Hunter Syndrome is an X-linked lysosomal storage disorder due to the deficit of iduronate 2-sulfatase, an enzyme catalysing the degradation of the glycosaminoglycans (GAG) dermatan- and heparan-sulfate. Treatment of the disease is mainly performed by Enzyme Replacement Therapy (ERT) with idursulfase, in use since 2006. Clinical efficacy of ERT has been monitored mainly by the Hunter Outcome Survey (HOS) while very few independent studies have been so far conducted. The present study is a 3.5-years independent follow-up of 27 Hunter patients, starting ERT between 1.6 and 27 years of age, with the primary aim to evaluate efficacy of the therapy started at an early age (5 and ≤ 12 years and > 12 years. Patients were analysed both as 3 separate groups and also as one group; in addition, the 20 patients who started ERT up to 12 years of age were analysed as one group. Finally, patients presenting a 'severe' phenotype were compared with "attenuated" ones. Data analysis revealed a statistically significant reduction of the urinary GAG in patients ≤5 years and ≤ 12 years and of the hepatomegaly in the group aged >5 and ≤ 12 years. Although other clinical signs improved in some of the patients monitored, statistical analysis of their variation did not reveal any significant changes following enzyme administration. The evaluation of ERT efficacy in relation to the severity of the disease evidenced slightly higher improvements as for hepatomegaly, splenomegaly, otological disorders and adenotonsillar hypertrophy in severe vs attenuated patients. Although the present protocol of idursulfase administration may result efficacious in delaying the MPS II somatic disease progression at some extent, in this study we observed that several signs and symptoms did not improve during the therapy. Therefore, a strict monitoring of the efficacy obtained in the patients under ERT is becoming mandatory for clinical, ethical and economic reasons.

Several reports highlighted how public health measures aimed at limiting severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) circulation have likely contributed to reducing the circulation of other respiratory viruses, particularly during the first year of the COVID-19 pandemic. We evaluated the epidemiology of acute respiratory infections in a large cohort of hospitalized children during the third year of the pandemic (2021–2022). We retrospectively analyzed data from the health records of children (<14 years) hospitalized for acute respiratory infections between 1 July 2021 and 31 March 2022. A total of 1763 respiratory panels were collected. Overall, 1269 (72%) panels hadpositive results for at least one pathogen. Most positive panels (53.8%) belonged to patients aged 1–12 months. The most detected pathogen was respiratory syncytial virus (RSV) (57.8% of positive panels). The RSV peak occurred in November 2021. Nine hundred and forty-five (74.5%) panels were positive for one pathogen while three hundred and twenty-four (25.5%) showed multiple infections. Patients with multiple infections were significantly older than those with a single infection. The 2021–2022 peak of RSV infection in Italy occurred earlier than in the previous pre-pandemic seasons. A high number of children have been hospitalized because of acute viral infections also due to less aggressive viruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may present with a wide variety of symptoms, including neurological manifestations. We investigated clinical, demographic, laboratory, neurophysiological and imaging characteristics of SARS-CoV-2-positive children with seizures and analyzed differences between children admitted during the periods with prevalent circulation of the Alpha/Delta and Omicron variants, respectively. Patients’ characteristics were analyzed according to the presence or absence of seizures and then according to the SARS-CoV-2 variants. Five-hundred and four SARS-CoV-2-positive patients were included: 93 (18.4%) with seizures and 411 (81.6%) without. Patients with seizures were older, had more commonly an underlying epilepsy and had more frequently altered C-reactive protein than those without seizures. Electroencephalography was abnormal in 5/38 cases. According to the SARS-CoV-2 variant, seizures were recorded in 4.7% of the total number of hospitalized patients during the Alpha/Delta period, and in 16.9% of patients admitted during the Omicron period. During the Alpha/Delta variants, seizures were more commonly observed in patients with epilepsy compared to those observed during the Omicron period. Our findings suggest that although SARS-CoV-2 may potentially trigger seizures, they are generally not severe and do not require intensive care admission.

