Search

Aim: To assess the incidence and the temporal trend of type 1 diabetes (T1D) and diabetic ketoacidosis (DKA) during the period 2014-2023 in youths aged 0-14 years in the Trentino-Alto Adige region, Italy., Methods: A retrospective review of all incident cases of T1D diagnosed at the two Pediatric Diabetes Centers of Bolzano and Trento was matched with diabetes exemptions (No. 344). Demographic, clinical, and socioeconomic status (SES) data at first hospitalization were collected from subjects who agreed to participate (No. 272)., Results: The incidence of T1D was 21.5/100,000 person/years, with a peak of 31.1 in 2021 during the COVID-19 pandemic. The mean age at the onset was 8.8 ± 3.9 years. Seventy-nine percent of the subjects were Italians, primarily residents in rural areas, and SES was equally represented. The mean incidence of DKA was 36.9%. The logistic regression analysis showed that the independent characteristics of the patients with DKA were of a younger age and displayed higher glycated hemoglobin (HbA1c) values. No relation of DKA with seasonality, ethnicity, or first-degree relative (FDR) with T1D or SES was detected., Conclusions: Our study revealed an incidence of T1D in the Trentino-Alto Adige region comparable to other areas in the North of Italy. The DKA rate negatively correlated with age; therefore, targeted prevention educational campaigns to increase awareness are needed.

Background: sepiapterine reductase deficiency (SRD) is a rare levodopa (L-dopa)-responsive disorder treated with a combination therapy of controlled-release L-dopa and carbidopa. The currently available formulation of controlled-release carbidopa/L-dopa does not entirely meet the requirements for the long-term therapy in pediatric patients. In fact, administration of a manufactured tablet at a dose intended for adults necessitates its adjustment to the child's needs, as the splitting of the tablet into smaller portions or its dilution in water. It's essential to emphasize that tablets must not be crushed, as this can compromise the controlled-release mechanism and affect the efficacy of the medication. At the moment, commercial liquid formulations are not available. Given these limitations, in house drug preparation in hospitals and community pharmacies is a valid option to ensure the proper therapeutic management of these patients., Materials and Methods: we described sample preparation, physical and microbiological analyses, taste testing, and tolerability of a 1:10 ratio carbidopa/L-dopa flavored (mint, raspberry, cacao, berries) and unflavored oral formulation (no sweetening agents were added). We also reported long-term follow-up of two pediatric patients with SRD., Results: we documented the stability for 28 days at 25 °C of the liquid solution. All formulations were well-tolerated, and no adverse events were observed during or after assessing taste and tolerability. The long-term follow up of two patients was characterized by effective symptom control and optimal treatment adherence and compliance., Conclusions: in-house liquid drug formulations can be a valid option for pediatric patients with SRD. Given the significant impact of taste on medication adherence, the use of flavoring agents in the development of liquid formulations of L-dopa/carbidopa results a very useful strategy to obtain optimal adherence in the pediatric population., 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 Elsevier B.V. All rights reserved.)

Methylmalonyl-CoA epimerase enzyme (MCEE) is responsible for catalyzing the isomeric conversion between D- and L-methylmalonyl-CoA, an intermediate along the conversion of propionyl-CoA to succinyl-CoA. A dedicated test for MCEE deficiency is not included in the newborn screening (NBS) panels but it can be incidentally identified when investigating methylmalonic acidemia and propionic acidemia. Here, we report for the first time the biochemical description of a case detected by NBS. The NBS results showed increased levels of propionylcarnitine (C3) and 2-methylcitric acid (MCA), while methylmalonic acid (MMA) and homocysteine (Hcy) were within the reference limits. Confirmatory analyses revealed altered levels of metabolites, including MCA and MMA, suggesting a block in the propionate degradation pathway. The analysis of methylmalonic pathway genes by next-generation sequencing (NGS) allowed the identification of the known homozygous nonsense variation c.139C>T (p.R47X) in exon 2 of the MCE gene. Conclusions: Elevated concentrations of C3 with a slight increase in MCA and normal MMA and Hcy during NBS should prompt the consideration of MCEE deficiency in differential diagnosis. Increased MMA levels may be negligible at NBS as they may reach relevant values beyond the first days of life and thus could be identified only in confirmatory analyses.

Aims: In this study, we aimed to analyze the possible change in Time In Range (TIR) in subjects with type 1 diabetes (T1D) using the Ambulatory Glucose Profile (AGP) and to identify the main socio-demographic and clinical predictors of sustained use., Methods: 143 youths wearing instant-scanning CGM received structured counseling on the AGP report interpretation, and who were able to use AGP at least every 14 days were enrolled in group A (n = 100), whereas no users were considered as group B (n = 43). Socio-demographic data at the enrollment, clinical data, and glucose metrics were collected at baseline and during quarterly consultations. Metabolic outcomes were evaluated during follow-up, and a comparison between groups A and B was performed., Results: In group A compared to group B, at 12 months, the percentage of sensor usage and TIR were higher (p = 0.04 and p = 0.02), and Time Above Range and HbA1c were lower (p = 0.0004, p < 0.0001, respectively). Multiple logistic regression analysis did not show a significant relationship between sustained AGP software usage and the variables analyzed., Conclusions: Systematic use of the AGP software was feasible and showed improved metabolic control in youths with T1D. This may be related to increased sensor usage and more informed decisions., 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 Elsevier B.V. All rights reserved.)

