathogenesis and current role of MetS in children and adolescents with particular reference to applicability in clinical practice in childhood obesity.

Thousands of natural or manufactured chemicals were defined as endocrine-disrupting chemicals (EDCs) because they can interfere with hormone activity and the endocrine system. We summarize and discuss what we know and what we still need to learn about EDCs' pathogenic mechanisms of action, as well as the effects of the most common EDCs on endocrine system health in childhood. The MEDLINE database (PubMed) was searched on 13 May 2022, filtering for EDCs, endocrine diseases, and children. EDCs are a group of compounds with high heterogeneity, but usually disrupt the endocrine system by mimicking or interfering with natural hormones or interfering with the body's hormonal balance through other mechanisms. Individual EDCs were studied in detail, while humans' "cocktail effect" is still unclear. In utero, early postnatal life, and/or pubertal development are highly susceptible periods to exposure. Human epidemiological studies suggest that EDCs affect prenatal growth, thyroid function, glucose metabolism, obesity, puberty, and fertility through several mechanisms. Further studies are needed to clarify which EDCs can mainly act on epigenetic processes. A better understanding of EDCs' effects on human health is crucial to developing future regulatory strategies to prevent exposure and ensure the health of children today, in future generations, and in the environment.

Background: Gonadotropin-releasing hormone analogs (GnRHas) are effective in increasing the final height of children with idiopathic central precocious puberty (ICPP). However, in previous years, some transient metabolic complications have been described during this treatment, for which there are no long-term outcome data. Our study aimed to evaluate the efficacy of GnRHas and clarify if body mass index (BMI) at diagnosis of ICPP could influence long-term outcomes., Methods: This was an observational, retrospective study that recruited a cohort of girls with ICPP. Data for anthropometric measures, fasting lipid profile, and glucose metabolism were collected at baseline [when GnRHas treatment started (T1)], at the end of the treatment (T2), and near-final height (nFH) or final height (FH) (T3). Predicted adult height (PAH) was calculated at T1 following Bayley and Pinneau's method. Analysis was carried out using BMI standard deviation score (SDS) categories at T1 (group A, normal weight, vs. group B, overweight/obese)., Results: Fifty-seven girls with ICPP who were treated with GnRHas were enrolled in the study (group A vs. group B: 33 vs. 24 patients, aged 7.86 ± 0.81 vs. 7.06 ± 1.61 years, respectively; p < 0.05). In the study population, nFH/FH was in line with the target height (TH) ( p = 0.54), with a mean absolute height gain of 11.82 ± 5.35 cm compared with PAH. Even if the length of therapy was shorter (group A vs. group B: 1.84 ± 2.15 vs. 2.10 ± 0.81 years, respectively; p < 0.05) and the age at menarche was younger (group A vs. group B: 10.56 ± 1.01 vs. 11.44 ± 0.85 years, respectively; p < 0.05) in group B than in group A, the nFH/FH gain was still comparable between the two groups ( p = 0.95). At nFH/FH, BMI SDS was still greater in group B than in group A ( p = 0.012), despite the fact that BMI SDS significantly increased in group A only ( p < 0.05). Glucose metabolism got worst during GnRHa with a complete restoring after it, independently from pre-treatment BMI. The ratio of low-density to high-density lipoprotein cholesterol transiently deteriorated during treatment with GnRHas in group A only ( p = 0.030)., Conclusions: Our results confirm the effectiveness of treatment with GnRHas on growth and do not support the concern that being overweight and obese can impair the long-term outcomes of GnRHas therapy. However, the observed transient impairment of metabolic parameters during treatment suggests that clinicians should encourage ICPP girls treated with GnRHas to have a healthy lifestyle, regardless of their pretreatment BMI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bruzzi, Valeri, Sandoni, Madeo, Predieri, Lucaccioni and Iughetti.)

