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Antibodies are critical tools for research into extracellular vesicles (EVs) and other extracellular nanoparticles (ENPs), where they can be used for their identification, characterization, and isolation. However, the lack of a centralized antibody platform where researchers can share validation results thus minimizing wasted personnel time and reagents, has been a significant obstacle. Moreover, because the performance of antibodies varies among assay types and conditions, detailed information on assay variables and protocols is also of value. To facilitate sharing of results on antibodies that are relevant to EV/ENP research, the EV Antibody Database has been developed by the investigators of the Extracellular RNA Communication Consortium (ERCC). Hosted by the ExRNA Portal (https://exrna.org/resources/evabdb/), this interactive database aggregates and shares results from antibodies that have been tested by research groups in the EV/ENP field. Currently, the EV Antibody Database includes modules for antibodies tested for western Blot, EV Flow Cytometry, and EV Sandwich Assays, and holds 110 records contributed by 6 laboratories from the ERCC. Detailed information on antibody sources, assay conditions, and results is provided, including negative results. We encourage ongoing expert input and community feedback to enhance the databases utility, making it a valuable resource for comprehensive validation data on antibodies and protocols in EV biology.

Francesco Malfona, Anna Maria Testi, Sabina Chiaretti, Maria Luisa Moleti Department of Translational and Precision Medicine, ‘Sapienza’ University, Rome, ItalyCorrespondence: Maria Luisa Moleti, Hematology Institute, Via Benevento 6, Rome, 00161, Italy, Tel +39 3384714201, Fax +39 0644641984, Email moleti@bce.uniroma1.itAbstract: Despite excellent results in frontline therapy, particularly in pediatric age, refractory Burkitt lymphoma still remains a therapeutic challenge, with dismal outcome. The prognosis is very poor, ranging from less than 10% to 30– 40%, with longer survival only in transplanted patients. On account of the paucity of data, mostly reporting on small series of patients, with heterogeneous characteristics and salvage treatments, at present it is impossible to draw definitive conclusions on the treatment of choice for this difficult to treat subset of patients. New insights into Burkitt lymphoma/leukemia cell biology have led to the development of new drugs, currently being tested, directed at different specific targets. Herein, we describe the results so far reported in refractory Burkitt lymphoma/leukemia, with standard treatments and hematopoietic stem cell transplant, and we review the new targeted drugs currently under evaluation.Keywords: Burkitt lymphoma, target therapy, relapse, refractory, outcome

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BackgroundOut-of-hospital cardiac arrest (OHCA) is one of the most dramatic events in pediatric age and, despite advanced neurointensive care, the survival rate remains low. Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. Nerve Growth Factor (NGF) is a neurotrophin potentially able to counteract many of the deleterious effects triggered by OHCA. Transcranial Direct Current Stimulation (tDCS) has been reported to be neuroprotective in many neurological diseases, such as motor deficit and cognitive impairment. Children with the diagnosis of chronic vegetative state after OHCA were enrolled. These patients underwent a combined treatment of intranasal administration of human recombinant NGF (hr-NGF), at a total dose of 50 gamma/kg, and tDCS, in which current intensity was increased from zero to 2 mA from the first 5 s of stimulation and maintained constant for 20 min. The treatment schedule was performed twice, at one month distance each. Neuroradiogical evaluation with Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG) and Power Spectral Density of the brain (PSD) was determined before the treatment and one month after the end. Neurological assessment was deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale.ResultsThree children with a chronic vegetative state secondary to OHCA were treated. The combined treatment with hr-NGF and tDCS improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary finger movements, improved facial mimicry and reaction to painful stimuli. No side effects were reported.ConclusionsThese promising preliminary results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the

No abstract available

Background and PurposeTraumatic brain injury (TBI) comprises a primary injury directly induced by impact, which progresses into a secondary injury leading to neuroinflammation, reactive astrogliosis, and cognitive and motor damage. To date, treatment of TBI consists solely of palliative therapies that do not prevent and/or limit the outcomes of secondary damage and only stabilize the deficits. The neurotrophin, nerve growth factor (NGF), delivered to the brain parenchyma following intranasal application, could be a useful means of limiting or improving the outcomes of the secondary injury, as suggested by pre-clinical and clinical data. Experimental ApproachWe evaluated the effect of acute intranasal treatment of young (20-postnatal day) rats, with NGF in a TBI model (weight drop/close head), aggravated by hypoxic complications. Immediately after the trauma, rats were intranasally treated with human recombinant NGF (50 mu g center dot kg(-1)), and motor behavioural test, morphometric and biochemical assays were carried out 24 h later. Key ResultsAcute intranasal NGF prevented the onset of TBI-induced motor disabilities, and decreased reactive astrogliosis, microglial activation and IL-1 beta content, which after TBI develops to the same extent in the impact zone and the hypothalamus. Conclusion and ImplicationsIntranasal application of NGF was effective in decreasing the motor dysfunction and neuroinflammation in the brain of young rats in our model of TBI. This work forms an initial pre-clinical evaluation of the potential of early intranasal NGF treatment in preventing and limiting the disabling outcomes of TBI, a clinical condition that remains one of the unsolved problems of paediatric neurology.

