Bronchiolitis 2021-2022 epidemic: multicentric analysis of the characteristics and treatment approach in 214 children from different areas in Italy.

Bronchiolitis causes a remarkable number of hospitalizations; its epidemiology follows that of respiratory syncytial virus (RSV), its main pathogen. The aim of this study was to evaluate the presenting features, treatment approach, and impact of medical therapy in four pediatric hospitals in Italy. Data on infants < 24 months of age hospitalized with bronchiolitis in the 2021-2022 season were collected. Between October 2021 and February 2022, 214 children were admitted. Median hospital stay was 5 days; none of the patients died. The distribution of the presenting features is largely comparable in the 33 (15.8%) RSV-negative versus the 176 (84.2%) RSV-positive children; also, no difference was observed in medical therapy provided: duration of oxygen therapy, administration of steroid, and duration of hospital stay. Systemic steroids, inhalation, or antibiotic therapy were given to 34.6%, 79.4%, and 49.1% of children respectively. Of the 214 patients with bronchiolitis, only 19 (8.8%) were admitted to ICU.   Conclusion: Our data suggest that, irrespective of treatments provided, RSV-positive and RSV-negative children had a similar clinical course. The results of our retrospective study further underline the need to improve adherence to existing guidelines on bronchiolitis treatment. What is Known: • Bronchiolitis is a common diseases with seasonal peak. The outcome is usually favorable but hospitalization and even ICU admission is not exceptional. What is New: • Children with RSV associated bronchiolitis do not have a different course and outcome. The analysis of the 2021-2022 cohort, following COVID pandemic peaking, did not show a different course and outcome. • Adherence to literature recommendation, i.e. to focus on oxygen and hydration therapy while avoiding unnecessary systemic therapy with steroid and antibiotics, should be improved.

Brimonidine Eye Drops within the Reach of Children: A Possible Foe.

Brimonidine, a selective alpha-2 adrenergic agonist used for the treatment of open-angle glaucoma, has been shown to cause neurological side effects such as unresponsiveness, lethargy, hypoventilation, and stupor, mimicking opioid toxicity. We report one case of transient encephalopathy in a toddler, in whom accidental brimonidine toxicity was suspected and then confirmed by a toxicology study. The healthy 8-month-old girl was taken to the pediatric ER since she was drowsy and hypotonic with miosis. The computed tomography scan of her brain and toxicological workup of her blood and urine were negative. Starting from the fourth hour, the child progressively improved, and by the sixth hour, she recovered to a normal state of consciousness. A survey of available drugs within the child's reach showed the presence of brimonidine. Thus, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to quantify the brimonidine in urine and plasma samples, showing levels of 8.40 ng/mL and 0.79 ng/mL, respectively. To our knowledge, this is the first report to determine brimonidine levels in urine and plasma using UPLC-MS/MS. Insufficient knowledge on the part of family members about the potential hazards of an apparently innocuous, topical medication such as eye drops may put children at a greater risk of poisoning. Necessary warnings should be given to parents with greater care when prescribing this medication.

Real-World Use of Dalbavancin for Treatment of Soft Tissue and Bone Infection in Children: Safe, Effective and Hospital-Time Sparing.

Acute bacterial skin and skin structure infections (ABSSSI) and osteoarticular infections compound the burden of morbidity, mortality and prolonged hospitalizations among gram-positive infections. Dalbavancin, a second-generation, intravenous lipoglycopeptide, due to its prolonged half-life, can be a valuable alternative in their treatment when administered as inpatient treatment at the price of an extended hospital stay. Between October 2019 and September 2023, 31 children and adolescents were treated with dalbavancin because of bone and joint infections (n = 12 patients, 39%), ABSSSI (n = 13 patients, 42%), mainly for the limbs, facial cellulitis or complicated ABSSSI (n = 6 patients, 19%), at five Italian pediatric centers. Microbiological study provided gram-positive bacterial isolate in 16 cases, in 11 cases from a positive blood culture; 9 of them were MRSA. Twenty-five patients were initially treated with a different antibiotic therapy: beta-lactam-based in 18 patients (58%), glycopeptide-based in 15 patients (48%) and daptomycin in 6 (19%). The median time that elapsed between admission and start of dalbavancin was 18 days. A total of 61 doses of dalbavancin were administered to the 31 patients: 16 received a single dose while the remaining 15 patients received between two (n = 9) and nine doses. The frequency of administration was weekly in five cases or fortnightly in nine patients. Median length of stay in hospital was 16 days. Median time to discharge after the first dose of dalbavancin was 1 day. Treatment was very well-tolerated: of the 61 administered doses, only four doses, administered to four patients, were associated with an adverse event: drug extravasation during intravenous administration occurred in two patients, with no sequelae; however, in two patients the first administration was stopped soon after infusion start: in one (ID #11), due to headache and vomiting; in another (ID #12) due to a systemic reaction. In both patients, drug infusion was not repeated. None of the remaining 29 patients reported treatment failure (resistant or recurrent disease) or an adverse effect during a median follow-up time of two months. The use of dalbavancin was safe, feasible and also effective in shortening the hospital stay in children and adolescents.