The prompt identification of at-risk newborns for drug-induced hypoglycemia can minimize the risk for adverse side effects, inappropriate investigations, and considerable unnecessary costs. Existing literature discusses drug-induced hypoglycemia, but a systematic description of neonatal hypoglycemia induced or exacerbated by maternal medications is missing. We reviewed the association between neonatal hypoglycemia and maternal medications. We systematically searched the literature according to the PICOS model on drug-induced hypoglycemia in neonates born to nondiabetic women treated with medications during the pregnancy or the labor. The main outcomes of the review were: (1) prevalence of hypoglycemia, (2) risk factors and potential confounders, (3) time at onset and severity of hypoglycemia, (4) dose-response gradient, (5) metabolic features of hypoglycemia, (6) modalities to treat hypoglycemia, and (7) quality of the studies. We included 69 studies in this review and we identified 11 groups of maternal drugs related to neonatal hypoglycemia. Results were classified for each outcome. Our review aims at supporting clinicians in the identification of the newborn at risk for hypoglycemia and in the differential diagnosis of neonatal hypoglycemia. Further studies are necessary to assess the risk of neonatal hypoglycemia associated with common maternal medications. KEY POINTS: · A systematic description of neonatal hypoglycemia induced or exacerbated by maternal medications is missing.. · In our review we identified 11 groups of maternal drugs related to neonatal hypoglycemia.. · Our review aims at supporting clinicians in the identification of the newborn at risk for hypoglycemia.., Competing Interests: None declared., (Thieme. All rights reserved.)

At 23 days of life a neonate presented to the emergency room with crying and decreased oral intake. His parents were positive to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), but he turned out negative. After one week he was admitted to NICU (neonatal intensive care unit) for respiratory failure, and nasopharyngeal swab (PCR test: polymerase chain reaction test) was positive for SARS-CoV-2. On examination the child had fever, tachy-dyspnea, reduced oxygen saturation, tachycardia, abdominal distension and tenderness, irritability and hypertonia. Blood exam showed respiratory acidosis, lymphocytopenia, hypoalbuminemia and coagulopathy; CRP (C reactive protein), procalcitonin, D-dimer, ferritin and NT-proBNP (N-terminal prohormone of brain natriuretic peptide) were elevated. Chest X-ray revealed bilateral interstitial infi ltration and abdomen ultrasound a thin fl uid effusion; echocardiography was normal. SARS-CoV-2 PCR tests on CSF (cerebrospinal fluid) and stool were also positive. He was started on non-invasive intermittent positive pressure respiratory ventilation, treated with antibiotic therapy, methylprednisolone, intravenous immunoglobulins, and antiplatelet therapy. Rapid clinical improvement was seen with remission of fever after eight days. The child complicated with bacterial super-infection presenting as pleural empyema. As presented in our case, it is not always easy to differentiate between severe forms of COVID-19 and MIS-C. Due to the rarity of these presentations in neonates, multicentric collaboration is needed to identify the specifi c characteristics of the two forms, better defi ne diagnostic criteria, and treatment options.

The initial step for the differential diagnosis of hypoglycemia is to determine whether it is hyperinsulinemic or non hyperinsulinemic. Existing literature discusses drug-related hypoglycemia, but it misses a focus on drug-induced hyperinsulinemic hypoglycemia (DHH). Here we reviewed the association existing between drugs and hyperinsulinemic hypoglycemia. We primarily selected on the main electronic databases (MEDLINE, EMBASE, Web of Science, and SCOPUS) the reviews on drug-induced hypoglycemia. Among the drugs listed in the reviews, we selected the ones linked to an increase in insulin secretion. For the drugs missing a clear association with insulin secretion, we investigated the putative mechanism underlying hypoglycemia referring to the original papers. Our review provides a list of the most common agents associated with hyperinsulinemic hypoglycemia (HH), in order to facilitate both the recognition and the prevention of DHH. We also collected data about the responsiveness of DHH to diazoxide or octreotide., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: During the COVID-19 pandemic, accesses to pediatric health care services decreased, as well as the consumption of traditional drugs, while the median cost per patient at the emergency department slightly increased and the cost of pediatric COVID-19 admissions to the pediatric ward too. Overall spending of a secondary level Pediatric Unit in the last two years has not been previously reported., Methods: This is a retrospective study conducted by the Pediatric Unit of S. Chiara Hospital of Trento, North of Italy. We collected data on consumption and spending before and during the COVID-19 pandemic (between January 2018 and December 2022)., Results: The total spending ranged from 2.141.220 to 2.483.931 euros between 2018 and 2022. COVID-19 spending accounted only for 5-8% of the overall budget, while two macro-areas of spending were identified: (i) biologic drugs for inherited metabolic diseases (IMDs), that impacted for 35.4-41.3%, and (ii) technology devices for type 1 diabetes (T1D), that accounted for 41.6-32.8% of the overall budget, in 2021 and 2022, respectively. Analysis of costs along with the different health care services revealed that: (i) the spending for COVID-19 antigen tests and personal protective equipment had a major impact on the Emergency room budget (from 54 to 68% in the two years); (ii) biological drugs accounted mainly on the Pediatric Ward (for 57%), Day Hospital (for 74%) and rare disease center budget (for 95% of the spending); (iii) the cost for T1D devices was mainly due to continuous glucose monitoring, and impacted for the 97% of the outpatient clinic budget., Conclusions: The main impact on the budget was not due to COVID-19 pandemic related costs, but to the costs for biologic drugs and T1D devices. Therefore, cost savings could be mainly achieved through generic and biosimilars introduction and with inter-regionals calls for technology devices. We emphasize how the control of spending in pediatric hospital care has probably moved from the bedside (savings on traditional drugs as antibiotics) to the bench of national or inter-regional round tables, to obtain discounts on the costs of biologic drugs and medical devices. Here we provide for the first-time in literature, data for bench-marking between secondary level Pediatric Units before and during the COVID-19 pandemic., (© 2023. The Author(s).)

