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Sore throat represents one of the main causes of antibiotic overprescription in children. Its management is still a matter of debate, with countries considering streptococcal pharyngotonsillitis a benign and self-limiting condition and others advocating for its antibiotic treatment to prevent suppurative complications and acute rheumatic fever. Italian paediatricians frequently prescribe antibiotics on a clinical basis regardless of microbiological results. Moreover, broad-spectrum antibiotics are inappropriately prescribed for this condition. In this regard, an intersociety consensus conference was issued to promote the judicious use of antibiotic therapy in paediatric outpatient settings. A systematic review of the literature was performed, and updated recommendations were developed according to the GRADE methodology. Antibiotic treatment with amoxicillin (50 mg/kg/day) for 10 days is recommended in all children with proven streptococcal pharyngitis. Benzathine-penicillin could be prescribed in children with impaired intestinal absorption or inability to tolerate enteral intake and in those at high risk of suppurative complications with low compliance to oral therapy. In children with suspected amoxicillin allergy, third-generation cefalosporins for five days are recommended in low-risk patients, and macrolides are recommended in high-risk ones. Candidates for tonsillectomy due to recurrent pharyngitis could be treated with amoxicillin-clavulanic acid, clindamycin, or combined therapy with amoxicillin plus rifampicin for four days, in an attempt to avoid surgery., (© 2024. The Author(s).)

Background: Despite its broad spectrum and excellent safety profile, fosfomycin is still rarely used in pediatrics, with very limited experience from clinicians., Methods: We retrospectively reviewed the medical records of all children admitted to Bambino Gesù Children's Hospital, IRCCS, Rome, Italy, and treated with fosfomycin for any serious infection. Children with immunodeficiency and oncologic diseases were excluded. Of each, we reported and analyzed demographic and clinical data., Results: The clinical charts of 20 patients were reviewed and analyzed. The mean age was 10.2 years. Most children were males (85%). Most patients treated had an osteo-articular infection (65%). In our sample, 7 patients (35%) had an underlying comorbidity. The causative agent was isolated in 14 cases (70%). All patients were treated with a combination of 2-3 antibiotics, including fosfomycin. The average duration of antibiotic treatment was 18 days. After treatment, 8 patients (40%) experienced a mild adverse reaction, possibly correlated with the administration of fosfomycin. All patients were discharged in good clinical condition., Conclusions: The present study reports on a sample of pediatric patients with complicated infections where administration of fosfomycin led to eradication of the disease with little or no side effects. Role of the underlying condition and concomitant medication in causing the reaction could not be ruled out. These data suggest that fosfomycin is an effective and safe antibiotic in the pediatric population, particularly for deep-seated infections sustained by multi-drug resistant pathogens., Competing Interests: All authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Invasive infections caused by Streptococcus pyogfenes (iGAS), commonly known as Group A Streptococcus, represent a significant public health concern due to their potential for rapid progression and life-threatening complications. Epidemiologically, invasive GAS infections exhibit a diverse global distribution, affecting individuals of all ages with varying predisposing factors. The pathogenesis of invasive GAS involves an array of virulence factors that contribute to tissue invasion, immune evasion, and systemic dissemination. In pediatrics, in the last few years, an increase in iGAS infections has been reported worldwide becoming a challenging disease to diagnose and treat promptly. This review highlights the current knowledge on pathogenesis, clinical presentations, and therapeutic approaches for iGAS in children.

Since its emergence, SARS-CoV-2 Omicron clade has shown a marked degree of variability and different clinical presentation compared with previous clades. Here we demonstrate that at least four Omicron lineages circulated in children since December 2021, and studied until November 2022: BA.1 (33.6%), BA.2 (40.6%), BA.5 (23.7%) and BQ.1 (2.1%). At least 70% of infections concerned children under 1 year, most of them being infected with BA.2 lineages (n = 201, 75.6%). Looking at SARS-CoV-2 genetic variability, 69 SNPs were found to be significantly associated in pairs, (phi <  - 0.3 or > 0.3 and p-value < 0.001). 16 SNPs were involved in 4 distinct clusters (bootstrap > 0.75). One of these clusters (A23040G, A27259C, T23617G, T23620G) was also positively associated with moderate/severe COVID-19 presentation (AOR [95% CI] 2.49 [1.26-4.89] p-value: 0.008) together with comorbidities (AOR [95% CI] 2.67 [1.36-5.24] p-value: 0.004). Overall, these results highlight the extensive SARS-CoV-2 Omicron circulation in children, mostly aged < 1 year, and provide insights on viral diversification even considering low-abundant SNPs, finally suggesting the potential contribution of viral diversification in affecting disease severity., (© 2024. The Author(s).)

