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BackgroundThe study of women exposures and child outcomes occurring in the first 1,000 days of life since conception enhances understanding of the relationships between environmental factors, epigenetic changes, and disease development, extending beyond childhood and spanning the entire lifespan. Generation Gemelli is a recently launched case-control study that enrolls mother-newborns pairs in one of the largest university hospitals in Italy, in order to examine the association between maternal environmental exposures and intrauterine growth restriction (IUGR) and the risk of premature birth. The study will also evaluate the association of maternal exposures and the health and growth of infants and children up to 24 months of age.MethodsThe study entails the set-up of a case-control study within a birth cohort. With approximately 4,000 annual deliveries, we aim to enroll 140 cases (newborns with IUGR and premature birth) and 280 controls per year, from September 2022. A comprehensive questionnaire will be used to gather information about various types of maternal environmental exposures before and during pregnancy. We will collect biological samples from both mothers and newborns (including vaginal swab, placenta sample, blood, saliva, meconium, and bronchoalveolar lavage fluid) at birth and within the early hours of the newborn's life. We will perform laboratory examinations including dosage of heavy metals and essential elements, investigation of placental distress and fetal brain damage of biomarkers, analysis of microbiota and of DNA methylation profile. We will conduct clinical follow-up assessments in both cases and controls at months 12 and 24 and we will collect anthropometric data, feeding types with particular reference to breastfeeding and its duration, pediatric emergency room visits, hospitalizations, medication usage, known allergies, and neuropsychological development.DiscussionThe Generation Gemelli case-control study holds the promise of significantly enhancing our comprehension of how maternal environmental exposures relate to the health of children and the broader population. The study of the exposome will provide insights into the relationships between environmental exposures, epigenetic changes and health outcomes during the first 1000 days of life and onward.

Virtual reality (VR) represents an innovative and effective tool for reducing pain and anxiety in children undergoing painful procedures in pediatric emergency departments and burn units. VR has the ability to modulate both the sensory and emotional components of pain by immersing children in a virtual world, effectively diverting their attention from the painful experience. Specifically, VR distraction competes for the patient’s attentional resources, reducing their focus on the painful stimulus and, consequently, diminishing the perception of pain. The primary objective of this review was to assess and summarize the current knowledge regarding the use of VR for painful procedures in pediatric emergency and burn units by comparing and analyzing the existing literature. Of the 340 articles reviewed, 25 met the selection criteria and were included in the analysis. These studies examined the use of VR in venous procedures (such as venipuncture, cannulation, and blood sampling) as well as other procedures, including laceration repair and burn wound care. The findings indicated that 20 studies reported a reduction in pain scores, while 9 studies noted a reduction in anxiety scores. Additionally, three studies demonstrated a reduction in procedural time. Overall, the studies supported the efficacy, safety, and feasibility of VR in managing procedural pain and anxiety in pediatric settings. Furthermore, VR use contributed to a reduction in parental and medical stress levels, as well as a decrease in the time spent in the pediatric emergency room. Studies involving larger sample sizes may provide further evidence of VR’s effectiveness across different procedures and age groups.

An advisory committee of Italian experts conducted a national, cross-sectional, web-based survey in June 2024 to describe the current management of fever and associated symptoms in different settings, including primary care, emergency departments, and hospital wards in pediatric and adult patients. The survey covered two domains: participants’ features and questions about the main drugs prescribed to treat fever and associated symptoms. A total of 832 questionnaires were analyzed. Paracetamol was the most prescribed drug to treat fever. Most participants were influenced by related symptoms when choosing the most appropriate drug. Almost all participants selected the oral route as their preferred one. This survey provides a current state of fever management among physicians in different settings throughout Italy. It highlights a trend in treating fever with antipyretics at appropriate doses and evaluating pain through validated scales.