Objective. Kabuki syndrome (KS) is associated with hyperinsulinemic hypoglycemia (HH) in 0.3-4% of patients, thus exceeding the prevalence in the general population. HH association is stronger for KS type 2 (KDM6A-KS, OMIM #300867) than KS type 1 (KMT2D-KS, OMIM #147920). Both the disease-associated genes, KMD6A and KMT2D, modulate the chromatin dynamic. As such, KS is considered to be the best characterized pediatric chromatinopathy. However, the exact pathogenetic mechanisms leading to HH in this syndrome remain still unclear. Methods. We selected on the electronic database PubMed all articles describing or hypothesizing the mechanisms underlying the dysregulated insulin secretion in KS. Results. The impact on the gene expression due to the KDM6A or KMT2D function loss may lead to a deregulated pancreatic β-cell differentiation during embryogenesis. Moreover, both KMT2D gene and KDM6A gene are implicated in promoting the transcription of essential pancreatic β-cell genes and in regulating the metabolic pathways instrumental for insulin release. Somatic KMT2D or KDM6A mutations have also been described in several tumor types, including insulinoma, and have been associated with metabolic pathways promoting pancreatic cell proliferation. Conclusions. The impact of pathogenic variants in KDM6A and KDM2D genes on β-cell insulin release remains to be fully clarified. Understanding this phenomenon may provide valuable insight into the physiological mechanisms of insulin release and into the pathological cascade causing hyperinsulinism in KS. The identification of these molecular targets may open new therapeutic opportunities based on epigenetic modifiers., (© 2023 Evelina Maines et al., published by Sciendo.)

The guidelines for the management of patients affected by propionic acidemia (PA) recommend standard cardiac therapy in the presence of cardiac complications. A recent revision questioned the impact of high doses of coenzyme Q10 on cardiac function in patients with cardiomyopathy (CM). Liver transplantation is a therapeutic option for several patients since it may stabilize or reverse CM. Both the patients waiting for liver transplantation and, even more, the ones not eligible for transplant programs urgently need therapies to improve cardiac function. To this aim, the identification of the pathogenetic mechanisms represents a key point. Aims: This review summarizes: (1) the current knowledge of the pathogenetic mechanisms underlying cardiac complications in PA and (2) the available and potential pharmacological options for the prevention or the treatment of cardiac complications in PA. To select articles, we searched the electronic database PubMed using the Mesh terms "propionic acidemia" OR "propionate" AND "cardiomyopathy" OR "Long QT syndrome". We selected 77 studies, enlightening 12 potential disease-specific or non-disease-specific pathogenetic mechanisms, namely: impaired substrate delivery to TCA cycle and TCA dysfunction, secondary mitochondrial electron transport chain dysfunction and oxidative stress, coenzyme Q10 deficiency, metabolic reprogramming, carnitine deficiency, cardiac excitation-contraction coupling alteration, genetics, epigenetics, microRNAs, micronutrients deficiencies, renin-angiotensin-aldosterone system activation, and increased sympathetic activation. We provide a critical discussion of the related therapeutic options. Current literature supports the involvement of multiple cellular pathways in cardiac complications of PA, indicating the growing complexity of their pathophysiology. Elucidating the mechanisms responsible for such abnormalities is essential to identify therapeutic strategies going beyond the correction of the enzymatic defect rather than engaging the dysregulated mechanisms. Although these approaches are not expected to be resolutive, they may improve the quality of life and slow the disease progression. Available pharmacological options are limited and tested in small cohorts. Indeed, a multicenter approach is mandatory to strengthen the efficacy of therapeutic options.

