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.

Disrupted Seasonality of Respiratory Viruses: Retrospective Analysis of Pediatric Hospitalizations in Italy from 2019 to 2023.

This multicenter study in Italian hospitals highlights the epidemiologic disruptions in the circulation of the 5 main respiratory viruses from 2019 to 2023. Our data reveal a resurgence of respiratory syncytial virus and influenza during the 2022-2023 winter season, with an earlier peak in cases for both viruses, emphasizing the importance of timely monitoring.

Outcome of primary hemophagocytic lymphohistiocytosis: a report on 143 patients from the Italian Registry.

Primary hemophagocytic lymphohistiocytosis (pHLH) is a severe, life-threatening hyperinflammatory syndrome caused by defects in genes of the granule-dependent cytotoxic pathway. Here we investigated the clinical presentation and outcome in a large cohort of 143 patients with pHLH diagnosed in the last 15 years and enrolled in the Italian registry. The median age at diagnosis was 12 months (IQR 2-81), and ninety-two patients (64%) fulfilled the HLH-2004 criteria. Out of 111 patients who received first-line combined therapy (HLH-94, HLH-2004, Euro-HIT protocols), 65 (59%) achieved complete response (CR) and 21 (19%) partial response (PR). Thereafter, 33 patients (30%) reactivated, and 92 (64%) received HSCT, 78 of whom (85%) survived and were alive at a median follow-up from diagnosis of 67 months. Thirty-six patients (25%) died before HSCT and 14 (10%) after. Overall, 93 patients (65%) were alive after a median follow-up of 30 months. Unadjusted predictors of non-response were age.

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.

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.

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.

Policy of vaccination of "fragile children": Results of a survey of 14 Italian children's hospitals.

Children with chronic disease are at higher risk of invasive infectious disease, including several vaccine-preventable infections. The Italian Association of Pediatric Hospitals (AOPI) carried out a survey of immunization practices: 14/16 AOPI hospitals completed the survey; 50% of them include 100-199 beds, while 21% have <100 beds. In 12/14 hospitals (86%) all vaccinations included in the National Immunization Plan (plus influenza e COVID-19 vaccines) are available for inpatients, in selected wards (n = 4), on single pediatrician initiative (n = 3), by a centralized in-hospital immunization service (n = 2), and the remaining 3 in a "protected vaccination area" or in a COVID-19 pathway. The wards in which vaccination is more frequently offered to in-patients are: General Pediatrics, Neonatology, Pediatric Hematology & Oncology, Pediatric Diabetology, Pediatric Cardiology, and Pediatric Infectious Diseases (range, 58% to 83%). In 58% of vaccinating hospitals, <500 vaccinations/year are reported, while in 17% this number is >2,000/year. A COVID-19 vaccination team is in place for any inpatient child older than 12 years in 42% of hospitals, in 42% only for "fragile" children. A centralized in-hospital immunization service is an emerging model that may contribute to increase compliance to vaccination of fragile patients and to fight against vaccination hesitancy.

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.

Acute, Severe Hepatitis of Unknown Origin: Should We Really Be Afraid of Another Obscure Enemy of Our Children?

On 31 March 2022, Public Health Scotland was alerted to five children aged 3-5 years, presenting to the Glasgow children's hospital with severe hepatitis of unknown etiology within a 3-week period [...].

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.

STOP Pain Project-Opioid Response in Pediatric Cancer Patients and Gene Polymorphisms of Cytokine Pathways.

Moderate to severe cancer pain treatment in children is based on the use of weak and strong opioids. Pharmacogenetics play a central role in developing personalized pain therapies, as well as avoiding treatment failure and/or intolerable adverse drug reactions. This observational study aimed to investigate the association between IL-6, IL-8, and TNFα genetic single nucleotide polymorphisms (SNPs) and response to opioid therapy in a cohort of pediatric cancer patients. Pain intensity before treatment (PIt0) significantly differed according to IL-6 rs1800797 SNP, with a higher PI for A/G and G/G individuals (p = 0.017), who required a higher dose of opioids (p = 0.047). Moreover, compared to G/G subjects, heterozygous or homozygous individuals for the A allele of IL-6 rs1800797 SNP had a lower risk of having a PIt0 > 4. Dose24h and Dosetot were both higher in G/G individuals for TNFα rs1800629 (p = 0.010 and p = 0.031, respectively), while risk of having a PIt0 > 4 and a ∆VAS > 2 was higher for G/G subjects for IL-6 rs1800795 SNP compared to carriers of the C allele. No statistically significant association between genotypes and safety outcomes was found. Thus, IL-6 and TNFα SNPs could be potential markers of baseline pain intensity and opioid dose requirements in pediatric cancer patients.