Traumatic brain injury is one of the main causes of mortality and disability worldwide. Traumatic brain injury is characterized by a primary injury directly induced by the impact, which progresses into a secondary injury that leads to cellular and metabolic damages, starting in the first few hours and days after primary mechanical injury. To date, traumatic brain injury is not targetable by therapies aimed at preventing and/or limiting the outcomes of secondary damage but only by palliative therapies. Nerve growth factor is a neurotrophin targeting neuronal and non-neuronal cells, potentially useful in preventing/limiting the outcomes of secondary damage in traumatic brain injury. This potential has further increased in the last two decades since the possibility of reaching neurotrophin targets in the brain through its intranasal delivery has been exploited. Indeed, molecules intranasally delivered to the brain parenchyma may easily bypass the blood-brain barrier and reach their therapeutic targets in the brain, with favorable kinetics, dynamics, and safety profile. In the first part of this review, we aimed to report the traumatic brain injury-induced dysfunctional mechanisms that may benefit from nerve growth factor treatment. In the second part, we then exposed the experimental evidence relating to the action of nerve growth factor (both in vitro and in vivo, after administration routes other than intranasal) on some of these mechanisms. In the last part of the work, we, therefore, discussed the few manuscripts that analyze the effects of treatment with nerve growth factor, intranasally delivered to the brain parenchyma, on the outcomes of traumatic brain injury.

BackgroundSevere traumatic brain injury (TBI) is one of the most dramatic events in pediatric age and, despite advanced neuro-intensive care, the survival rate of these patients remains low. Children suffering from severe TBI show long-term sequelae, more pronounced in behavioral, neurological and neuropsychological functions leading to, in the most severe cases, an unresponsive wakefulness syndrome (UWS). Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. In experimental animal models, human- recombinant Nerve Growth Factor (hr-NGF) promotes neural recovery supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated processes. Only a few studies reported the efficacy of intranasal hr-NGF administration in children with post- traumatic UWS.MethodsChildren with the diagnosis of post-traumatic UWS were enrolled. These patients underwent a treatment with intranasal hr-NGF administration, at a total dose of 50 gamma/kg, three times a day for 7 consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. Neuroradiogical evaluation by Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG), and Power Spectral Density (PSD) was determined before the treatment and one month after the end. Neurological assessment was also deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale.ResultsThree children with post-traumatic UWS were treated. hr-NGF administration improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary movements, facial mimicry, attention and verbal comprehension, ability to cry, cough reflex, oral motility, and feeding capacity, with a significant improvement

Sleep disorders are particularly important in the development of children, affecting the emotional, behavioural, and cognitive spheres. The incidence of these disorders has been assessed in different types of populations, including patients with a history of premature birth, who, from the literature data, would seem to have an increased incidence of sleep disorders at school age. The aims of the present study are: (i.) to assess the presence of sleep disorders in a population of very preterm infants at 6–36 months who are at low risk of neurological impairments using the Italian version of the Sleep Disturbance Scale for Children (SDSC) adapted for this age group, and (ii.) to identify possible differences from a control group of term-born infants. A total of 217 low-risk preterm and 129 typically developing infants and toddlers were included in the study. We found no differences in the SDSC total and the factor scores between these two populations of infants. Low-risk preterm infants and toddlers showed similar incidences of sleep disorders to their term-born peers. Further clinical assessments will be needed to confirm these data at school age.

No abstract available

Fever is the most common problem of children admitted to emergency department (ED). The management of febrile patients ≤ 60 d old admitted to the Pediatric Emergency Department in the last 5 y was evaluated, applying the invasive bacterial infection (IBI) score proposed to evaluate the reliability and safety of this score in the authors' setting.Medical records of 280 patients with fever reported and/or detected in ED were retrospectively analyzed. A total of 166 patients were enrolled, whose average IBI score was 2.98 IBI score < 2 showed a sensitivity of 100.00% [95% CI (71.5-100.0)] and a specificity of 28.39% [95% CI (21.4-36.2)] compared to blood culture. IBI score can be a valid support to identify patients with low risk of invasive infection.

BackgroundSpontaneous pneumothorax is a relatively uncommon and poorly studied condition in children. While several protocols have been developed to evaluate the use of lung ultrasound for dyspneic adult patients in the emergency department, no specific guidelines are present for pediatric emergency physicians. ObjectivesWe prospectively analyzed children with acute chest pain and clinical suspicion of pneumothorax evaluated at the pediatric emergency department. MethodsWe consecutively enrolled children aged 5-17 years presenting to the pediatric emergency department with clinically suspected pneumothorax based on sudden onset of acute chest pain. After clinical examination, all children underwent lung ultrasound followed by chest X-ray (reference standard). We enrolled 77 children, of which 13 (16.9%) received a final diagnosis of pneumothorax. ResultsThe lung point had a sensitivity of 92.3% (95% CI 77.8-100) and a specificity of 100% (95% CI 94.4-100) for the detection of pneumothorax. The "barcode sign" had a sensitivity of 100% (95% CI 75.3-100) and a specificity of 100% (95% CI 94.4-100) for the detection of pneumothorax. ConclusionLung ultrasound is highly accurate in detecting or excluding pneumothorax in children with acute chest pain evaluated in the pediatric emergency department. If pneumothorax is suspected, but the lung point is not visible, the barcode sign should always be sought as it could be a form of massive pneumothorax.