Background: Since the beginning of COVID-19 pandemic, an increase in new diagnoses and pediatric hospital admission for anorexia nervosa (AN) or atypical AN in adolescents have been reported, suggesting an adverse effect of COVID-19 on youth mental health. We hypothesized possible differences in prevalence of hospitalization and/or disease severity, related to socio-economic status and/or ethnicity., Methods: Retrospectively, patients were divided into two subgroups and compared according to the date of first hospital admission: "pre SARS-COV2 era" group (n. 45, 8th March 2016-8th March 2020) and "SARS-COV2 era" group (n. 43, 9th March 2020-8th March 2022)., Results: During the two years of the SARS-COV2 era, we reported an increase in hospital admission incidence more than doubled respect to the "pre-SARS-COV2 era". The "SARS-COV2 era group" showed a more rapid weight loss ( p = 0.005), a minor duration of weight loss from lifetime maximum to admission ( p = 0.019) and needed most frequently treatments with intravenous fluids ( p < 0.0001), oral dietetic supplements ( p < 0.001) and enteral nutrition by nasogastric tube ( p = 0.002). The same group presented higher prevalence of psychiatric comorbidities (63% vs. 22%, p < 0.0001) and required most frequently treatments with psychotropic drugs (56% vs. 24%, p = 0.002). We found higher family socioeconomic status (SES) in our patients with AN in both the periods and we did not find a shift in social class distribution over time., Conclusions: Our study confirms a significant increase in incidence of hospitalization and of psychiatric comorbidity in the pediatric population with AN during the second year of COVID-19 pandemic, regardless of SES or ethnic background. Further studies are needed to understand potential mechanisms that during COVID-19 pandemic trigger eating disorder symptoms., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Background: Precision medicine in type 1 diabetes (T1D) treatment considers context and environmental data to subclassify patients. Parental Health Locus of Control PHLOC) could influence behavior, self-management, and metabolic control of children with T1D. Methods: No. 135 pediatric patients with T1D (No. 57 with HbA1c ≤ 7.0%, “optimal” group, and No. 78 with >7.0%, “sub-optimal” group) were enrolled in the study. History, anthropometric and diabetes management data were collected, as well as caregiver’s data about socioeconomic status (SES). The PHLOC scale questionnaire and a semi-structured interview were administered. Results: Access to technology was lower in the “sub-optimal” group and, in particular, in the ethnic minority subgroup, only 8% used them. In the “sub-optimal” group ethnic minority status was higher (24%), the caregiver had a lower SES and showed lower internal HLOC. Conclusions: New care models have to be implemented to ensure equity in diabetes care and precision treatment, particularly for ethnic minority groups, because SES and external PHLOC are still an important barrier to “optimal” diabetes control. In the “sub-optimal” group, we have to implement strategies aimed at increasing self-efficacy, while in the “optimal” one, a personalised approach should be considered to facilitate the shifting of responsibilities within the family, avoiding psychological distress.

Spondylo-epi-metaphyseal dysplasia Shohat type (SEMDSH, OMIM # 602557) is a rare skeletal dysplasia. Until recently, only eight patients of five families have been reported. The disorder is characterized by severely disproportionate short stature with a short neck, small trunk with abdominal distension, and short lower limbs. Joint laxity and bowed legs are seen. The same homozygous splicing pathogenic variant in the DDRGK1 gene was found in four Iraqi families. Here we report a homozygous missense pathogenic variant in DDRGK1 in two children from unrelated two Moroccan families. The clinical and radiological phenotypes of the affected children were similar to those previously described., (© 2022 Wiley Periodicals LLC.)

Forearm fractures in children and adolescents are associated with increased body mass index (BMI). This bone site is non-weight-bearing and therefore is appropriate to explore the effect of BMI on bone mineral density (BMD) and bone geometry, avoiding the confounding effect of increased weight-associated mechanical loading. The aim of this review was to summarize available evidence on bone indices and body composition assessed by peripheral quantitative computed tomography (pQCT) or dual X-ray absorptiometry (DXA) at the forearm level in overweight (Ow) or obese (Ob) subjects. We conducted a review of the literature according to the PICOS model. A total of 46 studies were identified following the literature search. A final number of 12 studies were included in this review. pQCT studies evidenced that Ow and Ob children typically have normal or increased volumetric BMD (vBMD), total bone area and cortical area, with normal or reduced cortical thickness at the forearm. Outcomes from DXA evaluations are less conclusive. In almost all the studies fat mass and lean mass area at the forearm are increased. A higher fat-to-lean mass ratio has been observed in few studies. Bone strength was reported as normal or increased compared to normal weight peers. In Ow or Ob children-adolescents, vBMD, bone size and bone strength are not reduced compared to normal weight peers. The local higher fat-to-lean mass ratio may give a mismatch between bone strength and the load experienced by the distal forearm during a fall, resulting in increased risk of forearm fractures., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neonatal sepsis is a systemic condition characterized by haemodynamic changes and other clinical manifestations due to a presence of pathogenic microorganisms (bacteria, viruses, or fungi) in nor- mally sterile fluid that occurs in an infant younger than 90 days old. Neonatal sepsis may be divided into two types: early-onset neonatal sepsis (EOS) and late-onset neonatal sepsis (LOS). Gram-posi- tive microorganisms are the etiological agents in 62% of EOS, and in 43% of the total the identified microorganism is GBS. Gram-negative microorganisms comprise 37% of the etiological agents of EOS, of which 29% are caused by Escherichia coli. ESBL-producing Enterobacteriaceae represent a major worldwide threat among drug-resistant bacteria in both hospital and community settings. ESBLs are often located on large plasmids that also harbour genes resistant to other antimicrobial classes, resulting in multidrug-resistant isolates. Plasmid-encoded ESBLs of the CTX-M-type are increasingly reported worldwide in Gram-negative rods and now account for most of the ESBLs found in Enterobacteriaceae. We present one case of EOS by Multi Drug Resistant (MDR) and ESBL producing E. coli (CTX-M gene) in a neonate born to a mother recently immigrated from Africa. Maternal blood culture grew the same bacteria.