Limited Additive Diagnostic Impact of Isolated Gastrointestinal Involvement for the Triage of Children with Suspected COVID-19.

The strategy for the selection of patients with a suspected SARS-CoV-2 infection is relevant for the organization of a children's hospital to provide optimal separation into COVID-19 and non-COVID-19 areas and pathways. We analyzed the proportion of children with COVID-19 presenting with gastrointestinal (GI) symptoms in 137 consecutive patients admitted between January 2020 and August 2021. GI symptoms were present as follows: diarrhea in 35 patients (26%), vomiting in 16 (12%), and both of them in five (3%); the combination of fever, respiratory symptoms, and diarrhea was observed in 16 patients (12%). Of the 676 adult patients with COVID-19 admitted to our hospital in the same time interval, 62 (9.2%) had diarrhea, 30 (4.4%) had vomiting, and 11 (1.6%) had nausea; only one patient, a 38-year-old male, presented with isolated GI symptoms at the diagnosis. Although diarrhea was observed in one quarter of cases, one-half of them had the complete triad of fever, respiratory syndrome, and diarrhea, and only five had isolated diarrhea, of which two were diagnosed with a Campylobacter infection. The occurrence of either respiratory symptoms or gastrointestinal symptoms in our patients was not related to the patient age, while younger children were more likely to have a fever. Of the 137 patients, 73 (53%) could be tested for their serum level of SARS-CoV-2 specific IgG antibodies. The observed titer ranged between 0 (n = 3) and 1729 BAU/mL (median, 425 BAU/mL). Of 137 consecutive patients with COVID-19 admitted to our referral children's hospital, only three presented with an isolated GI manifestation. It is interesting to note that this finding turned out to be fully in keeping with what was observed on adult patients with COVID-19 in our hospital. The additive diagnostic impact of gastrointestinal involvement for the triage of children with suspected COVID-19 appears limited.

The use of quantitative ultrasound in a tertiary-level children hospital: role in the follow-up of chronically ill patients.

PURPOSE: To evaluate the use of QUS for the bone status assessment in children cared because of a chronic disease such as: inherited metabolic disorder, kidney disease and endocrine defect and considered by the attending physician as at specific risk. METHODS: QUS outputs were calculated for each disorder and compared to: sex, age, Tanner stage, Z-score for height, weight and BMI (body mass index). RESULTS: One-hundred-sixty-eight subjects aged between 3.5 and 18 years met the inclusion criteria. The overall bone quality indexes were under the normal range in all the groups considered. Impairment of bone quality parameters was more evident in the group of patients with inherited metabolic disorders, in which 65% of patients in charge were studied by QUS. Older age and sexual development were associated with less pronounced bone quality impairment, as measured by QUS, in the vast majority of conditions. Overall, the diseases for which the prediction of outcome was the strongest were: hyperphenylalaninemia, nephrotic syndrome and insulin dependent diabetes mellitus. CONCLUSIONS: QUS is capable to provide information on skeletal status in children. Initial evaluation by QUS may allow defining patients with chronic disorders who deserve further, more invasive diagnostic studies. Inherited metabolic disorders warrant specific attention and strict monitoring for their potential effect on bone.

Diagnosis of HLH: two siblings, two distinct genetic causes.

This report highlights case of two siblings who developed haemophagocytic lymphohystiocytosis due to distinct genetic abnormalities. Though their presentation was clinically similar, the cases demonstrate that a shared genetic diagnosis among siblings cannot be assumed.