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.

The lung ultrasound in children with SARS-COV-2 infection: a national multicenter prospective study.

Coronavirus disease-19 (COVID-19) caused hospitalizations, severe disease, and deaths in any age, including in the youngest children. The aim of this multicenter national study is to characterize the clinical and the prognostic role of lung ultrasound (LU) in children with COVID-19. We enrolled children between 1 month and 18 years of age with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection who underwent a LU within 6 h from the first medical evaluation. A total of 213 children were enrolled, 51.6% were male, median age was 2 years and 5 months (interquartile range (IQR) 4 months -11 years and 4 months). One hundred and forty-eight (69.4%) children were admitted in hospital, 9 (6.1%) in pediatric intensive care unit. We found an inverse correlation between the lung ultrasound score (LUS) and the oxygen saturation at the first clinical evaluation (r = -0.16; p = 0.019). Moreover, LUS was significantly higher in patients requiring oxygen supplementation (8 (IQR 3-19) vs 2 (IQR 0-4); p = 0.001). Among LU pathological findings, irregular pleural lines, subpleural consolidations, and pleural effusions were significantly more frequent in patients needing oxygen supplementation (p = 0.007, p = 0.006, and p = 0.001, respectively).  Conclusion: This multicenter study showed that LU in children with COVID-19 can highlight pleural line irregularities, vertical artifacts, and subpleural consolidation. Notably, children with higher LUS have a higher risk of hospitalization and need for oxygen supplementation, supporting LU as a valid and safe point-of-care first level tool for the clinical evaluation of children with COVID-19. What is Known: • Few children infected with SARS-CoV-2 develop a severe disease and need oxygen therapy. • Lung ultrasound can easily detect low respiratory tract infection during SARS-CoV-2. What is New: • Children with higher lung ultrasound score have a higher risk of need for oxygen supplementation. • Irregular pleural line, sub-pleural consolidations and pleural effusions were significantly more frequent in patients needing oxygen supplementation.

Off-label use of combined antiretroviral therapy, analysis of data collected by the Italian Register for HIV-1 infection in paediatrics in a large cohort of children.

BACKGROUND: Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children < 2 years of age and 60% in those aged 2-12 years, due to the lack of adequate paediatric clinical studies on pharmacokinetics, pharmacodynamics and drug safety in children. METHODS: An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. RESULTS: 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13-5.19; p = 0.024). Moreover, children < 2 years of age were at increased risk for receiving off-label HAART with respect to older children (OR: 3.24; 95% CI 1063-7.3; p = 0.001). Even if our safety data regarding off-label regimens where poor, no adverse event was reported. CONCLUSION: The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.

Quantitative Analysis of Gamma Interferon Release Assay Response in Children with Latent and Active Tuberculosis.

The use of interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) infection in children is still under debate because of concerns about the immature immune response in children. The aim of this study was to investigate quantitative values of the QuantiFERON-TB Gold In-Tube (QFT-IT) test, a commercially available IGRA, in a large cohort of children screened for TB infection. A retrospective analysis was conducted on samples from 517 children aged 0 to 14 years old at the Pediatric Unit of S. Orsola-Malpighi University Hospital of Bologna (Italy); quantitative responses to QFT-IT stimuli were analyzed according to diagnosis and age. Elevated IFN-γ values in the QFT-IT nil (background) tube were statistically associated with diagnosis of active TB. Quantitative IFN-γ response to Mycobacterium tuberculosis-specific antigens (TB Ag) was not significantly different in children with active TB compared to those with latent TB infection (LTBI), even though the median values were higher in the first group. When children were grouped by age, those less than 5 years old produced significantly higher levels of IFN-γ in response to TB Ag if they had active TB (median 10 IU/ml) than those with LTBI (median 1.96 IU/ml). IFN-γ response to mitogen increased with age. The overall rate of indeterminate results was low (3.9%), and no indeterminate QFT-IT values were observed in active or latent TB patients. In conclusion, quantitative QFT-IT values could provide further information to clinicians to manage TB in children, and these observations could be transferred to the new version of the test, QuantiFERON-TB Gold Plus, which to date lacks data from the pediatric population.

Assessment of clinical outcome of children with sepsis outside the intensive care unit.

In 2016, in order to identify adult patients with sepsis who are likely to have poor outcomes, the Third International Consensus Definitions Task Force introduced a new bedside index, called the quick Sepsis-related Organ Failure Assessment (qSOFA) score. However, these new criteria have not been validated in the pediatric population. In this study, we sought to assess the qSOFA score for children with sepsis, who are being treated outside the pediatric intensive care units. The qSOFA criteria were revised and applied to a study population of 89 pediatric patients with sepsis, admitted in a pediatric tertiary referral center from 2006 to 2016. The analysis of prognostic performance of qSOFA score for the prediction of severe sepsis showed a sensitivity of 46% (95% CI, 27-67%), a specificity of 74% (95% CI, 62-85%), a positive predictive value of 43% (95% CI, 34-52%), and a negative predictive value of 77% (95% CI, 71-82%). The area under ROC curve for qSOFA score ≥ 2 was 0.602 (95% CI 0.492-0.705).Conclusion: The qSOFA score showed a low accuracy to identify children in the pediatric ward at risk for severe sepsis. Clinical tools are needed to facilitate the diagnosis of impending organ dysfunction in pediatric infection outside of the ICU. What is Known: • One of the major challenges for clinicians is to identify and recognize children with sepsis and impending organ dysfunction, in the emergency and in the pediatric department. • In 2016, members of the Sepsis-3 task force proposed qSOFA, an empirically derived score using simple clinical criteria, to assist clinicians in identifying adult patients with sepsis at risk for poor outcome. What is New: • qSOFA demonstrated insufficient clinical value to be recommended as a screening tool for pediatric sepsis outside ICU. • D-dimer level and blood glucose may be useful biomarkers to identify children at risk for severe sepsis.

