Endocrine, auxological and metabolic profile in children and adolescents with Down syndrome: from infancy to the first steps into adult life.

Down syndrome (DS) is the most common chromosomal disorder worldwide. Along with intellectual disability, endocrine disorders represent a remarkable share of the morbidities experienced by children, adolescents and young adults with DS. Auxological parameters are plotted on syndrome-specific charts, as growth rates are reduced compared to healthy age- and gender-matched peers. Furthermore, children with DS are at increased risk for thyroid dysfunctions, diabetes mellitus, osteopenia and obesity compared to general population. Additionally, male individuals with DS often show infertility, while women tend to experience menopause at an overall younger age than healthy controls. Given the recent outstanding improvements in the care of severe DS-related comorbidities, infant mortality has dramatically decreased, with a current average life expectancy exceeding 60 years. Accordingly, the awareness of the specificities of DS in this field is pivotal to timely detect endocrine dysfunctions and to undertake a prompt dedicated treatment. Notably, best practices for the screening and monitoring of pediatric endocrine disorders in DS are still controversial. In addition, specific guidelines for the management of metabolic issues along the challenging period of transitioning from pediatric to adult health care are lacking. By performing a review of published literature, we highlighted the issues specifically involving children and adolescent with DS, aiming at providing clinicians with a detailed up-to-date overview of the endocrine, metabolic and auxological disorders in this selected population, with an additional focus on the management of patients in the critical phase of the transitioning from childhood to adult care.

Hemodynamic evaluation in preterm infants using ultrasonic cardiac output monitor (USCOM).

We aimed to establish reference ranges for USCOM parameters in preterm infants, determine factors that affect cardiac output, and evaluate the measurement repeatability. This retro-prospective study was performed at Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. We included infants below 32 weeks of gestational age (GA) and/or 1500 g of birth weight (BW). We excluded infants with congenital heart diseases or hemodynamic instability. Measurements were performed at 3 ± 1, 7 ± 2, and 14 ± 2 postnatal days. We analyzed 204 measurements from 92 patients (median GA = 30.57 weeks, BW = 1360 g). The mean (SD) cardiac output (CO) was 278 (55) ml/min/kg, cardiac index (CI) was 3.1 (0.5) L/min/m2, and systemic vascular resistance (SVRI) was 1292 (294) d*s*cm-5/m2. CO presented a negative correlation with postmenstrual age (PMA), while SVRI presented a positive correlation with PMA. The repeatability coefficient was 31 ml/kg/min (12%).  Conclusion: This is the first study describing reference values for USCOM parameters in hemodynamically stable preterm infants and factors affecting their variability. Further studies to investigate the usefulness of USCOM for the longitudinal assessment of patients at risk for cardiovascular instability or monitoring the response to therapies are warranted. What is Known: • The ultrasonic cardiac output monitoring (USCOM) has been widely used on adult and pediatric patients and reference ranges for cardiac output (CO) by USCOM have been established in term infants. What is New: • We established reference values for USCOM parameters in very preterm and very-low-birth-weight infants; the reference ranges for CO by USCOM in the study population were 198-405 ml/kg/min. • CO normalized by body weight presented a significant negative correlation with postmenstrual age (PMA); systemic vascular resistance index presented a significant positive correlation with PMA.

Haemochromatosis in children: A national retrospective cohort promoted by the A.I.E.O.P. (Associazione Italiana Emato-Oncologia Pediatrica) study group.

Haemochromatosis (HC) encompasses a range of genetic disorders. HFE-HC is by far the most common in adults, while non-HFE types are rare due to mutations of HJV, HAMP, TFR2 and gain-of-function mutations of SLC40A1. HC is often unknown to paediatricians as it is usually asymptomatic in childhood. We report clinical and biochemical data from 24 paediatric cases of HC (10 cases of HFE-, 5 TFR2-, 9 HJV-HC), with a median follow-up of 9.6 years. Unlike in the adult population, non-HFE-HC constitutes 58% (14/24) of the population in our series. Transferrin saturation was significantly higher in TFR2- and HJV-HC compared to HFE-HC, and serum ferritin and LIC were higher in HJV-HC compared to TFR2- and HFE-HC. Most HFE-HC subjects had relatively low ferritin and LIC at the time of diagnosis, so therapy could be postponed for most of them after the age of 18. Our results confirm that HJV-HC is a severe form already in childhood, emphasizing the importance of early diagnosis and treatment to avoid the development of organ damage and reduce morbidity and mortality. Although phlebotomies were tolerated by most patients, oral iron chelators could be a valid option in early-onset HC.

Treatment Dilemma in Children with Late-Onset Pompe Disease.

In recent years, there has been a significant increase in the diagnosis of asymptomatic Late-Onset Pompe Disease (LOPD) patients, who are detected via family screening or Newborn Screening (NBS). The dilemma is when to start Enzyme Replacement Therapy (ERT) in patients without any clinical sign of the disease, considering its important benefits in terms of loss of muscle but also its very high cost, risk of side effects, and long-term immunogenicity. Muscle Magnetic Resonance Imaging (MRI) is accessible, radiation-free, and reproducible; therefore, it is an important instrument for the diagnosis and follow-up of patients with LOPD, especially in asymptomatic cases. European guidelines suggest monitoring in asymptomatic LOPD cases with minimal MRI findings, although other guidelines consider starting ERT in apparently asymptomatic cases with initial muscle involvement (e.g., paraspinal muscles). We describe three siblings affected by LOPD who present compound heterozygosis and wide phenotypic variability. The three cases differ in age at presentation, symptoms, urinary tetrasaccharide levels, and MRI findings, confirming the significant phenotypic variability of LOPD and the difficulty in deciding when to start therapy.