While there is evidence of high use of wide-spectrum antibiotics in children evaluated in the pediatric emergency departments, determinants of this behavior are still unclear. This study was aimed at defining the demographic, social, clinical, and laboratory factors that affect antibiotic prescriptions in children discharged from the emergency department. We performed a retrospective observational study of children aged younger than 18 years discharged from a pediatric university hospital between Jan. 1, 2015 and Dec. 31, 2020. We determined the proportion and type of antibiotic prescription according to demographic, social, clinical, laboratory, and imaging data, as well as doctor’s expertise. Fifty-one thousand six hundred thirty-three children were included, and 13,167 (25.5%) received an antibiotic prescription. Amoxicilline/clavulanate (Am/Cl) was the most prescribed antibiotic (8453, 64.2% of all prescriptions). Factors independently associated with an antibiotic prescription were older age (OR = 1.62 [1.53–1.73] for age 2–5 years, OR = 1.77 [1.64–1.91] for age 6–10 years, OR = 1.36 [1.25–1.49] for age 11–18 years, p < 0.001 for all groups); being evaluated by a physician with > 3 years of pediatric expertise (OR = 1.22 [1.13–1.31], p < 0.001); fever peak higher than 40 °C (OR = 1.37 [1.21–1.54], p < 0.001); abnormal findings on auscultation (OR = 1.95 [1.75–2.17], p < 0.001), CRP values (OR = 1.63 [1.26–2.10] for CRP < 50 mg/L, and OR = 3.78 (2.75–5.21) for CRP ≥ 50 mg/L with respect to CRP not requested; p < 0.01); CXR results whatever positive (OR = 4.47 [3.62–5.52], p < 0.001) or negative (1.82 [1.62–2.04], p < 0.001); being diagnosed with upper respiratory tract infections (OR = 4.27 [4.04–4.51], p < 0.001), lower respiratory tract infections (OR = 5.35 [4.88–5.85]; p < 0.001), and UTI (OR = 9.33 [8.14–10.71], p < 0.001). Conclusions: Overprescription of antibiotics, including Am

Aim Myopericarditis after COVID-19 vaccination were the most serious adverse events reported in children over 5 years of age. We want to summarise these cases, describing their incidence, clinical features, diagnostic pathways, therapeutic strategies and outcome. Methods A systematic review of the literature was conducted until 20 March 2022 by bibliographic electronic databases. We included all reports of post-vaccination myopericarditis in children aged between 5 and 18 years. Results All reported cases had elevated serum Troponin levels, associated with electrocardiogram changes, but often with normal echocardiogram. Cardiac magnetic resonance images always showed typical alterations. The pathogenetic mechanism is still unknown. Myocarditis following post-COVID vaccination is more frequent in boys with an average age of about 15 years. Treatment involves the usage of non-steroidal anti-inflammatory drugs, and the average hospitalisation is about 3 days. The long-term consequences are not yet known, so these patients should be studied in a cardiological follow-up and abstention from physical activity should be recommended. Conclusion The benefits of COVID-19 vaccination in children and adolescents appear to outweigh the risk of developing post-vaccination myopericarditis. We can also speculate a possible approval of vaccination in children under 5 years for the coming winter.

Early recognition of Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) cases could impact on the management and outcome of this subset of B-lineage ALL. In order to assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)driven trial, we screened 88 B-lineage ALL cases negative for major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the “BCR/ABL1-like predictor” - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission rate was significantly lower in Ph-like compared to non-Ph-like cases (74.1% vs. 91.5%, P=0.044); ii) at time point 2, decisional for transplant allocation, 52.9% of Ph-like cases versus 20% of non-Ph-like were MRD-positive (P=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at time point 2 (P=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs. 66.2%, P=0.005 and 45.5% vs. 72.3%, P=0.062, respectively). This study documents that Ph-like patients have a lower complete remission rate, event-free survival and disease-free survival, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies.

Kawasaki disease (KD) is a childhood vasculitis of unknown etiology. The present study describes a case of KD shock syndrome that occurred in an infant (age, 16 months) following 7 days of high fever and persistent rash characterized by target-like and purpuric skin lesions. The child developed neurological manifestations such as altered consciousness and irritability. Consequently, brain magnetic resonance imaging (MRI) was performed, revealing an inflammatory involvement of the anterior perforated substance and the hypothalamus. Cerebral involvement on brain MRI is rarely described in KD but when reported is characterized mostly by cerebral vasculitis. We illustrate for the first time in KD an inflammation in the brain not related to vasculitis, reporting peculiar neuroradiological findings. This last aspect has fascinated us in light of recent evidence about the immunological spectrum of Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki-like syndrome in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak.

Aim: To assess the impact of the coronavirus disease 2019 (COVID-19) outbreak on pediatric emergency department (ED) visits for acute bronchiolitis during the epidemic season. Methods: A retrospective analytical cross-sectional study was performed in our hospital, analyzing medical charts of all children under 2 years of age with a diagnosis of acute bronchiolitis admitted to our ED in the last years. Demographics and clinical data of patients affected with acute bronchiolitis during the 2020–2021 season—COVID-19 outbreak—were compared to those of the 5 previous years. Results: We observed an average drop of 84% of the rate of acute bronchiolitis managed by pediatricians in ED in 2020–2021 compared with bronchiolitis seasons of 5 previous years. We also reported, during the COVID-19 outbreak, a higher number of children affected by acute bronchiolitis referred to ED as Emergency Consultations who required hospitalization. Regarding etiological agents, no differences in respiratory virus circulation, especially RSV, were observed in the two groups. The multivariate analysis showed no correlation between the diagnosis of RSV bronchiolitis and COVID-19 period or prematurity; lower age was associated with an increased likelihood of exhibiting RSV bronchiolitis (odds ratio 0.9; 95% confidence interval 0.86–0.95 p <.01). Conclusion: Our data emphasize the reduction in the rate of admission to pediatric ED for acute bronchiolitis during the COVID-19 outbreak, regardless of changes in circulating respiratory viruses. Therefore we want to highlight the importance of nonpharmacological preventive hygiene measures that should be maintained even at the end of the COVID-19 outbreak.