Aim: Higher number of monocytes and neutrophils may correlate with active tuberculosis (TB) in children. However, the few paediatric studies available are limited by the small numbers of children with TB disease or infection included., Methods: We calculated the monocyte-to-lymphocyte-ratio (MLR), neutrophil-to-lymphocyte-ratio (NLR) and neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) in children with active TB, latent TB infection (LTBI), other infectious and non-infectious conditions and healthy children evaluated in two referral centres in Rome., Results: Overall, 649 children were included (41.8% females, mean age of 5.74 years). MLR, NLR and NMLR values were always significantly higher in patients with TB compared with the other groups (p < 0.001). Considering the entire population with the outcome of TB diagnosis, NMLR, with a cut-off of 1.2, had a sensitivity of 63% and a specificity of 76% (AUC: 0.71 [0.64-0.78]); NLR, with a cut-off of 1.5, had a sensitivity of 61% and a specificity of 79% (AUC: 0.72 [0.65-0.79]); MLR, considering a cut-off of 0.2, was less sensitive (56%) but more specific (82%) with a similar AUC (0.72 [0.65-0.79])., Conclusion: Our study provides further evidence that MLR, NLR and NMLR can serve as first level diagnostics to support the clinical suspicion of TB in children., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Oxidative stress is known to be the cause of several neurovascular diseases, including neurodegenerative disorders, since the increase of reactive oxygen species (ROS) levels can lead to cellular damage, blood-brain barrier leaking, and inflammatory pathways. Herein, we demonstrate the therapeutic potential of 5 nm platinum nanoparticles (PtNPs) to effectively scavenge ROS in different cellular models of the neurovascular unit. We investigated the mechanism underlying the PtNP biological activities, analyzing the influence of the evolving biological environment during particle trafficking and disclosing a key role of the protein corona, which elicited an effective switch-off of the PtNP catalytic properties, promoting their selective in situ activity. Upon cellular internalization, the lysosomal environment switches on and boosts the enzyme-like activity of the PtNPs, acting as an intracellular "catalytic microreactor" exerting strong antioxidant functionalities. Significant ROS scavenging was observed in the neurovascular cellular models, with an interesting protective mechanism of the Pt-nanozymes along lysosomal-mitochondrial axes.

Background: The spread of carbapenem-resistant organisms (CROs) is an increasingly serious threat globally, especially in vulnerable populations, such as intensive care unit (ICU) patients. Currently, the antibiotic options for CROs are very limited, particularly in pediatric settings. We describe a cohort of pediatric patients affected by CRO infections, highlighting the important changes in carbapenemase production in recent years and comparing the treatment with novel cephalosporins (N-CEFs) to Colistin-based regimens (COLI)., Methods: All patients admitted to the cardiac ICU of the Bambino Gesù Children's Hospital in Rome during the 2016-2022 period with an invasive infection caused by a CRO were enrolled., Results: The data were collected from 42 patients. The most frequently detected pathogens were Pseudomonas aeruginosa (64%), Klebsiella pneumoniae (14%) and Enterobacter spp. (14%). Thirty-three percent of the isolated microorganisms were carbapenemase producers, with a majority of VIM (71%), followed by KPC (22%) and OXA-48 (7%). A total of 67% of patients in the N-CEF group and 29% of patients in the comparative group achieved clinical remission ( p = 0.04)., Conclusion: The increase over the years of MBL-producing pathogens in our hospital is challenging in terms of therapeutic options. According to the present study, N-CEFs are a safe and effective option in pediatric patients affected by CRO infections.