The bronchiolitis epidemic in 2021-2022 during the SARS-CoV-2 pandemic: experience of a third level centre in Northern Italy.

BACKGROUND: The aim of this study is to compare the 2021-2022 bronchiolitis season to the four previous years (2017-2018, 2018-2019, 2019-2020, 2020-2021) to see if there was an anticipation of the peak, an overall increase of cases, and an increased need of intensive care. METHODS: A retrospective single-centre study in the San Gerardo Hospital Fondazione MBBM, Monza, Italy was performed. Emergency Departments (ED) visits of patients aged < 18 years and ≤ 12 months were analyzed: the incidence of bronchiolitis on total assessments, the urgency level at triage and the hospitalization rate were compared. Data of children admitted to the Pediatric Department due to bronchiolitis were analyzed in terms of need of intensive care, respiratory support (type and duration), length of hospital stay, main etiological agent, patient characteristics. RESULTS: During 2020-2021 (first pandemic period) an important reduction in the ED attendance for bronchiolitis was observed, while in 2021-2022 there was an increase in incidence of bronchiolitis (13% of visits in infants < 1 year) and in the rate of urgent accesses (p = 0.0002), but hospitalization rates did not differ compared to previous years. Furthermore, an anticipated peak in November 2021 was observed. In the 2021-2022 cohort of admitted children to the Pediatric Department, a statistically significative increased need of intensive care unit was detected (Odds Ratio 3.1, 95% CI 1.4-6.8 after adjustment for severity and clinical characteristics). Instead, respiratory support (type and duration) and length of hospital stay did not differ. RSV was the main etiological agent and RSV-bronchiolitis determined a more severe infection (type and duration of breathing support, intensive care need and length of hospital stay). CONCLUSIONS: During Sars-CoV-2 lockdowns (2020-2021), there was a dramatic decrease of bronchiolitis and others respiratory infections. In the following season, 2021-2022, an overall increase of cases with an anticipated peak was observed and data analysis confirmed that patients in 2021-2022 required more intensive care than children in the four previous seasons.

Mucopolysaccharidosis-Plus Syndrome, a Rapidly Progressive Disease: Favorable Impact of a Very Prolonged Steroid Treatment on the Clinical Course in a Child.

Mucopolysaccharidosis-plus syndrome (MPS-PS) is a novel autosomal recessive disorder caused by a mutation in the VPS33A gene. This syndrome presents with typical symptoms of mucopolysaccharidosis, as well as congenital heart defects, renal, and hematopoietic system disorders. To date, twenty-four patients have been described. There is no specific therapy for MPS-PS; clinical management is therefore limited to symptoms management. The clinical course is rapidly progressive, and most patients die before 1-2 years of age. We describe a currently 6-year-old male patient with MPS-PS presenting with multiorgan involvement. Symptoms started at four months of age when he progressively suffered from numerous acute and potentially life-threatening events. When he was two years old, he developed secondary hemophagocytic lymphohistiocytosis (HLH), which was successfully treated with steroids. To date, this child represents the oldest patient affected by MPS-PS described in the literature and the first one presenting with a life-threatening secondary HLH. The prolonged steroid treatment allowed a stabilization of his general and hematological conditions and probably determined an improvement of his psychomotor milestones and new neurological acquisitions with an improvement of quality of life. HLH should be suspected and adequately treated in MPS-PS patients presenting with suggestive symptoms of the disease. The usefulness of a prolonged steroid treatment to improve the clinical course of children with MPS-PS deserves further investigation.

Thyroid function disorders and secondary cancer following haematopoietic stem cell transplantation in pediatrics: State of the art and practical recommendations for a risk-based follow-up.

Thyroid disorders (TD) represent a remarkable share of all the late morbidities experienced following pediatric haematopoietic stem cell transplantation (HSCT), with long-term reported occurrence often exceeding 70%. In addition, the data collected on wide cohorts of survivors assessed longitudinally outlined a progressive increase in the cumulative incidence of TD as far as 30 years following transplantation. Accordingly, a life-long monitoring of thyroid health is warranted among patients exposed to HSCT in childhood, in order to early detect TD and undertake a prompt dedicated treatment. Although several national and international consortia have provided recommendations for the early detection of thyroid disorders among childhood cancer survivors exposed to radiotherapy and alkylating agents, no guidelines specifically and thoroughly focused on HSCT-related TD have been published to date. As stem cell transplantation has become the standard-of-care in a growing body of non-oncological conditions, this urge has become pivotal. To highlight the challenging issues specifically involving this cohort of patients and to provide clinicians with the proposal of a practical follow-up protocol, we reviewed published literature in the light of the shared experience of a multidisciplinary team of pediatric oncologists, transplantologists, pathologists and endocrinologists involved in the long-term care of HSCT survivors. As a final result, we hereby present the proposals of a practical and customized risk-based approach to tailor thyroid health follow-up based on HSCT-related detrimental factors.