Introduction: Extra-uterine growth restriction (EUGR) is a condition caused by the failure of very preterm infants to reach their potential growth during the NICU hospital stay. Despite enormous improvements in nutritional support and strategies, the growth pattern of preterm infants is still far from the one expected., Areas Covered: This review focuses on what EUGR is, highlighting controversial aspects of this topic. EUGR is still missing a univocal definition, and the international debate is also open on what is the best growth chart to use. Moreover, professionals in NICU may not be trained on how to perform anthropometric measurements, increasing the risk of over- or underestimation, especially for length assessment. EUGR has recently been described as one of the main comorbidities in NICU, influencing growth, metabolism, and neurodevelopment later in life., Expert Opinion: There is still much to investigate about what the best growth pattern in the NICU should be. What is known so far is that the majority of preterm neonates develop EUGR, and this leads to several short- and long-term consequences. It is imperative that neonatologists and pediatric endocrinologists work together, to modulate growth in the NICU.

[This corrects the article .]., (Copyright © 2022 Cherubini, Marino, Scaramuzza, Tiberi, Bobbio, Delvecchio, Piccinno, Ortolani, Innaurato, Felappi, Gallo, Ripoli, Ricciardi, Pascarella, Stamati, Citriniti, Arnaldi, Monti, Graziani, De Berardinis, Giannini, Chiarelli, Zampolli, De Marco, Bracciolini, Grosso, De Donno, Piccini, Toni, Coccioli, Cardinale, Bassi, Minuto, D’Annunzio, Maffeis, Marigliano, Zanfardino, Iafusco, Rollato, Piscopo, Curto, Lombardo, Bombaci, Sordelli, Mameli, Macedoni, Rigamonti, Bonfanti, Frontino, Predieri, Bruzzi, Mozzillo, Rosanio, Franzese, Piredda, Cardella, Iovane, Calcaterra, Berioli, Lasagni, Pampanini, Patera, Schiaffini, Rutigliano, Meloni, De Sanctis, Tinti, Trada, Guerraggio, Franceschi, Cauvin, Tornese, Franco, Musolino, Maltoni, Talarico, Iannilli, Lenzi, Matteoli, Pozzi, Moretti, Zucchini, Rabbone and Gesuita.)

Context: There is growing evidence of the role of epigenetic regulation of growth, and miRNAs potentially play a role., Objective: The aim of this study is to identify changes in circulating miRNAs following GH treatment in subjects with isolated idiopathic GH deficiency (IIGHD) after the first 3 months of treatment, and verify whether these early changes can predict growth response., Design and Methods: The expression profiles of 384 miRNAs were analyzed in serum in 10 prepubertal patients with IIGHD (5 M, 5 F) at two time points before starting GH treatment (t-3, t0), and at 3 months on treatment (t+3). MiRNAs with a fold change (FC) >+1.5 or <-1.5 at t+3 were considered as differentially expressed. In silico analysis of target genes and pathways led to a validation step on 8 miRNAs in 25 patients. Clinical and biochemical parameters were collected at baseline, and at 6 and 12 months. Simple linear regression analysis and multiple stepwise linear regression models were used to explain the growth response., Results: Sixteen miRNAs were upregulated and 2 were downregulated at t+3 months. MiR-199a-5p ( p = 0.020), miR-335-5p ( p = 0.001), and miR-494-3p ( p = 0.026) were confirmed to be upregulated at t+3. Changes were independent of GH peak values at testing, and levels stabilized after 12 months. The predicted growth response at 12 months was considerably improved compared with models using the common clinical and biochemical parameters., Conclusions: MiR-199a-5p, miR-335-5p, and miR-494-3p changed after 3 months of GH treatment and likely reflected both the degree of GH deficiency and the sensitivity to treatment. Furthermore, they were of considerable importance to predict growth response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Catellani, Ravegnini, Sartori, Righi, Lazzeroni, Bonvicini, Poluzzi, Cirillo, Predieri, Iughetti, Giorgi Rossi, Angelini and Street.)