Background: Aggregatibacter actinomycetemcomitans (Aa), previously known as Actinobacillus actinomycetemcomitans, is a slow-growing Gram-negative coccobacillus, member of the HACEK group of bacteria colonizing oral flora. Besides causing infectious diseases in the oral cavity such as dental caries and periodontitis, it is responsible for severe extra-oral infections secondary to hematogenous spread or aspiration, such as endocarditis, soft tissue abscesses and osteomyelitis. The diagnosis depends on prolonged bacterial culture of biological material obtained through biopsy. Aa is susceptible to most antibiotics but complete eradication often requires a long term treatment., Case Presentation: We report the case of a 15-year-old previously healthy boy diagnosed with both pulmonary empyema and subphrenic chest wall abscess caused by Aa. He was admitted to our Pediatric Emergency department for evaluation of a right mass associated with marked asthenia and dry cough. After radiological findings etiological diagnosis was made by culture of fluid drainage of pleural empyema. He started empirical antibiotic therapy with intravenous piperacillin/tazobactam, whose sensibility was confirmed by the antibiogram, then, for occurrance of hepatopathy it was switched to ciprofloxacin: the patient almost completely recovered after 6-month therapy., Conclusions: Extra-oral infections caused by Aa are extremely rare, especially in children, and not well described yet. To our knowledge, there is only another similar case described in literature. However, the case described in our manuscript represents the only one presenting with pulmonary empyema without involvement of lung parenchyma in children. We also conducted a brief review of published cases of Aa infection in the pediatric population. This case report reminds us the importance of an accurate inspection of the oral cavity during the examination of pediatric patients., (© 2023. The Author(s).)

Rationale: In 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB)., Objectives: This study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe., Methods: Multicentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases <18 years-of-age diagnosed between January 2009 and December 2019., Measurements and Main Results: 1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4-12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT. TB in 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT. TB 77.6% (95% CI 66.9% to 88.3%) and TST (cut-off ≥10 mm) 83.3% (95% CI 83.3% to 86.2%). There was a trend for tests to have lower sensitivity in patients with miliary and/or central nervous system (CNS) TB (73.1%, 70.9%, 63.6% and 43.5%, respectively), and in immunocompromised patients (75.0%, 59.6%, 45.5% and 59.1%, respectively)., Conclusions: The results indicate that the latest generation IGRA assay, QFT-Plus, does not perform better than previous generation IGRAs or the TST in children with TB disease. Overall, tests performed worse in CNS and miliary TB, and in immunocompromised children. None of the tests evaluated had sufficiently high sensitivity to be used as a rule-out test in children with suspected TB., Competing Interests: Competing interests: DB participated in a Qiagen advisory board meeting on the use of IGRAs in children <5 years of age. The manufacturers had no influence on the study design, data collection, analysis or interpretation, writing of the manuscript or the decision to submit the data for publication. BS-G and MT have received support from Cepheid for a project on molecular TB diagnostics unrelated to the study reported here. MT has received QuantiFERON-TB assays at reduced pricing or free of charge for TB diagnostics projects from the manufacturer (Cellestis/Qiagen) in the past, and has received support for conference attendance from Cepheid., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Iron oxide nanoparticles (IONPs) have been largely investigated in a plethora of biological fields for their interesting physical-chemical properties, which make them suitable for application in cancer therapy, neuroscience, and imaging. Several encouraging results have been reported in these contexts. However, the possible toxic effects of some IONP formulations can limit their applicability. In this work, IONPs were synthesized with a carbon shell (IONP@C), providing enhanced stability both as colloidal dispersion and in the biological environment. We conducted a careful multiparametric evaluation of IONP@C biological interactions in vitro , providing them with an in vivo -like biological identity. Our hybrid nanoformulation showed no cytotoxic effects on a widely employed model of alveolar epithelial cells for a variety of concentrations and exposure times. The IONP@C were efficiently internalized and TEM analysis allowed the protective role of the carbon shell against intracellular degradation to be assessed. Intracellular redistribution of the IONP@C from the lysosomes to the lamellar bodies was also observed after 72 hours.