Noninvasive DBS-Based Approaches to Assist Clinical Diagnosis and Treatment Monitoring of Gaucher Disease.

Gaucher disease (GD) is an autosomal recessive inborn error of metabolism, belonging to the group of lysosomal storage diseases (LSDs). GD is caused by a defect in lysosomal glucocerebrosidase, responsible for glucosylceramide breakdown into glucose and ceramide. Because of this dysfunction, glucosylceramide progressively accumulates in the liver, spleen, bone marrow, bones, and in other tissues and organs, also causing anemia, hepatosplenomegaly, thrombocytopenia, and bone symptoms. Depending on neurological symptoms, GD is classified into three main types. Treatment options for LSDs, including enzyme replacement therapy, hematopoietic stem cell transplantation, small molecular weight pharmacologic chaperones, and, for some LSDs, gene therapy, are increasingly available. For this reason, many efforts are aimed at implementing newborn screening for LSDs since early detection accompanied by a prompt intervention has been demonstrated to be essential for reducing morbidity and mortality and for improved clinical outcomes. Herein, we report two siblings of preschool age, presenting with hepatosplenomegaly and thrombocytopenia. The initial suspicion of GD based on the clinical picture was further supported by biochemical confirmation, through newborn screening workflow, including first- and second-level testing on the same dried blood spot samples, and finally by molecular testing.

A High Copy Number from a Pharyngeal Swab Is Not Associated with Different Presenting Features in 100 Children with Acute Adenovirus Infection from a Cluster in Italy.

Human mastadenoviruses, frequently denominated adenoviruses (HAdVs), may cause respiratory tract, gastrointestinal or, less frequently, other involvements. Epidemics of HAdV infections occur globally, in communities, and in closed or crowded settings. In our institution, a cluster of infants and children admitted for HAdV infection was recently observed. The aim of this study was to describe the pattern of their presenting features and investigate the possible correlation between the HAdV copy number and the clinical picture. Two main patterns of clinical presentation were observed: 68 patients had mainly respiratory symptoms (pharyngitis n = 67, cough n = 44; tonsillar exudate n = 17; other respiratory signs n = 4) while 26 patients showed prevalent gastrointestinal involvement (diarrhea n = 26, vomiting n = 8). Patients with respiratory symptoms had a significantly higher count of WBC, PMN, and platelets, while CRP level approached statistical significance (p = 0.07) for higher values in the patients with diarrhea. In order to explore the impact of selected presenting features, the possible association between the level of CRP and the presence of pharyngeal exudate, cough, vomiting, diarrhea, duration of fever, number of neutrophils, and administration of antibiotics was analyzed. Patients falling in the tertile with more elevated CRP values had tonsillar exudate and diarrhea significantly more often, while those in the lower tertile had a 4.4-day duration fever vs. ≥5.0 days in the remaining patients. Antibiotic therapy was administered more frequently to patients with higher values of CRP (p = 0.006). The duration of hospitalization was not associated with the CRP level. The median time from the receipt of a positive HAdV PCR test result to patient discharge was 1 day in 73% of cases. The number of copies of HAdV detected via PCR ranged between 47 million and 15/µL. Falling in the highest tertile of copy number was significantly associated with pharyngitis. The 24 patients with evidence of viral coinfection had no difference in the demographics or presenting features, with the only exception being a significantly higher leukocyte count. The rapid turn-around of the results of the molecular testing of the HAdV genome on a pharyngeal swab allowed us to rapidly diagnose HAdV infection, allowing us to stop antibiotic therapy and immediately discharge the patients, with reduced discomfort for the families and more appropriate use of hospital beds. A high copy number of HAdV from a pharyngeal swab should not be taken as an indicator of worse prognosis, thus allowing for the preferential use of qualitative rather than quantitative assay.

CYPRUS VIRUS INFECTION: A RARE BUT LIFE-THREATENING DIAGNOSIS IN CHILDREN.

A 3.8-year-old Italian girl presenting with high fever and headache developed a decrease in the state of consciousness, apneas, bradycardia thus requiring intensive care and mechanical ventilation. Sandfly fever due to Cyprus virus, previously not reported in a child, outside an endemic area, must be included in the differential diagnosis of acute encephalopathy with apparently no explanation from the usual laboratory work-up.