Aims: Data about sleep quality and quantity are not available in patients with type 1 diabetes (T1D) using intermittently scanned continuous glucose monitoring (isCGM). We questioned whether the isCGM with alarms could fragment sleep in patients and parents, compared to isCGM without alarms., Methods: A prospective, observational study including 47 child-adolescents with T1D who had experience with isCGM without alarms (Freestyle Libre 1-FSL1). They were asked to wear the isCGM with alarms (Freestyle Libre 2-FSL2) for 14 days. Patients enrolled and their caregiver (s), during a 14 day period with FSL1 and the following 14 days with FSL2, completed psychosocial and sleep-related questionnaires. Furthermore they wore an actigraph that was downloaded to a web platform and processed by the validated and certified algorithm "Dormi ® .", Results: By the switch to the alarmed FSL2 we found about a 5% increase in Time In Range (from 62.5 to 67.8%), a reduction in time spent in hypoglycemia, number of weekly hypoglycemic events, and coefficient of variation. We did not find significant differences in sleep parameters in patients and their parents; therefore, alarms did not worsen the duration and quality of sleep. A significant improvement in the Quality of Life was perceived by parents using FSL2., Conclusions: Introduction of alarms in isCGM systems gives, in the short term, an improvement in metabolic control in terms of time in range and reduction in hypoglycemia, without worsening duration and quality of sleep, measured by actigraphy, in children-adolescent and their parents., (© 2022. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Background: Use of Continuous Glucose Monitoring (CGM) systems early in the course of diabetes has the potential to help glycemic management and to improve quality of life (QoL). No previous research has examined these outcomes in children-adolescents with type 1 diabetes (T1D) who use intermittently scanned CGM (isCGM) starting within the first month after diagnosis., Aim: To evaluate the impact of isCGM early after T1D diagnosis, on metabolic control and QoL, comparing a group who started the use of the device within one month from the onset with another one who started at least one year later., Subjects and Methods: Patients who used isCGM within 1 month from T1D diagnosis were enrolled in group A; those who didn't have the device during the first year were considered as control group (group B). HbA1c and total daily insulin were evaluated at 3 (T1), 6 (T2) and 12 (T3) months post-baseline (T0, diabetes onset), QoL after 1 year. In group A, isCGM glucose metrics were also recorded., Results: 85 patients were enrolled in group A and 67 patients in group B. In group A isCGM was well accepted during follow up: no patient dropped out; percentage of time with active sensor was in mean > 87%; number of scans/day remained stable. QoL was higher in group A than in group B both in children-adolescents (p<0.0001) and in parents (p 0.003). Group A presented lower HbA1c during the first year after diagnosis (p<0.001), and this data correlated with glucose management indicator (GMI), time in range (TIR) and mean glucose. The honeymoon period lasted more in group A than in B (p 0.028). Furthermore, the mean hypoglycemia duration decreased during follow-up (p 0.001) in group A., Conclusions: Early use of isCGM, starting within the first month after diagnosis, improves metabolic control and QoL in pediatric patients with T1D., 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 Franceschi, Cauvin, Stefani, Berchielli, Soffiati and Maines.)

Purpose: The aim was to verify in a pediatric population with Hashimoto's thyroiditis whether there is a relationship between antithyroid antibodies and inflammatory status on thyroid ultrasound and thyroid function., Subjects and Methods: A total of 154 children and adolescents, aged 4 to 18 years, diagnosed with Hashimoto's thyroiditis with normal body weight were followed up for 1 year., Results: Patients with only antiperoxidase antibodies presented with higher TSH levels than subjects with only antithyroglobulin antibodies (p 0.027) but with similar FT4 levels and thyroid score. Prevalence of seronegative Hashimoto's thyroiditis in this cohort was 12.3% (19/154). At diagnosis, the seronegative group presented with lower prevalence of overt hypothyroidism, symptoms of hypothyroidism, and thyroid score, meaning less severe thyroid involvement. In contrast, similar TSH and FT4 values were found at diagnosis and during follow-up in both the seronegative and seropositive groups. A comparison between patients with seronegative Hashimoto's thyroiditis and an overweight/obese antibody-negative population, who presented superimposable altered parenchymal pattern on thyroid ultrasound without circulating antithyroid antibodies, presented similar clinical data., Conclusion: We report for the first time in the literature that seronegative Hashimoto's thyroiditis in the pediatric age group has a less severe pattern. The seronegative group presents similar characteristics to those of overweight/obese children and adolescents with ultrasound changes, but, according to the established knowledge, the latter condition is reversible and does not need follow-up examinations., (© 2022. Hellenic Endocrine Society.)

Niemann-Pick disease (NPD) type A and type B are part of the spectrum disease of the acid sphingomyelinase deficiency (ASMD). Plasma lipid abnormalities are frequently associated with both NPD-A and NPD-B, and include decreased high-density lipoprotein cholesterol (HDL-C), increased low-density lipoprotein cholesterol (LDL-C), and hypertriglyceridemia. The atherogenic lipid profile has been associated to early atherosclerotic vascular disease and coronary artery disease in NPD-B patients. Thus, early treatment of dyslipidemia in these patients is advisable. We present here a pediatric case of NPD-B with an atherogenic lipid profile not responding to lifestyle changes, low fat diet, and daily supplementation with plant sterols. We reviewed the existing literature about the treatment strategies for dyslipidemia in ASMD patients, with a special focus on the pediatric age. Finally, we speculated on the mechanisms underlying dyslipidemia in this disorder. The clinical experiences in lipid-lowering strategies in NPD-B patients are limited, in particular in the pediatric age. Olipudase alfa appears as the most promising candidate for improving lipid profile. Since olipudase alfa is not yet approved and, due to its costs, it will probably not be available for all patients worldwide, further research is needed to broaden our knowledge on this clinical need and to evaluate the efficacy and the long-term effects of lipid-lowering agents in ASMD patients. A deep understanding of the pathophysiology of dyslipidemia in ASMD may promote the identification of new targets and support the identification of new therapeutic strategies., Competing Interests: Declaration of Competing Interest All authors state that they have no competing interests to declare. None of the authors accepted any reimbursements, fees or funds from any organization that may in any way gain or lose financially from the results of this study., (Copyright © 2022. Published by Elsevier Inc.)