Aim/hypothesis: To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019., Methods: Forty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019., Results: Overall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, p<0.001). DKA and severe DKA increased during the early pandemic period by 10.4% (p=0.004) and 8% (p=0.002), respectively, and the increase continued throughout 2020. Immigrant background increased and high household income decreased the probability of presenting with DKA (OR: 1.55; 95%CI, 1.24-1.94; p<0.001 and OR: 0.60; 95 CI, 0.41-0.88; p=0.010, respectively)., Conclusions/interpretation: There was an increase in the frequency of DKA and severe DKA in children newly diagnosed with type 1 diabetes during the COVID-19 pandemic in 2020, with no apparent association with the severity of COVID-19 infection severity or containment measures. There has been a silent outbreak of DKA in children during the pandemic, and preventive action is required to prevent this phenomenon in the event of further generalized lockdowns or future outbreaks., Competing Interests: No author reported any conflict of interest as regards this study. The following conflicts of interest pointed out are referred to a period from January 2020 to the submission of this manuscript. VCh’s institution has received research grants from AstraZeneca, Novonordisk, Eli Lilly, Movi, Dompè, and Menarini, and VCh received honoraria from Eli Lilly, Tandem, and Insulet for participating on speakers’ bureaus and scientific advisory boards. CR, DT, IRa, BPr, BPi, SZ, ST, and AR has received support Eli Lilly. In addition, SZ’s institution has received support from Pfeizer, ST, BPi, and DT have received support from Abbott and Theras. MM and AR have received support from Menarini. BPr and PB received honoraria for participating on speakers’ bureaus and scientific advisory boards for Sandoz. Lastly, RS has received research grants by Sanofi and received honoraria for participating on speakers’ bureaus and scientific advisory boards for Movi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cherubini, Marino, Scaramuzza, Tiberi, Bobbio, Delvecchio, Piccinno, Ortolani, Innaurato, Felappi, Gallo, Ripoli, Ricciardi, Pascarella, Stamati, Citriniti, Arnaldi, Monti, Graziani, De Berardinis, Giannini, Chiarelli, Zampolli, De Marco, Bracciolini, Grosso, De Donno, Piccini, Toni, Coccioli, Cardinale, Bassi, Minuto, D’Annunzio, Maffeis, Marigliano, Zanfardino, Iafusco, Rollato, Piscopo, Curto, Lombardo, Bombaci, Sordelli, Mameli, Macedoni, Rigamonti, Bonfanti, Frontino, Predieri, Bruzzi, Mozzillo, Rosanio, Franzese, Piredda, Cardella, Iovane, Calcaterra, Berioli, Lasagni, Pampanini, Patera, Schiaffini, Rutigliano, Meloni, De Sanctis, Tinti, Trada, Guerraggio, Franceschi, Cauvin, Tornese, Franco, Musolino, Maltoni, Talarico, Iannilli, Lenzi, Matteoli, Pozzi, Moretti, Zucchini, Rabbone and Gesuita.)