The causal connection between serum biomarkers and COVID-19 severity or pathogenicity in children is unclear. The aim of this study was to describe clinical and immunological features of children affected by COVID-19. The secondary aim was to evaluate whether these cytokines could predict severity of COVID-19. All children (aged 0−18) admitted to the Pediatric Emergency Department and tested with nasopharyngeal swab for SARS-CoV-2 were recruited and assigned to three groups: COVID-19, other infections, control group. Clinical and laboratory data of these patients, including circulating cytokine levels, were analyzed in three groups. Fever was the most frequent symptom in COVID-19 (67.3%). Neutropenia was found in the COVID-19 group (p < 0.05); no difference was observed for lymphocyte counts in the three groups. Higher levels of IL-6 and TNF-alpha were found in the COVID-19 group compared to other infections and control groups (p = 0.014 and p = 0.001, respectively). Whereas, in the COVID-19 group, no difference was observed as for the same cytokines among sub-groups of different disease severity (p = 0.7 and p = 0.8). Serum levels of IL-6 and TNF-alpha were higher in COVID-19 children than in children with other infectious diseases, but those levels did not correlate with disease severity. Clinical studies in a large pediatric population are necessary to better define the role of the immune-mediated response in SARS-CoV-2 infections in children.

Invasive diagnostics and minor surgical procedures with deep sedation on pediatric patients, such as fibroscopic examination, have increased over the past decade. The aim of this study was to evaluate the usefulness and safety of an anesthesiological technique, based on the use of midazolam and ketamine, conducted in spontaneous breathing on a population of pediatric patients with suspected tracheobronchial pathologies. Pediatric patients from birth to 18 years old who underwent sedation diagnostic fibroscopy between April 2018 and March 2019, were enrolled. The anesthesiological technique provided was the intravenous administration of midazolam 0.2 mg/kg and ketamine 2 mg/kg in spontaneous breathing using a face mask with support of O2 and air. Vital signs such as Heart rate (HR), Systolic and Diastolic blood pressure (PAS and PAD) and Arterial oxygen saturation were recorded at the beginning of the procedure, 10 minutes and 30 minutes from the start. Other parameter evaluated were patient’s level of consciousness, quality of the procedure, major and minor complications, adequate recovery of the waking state. Sixteen patients were enrolled, 12 males and 4 females aged between 2 days of life and 7 years. Laryngomalacia tracheomalacia, tracheoesophageal fistula, and congenital airway malformations were the most frequent diseases. As for vital signs: the HR has gone from an average value of 133.4 ± 16.26 bpm at T0 to an average value of 129.3 ± 16.55 bpm at T10 and 133.7 ± 17.35 bpm at T30; PAS and PAD had not significant variations. Among drugs available for the fibroscopic examinations, the combined use of intravenous midazolam 0.2 mg/kg and ketamine 2 mg/kg is safe and well tolerated, reducing the anxiety associated with the examination, without major complications. The current literature is lacking in studies that have included such small and low weight patients. It would be interesting to make a comparison between various sedation techniques in order to identify

Botulism is a neuroparalytic syndrome caused by a neurotoxin produced by Clostridium botulinum. We describe a patient with neurological symptoms associated with intoxication by Clostridium botulinum and infection by SARSCoV2. This report underlines that it is mandatory, even in case of SARS-CoV-2 positivity, to investigate all the causes of a clinical pattern.

Since the 1980s, the development of a pharmacology based on nerve growth factor (NGF) has been postulated for the therapy of Alzheimer’s disease (AD). This hypothesis was based on the rescuing effect of the neurotrophin on the cholinergic phenotype of the basal forebrain neurons, primarily compromised during the development of AD. Subsequently, the use of NGF was put forward to treat a broader spectrum of neurological conditions affecting the central nervous system, such as Parkinson’s disease, degenerative retinopathies, severe brain traumas and neurodevelopmental dysfunctions. While supported by solid rational assumptions, the progress of a pharmacology founded on these hypotheses has been hampered by the difficulty of conveying NGF towards the brain parenchyma without resorting to invasive and risky delivery methods. At the end of the last century, it was shown that NGF administered intranasally to the olfactory epithelium was able to spread into the brain parenchyma. Notably, after such delivery, pharmacologically relevant concentration of exogenous NGF was found in brain areas located at considerable distances from the injection site along the rostral-caudal axis. These observations paved the way for preclinical characterization and clinical trials on the efficacy of intranasal NGF for the treatment of neurodegenerative diseases and of the consequences of brain trauma. In this review, a summary of the preclinical and clinical studies published to date will be attempted, as well as a discussion about the mechanisms underlying the efficacy and the possible development of the pharmacology based on intranasal conveyance of NGF to the brain.