Background: Severe bradycardia is an indication supporting hospitalization in adolescents with eating disorders. Some adolescents with anorexia nervosa (AN) and significant weight loss present with a normal pulse rate at admission, whereas others have severe bradycardia, suggesting that total weight loss is not the most important determinant of bradycardia. The aims of this study were to define the prevalence of severe bradycardia as the cause for hospital admission in adolescents with AN, to evaluate correlations between known determinants of severe bradycardia and pulse rate at admission, and to evaluate the average time required to recover from severe bradycardia after re-feeding., Methods: Ninety-nine hospitalized patients with AN were enrolled. Weight loss history, anthropometric, laboratory, and electrocardiogram data were collected at admission to and at discharge from hospital. Multivariate analysis was performed to detect the most important determinants of severe bradycardia., Results: Forty-eight percent of the AN patient admissions were due to severe bradycardia (AN-B+ group). Patients in this group had a higher maximum lifetime weight (P = 0.0045), greater premorbid weight loss (P = 0.0011), and more rapid weight loss (P = 0.0001). Multivariate analysis showed that recent weight loss is an independent predictor of bradycardia at hospital admission (R 2 : 0.35, P = 0.0001). Severe bradycardia normalized after minimal weight gain of 0.25 ± 0.18 kg/day for 3-10 days., Conclusions: This study confirms that recent weight loss is probably the most important determinant of severe bradycardia in adolescents with AN., (© 2021 Japan Pediatric Society.)

Introduction: The PI3K/AKT/mTOR signaling pathway is important for the regulation of multiple biological processes, including cellular growth and glucose metabolism. Defects of the PI3K/AKT/mTOR signaling pathway are not usually considered among the genetic causes of recurrent hypoglycemia in childhood. However, accumulating evidence links hypoglycemia with defects of this pathway., Case Reports and Review: We describe here two cases of macrocephaly and hypoglycemia bearing genetic defects in genes involved in the PI3K/AKT/mTOR pathway. The first patient was diagnosed with a PTEN hamartoma tumour syndrome (PTHS) due to the de novo germline missense mutation c.[492 + 1G > A] of the PTEN gene. The second patient presented the autosomal dominant mental retardation-35 (MDR35) due to the heterozygous missense mutation c.592G > A in the PPP2R5D gene. A review of the literature on hypoglycemia and PI3K/AKT/mTOR signaling pathway defects, with a special focus on the metabolic characterization of hypoglycemia, is included., Conclusions: PI3K/AKT/mTOR pathway defects should be included in the differential diagnosis of patients with hypoglycemia and macrocephaly. Clinical suspicion and molecular confirmation are important, not just for an accurate genetic counselling but also for defining the follow-up management, including cancer surveillance. The biochemical profile of hypoglycemia varies among patients. While most patients are characterized by low plasmatic insulin levels, hyperinsulinemia has also been observed. Large patient cohorts are needed to gain a comprehensive profile of the biochemical patterns of hypoglycemia in such defects and eventually guide targeted therapeutic interventions., (© 2021. Hellenic Endocrine Society.)

Background: The thermal servo-controlled systems are routinely used in neonatal intensive care units (NICUs) to accurately manage patient temperature, but their role during the immediate postnatal phase has not been previously assessed., Objective: To compare two modalities of thermal management (with and without the use of a servo-controlled system) immediately after birth., Study Design and Setting: Multicentre, unblinded, randomised trial conducted 15 Italian tertiary hospitals., Participants: Infants with estimated birth weight <1500 g and/or gestational age <30 +6 weeks., Intervention: Thermal management with or without a thermal servo-controlled system during stabilisation in the delivery room., Primary Outcome: Proportion of normothermia at NICU admission (axillary temperature 36.5°C-37.5°C)., Results: At NICU admission, normothermia was achieved in 89/225 neonates (39.6%) with the thermal servo-controlled system and 95/225 neonates (42.2%) without the thermal servo-controlled system (risk ratio 0.94, 95% CI 0.75 to 1.17). Thermal servo-controlled system was associated with increased mild hypothermia (36°C-36.4°C) (risk ratio 1.48, 95% CI 1.09 to 2.01)., Conclusions: In very low birthweight infants, thermal management with the servo-controlled system conferred no advantage in maintaining normothermia at NICU admission, while it was associated with increased mild hypothermia. Thermal management of preterm infants immediately after birth remains a challenge., Trial Registration Number: NCT03844204., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of the "Smuovi La Salute" ("Shake Your Health") project was to implement an integrated and comprehensive model to prevent and treat overweight and obesity in low socioeconomic status (SES) and minority groups living in three different districts in the north of Italy. An app and a cookbook promoting transcultural nutrition and a healthy lifestyle were developed, and no-cost physical activities were organized. Healthy lifestyle teaching was implemented in 30 primary school classrooms. Learning was assessed through pre- and post-intervention questionnaires. At the Obesity Pediatric Clinic, overweight and obese children of migrant background or low SES were trained on transcultural nutrition and invited to participate in the project. Primary school students increased their knowledge about healthy nutrition and the importance of physical activity ( p -value < 0.001). At the Obesity Pediatric Clinic, after 6 months, pre-post-intervention variation in their consumption of vegetables and fruit was +14% ( p < 0.0001) and no variation in physical activity habits occurred ( p = 0.34). In this group, the BMI z -score was not significantly decreased (-0.17 ± 0.63, p = 0.15). This study demonstrates the feasibility and efficacy of telematic tools and targeted community approaches in improving students' knowledge with regard to healthy lifestyle, particularly in schools in suburbs with a high density of migrants and SES families. Comprehensive and integrated approaches provided to the obese patients remain mostly ineffective.