Objective: To evaluate the six-month impact of the advanced automated functions of a closed-loop control (CLC) system (Control-IQ) and a virtual educational camp (vEC) on emotions and time in range (TIR) of children and adolescents with type 1 diabetes., Methods: Children and their parents participated in a three-day vEC. Clinical, glucose, and emotion data were evaluated before, just after, and six months after the vEC. Emotions were evaluated using adapted Plutchik's and Geneva Emotion Wheels., Results: Forty-three children and adolescents (7-16 years) showed significant improvements in positive emotions immediately and six months after the vEC (67% and 65% vs 38%, p < 0.05, respectively), while mixed emotions were reduced (32% and 15% vs 61%, p < 0.05 and p < 0.001, respectively). The median percentage TIR increased from 64% (IQR 54-72) to 75% (IQR 70-82) with Control-IQ (p < 0.001) six months after the vEC., Conclusions: Positive emotions (joy, serenity, and satisfaction) significantly improved while mixed emotions were significantly worse six months after the initiation of a CLC system (Control-IQ) and a vEC., (© 2022. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Febrile urinary tract infection (UTI) is currently considered the most frequent cause of serious bacterial illness in children in the first 2 years of life. UTI in paediatrics can irreversibly damage the renal parenchyma and lead to chronic renal insufficiency and related problems. To avoid this risk, an early effective antibiotic treatment is essential. Moreover, prompt treatment is mandatory to improve the clinical condition of the patient, prevent bacteraemia, and avoid the risk of bacterial localization in other body sites. However, antibiotic resistance for UTI-related bacterial pathogens continuously increases, making recommendations rapidly outdated and the definition of the best empiric antibiotic therapy more difficult. Variation in pathogen susceptibility to antibiotics is essential for the choice of an effective therapy. Moreover, proper identification of cases at increased risk of difficult-to-treat UTIs can reduce the risk of ineffective therapy. In this review, the problem of emerging antibiotic resistance among pathogens associated with the development of paediatric febrile UTIs and the best potential solutions to ensure the most effective therapy are discussed. Literature analysis showed that the emergence of antibiotic resistance is an unavoidable phenomenon closely correlated with the use of antibiotics themselves. To limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be made. An increased use of antibiotic stewardship can be greatly effective in this regard., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the last few decades, many studies have reported an increasing global incidence of type 1 diabetes. Studies on migrant populations have underlined the importance of both environmental and genetic factors., Aims: Evaluate the incidence of type 1 diabetes in North African vs Italian children aged 0-14 years from 1 January 2015, to 31st December 2018, in Emilia-Romagna region, Italy., Methods: Clinical and epidemiological data about childhood onset type 1 diabetes in Emilia Romagna region were retrospectively collected by the regional centers of pediatric diabetology and matched using 3 different data sources., Results: 365 new cases were diagnosed. Total cumulative incidence was 15.4/100,000/year. North African cases showed a cumulative incidence of 53.8/100,000/year, statistically significant compared to cumulative incidence of the Italian cases alone 13.1/100,000/year (p value < 0.001). The annual incidence did not differ in the 4 years for both groups.  Conclusion: The incidence of type 1 diabetes in the pediatric age (0 14 years) was significantly higher in the North African population than in the Italian one, suggesting that a mix of genetic and environmental factors may have caused the increase in newly diagnosed cases., What Is Known: • The incidence of type 1 diabetes largely varies worldwide. • Study on immigrants helped to better understand the interplay role between genetics and environment., What Is New: • This is the first study focused on the incidence of children and adolescents of North African migrants in Italy. • The incidence of children and adolescents of North African migrants in Emilia Romagna region, Italy, seems to be higher than that reported in the host countries, and, above all, than that reported in highest-incidence countries in Europe and in the world., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Endocrine disrupting chemicals (EDCs) are present in many areas and materials of the common life, and exposure to these chemicals can occur from products to personal care, from air and food. This review aims to summarize the more recent epidemiological findings for the impact of EDCs on endocrine system health in children, including effects in growth, metabolism, sexual development, and reproduction., Sources: The MEDLINE database (PubMed) was searched on August 24th, 2021, filtering for EDCs, endocrine disruptors, children, and humans., Summary of the Findings: Intrauterine exposure of EDCs can have transgenerational effects, thus laying the foundation for disease in later life. The dose-response relationship may not always be predictable as even low-level exposures that may occur in everyday life can have significant effects on a susceptible individual. Although individual compounds have been studied in detail, the effects of a combination of these chemicals are yet to be studied to understand the real-life situation where human beings are exposed to a "cocktail effect" of these EDCs. Epidemiological studies in humans suggest EDCs' effects on prenatal growth, thyroid function, glucose metabolism, obesity, puberty, and fertility mainly through epigenetic mechanisms., Conclusions: EDCs cause adverse effects in animals, and their effects on human health are now known and irrefutable. Because people are typically exposed to multiple endocrine disruptors, assessing public health effects is difficult. Legislation to ban EDCs and protect especially pregnant women and young children is required and needs to be revised and adjusted to new developments on a regular basis., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021. Published by Elsevier Editora Ltda.)