During the COVID-19 pandemic, the lung ultrasound (LU) turned out to be a pivotal tool to study the lung involvement in the adult population, but the same was not well evaluated in children. We detected the LU patterns through an integrated approach with clinical−laboratory features in children hospitalized for COVID-19 in relation to the temporal trend of the Italian epidemic. We conducted a retrospective study which took place at a pediatric tertiary hospital from 15 March 2020 to 15 March 2021. We compared the characteristics of the initial phase of the first COVID-19 year—in the spring and summer (15 March−30 September 2020)—and those of the second phase—in the autumn and winter (1 October 2020−15 March 2021). Twenty-eight patients were studied both in the first and in the second phase of the first COVID-19 year. The disease severity score (DSS) was significantly greater in the second phase (p = 0.015). In the second phase of the first COVID-19 year, we detected a more significant occurrence of the following LU features than in the first phase: the irregular pleural line (85.71% vs. 60.71%; p = 0.035), the B-lines (89.29% vs. 60%; p = 0.003) and the several but non-coalescent B-lines (89.29% vs. 60%; p = 0.003). The LU score correlated significantly with the DSS, with a moderate relationship (r = 0.51, p < 0.001). The combined clinical, laboratory and ultrasound approaches might be essential in the evaluation of pulmonary involvement in children affected by COVID-19 during different periods of the pandemic.

While there are numerous studies regarding Clostridioides difficile infection (CDI) in adults, literature on the pediatric population is scarce. Therefore, we performed a 5-year retrospective study between January 2014 and December 2018 in two referral centers in Rome, Italy. There were 359 patients tested for CDI who were enrolled: 87 resulted in positive and 272 in negative. CDI children had a higher number of previous-day hospital admissions ( p = 0.024), hospitalizations ( p = 0.001), and total hospital admissions ( p = 0.008). Chronic comorbidities were more frequent in the CDI group (66.7% vs. 33.3%). Previous use of proton pump inhibitors and antibiotics was associated with CDI ( p < 0.001). Among the antibiotics, only fluoroquinolones were significantly associated with CDI. Also, CDI children were more frequently exposed to antibiotics during the episode of hospitalization when children were tested. Our study provides an updated clinical and epidemiological analysis of children with CDI compared with a control group of children who tested negative. Further prospective studies could better define risk factors and preventive methods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Buonsenso, Graffeo, Pata, Valentini, Palumbo, Masucci, Ruggiero, Attinà, Onori, Lancella, Lucignano, Giuseppe, Bernaschi and Cursi.)

The progress achieved over the last three decades in the field of bioconjugation has enabled the preparation of sophisticated nanomaterial-biomolecule conjugates, referred to herein as bionanoconstructs, for a multitude of applications including biosensing, diagnostics, and therapeutics. However, the development of bionanoconstructs for the active targeting of cells and cellular compartments, both in vitro and in vivo , is challenged by the lack of understanding of the mechanisms governing nanoscale recognition. In this review, we highlight fundamental obstacles in designing a successful bionanoconstruct, considering findings in the field of bionanointeractions. We argue that the biological recognition of bionanoconstructs is modulated not only by their molecular composition but also by the collective architecture presented upon their surface, and we discuss fundamental aspects of this surface architecture that are central to successful recognition, such as the mode of biomolecule conjugation and nanomaterial passivation. We also emphasize the need for thorough characterization of engineered bionanoconstructs and highlight the significance of population heterogeneity, which too presents a significant challenge in the interpretation of in vitro and in vivo results. Consideration of such issues together will better define the arena in which bioconjugation, in the future, will deliver functional and clinically relevant bionanoconstructs.

Monoclonal antibody therapies for COVID-19 have been frequently used in adults, whereas there are little data regarding the safety or efficacy of monoclonal antibody treatments in pediatric patients affected by COVID-19. We report our experience in the administration of mAb as a treatment for SARS-CoV-2 infection in children aged from 24 days to 18 years old.