Generalized Arterial Calcification of Infancy (GACI) is a rare disease inherited in a recessive manner, with severe and diffuse early onset of calcifications along the internal elastic lamina in large and medium size arteries. The diagnosis results are from clinical manifestations, imaging, histopathologic exams, and genetic tests. GACI is predominantly caused by biallelic pathogenic variant in the ENPP1 gene (GACI1, OMIM#208000) and, to a lesser extent, by pathogenic variants in the ABCC6 gene (GACI2, OMIM#614473). We present a novel variation in the ENPP1 gene identified in a patient clinically diagnosed with GACI and confirmed by genetic investigation and autopsy as GACI type 1. The sequence analysis of the patient's ENPP1 gene detected two heterozygous variants c.1412A>G (p.Tyr471Cys) and c.1715T>C (p.Leu572Ser). The variant c.1715T>C (p.Leu572Ser) has not been described yet in the literature and in mutation databases. A genetic analysis was also carried out for the parents of the newborn; the heterozygous pathogenic variant c.1412A>G (p.Tyr471Cys) was detected in the mother's ENPP1 gene, and a sequence analysis of the father's ENPP1 gene revealed the novel heterozygous variant c.1715T>C (p.Leu572Ser) . Our results showed that the variant c.1715T>C (p.Leu572Ser) may have a pathogenic role in the development of GACI type1 (GACI1, OMIM#208000), at least when associated with the pathogenic c.1412A>G (p.Tyr471Cys) variant. The identification of novel mutations potentially enabled genotype/phenotype associations that will ultimately have an impact on clinical management and prognosis for the disease.

Background: Failure to thrive is a common reason for referral to paediatric services. Malnutrition or inadequate caloric intake is the most common cause, while organic form is unlikely in children who are asymptomatic and healthy on examination. By this study we evaluate the application of a cost-effective flow chart that helps the clinician in a hospital setting discern accurately organic and non-organic failure to thrive., Methods: Conduct a prospective single-center study in children up to 2 years of age with growth faltering. The pediatricians used a practical flow chart, took the medical history, created a growth chart, performed clinical examinations, and requested blood test and consultations in a step by step approach., Results: Among the 74 subjects included in the study, the diagnosis of organic failure to thrive was reached by 42%. Gastrointestinal and genetic diagnoses were the most frequent. Patients with organic failure to thrive had significantly lower gestational age and birth weight. Age at diagnosis and Z-score weight were lower in organic than in non-organic forms. Most patients with non-organic forms (88%) did not undergo in-depth blood test or specialist advice., Conclusion: The flow chart we presented was accurate for diagnosing children with failure to thrive in a hospital setting and distinct organic and non-organic forms. It was cost-effective to avoid unnecessary blood test or consultations in most non-organic diagnoses.

Objective: To describe the model build up to take care of fetuses and newborns eligible to perinatal palliative care (PnPC) followed in an Italian II level perinatal center. Methods: Retrospective chart review of all fetuses and newborn infants eligible to PnPC admitted to level II perinatal center within a 4 years period. Results: Forty-five of 848 infants (0.5%) referred to II level NICU were eligible to PnPC. Twenty-seven percentage had fetal diagnosis. Twenty percentage were preterm infants at the limit of viability, 35% were newborns with life limiting or life threatening disease diagnosed in utero or at the postnatal ward, 45% were newborns not responding to intensive care intervention with high health care needs or medical complexity. Fifty-seven percentage of neonates admitted to NICU died before discharge, while 16 (35% of population considered) were discharged home. Median age at death was 4 days after birth, and delivery room death immediately after birth occurred in six patients (13%). Conclusions: Despite the paucity of our population and the high variability in disease trajectories the perinatal palliative care program build up in our region provides a reproducible method for a structured taking in charge of fetuses and neonates eligible to PnPC and their families, from the time of diagnosis to bereavement, in both outpatient and inpatient settings., 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 © 2021 Bolognani, Morelli, Scolari, Dolci, Fiorito, Uez, Graziani, Stefani, Zeni, Gobber, Bravi, Tateo and Soffiati.)