Background: Suspending ordinary care activities during the COVID-19 pandemic made it necessary to find alternative routes to comply with care recommendations not only for acute health needs but also for patients requiring follow-up and multidisciplinary visits. We present the ‘Contactless’ model, a comprehensive operational tool including a plurality of services delivered remotely, structured according to a complexity gradient, aimed to cover diagnostic procedures and monitor disease progression in chronic pediatric patients. Methods: A multidisciplinary and multiprofessional project team was recruited, in collaboration with patients’ associations, to map a panel of available Evidence-Based solutions and address individual needs in full respect of the concept of personalized medicine. The solutions include a number of services from videoconsultations to more structure videotraining sessions. Results: A modular framework made up of four three Macro-levels of complexity - Contactless Basic, Intermediate and Advanced - was displayed as an incremental set of services and operational planning establishing each phase, from factors influencing eligibility to the delivery of the most accurate and complex levels of care. Conclusion: The multimodal, multidisciplinary ‘Contactless’ model allowed the inclusion of all Units of our Pediatric Department and families with children with disability or complex chronic conditions. The strengths of this project rely on its replicability outside of pediatrics and in the limited resources needed to practically impact patients, caregivers and professionals involved in the process of care. Its implementation in the future may contribute to reduce the duration of hospital admissions, money and parental absence from work.

OBJECTIVE: Probiotics are living microorganisms that, when administered per os in adequate amounts, may confer a health benefit on the host by the regularization of an unbalanced gastroenteric microbiota. The objective of this study was to evaluate treatment effectiveness, safety, and palatability of a probiotic’s combination (Lactobacillus reuteri LRE02-DSM 23878 and Lactobacillus rhamnosus LR04-DSM 16605) in a pediatric Emergency Department setting with functional gastrointestinal disorders. PATIENTS AND METHODS: Three groups were enrolled: children with functional abdominal pain; children with gastroenteritis; children with gas colic. Self-reporting sheets were delivered to each patient/parent after probiotics treatment. The primary outcome was to evaluate the evolution of clinical conditions in enrolled children. RESULTS: The outcomes showed a statistical difference among children treated with probiotics and those who did not. In the functional abdominal pain group, 58.2% of patients had a moderate symptoms improvement and 33.5% had a complete disappearance of symptoms, while in the gas colic group, 68.2% of the infants had a moderate improvement and 23.2% had a complete resolution. In the gastroenteritis group, stool consistency and number of evacuations improved in children who took probiotic administration as well. CONCLUSIONS: Probiotics therapy, at the recommended dosage of five drops per day for 15 days, is associated with symptoms improvement. Moreover, the use of probiotics led to a stool consistency’s normalization in a shorter time, evaluated with BSS. A randomized trial is needed to confirm these results.

Background: Observation Units (OU), as part of emergency department (ED), are areas reserved for short-term treatment or observation of patients with selected diagnoses to determine the need for hospitalization or home referral. Methods: In this retrospective cohort study, we analyzed similarities and differences of children admitted to the pediatric ED of the Fondazione Policlinico Universitario A. Gemelli IRCCS hospital in the first 2 years of OU activity, analyzing general patient characteristics, access modalities, diagnosis, triage, laboratory and instrumental examinations, specialist visits, outcome of OU admission and average time spent in OU. Furthermore, we compared total numbers and type of hospitalization of the first 2 years of OU activity with those of previous 2 years. Results: The most frequent diagnoses were abdominal pain, minor head injury without loss of consciousness, vomiting, epilepsy and acute bronchiolitis. The most performed laboratory examinations were blood count. The most commonly performed instrumental examination was abdominal ultrasound. Neurological counseling was the most commonly requested. Average time spent in OU was 13 h in 2016 and 14.1 h in 2017. Most OU admissions did not last longer than 24 h (90.5% in 2016 and 89.5% in 2017). In the years 2014–2015, 13.4% of pediatric patients accessing the ED were hospitalized, versus 9.9% the years 2016–2017 reducing pediatric hospital admissions by 3.6% (p < 0.001). Conclusions: This study demonstrate that OU is a valid alternative to ordinary wards for specific pathologies. In accordance with the literature, our study showed that, in the first 2 years of the OU activity, admissions to hospital ward decreased compared with the previous 2 years with an increase of complex patients.

Acute pain is one of the most common symptoms in children admitted to the Pediatric Emergency Department (PED) and its management represents a real clinical challenge for pediatricians. Different painful procedures can be very stressful for young children and their perception of pain can be enhanced by emotional factors, such as anxiety, distress, or anger. Adequate procedural sedation reduces anxiety and emotional trauma for the patient, but it reduces also stress for operators and the time for procedures. We have reviewed the literature on this topic and the drugs covered in these papers were: midazolam, fentanyl, ketamine, and dexmedetomidine. There are several routes of administering for these drugs to provide analgesia and anxiolysis to children: oral, parenteral, or intranasal (IN). Intravenous (IV) sedation, since it involves the use of needles, can be stressful; instead, IN route is a non-invasive procedure and generally well tolerated by children and it has become increasingly widespread. Some medications can be administered by a mucosal atomizer device (MAD) or by drops. The benefits of the atomized release include less drug loss in the oropharynx, higher cerebrospinal fluid levels, better patient acceptability, and better sedative effects. IN midazolam has a sedative, anxiolytic and amnesic effect, but without analgesic properties. Fentanyl and ketamine are mainly used for pain control. Dexmedetomidine has anxiolytic and analgesic properties. In conclusion, IN analgo-sedation is a simple, rapid and painless option to treat pain and anxiety in the PED requiring brief training on the administration process and experience in sedation.