Background: Hypospadias is one of the most common congenital abnormalities in male newborn. There is no universal approach to hypospadias surgical repair, with more than 300 corrective procedures described in current literature. The reoperation rate within 6-12 months of the initial surgery is most frequently used as an outcome measure. These short-term outcomes may not reflect those encountered in adolescence and adult life. This study aims to identify the long-term cosmetic, functional and psychosexual outcomes., Methods: Medical records of boys who had undergone surgical repair of hypospadias by a single surgical team led by the same surgeon at a single centre between August 2001 and December 2017 were reviewed. Families were contacted by telephone and invited to participate. Surgical outcome was assessed by combination of clinical examination, a life-related interview and 3 validated questionnaires (the Penile Perception Score-PPS, the Hypospadias Objective Score Evaluation-HOSE, the International Index of Erectile Function-5-IIEF5). Outcomes were compared according to age, severity of hypospadias, and respondent (child, parent and surgeon)., Results: 187 children and their families agreed to participate in the study. 46 patients (24.6%) presented at least one complication after the repair, with a median elapsed time of 11.5 months (6.5-22.5). Longitudinal differences in surgical corrective procedures (p < 0.01), clinical approach (p < 0.01), hospitalisation after surgery (p < 0.01) were found. Cosmetic data from the PPS were similar among children and parents, with no significant differences in child's age or the type of hypospadias: 83% of children and 87% of parents were satisfied with the cosmetic result. A significant difference in functional outcome related to the type of hypospadias was reflected responses to HOSE amongst all groups of respondents: children (p < 0.001), parents (p=0.02) and surgeon (p < 0.01). The child's HOSE total score was consistently lower than the surgeon (p < 0.01). The HOSE satisfaction rate on functional outcome was 89% for child and 92% for parent respondents., Conclusion: Surgeons and clinicians should be cognizant of the long-term outcomes following hypospadias surgical repair and this should be reflected in a demand for a standardised approach to repair and follow-up., (© 2021. The Author(s).)

Background and Aim: Children with heterozygous familial hypercholesterolemia (heFH) are at risk of premature atherosclerosis. Aims of this study were: (a) to longitudinally evaluate the endothelial dysfunction, estimated through brachial flow mediated dilation (FMD), as first sign of subclinical atherogenesis in a group of children and adolescents affected by heFH in comparison to normo-lipidemic controls, and (b) to identify predictive factors influencing the endothelial function and its development in the same cohort of patients., Methods: This is a prospective, longitudinal and cross-sectional study. Physical examination, plasma lipid profile and brachial artery FMD were measured at baseline and after follow-up., Results: At baseline, FMD did not differ between heFH children (n.24, median age 9.71) and controls (n. 24, median age 10.29) (7.67 ± 9.26 vs. 11.18 ± 7.28 %, p 0.09). Nevertheless, during follow-up (median length of lipid-lowering diet 4.52 years), FMD got worse in 54% of heFH subjects and its worsening correlated to the increasing of low-density lipoprotein cholesterol (r -0.21, p < 0.05). Moreover, being male (β -0.46, p 0.03), undergoing puberty (β -0.61, p 0.03) and increasing of body mass index standard deviation score (β -0.39, p 0.03) were identified as main independent predictor factors of FMD drop., Conclusions: During the first decades of life, not only hypercholesterolemia, but also clusters of pro-atherogenic conditions and their persistence, could affect the endothelial function and its trend. (www.actabiomedica.it).

Aim: To evaluate the impact of a virtual educational camp (vEC) on glucose control in children and adolescents with type 1 diabetes using a closed-loop control (CLC) system., Materials and Methods: This was a prospective multicentre study of children and adolescents with type 1 diabetes using the Tandem Basal-IQ system. Insulin pumps were upgraded to Control-IQ, and children and their parents participated in a 3-day multidisciplinary vEC. Clinical data, glucose metrics and HbA1c were evaluated over the 12 weeks prior to the Control-IQ update and over the 12 weeks after the vEC., Results: Forty-three children and adolescents (aged 7-16 years) with type 1 diabetes and their families participated in the vEC. The median percentage of time in target range (70-180 mg/dL; TIR) increased from 64% (interquartile range [IQR] 56%-73%) with Basal-IQ to 76% (IQR 71%-81%) with Control-IQ (P < .001). After the vEC, more than 75% of participants achieved a TIR of more than 70%. The percentage of time between 180 and 250 mg/dL and above 250 mg/dL decreased by 5% (P < .01) and 6% (P < .01), respectively, while the time between 70 and 54 mg/dL and below 54 mg/dL remained low and unaltered. HbA1c decreased by 0.5% (P < .01). There were no episodes of diabetic ketoacidosis or severe hypoglycaemia., Conclusions: In this study of children managing their diabetes in a real-world setting, more than 75% of children who participated in a vEC after starting a CLC system could obtain and maintain a TIR of more than 70%. The vEC was feasible and resulted in a significant and persistent improvement in TIR in children and adolescents with type 1 diabetes., (© 2021 John Wiley & Sons Ltd.)