The acquisition and development of the infant microbiome are key to establishing a healthy host-microbiome symbiosis. The maternal microbial reservoir is thought to play a crucial role in this process. However, the source and transmission routes of the infant pioneering microbes are poorly understood. To address this, we longitudinally sampled the microbiome of 25 mother-infant pairs across multiple body sites from birth up to 4 months postpartum. Strain-level metagenomic profiling showed a rapid influx of microbes at birth followed by strong selection during the first few days of life. Maternal skin and vaginal strains colonize only transiently, and the infant continues to acquire microbes from distinct maternal sources after birth. Maternal gut strains proved more persistent in the infant gut and ecologically better adapted than those acquired from other sources. Together, these data describe the mother-to-infant microbiome transmission routes that are integral in the development of the infant microbiome., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Early discharge (ED) of healthy term infants has become a common practice due to current social and economic needs. The primary objective of the present study was to evaluate trends in early discharge of healthy term neonates (≥ 37 gestational weeks) by delivery method (cesarean and vaginal) in maternity units in the Province of Trento. The secondary objective was to identify the socio-demographic characteristics (including the area of residence and distance from the designated hospital) and clinical characteristics of mothers whose infants were discharged early. This retrospective study reviewed records of live births from 2006 to 2016, for a total of 45, 314 healthy term infants. The trend for ED grew significantly during the period 2006-2016, for both cesarean and vaginal deliveries. The multiple logistic regression analysis shows how the determinants of ED are maternal age, birth order, citizenship of mother, maternal smoking, maternal employment status, and the number of births at the hospital on the day of birth., Conclusion: The post-partum length of stay should be adjusted based on the characteristics and needs of the mother-infant dyad, identifying the criteria for safe discharge. In Trento, various procedures and programs are becoming more uniform today with the intention to provide family assistance service. What is Known: • Admission for childbirth is one of the primary causes of hospitalization in industrialized countries. • The length of stay for childbirth has been steadily declining in recent decades, with the aim of reducing costs while also demedicalizing pregnancy. What is New: • A higher rate of early discharge (ED) was recorded for neonates of women having foreign citizenship, < 30 years, pluriparous, smoked during pregnancy, housewife, and, if emplyed, entrepreneurs, self-employed professionals or managers. • ED was more common when the new mother gave birth on a day in which there was a higher number of births at the hospital, indicating overcrowding in the maternity unit.

Background: The correct establishment of the human gut microbiota represents a crucial development that commences at birth. Different hypotheses propose that the infant gut microbiota is derived from, among other sources, the mother's fecal/vaginal microbiota and human milk., Results: The composition of bifidobacterial communities of 25 mother-infant pairs was investigated based on an internal transcribed spacer (ITS) approach, combined with cultivation-mediated and genomic analyses. We identified bifidobacterial strains/communities that are shared between mothers and their corresponding newborns. Notably, genomic analyses together with growth profiling assays revealed that bifidobacterial strains that had been isolated from human milk are genetically adapted to utilize human milk glycans. In addition, we identified particular bacteriophages specific of bifidobacterial species that are common in the viromes of mother and corresponding child., Conclusions: This study highlights the transmission of bifidobacterial communities from the mother to her child and implies human milk as a potential vehicle to facilitate this acquisition. Furthermore, these data represent the first example of maternal inheritance of bifidobacterial phages, also known as bifidophages in infants following a vertical transmission route.

Aim: The aim of this trial is to evaluate the role Lactobacillus paracasei in Bell's stage 2 in order to prevent the clinical progression to stage 3., Methods: A prospective study was approved and started in December 2008. Patients were infants with birth weight 600 to 1500 g. One group received probiotic supplementation (L. paracasei susp.paracasei F-19) and the control group received only standard medical treatment. The primary outcome was the progression to stage 3 as defined by Bell's modified criteria. Inclusion and exclusion criteria were created and discussed with parents before treatment., Results: Thirty-two patients (stage 2 NEC) were considered eligible for the study. Group A: 18 patients and Group B: 14 patients. Three patients in group A and six patients in group B had a clinical history of Bell's stage 3 NEC (P<0.05); oral supplementation of L. paracasei reduced the clinical progression of NEC. It was considered that an improvement in intestinal motility might have contributed to this result., Conclusion: The use of Lactobacillus paracasei subsp. paracasei F-19 is safe; the low progression rate to stage 3 NEC suggests that the use of this probiotic in stage 2 NEC could be a valuable therapeutic option.

Neurally adjusted ventilator assist (NAVA) is a new mode of partial ventilatory support, in which neural inspiratory activity is monitored through the continuous esophageal recording of the electrical activity of the diaphragm. Assistance is triggered and cycled off in according to this signal and is delivered in proportion to its intensity. NAVA can improve patient-ventilator synchrony while maintaining spontaneous breathing. Small preliminary studies have shown that NAVA can be successfully used also in term and preterm infants, being safe and well tolerated. However, much additional work is still needed before NAVA can be recommended in the everyday practice of the neonatologist.

In the neonatal population, pleural effusion and particularly tension pneumothorax can be a deadly situation. Pneumothorax occurs more often in the neonatal period that any other time of life. Tension pneumothorax can result in very high pressures within the pleural space, collapsing the lung on the involved side and resulting in immediate hypoxia, hypercapnia and subsequent circulatory collapse. For these reasons, the ability to recognize, understand and treat these pathologies is essential for neonatal health and a good outcome. Neonates have many factors that can contribute to. these problems. These include respiratory distress syndrome, mechanical ventilation, sepsis, pneumonia, aspiration of meconium, congentital malformation, hydrothorax, congenital or acquired chylothorax. The diagnosis can be made by clinical examination, transillumination (pneumothorax) and chest x-ray. Besides, lung ultrasound constitutes a visual medicine and provides a transparent approach to the acutely ill patient, newborn included, guiding diagnosis, management and care. Newborns with moderate to severe symptoms and those receiving positive pressure ventilation require tube thoracostomy. If a tension pneumothorax is suspected, emergency needle decompression in the second intercostal space in the midclavicular line is required. In this article, we describe the management of tube thoracostomy using trocar tubes or pigtail catheters. Besides, we pay attention to the use of pain control for neonates undergoing painful procedures such as chest tube insertion.