BackgroundVery few studies describe factors associated with COVID-19 diagnosis in children.AimWe here describe characteristics and risk factors for COVID-19 diagnosis in children tested in 20 paediatric centres across Italy.MethodsWe included cases aged 0-18 years tested between 23 February and 24 May 2020. Our primary analysis focused on children tested because of symptoms/signs suggestive of COVID-19.ResultsAmong 2,494 children tested, 2,148 (86.1%) had symptoms suggestive of COVID-19. Clinical presentation of confirmed COVID-19 cases included besides fever (82.4%) and respiratory signs or symptoms (60.4%) also gastrointestinal (18.2%), neurological (18.9%), cutaneous (3.8%) and other unspecific influenza-like presentations (17.8%). In multivariate analysis, factors significantly associated with SARS-CoV-2 positivity were: exposure history (adjusted odds ratio (AOR): 39.83; 95% confidence interval (CI): 17.52-90.55; p < 0.0001), cardiac disease (AOR: 3.10; 95% CI: 1.19-5.02; p < 0.0001), fever (AOR: 3.05%; 95% CI: 1.67-5.58; p = 0.0003) and anosmia/ageusia (AOR: 4.08; 95% CI: 1.69-9.84; p = 0.002). Among 190 (7.6%) children positive for SARS-CoV-2, only four (2.1%) required respiratory support and two (1.1%) were admitted to intensive care; all recovered.ConclusionRecommendations for SARS-CoV-2 testing in children should consider the evidence of broader clinical features. Exposure history, fever and anosmia/ageusia are strong risk factors in children for positive SARS-CoV-2 testing, while other symptoms did not help discriminate positive from negative individuals. This study confirms that COVID-19 was a mild disease in the general paediatric population in Italy. Further studies are needed to understand risk, clinical spectrum and outcomes of COVID-19 in children with pre-existing conditions.

Neurotrophins are a family of proteins that support neuronal proliferation, survival, and differentiation in the central and peripheral nervous systems, and are regulators of neuronal plasticity. Nerve growth factor is one of the best-described neurotrophins and has advanced to clinical trials for treatment of ocular and brain diseases due to its trophic and regenerative properties. Prior trials over the past few decades have produced conflicting results, which have principally been ascribed to adverse effects of systemic nerve growth factor administration, together with poor penetrance of the blood-brain barrier that impairs drug delivery. Contrastingly, recent studies have revealed that topical ocular and intranasal nerve growth factor administration are safe and effective, suggesting that topical nerve growth factor delivery is a potential alternative to both systemic and invasive intracerebral delivery. The therapeutic effects of local nerve growth factor delivery have been extensively investigated for different ophthalmic diseases, including neurotrophic keratitis, glaucoma, retinitis pigmentosa, and dry eye disease. Further, promising pharmacologic effects were reported in an optic glioma model, which indicated that topically administered nerve growth factor diffused far beyond where it was topically applied. These findings support the therapeutic potential of delivering topical nerve growth factor preparations intranasally for acquired and degenerative brain disorders. Preliminary clinical findings in both traumatic and non-traumatic acquired brain injuries are encouraging, especially in pediatric patients, and clinical trials are ongoing. The present review will focus on the therapeutic effects of both ocular and intranasal nerve growth factor delivery for diseases of the brain and eye.

Background: Placement of central venous access devices is a clinical procedure associated with some risk of adverse events and with a relevant cost. Careful choice of the device, appropriate insertion technique, and proper management of the device are well-known strategies commonly adopted to achieve an optimal clinical result. However, the environment where the procedure takes place may have an impact on the overall outcome in terms of safety and cost-effectiveness. Methods: We carried out a retrospective analysis on pediatric patients scheduled for a major neurosurgical operation, who required a central venous access device in the perioperative period. We divided the patients in two groups: in group A the central venous access device was inserted in the operating room, while in group B the central venous access device was inserted in the sedation room of our Pediatric Intensive Care Unit. We compared the two groups in terms of safety and cost-effectiveness. Results: We analyzed 47 central venous access devices in 42 children. There were no insertion-related complications. Only one catheter-related bloodstream infection was recorded, in group A. However, the costs related to central venous access device insertion were quite different: €330–€540 in group A versus €105–€135 in group B. Conclusion: In the pediatric patient candidate to a major neurosurgical operation, preoperative insertion of the central venous access device in the sedation room rather than in the operating room is less expensive and equally safe.

Background: Placement of central venous access devices is a clinical procedure associated with some risk of adverse events and with a relevant cost. Careful choice of the device, appropriate insertion technique, and proper management of the device are well-known strategies commonly adopted to achieve an optimal clinical result. However, the environment where the procedure takes place may have an impact on the overall outcome in terms of safety and cost-effectiveness. Methods: We carried out a retrospective analysis on pediatric patients scheduled for a major neurosurgical operation, who required a central venous access device in the perioperative period. We divided the patients in two groups: in group A the central venous access device was inserted in the operating room, while in group B the central venous access device was inserted in the sedation room of our Pediatric Intensive Care Unit. We compared the two groups in terms of safety and cost-effectiveness. Results: We analyzed 47 central venous access devices in 42 children. There were no insertion-related complications. Only one catheter-related bloodstream infection was recorded, in group A. However, the costs related to central venous access device insertion were quite different: €330–€540 in group A versus €105–€135 in group B. Conclusion: In the pediatric patient candidate to a major neurosurgical operation, preoperative insertion of the central venous access device in the sedation room rather than in the operating room is less expensive and equally safe.