Background: Although SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs; thus, it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study sought to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology., Methods: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic (SY) children, stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swab samples. To define anti-SARS-CoV-2 antibodies, we measured neutralization activity and total IgG load (DiaSorin). We also evaluated antigen-specific B and CD8+T cells, using a labeled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink., Results: Virological profiling showed that AS patients had lower viral load at diagnosis (p = .004) and faster virus clearance (p = .0002) compared with SY patients. Anti-SARS-CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY patients showed similar titers of SARS-CoV-2 IgG, levels of neutralizing activity, and frequency of Ag-specific B and CD8+ T cells, whereas pro-inflammatory plasma protein profile was found to be associated with symptomatology., Conclusion: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regard to symptomatology, suggesting the ability of both SY and AS patients to contribute toward herd immunity. The virological profiling of AS patients suggested that they have lower virus load associated with faster virus clearance., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Despite the high level of interest in bio-nano interactions, detailed intracellular mechanisms that govern nanoscale recognition and signalling still need to be unravelled. Magnetic nanoparticles (NPs) are valuable tools for elucidating complex intracellular bio-nano interactions. Using magnetic NPs, it is possible to isolate cell compartments that the particles interact with during intracellular trafficking. Studies at the subcellular scale rely heavily on optical microscopy; therefore, combining the advantages of magnetic recovery with excellent imaging properties to allow intracellular NP tracking is of utmost interest for the nanoscience field. However, it is a challenge to prepare highly magnetic NPs with a suitable fluorescence for the fluorescence imaging techniques typically used for biological studies. Here we present the synthesis of biocompatible multifunctional superparamagnetic multicore NPs with a bright fluorescent silica shell. The incorporation of an organic fluorophore in the silica surrounding the magnetic multicore was optimised to enable the particles to be tracked with the most common imaging techniques. To prevent dye loss resulting from silica dissolution in biological environments, which would reduce the time that the particles could be tracked, we added a thin dense encapsulating silica layer to the NPs which is highly stable in biological media. The synthesised multifunctional nanoparticles were evaluated in cell uptake experiments in which their intracellular location could be clearly identified using fluorescence imaging microscopy, even after 3 days. The magnetic properties of the iron oxide core enabled both efficient recovery of the NPs from the intracellular environment and the extraction of cell compartments involved in their intracellular trafficking. Thus, the NPs reported here provide a promising tool for the study of the processes regulating bio-nano interactions.

Background: Since December 2019 coronavirus disease (COVID-19) emerged in Wuhan and spread rapidly worldwide. Despite the high number of people affected, data on clinical features and prognostic factors in children and adolescents are limited. We propose a retrospective study aimed to evaluate clinical characteristics of children infected with SARS-CoV-2 in Italy., Methods: A pediatric population admitted with COVID-19 to Bambino Gesù Children's Hospital of Rome (Italy) in the period from the end of February to July 2020 has been studied. Medical history, comorbidities, symptoms and laboratory findings were obtained from patients' electronic medical records., Results: In 66 patients (35 males and 31 females) we found that: i) fever and cough were the dominant symptoms, while vomit and convulsions were rare symptoms; and ii) all ages of childhood were susceptible to COVID-19. Furthermore, we found that, compared to females, males with COVID-19, although not significantly, had higher values of inflammatory markers such as C-reactive protein (CRP) and ESR. Conversely, we found that COVID-19 positive females were older than males and required more days of hospitalization. Both males and females COVID-19 positives had procalcitonin values within the normal range and D-Dimer values slightly higher than the normal range. With regard to this latter marker, the value measured in females, although not significant, was higher than that measured in males. Interestingly, the presence of leukopenia was found in both sexes., Conclusions: Compared to the adults we found that COVID-19 infection in children is a non-severe inflammatory disease in both males and females. In any case, many detailed studies should be conducted.