Valproate-induced insulin resistance and obesity in children.

BACKGROUND: Valproic acid (VPA), a widely used antiepileptic drug, has broad-spectrum activity against both generalized and partial epilepsy. Among the side effects of VPA, weight gain is frequently reported, although the real incidence and magnitude of this problem is unknown. Its pathogenesis is most likely multifactorial, and is controversial. METHODS: In order to evaluate the role of hyperinsulinemia and related hormonal abnormalities in VPA-induced obesity, data from the existing literature have been analyzed and discussed critically. RESULTS: Patients suffering from weight gain show various metabolic and endocrinologic abnormalities. The most frequent are hyperinsulinemia and insulin resistance, hyperleptinemia and leptin resistance, and an increase in the availability of long-chain free fatty acids. Significant weight gain is associated with increased levels of insulin and leptin, suggesting a close relationship between obesity-induced hyperinsulinemia and hyperleptinemia. VPA can directly stimulate pancreatic beta-cells and indirectly enhance insulin resistance by suppressing insulin-mediated peripheral glucose uptake. Leptin activation seems to be similar in obese VPA-treated subjects to that seen in otherwise obese subjects. CONCLUSIONS: The mechanisms of hyperinsulinemia in VPA-induced weight gain remain unclear, although it is likely that obesity is the cause of hyperinsulinemia and all related metabolic changes. However, this heterogeneous metabolic disorder requires further research.

Anticonvulsant hypersensitivity syndrome in children: incidence, prevention and management.

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, but potentially fatal, adverse reaction that occurs in patients, including children, who are treated with anticonvulsants. During metabolism of the anticonvulsant, toxic arene-oxide compounds are produced. AHS is associated with both cutaneous and systemic symptoms and is associated with multiorgan involvement. Liver damage, in particular, seems to be associated with fatal outcomes. The pathophysiology of AHS is still uncertain but it may be linked to a genetically determined inability to detoxify reactive drug metabolites. The prompt recognition of the first clinical signs of AHS, and the rapid withdrawal of the anticonvulsant, often avoids the progression of symptoms. Pharmacological treatment is essentially based on systemic corticosteroids in association with enteral nutrition, intravenous fluid augmentation, pain relief and ocular care. Intravenous immunoglobulins may also have a possible therapeutic role in some cases. Diagnostic tests, such as patch tests or in vitro assays, for AHS could help to identify patients at risk of developing the syndrome and could represent a first step of primary prevention when applied to relatives of patients.

Intermittent oral diazepam prophylaxis in febrile convulsions: its effectiveness for febrile seizure recurrence.

In order to evaluate the effectiveness of diazepam for the reduction in the recurrence of febrile seizures we carried out a prospective study in two groups of children; Group A: 45 children (25 female, 20 male), receiving oral prophylaxis with diazepam, and Group B: 65 children (35 female, 30 male) who did not receive any oral prophylaxis. All subjects of both groups were followed for at least 4 years and finally re-evaluated at the mean age of 6.7+/-1.4 years. Among the patients of Group A, recurrent febrile seizures (FS) occurred in five of the 45 children (11.1%). Among the 65 children of Group B, 20 (30.7%) went on to have one or more additional episodes. In conclusion, our study demonstrates that oral diazepam, given only when fever is present, is an effective means of reducing the risk of recurrences of FS.

Preventing microvascular diabetic complications in children and adolescents: looking beyond glycaemic control.

Type 1 diabetes mellitus is associated with the development of micro- and macrovascular disease, and diabetic angiopathy in children and adolescents. It is represented mainly by microangiopathy, characterised by structural changes in the eye, renal glomeruli and peripheral nerves. The pathogenesis of the vascular complications of diabetes is controversial, but without any doubt, endothelial dysfunction play an important role in the pathogenesis of glomerulosclerosis and atherosclerosis. Preventive strategies for these three major complications are discussed in this review. Appropriate surveillance for the earliest evidence of microvascular disease should begin at the onset of puberty, and after 3 - 5 years of diabetes. Therapeutic interventions, particularly excellent metabolic control, may be almost effective in preventing complication onset, or significantly retarding the rate of progression.

Photosensitivity and epilepsy.

Photosensitive epilepsy is a well-known condition characterized by seizures in patients who show photoparoxysmal responses on electroencephalography (EEG) elicited by intermittent photic stimulation. Photoparoxysmal responses can be defined as epileptiform EEG responses to intermittent photic stimulation or to other visual stimuli of everyday life and are frequently found in nonepileptic children. The modern technologic environment has led to a dramatic increase in exposure to potential trigger stimuli; nowadays, television and video games are among the most common triggers in daily life. There is ample evidence for genetic transmission of photoparoxysmal responses; systematic family studies have provided data for an autosomal dominant mode of inheritance with age-dependent penetrance for photosensitivity. The age of maximum penetrance is between 5 and 15 years. The prognosis for control of seizures induced by visual stimulation is generally very good. The large majority of patients do not need anticonvulsant therapy, but, when needed, the drug of choice is valproate. Stimulus avoidance and stimulus modification can be an effective treatment in some patients and can sometimes be combined with antiepileptic drug treatment.