BackgroundFluid resuscitation is the standard treatment to restore circulating blood volume and pressure after massive haemorrhage and shock. Packed red blood cells (PRBC) are transfused to restore haemoglobin levels. Restoration of microcirculatory flow and tissue oxygen delivery is critical for organ and patient survival, but these parameters are infrequently measured. Patient Blood Management is a multidisciplinary approach to manage and conserve a patient’s own blood, directing treatment options based on broad clinical assessment beyond haemoglobin alone, for which tissue perfusion and oxygenation could be useful. Our aim was to assess utility of non-invasive tissue-specific measures to compare PRBC transfusion with novel crystalloid treatments for haemorrhagic shock.MethodsA model of severe haemorrhagic shock was developed in an intensive care setting, with controlled haemorrhage in sheep according to pressure (mean arterial pressure 30–40 mmHg) and oxygen debt (lactate 4 mM) targets. We compared PRBC transfusion to fluid resuscitation with either PlasmaLyte or a novel crystalloid. Efficacy was assessed according to recovery of haemodynamic parameters and non-invasive measures of sublingual microcirculatory flow, regional tissue oxygen saturation, repayment of oxygen debt (arterial lactate), and a panel of inflammatory and organ function markers. Invasive measurements of tissue perfusion, oxygen tension and lactate levels were performed in brain, kidney, liver, and skeletal muscle. Outcomes were assessed during 4 h treatment and post-mortem, and analysed by one- and two-way ANOVA.ResultsEach treatment restored haemodynamic and tissue oxygen delivery parameters equivalently (p 0.05), despite haemodilution after crystalloid infusion to haemoglobin concentrations below 70 g/L (p 0.001). Recovery of vital organ-specific perfusion and oxygen tension commenced shortly before non-invasive measures improved. Lactate declined in all tissues and correlated with art

BackgroundFluid resuscitation is the standard treatment to restore circulating blood volume and pressure after massive haemorrhage and shock. Packed red blood cells (PRBC) are transfused to restore haemoglobin levels. Restoration of microcirculatory flow and tissue oxygen delivery is critical for organ and patient survival, but these parameters are infrequently measured. Patient Blood Management is a multidisciplinary approach to manage and conserve a patient’s own blood, directing treatment options based on broad clinical assessment beyond haemoglobin alone, for which tissue perfusion and oxygenation could be useful. Our aim was to assess utility of non-invasive tissue-specific measures to compare PRBC transfusion with novel crystalloid treatments for haemorrhagic shock.MethodsA model of severe haemorrhagic shock was developed in an intensive care setting, with controlled haemorrhage in sheep according to pressure (mean arterial pressure 30–40 mmHg) and oxygen debt (lactate 4 mM) targets. We compared PRBC transfusion to fluid resuscitation with either PlasmaLyte or a novel crystalloid. Efficacy was assessed according to recovery of haemodynamic parameters and non-invasive measures of sublingual microcirculatory flow, regional tissue oxygen saturation, repayment of oxygen debt (arterial lactate), and a panel of inflammatory and organ function markers. Invasive measurements of tissue perfusion, oxygen tension and lactate levels were performed in brain, kidney, liver, and skeletal muscle. Outcomes were assessed during 4 h treatment and post-mortem, and analysed by one- and two-way ANOVA.ResultsEach treatment restored haemodynamic and tissue oxygen delivery parameters equivalently (p 0.05), despite haemodilution after crystalloid infusion to haemoglobin concentrations below 70 g/L (p 0.001). Recovery of vital organ-specific perfusion and oxygen tension commenced shortly before non-invasive measures improved. Lactate declined in all tissues and correlated with art

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Background: Although children with special health care needs (CSHCN) represent a minority of the population, they go through more hospitalizations, more admissions to the Emergency Department (ED), and receive a major number of medical prescriptions, in comparison to general pediatric population. Objectives of the study were to determine the reasons for admission to the ED in Italian CSHCN, and to describe the association between patient’s demographic data, clinical history, and health services requirements. Methods: Ad hoc web site was created to collect retrospective data of 3479 visits of CSHCN to the ED in 58 Italian Hospitals. Results: Seventy-two percent of patients admitted to ED were affected by a previously defined medical condition. Most of the ED admissions were children with syndromic conditions (54%). 44.2% of the ED admissions were registered during the night-time and/or at the weekends. The hospitalization rate was of 45.6% among patients admitted to the ED. The most common reason for admission to the ED was the presence of respiratory symptoms (26.6%), followed by gastrointestinal problems (21.3%) and neurological disorders (18.2%). 51.4% of the access were classified as ‘urgent’, with a red/yellow triage code. Considering the type of ED, 61.9% of the visits were conducted at the Pediatric EDs (PedEDs), 33.5% at the Functional EDs (FunEDs) and 4.6% at the Dedicated EDs (DedEDs). Patients with more complex clinical presentation were more likely to be evaluated at the PedEDs. CSHCN underwent to a higher number of medical procedures at the PedEDs, more in comparison to other EDs. Children with medical devices were directed to a PedED quite exclusively when in need for medical attention. Subjects under multiple anti-epileptic drug therapy attended to PedEDs or FunEDs generally. Patients affected by metabolic diseases were more likely to look for medical attention at FunEDs. Syndromic patients mostly required medical attention at the DedEDs. Conclusions