The field of nanomedicine has the potential to be a game-changer in global health, with possible applications in prevention, diagnostics, and therapeutics. However, despite extensive research focus and funding, the forecasted explosion of novel nanomedicines is yet to materialize. We believe that clinical translation is ultimately hampered by a lack of understanding of how nanoparticles really interact with biological systems. When placed in a biological environment, nanoparticles adsorb a biomolecular layer that defines their biological identity. The challenge for bionanoscience is therefore to understand the evolution of the interactions of the nanoparticle-biomolecules complex as the nanoparticle is trafficked through the intracellular environment. However, to progress on this route, scientists face major challenges associated with isolation of specific intracellular compartments for analysis, complicated by the diversity of trafficking events happening simultaneously and the lack of synchronization between individual events. In this perspective article, we reflect on how magnetic nanoparticles can help to tackle some of these challenges as part of an overall workflow and act as a useful platform to investigate the bionano interactions within the cell that contribute to this nanoscale decision making. We discuss both established and emerging techniques for the magnetic extraction of nanoparticles and how they can potentially be used as tools to study the intracellular journey of nanomaterials inside the cell, and their potential to probe nanoscale decision-making events. We outline the inherent limitations of these techniques when investigating particular bio-nano interactions along with proposed strategies to improve both specificity and resolution. We conclude by describing how the integration of magnetic nanoparticle recovery with sophisticated analysis at the single-particle level could be applied to resolve key questions for this field in the future., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Mild encephalopathy with a reversible splenial lesion (MERS) is an uncommon clinico-radiological entity characterized by magnetic resonance imaging (MRI) findings of a reversible lesion in the splenium of corpus callosum associated with a significant neurological manifestation of encephalopathy. The majority of reported cases involve the Asiatic population and are closely associated with infection. We report the case of an adolescent with an HHV6-related MERS presenting with hyponatremia and urinary and fecal retention. To our knowledge, urinary retention is not a constant aspect of the disease and has rarely been described, while fecal retention has never been reported before. Despite the self-limiting nature of the disease, it is mandatory to suspect it for a faster diagnosis and it might be useful to know its rare occurrences in order to better understand its etiopathogenetic mechanisms.

Background: Acute cerebellitis (AC) and acute cerebellar ataxia (ACA) are the principal causes of acute cerebellar dysfunction in childhood. Nevertheless. there is no accepted consensus regarding the best management of children with AC/ACA: the aim of the study is both to assess clinical, neuroimaging and electrophysiologic features of children with AC/ACA and to evaluate the correlation between clinical parameters, therapy and outcome., Methods: A multicentric retrospective study was conducted on children ≤ 18 years old admitted to 12 Italian paediatric hospitals for AC/ACA from 01/01/2003 to 31/12/2013. A score based on both cerebellar and extracerebellar signs/symptoms was computed for each patient. One point was given for each sign/symptom reported. Severity was divided in three classes: low, moderate, severe., Results: A total of 124 children were included in the study. Of these, 118 children received a final diagnosis of ACA and 6 of AC. The most characteristic finding of AC/ACA was a broad-based gait disturbance. Other common symptoms included balance disturbances, slurred speech, vomiting, headache and fever. Neurological sequelae were reported in 6 cases (5%) There was no correlation among symptoms, cerebrospinal fluid findings, clinical outcome. There was no correlation between clinical manifestations and clinical score on admission and length of hospital stay, sex, age and EEG findings with sequelae (P > 0.05). Children with pathological magnetic resonance imaging (MRI) or computed tomography (CT) had a higher probability of having clinical sequelae. Treatment was decided independently case by case. Patients with a higher clinical score on admission had a higher probability of receiving intravenous steroids., Conclusions: We confirmed the literature data about the benign course of AC/ACA in most cases but we also highlighted a considerable rate of patients with neurological sequelae (5%). Pathological MRI or CT findings at admission correlate to neurological sequelae. These findings suggest the indication to perform an instrumental evaluation in all patients with AC/ACA at admission to identify those at higher risk of neurological outcome. These patients may benefit from a more aggressive therapeutic strategy and should have a closer follow-up. Randomized controlled trials are needed to confirm these observations. The ultimate goal of these studies could be to develop a standardized protocol on AC/ACA. The MRI/CT data, associated with the clinical manifestations, may allow us to define the class risk of patients for a neurological outcome.