Use of transrenal DNA for the diagnosis of extrapulmonary tuberculosis in children: a case of tubercular otitis media.

The diagnosis of tuberculosis (TB) is difficult in children, especially for smear-negative pulmonary and extrapulmonary TB, which are common at this age. We report an 11-year-old girl with TB otitis media with negative smear microscopy and Xpert MTB/RIF but positive Mycobacterium tuberculosis-specific transrenal DNA (Tr-MTB-DNA) test results and culture for M. tuberculosis.

Serial cardiac magnetic resonance imaging for guidance of therapy management in patients treated with anakinra due to recurrent pericarditis.

Aims: To determine the utility of serial cardiac magnetic resonance (CMR) imaging for guidance of therapy management in patients treated with anakinra due to recurrent pericarditis (RP), compared with C-reactive protein (CRP) assay alone. Methods and results: In 2018-21, we enrolled 18 (14.5 ± 1.8 years old, 72% males) consecutive RP patients treated with anakinra (100 mg/day in patients ≥ 18 years old; 2 mg/kg/day < 18 years old) due to RP corticosteroid-dependent or not responsive to colchicine or non-steroidal anti-inflammatory drugs. After hospitalization, they were 1:1 randomized to CMR [no pericardial oedema and/or late gadolinium enchantment (LGE)] or CRP (<0.6 mg/dL). Tests were repeated every 3 months until negative to halve the anakinra dosage and cessation. The idiopathic aetiology was the most prevalent (n = 8, 44%), followed by post-pericardiotomy (n = 6, 33%). After a median treatment period of 8.7 ± 3.6 months, CRP-guided RP patients experienced more recurrences than CMR-guided ones (6 vs. 1, P = 0.016), with the worst prognosis in terms of recurrences (log-rank, P = 0.025) and significantly increased time of treatment (12.7 ± 2 vs. 16.1 ± 3.4 months, P = 0.019). In a multivariable exploratory Cox regression model, the number of previous recurrences and the idiopathic aetiology were independent predictors of RP during the anakinra treatment. New recurrences were subsequently directed to CMR imaging, and therapy was modified according to the LGE/oedema trend. After 1-year follow-up, no further recurrence was detected. Conclusion: Among patients with RP and treated with anakinra, serial CMR imaging of the pericardium can be utilized as an imaging biomarker, more informative for therapy duration than the solely CRP assessment. ClinicalTrialsgov Identifier: NCT06071156.

A patient with pancreas divisum, recurrent acute pancreatitis, and homozygosity for the cystic fibrosis transmembrane regulator-associated protein 5T allele.

Mutations in the gene encoding the cystic fibrosis transmembrane regulator (CFTR) have been reported to increase the risk of recurrent acute pancreatitis in patients with pancreas divisum. We assessed the CFTR gene in a young male patient with pancreas divisum and recurrent acute pancreatitis. Magnetic resonance cholangiopancreatography and computed tomography revealed that the patient had pancreas divisum, with an enlarged and tortuous pancreatic duct; he also had positive results from the cystic fibrosis sweat test. Genetic analysis did not identify any common CFTR mutations, but did show that he was homozygous for the 5T allele in intron 8 IVS8 5T-12TG (which affects splicing at intron 8). Endoscopic sphincterotomy and stenting of papilla minor was performed. The IVS8 5T-12TG variant has been associated with abnormal organ development, therefore it is possible that CFTR has an important role in the development of the pancreatic duct. We propose this patient has recurrent acute pancreatitis resulting from a developmental defect associated with a suboptimal CFTR function.

A foreign body aspiration in a preschool child mimicking a multitrigger wheezing: a case report and review of the literature.

We report a child with a history of recurrent episodes of wheezing. At 3 months of age, the frequency of these episodes began to increase. Wheezing was associated with persistent cough and dyspnea with nocturnal awakening. The skin prick test was positive for pollen and pet dander. Airway endoscopy revealed the presence of a peanut, which obstructed the left main bronchus. Chronic cough and recurrent wheezing with symptoms between acute exacerbations could be signs not only of asthma but also of other disorders. Therefore, coexisting conditions should be evaluated whenever symptoms seem to be unusually severe or frequent.

Something Is Changing in Viral Infant Bronchiolitis Approach.

Acute Viral Bronchiolitis is one of the leading causes of hospitalization in the first 12-24 months of life. International guidelines on the management of bronchiolitis broadly agree in recommending a minimal therapeutic approach, not recommending the use of bronchodilators. Guidelines, generally, consider bronchiolitis as a "unique disease" and this runs the risk of not administering therapy in some patients who could benefit from the use of bronchodilators, for instance, in those who will develop asthma later in their life and face first episode in the age of bronchiolitis. Today, there is growing evidence that bronchiolitis is not a single illness but can have different "endotypes" and "phenotypes," based on age, personal or family history of atopy, etiology, and pathophysiological mechanism. There is evidence that some phenotypes of bronchiolitis are more strongly associated with asthma features and are linked to higher risk for asthma development. In these populations, possible use of bronchodilators might have a better impact. Age seems to be the main feature to suggest a good response to a bronchodilator-trial, because, among children > 6 months old with bronchiolitis, the presence of a subset of patients with virus-induced wheezing or the first episode of asthma is more likely. While waiting for new research to define the relationship between therapeutic options and different phenotypes, a bronchodilator-trial (using short-acting ß2 agonists with metered-dose inhalers and valved holding chambers) seems appropriate in every child with bronchiolitis and age > 6 months.