New trends in the treatment of diabetic nephropathy in children.

Nephropathy is the main cause of morbidity and mortality in patients with Type 1 diabetes and persistent microalbuminuria is the best marker of the consequent risk for its development in adults. In the paediatric population, puberty has long been recognised as a major risk period for the development of microangiopathic complications, although it is not necessarily associated with the progression to frank proteinuria. In fact, as many as 50% of subjects might revert to normoalbuminuria. Hypertension is a further risk factor and accelerates the progression of micro and macrovascular complications. There is evidence that angiotensin-converting enzyme inhibitors reduce renal damage by one or more mechanisms independent of their antihypertensive effects and they are the drug class of choice for the treatment of diabetic nephropathy. However, as angiotensin II receptor antagonists are more specific they might become the obvious treatment choice in the near future. There is no consensus on who should be treated with reno-protective drugs in the paediatric population, and when this should occur, due to the lack of a clear definition of the natural history of microalbuminuria in this age group. In this review controversial aspects of this issue are presented and discussed.

Factors associated with poor control in partial complex epilepsy.

To evaluate the predictive factors of response to anticonvulsant therapy in children with complex partial epilepsy, we studied prospectively 74 children and adolescents suffering from this type of epilepsy. All children were prospectively followed for at least 2 years after the beginning of anticonvulsant therapy. At the end of follow-up, the children were subdivided into two groups according to the frequency of seizures: group A, children who were seizure free in the last year, and group B, children with at least six seizures in the previous year. Children with a poor response to anticonvulsant therapy had a more frequent personal history of neonatal seizures, an interval of less than 6 months between the first and the second seizures, and persistent abnormal electroencephalograms than the seizure-free patients and were often treated with polytherapy.

Insulin resistance in epileptic girls who gain weight after therapy with valproic acid.

Valproic acid is effective for treatment of many types of epilepsy, but its use in epileptic patients can be associated with an increase in body weight that could interfere with treatment compliance. The weight gain may result from different mechanisms, but the exact pathogenesis is still unknown. To evaluate insulin sensitivity in adolescents who gained weight during treatment with valproic acid, we studied 20 girls with different types of epilepsy: 15 patients had primary generalized seizures, including absence seizures (3 cases), and 5 patients had partial seizures. After 1 year of valproic acid treatment, the obese patients had serum insulin levels significantly higher than patients who did not gain weight (51.4 +/- 25.3 versus 28.2 +/- 12.9). Moreover, we observed that epileptic patients who gained weight were also insulin resistant in comparison with nonobese epileptic subjects. At the end of treatment, all patients showed normal levels of serum testosterone, androstenedione, dehydroepiandrosterone sulfate, follicle-stimulating hormone (FSH), and luteinizing hormone. We found no significant correlation between insulinemia and serum valproic acid concentrations in obese and nonobese patients treated with valproic acid. Our study demonstrates that basal hyperinsulinemia and insulin resistance can be present in patients who develop obesity during valproic acid treatment. Therefore, these obese patients could be exposed to the risks related to these metabolic abnormalities; if these data are confirmed in longer studies, these side effects may raise some concerns about the safety of valproic acid.

Magnetoencephalography in pediatric neurology and in epileptic syndromes.

In recent years, great advances in the knowledge of neuromagnetism have permitted the application of Superconducting Quantum Interference Devices to the pathophysiologic study of the human brain. In particular, in pediatric neurology, the integration of biomagnetism with magnetic resonance imaging and other techniques for medical imaging have allowed for precise neuromagnetic measurements of the human brain. The more frequently used technique is magnetoencephalography. Recent data have illustrated the usefulness of magnetoencephalography in mapping activity of sensory and motor areas and in studying the spatiotemporal pattern of brain activation specific to somatosensory function. Moreover, magnetoencephalography is an important tool to localize epileptic activity; magnetic source imaging superimposes magnetoencephalographic localizations on the magnetic resonance imaging and yields improved spatial resolution as compared with surface electroencephalography. The role of magnetoencephalography in evaluating patients with epilepsy continues to evolve; in fact, it seems to be very useful in the localization of the epileptogenic zone in patients with partial epilepsy. This application of magnetoencephalography is essential in the selection of epileptic children candidates to surgical treatment of seizures.