RASopathies are a group of genetic syndromes caused by germline mutations in genes involved in the RAS/Mitogen-Activated Protein Kinase signaling pathway, which regulates cellular proliferation, differentiation, and angiogenesis. Despite their involvement at different levels of this pathway, RASopathies share overlapping clinical phenotypes. Noonan syndrome is the most prevalent RASopathy, with an estimated incidence of 1 in 2500 live births, and it is typically inherited in an autosomal dominant manner, with 50% of cases involving gain-of-function mutations in the PTPN11 gene. De novo mutations are common, accounting for 60% of cases. The phenotype of Noonan syndrome includes characteristic facial and physical features, congenital cardiac defects, lymphatic and cerebrovascular anomalies, renal malformations, hematological abnormalities, developmental issues, and an increased risk of cancer. Severe congenital cardiac defects and lymphatic abnormalities significantly impact prognosis, contributing to increased morbidity and mortality. Recent therapeutic advancements have introduced trametinib, an MEK1/2 inhibitor, for treating Noonan syndrome patients with severe cardiac and lymphatic complications. To assess its efficacy, here, we present a case of a newborn with Noonan syndrome who exhibited refractory chylothorax, ventricular hypertrophy, and pulmonary stenosis who was treated with trametinib. The patient demonstrated significant improvement in chylothorax and left ventricular hypertrophy, though pulmonary stenosis persisted. This case further confirms trametinib’s potential as a therapeutic option for severe Noonan syndrome complications, emphasizing the need for further clinical trials to optimize treatment protocols and evaluate long-term outcomes.

Background: Acute otomastoiditis (AOM) may occasionally progress to severe intracranial complications in children. While immunological and microbiological factors have been studied, the role of temporal bone anatomical variants remains less well-defined. The aim of this study is to investigate the prevalence of anatomical variants in pediatric patients with acute complicated otomastoiditis (ACOM) compared to those with uncomplicated ones (AUOM) and healthy controls (HC) and assess their potential association with intracranial complication patterns. Methods: This retrospective, single-center study reviewed clinical and neuroradiological data of patients aged 0–16 years admitted for AOM between 2018 and 2025. ACOM patients were compared to AUOM and HC groups (the latter undergoing neuroimaging for minor head trauma). Two experienced neuroradiologists evaluated imaging to identify anatomical variants involving the following: (1) sigmoid sinus and emissary veins; (2) tegmen tympani; and (3) mastoid pneumatization. Statistical analyses assessed prevalence differences across groups. Results: Among 282 AOM patients, 58 had intracranial complications. Anatomical variants were significantly more frequent in ACOM patients versus both AUOM and HC (p < 0.01). In this subgroup, vascular anatomical variants were notably associated with vascular or combined (vascular and infectious) complications; tegmen tympani and mastoid pneumatization variants showed no significant subgroup associations. Conclusion: Anatomical variants, particularly vascular anomalies of the sigmoid sinus and emissary veins, appear to increase pediatric AOM patients’ susceptibility to intracranial complications. Recognition of these configurations through early neuroimaging could aid risk stratification and improve diagnostic and therapeutic strategies.

Background: Acute mastoiditis is the most frequent suppurative complication of acute otitis media in children. AM can lead to both extracranial complications and intracranial complications. Recent studies suggest an increase in cases after the COVID-19 pandemic. Objective: To compare the epidemiological and clinical characteristics of pediatric patients diagnosed with acute mastoiditis admitted to Santobono-Pausilipon Children’s Hospital before and after COVID-19. Methods: We conducted a retrospective study including all patients aged 0–16 years with AM admitted to our hospital between January 2017 and December 2024. Patients were stratified into three groups: pre-COVID-19: 1 January 2017–28 February 2020; COVID-19: 1 March 2020–31 December 2021; and post-COVID-19: 1 January 2022–31 December 2024. Demographic data, clinical presentations, complications, laboratory findings, and treatment modalities were analyzed and compared between groups. Results: A total of 276 children (153 males and 123 females; median age: 49 months, age range: 1–177 months) were included. Hospital admissions for AM increased in the post-COVID-19 period, reaching more than a threefold increase in 2024 compared with the pre-COVID-19 years. Similar to the overall number of AM cases, the absolute number of complications, especially IC, such as thrombosis and empyema, increased. The rate of surgical procedures increased during the post-COVID-19 period, with an overall increase of 88.5%. Both the duration of antibiotic therapy and hospital stay were significantly longer in the post-COVID-19 period. Conclusions: The COVID-19 pandemic has been associated with epidemiological and clinical changes in pediatric AM patients. These findings highlight the need for effective preventive strategies, including enhanced vaccination coverage and the promotion of early diagnosis. Additionally, implementing standardized clinical protocols could support more efficient and consistent management, reducing hospital stays and recurrence rates.