OBJECTIVE: A computerized system of telephone consultation has been experimented at the Pediatric Emergency Department (ED) of Policlinico Gemelli Hospital in Rome during the outbreak of Coronavirus Disease 2019 (COVID-19). MATERIALS AND METHODS: Twenty monothematic items with a series of questions to evaluate child’s clinical conditions have been set up in order to evaluate the different situations according to their severity. All items were highlighted according to conventional scores corresponding to the different answers (yes/no) given by the child’s parents. This system has been implemented with large diffusion of computer programs and applications by the availability of a computer station in every ED room. RESULTS: The system allows healthcare workers to establish the medical check-up urgency which may be immediate, within the next 24 hours or scheduled in the pediatric ward. Therefore, it has been implemented a telephone triage consultation with a standardized method. CONCLUSIONS: Telephone consultation during outbreaks, considering the risks of contagion, allows healthcare workers to decrease the concern of families and to reduce indiscriminate access to ED. The remote approach will not solve logistic and setting problems related to COVID-19 outbreak17, but it would be a valid tool to improve medical evaluation without deep change in infrastructure and clinical organization.

The unexpected outbreak of Corona Virus Disease 19 had several consequences worldwide and on the Italian Health System. We report our experience in the reorganization of our Pediatric Department to prevent the risk of infection for both children and staff. We strongly believe that the need to face an unpredictable emergency situation should not affect the quality of the assistance to the non-Corona Virus Disease patients.

Background: Although children with special health care needs (CSHCN) represent a minority of the population, they go through more hospitalizations, more admissions to the Emergency Department (ED), and receive a major number of medical prescriptions, in comparison to general pediatric population. Objectives of the study were to determine the reasons for admission to the ED in Italian CSHCN, and to describe the association between patient’s demographic data, clinical history, and health services requirements. Methods: Ad hoc web site was created to collect retrospective data of 3479 visits of CSHCN to the ED in 58 Italian Hospitals. Results: Seventy-two percent of patients admitted to ED were affected by a previously defined medical condition. Most of the ED admissions were children with syndromic conditions (54%). 44.2% of the ED admissions were registered during the night-time and/or at the weekends. The hospitalization rate was of 45.6% among patients admitted to the ED. The most common reason for admission to the ED was the presence of respiratory symptoms (26.6%), followed by gastrointestinal problems (21.3%) and neurological disorders (18.2%). 51.4% of the access were classified as ‘urgent’, with a red/yellow triage code. Considering the type of ED, 61.9% of the visits were conducted at the Pediatric EDs (PedEDs), 33.5% at the Functional EDs (FunEDs) and 4.6% at the Dedicated EDs (DedEDs). Patients with more complex clinical presentation were more likely to be evaluated at the PedEDs. CSHCN underwent to a higher number of medical procedures at the PedEDs, more in comparison to other EDs. Children with medical devices were directed to a PedED quite exclusively when in need for medical attention. Subjects under multiple anti-epileptic drug therapy attended to PedEDs or FunEDs generally. Patients affected by metabolic diseases were more likely to look for medical attention at FunEDs. Syndromic patients mostly required medical attention at the DedEDs. Conclusions

The unexpected outbreak of Corona Virus Disease 19 had several consequences worldwide and on the Italian Health System. We report our experience in the reorganization of our Pediatric Department to prevent the risk of infection for both children and staff. We strongly believe that the need to face an unpredictable emergency situation should not affect the quality of the assistance to the non-Corona Virus Disease patients.

No abstract available

Chest pain is a common cause to admission to the pediatric emergency department and often leads to an extensive cardiac evaluation. The objective of this study was to evaluate the usefulness of the troponin (TN) plasma level determination in the initial phase of the differential diagnosis of chest pain in children. This is a retrospective observational study on 107 patients, aged 0 to 19 years, admitted for chest pain to the pediatric emergency department of our institution. Demographics, clinical data, and patient outcomes were analyzed. Troponin values of >0.03 ng/mL but <0.1 ng/mL were considered suspected for cardiac pathology, whereas levels of >0.1 ng/mL were indicative of cardiac pathology. In these latter patients, an echocardiographic examination was also performed. Only 99 patients were evaluated with electrocardiogram (ECG). In 91 of 99 patients of our series, both TN determination and ECG recording were performed. Troponin was higher than the cutoff value (0.03 ng/mL) in 9 patients (9.1%). Only 2 of the 9 patients who presented high TN values showed a nonpathological ECG, whereas 16 (17.5%) of 91 patients in whom both ECG and TN determination were performed had ECG abnormalities without a simultaneous elevation of TN. Of the 26 patients who had medical history and suggestive targets of cardiac pathology, only in 6 (23.1%) of them the diagnosis was confirmed. The final diagnosis of the 99 patients was idiopathic chest pain in 45.4% of cases. Conclusions: Even with the low cost and the relatively easiness for the plasma level determination, TN should be measured only in children with chest pain associated to familiar history suggestive of cardiovascular disease and/or clinical symptoms and/or ECG alterations.