NK cell cytotoxicity in Chédiak-Higashi syndrome (CHS) is strongly impaired as lytic granules are not released upon NK-target cell contact, contributing to several defects typical of this severe immunodeficiency. Correction of NK cell defects in CHS should improve the outcome of hematopoietic stem-cell transplantation, proposed as therapy. We investigated NK cell functions in a CHS patient before and after cord-blood transplantation, and the ability of in vitro IL-2 treatment to restore them. Before the transplant, the strong defect in NK cell-mediated natural and antibody-dependent cytotoxicity, as well as in IFN-γ production, could be restored up to normal levels by in vitro IL-2 treatment. This cytokine also caused the appearance of smaller lysosomal granules and their orientation towards the NK-target cell contact area, thus suggesting that IL-2 had a more general capacity to restore NK cell effector functions. Moreover after the transplant, although the successful engraftment, NK cell cytotoxicity resulted still partially impaired at one year, almost normal at ten years and, anyhow, fully recovered by in vitro IL-2 treatment. Taken together, our results indicate that IL-2 had a wide capacity to restore NK cell effector functions, being able to reverse the altered cytotoxic activity, lytic granule pattern, and cytokine production observed in the CHS patient., (Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Background: The spread of carbapenem-resistant Enterobacteriaceae (CRE) is a health problem of major concern. CRE-related infections have significant morbidity and mortality, but data on CRE infection in pediatric population are limited. The aim of this study was to analyze epidemiologic and clinical characteristics, risk factors, therapeutic options and outcome of CRE infections in children in Italy., Methods: We performed a retrospective, multicenter, observational study of children with confirmed CRE infection or colonization admitted between January 1, 2011, and March 1, 2014, to 7 Italian pediatric centers., Results: Sixty-nine patients presenting 74 CRE infections and/or colonization were included. The most frequently isolated strain was Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Children with CRE infections had longer length of stay in hospital (P < 0.001), duration of disease (P = 0.001) and antimicrobial treatment (P < 0.001) than colonized children. Oncologic/immunosuppressive conditions are one of the factors significantly associated with a fatal outcome among children with CRE infections., Conclusions: Our study confirms that CRE infections affect mostly children with oncologic diseases and immunosuppression. Controlled studies in large cohorts are needed to evaluate the best therapeutic options and to assess further risk factors influencing outcomes and the survival of pediatric patients with infections caused by CRE.

Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large cohorts. A multicenter study was conducted in 27 pediatric hospitals, pediatric wards, and public health centers in Italy using a standardized form, covering the period of time between 1 January 2010 and 31 December 2012. Children with active TB, latent TB, and those recently exposed to TB or recently adopted/immigrated from a high TB incidence country were enrolled. Overall, 4234 children were included; 554 (13.1%) children had active TB, 594 (14.0%) latent TB and 3086 (72.9%) were uninfected. Among children with active TB, 481 (86.8%) patients had pulmonary TB. The treatment of active TB cases was known for 96.4% (n = 534) of the cases. Overall, 210 (39.3%) out of these 534 children were treated with three and 216 (40.4%) with four first-line drugs. Second-line drugs where used in 87 (16.3%) children with active TB. Drug-resistant strains of Mycobacterium tuberculosis were reported in 39 (7%) children. Improving the surveillance of childhood TB is important for public health care workers and pediatricians. A non-negligible proportion of children had drug-resistant TB and was treated with second-line drugs, most of which are off-label in the pediatric age. Future efforts should concentrate on improving active surveillance, diagnostic tools, and the availability of antitubercular pediatric formulations, also in low-endemic countries.

Spinocerebellar ataxia type 2 (SCA2) is a late-onset autosomal dominant cerebellar ataxia caused by triplet CAG/CTG expansion in the ATX2 gene. The initial symptoms usually appear when subjects are in their 30s.Pediatric onset is less common and usually associated with larger triplet expansions. We here report the case of a 1-year-old girl who presented with facial dysmorphism,dystonic features, developmental delay, and retinitis pigmentosa.She was diagnosed as carrying an expanded CAG/CTG tract (92 repeats) before a molecular diagnosis of SCA2 was made in her father. Facial dysmorphism associated with developmental delay and retinitis pigmentosa in early childhood should prompt a careful family investigation for ataxia and study of ATX2.

It has been demonstrated that HIV infection may affect the levels of thymidine kinase (TK) and deoxycytidine kinase (dCK) in peripheral blood mononuclear cells from HIV infected adults. The aim of this study was to examine the effect of HIV infection and/or antiretroviral therapy on the activity of the above enzymes in HIV-infected children. The results showed that an inter-individual variability in TK and dCK activities does exist in both HIV infected and uninfected children. TK and dCK levels in PBMC from HIV infected and non infected children did not significantly differ. Furthermore, the therapeutic regimen, including zidovudine, does not seem to affect TK activity.