Introduction: Traumatic brain injury (TBI) in pediatric population is responsible for significant mortality and morbidity, particularly among children aged 0–4 and young adults aged 15–24. The developing brain’s unique characteristics may increase vulnerability to injuries, potentially leading to long-term cognitive and motor deficits. Current therapeutic options for neuronal regeneration post-TBI are limited, although neurotrophins, especially nerve growth factor (NGF), show promise in enhancing recovery. NGF can mitigate excitotoxicity and promote neuroprotection, particularly by intranasal administration, which is attractive because of its non-invasive nature. Case Presentation: A three-year-old boy suffered from severe TBI due to a car accident, leading to multiple complications, including a basilar skull fracture and cerebral venous sinus thrombosis. Initial assessments revealed significant neurological impairments. After intensive care and rehabilitation, the child exhibited gradual improvements in consciousness and motor functions but continued to face challenges, particularly with left-sided hemiparesis. Nine months post-injury, he began intranasal administration of human-recombinant NGF (hr-NGF) as part of a clinical trial. Discussion: Following hr-NGF treatment, the child demonstrated notable advancements in motor function, achieving independent standing and walking. Cognitive assessments indicated improvements in various domains, including verbal comprehension and executive functioning. EEG results showed reduced epileptiform activity. These findings suggest that hr-NGF may facilitate recovery in pediatric TBI cases by enhancing both motor and cognitive outcomes. Conclusions: This case highlights the potential role of intranasal hr-NGF administration as a therapeutic strategy for improving neurological recovery in children with severe TBI. The positive clinical outcomes support further exploration of NGF as a viable treatment option to mitigate long-term sequelae associated with pediatric brain injuries.

Background/Objectives: The anteroposterior renal pelvis diameter (APRPD) is used to assess the grade of urinary tract dilatation (UTD). There is no univocal method stratifying the risk of complications related to postnatal UTD. This study aims to identify APRPD cut-offs at birth to determine outcome stratification and second-level exams. Methods: The records of a cohort of newborns with unilateral or bilateral UTD confirmed or detected by ultrasound after birth between 2010 and 2020 were analyzed. These children underwent further examinations at 3, 6, 12, and 24 months of age. Results: We managed 500 children with postnatal UTD, with a median APRPD at 0–2 months of age of 7.7 mm [IQR 6.0–10.0]. As for UTD resolution, 279 (55.8%) patients had a complete resolution at the age of 6 months; an additional 55, for a total of 344 (68.8%), at 9–12 months; and 19, for a total of 353 (70.6%), at 24 months. An APRPD value ≤ 8.5 mm showed a sensitivity of 80.4% (95% CI [76.0–84.4]) and a specificity of 100.0% (95% CI [76.8–100.0]) in identifying candidates for spontaneous resolution within 24 months of life. An APRPD value ≤ 8.5 mm was also an independent prognostic factor of resolution at the age of 24 months (p = 0.000). Conclusions: Isolated hydronephrosis is the most frequent urinary tract abnormality detected in pregnancy. A well-structured prenatal and postnatal management plan is indeed necessary. According to our analyses, 8.5 mm can be used as a cut-off to reassure parents and clinicians of the benignity of the postnatal dilatation.

Abstract Background Severe 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. Methods Children 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. Results Three 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 of their neurological scores. No side effects were reported. Conclusion These promising results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from severe TBI and in patients with better baseline neurological conditions, to explore more thoroughly the benefits of this new approach on neuronal function recovery after traumatic brain damage.

Nerve growth factor (NGF) is a neurotrophic peptide largely revealed for its ability to regulate the growth and survival of peripheral sensory, sympathetic, and central cholinergic neurons. The pro-survival and regenerative properties of neurotrophic factors propose a therapeutic potential in a wide range of brain diseases, and NGF, in particular, has appeared as an encouraging potential treatment. In this review, a summary of clinical studies regarding NGF and its therapeutic effects published to date, with a specific interest in the pediatric context, will be attempted. NGF has been studied in neurological disorders such as hypoxic–ischemic encephalopathy, traumatic brain injury, neurobehavioral and neurodevelopmental diseases, congenital malformations, cerebral infections, and in oncological and ocular diseases. The potential of NGF to support neuronal survival, repair, and plasticity in these contexts is highlighted. Emerging therapeutic strategies for NGF delivery, including intranasal administration as well as advanced nanotechnology-based methods, are discussed. These techniques aim to enhance NGF bioavailability and target specificity, optimizing therapeutic outcomes while minimizing systemic side effects. By synthesizing current research, this review underscores the promise and challenges of NGF-based therapies in pediatric neurology, advocating for continued innovation in delivery methods to fully harness NGF’s therapeutic potential.

Abstract Background Out-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. Results Three 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. Conclusions These promising preliminary results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from OHCA and in patients with better baseline neurological conditions, in order to explore more thoroughly the benefits of this new approach on neuronal function recovery after OHCA.

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.

Sepsis is a life-threatening condition that affects 1.2 million children annually. Although there are several criteria for diagnosing this condition, signs are often nonspecific, and identifying sepsis is challenging. In this context, presepsin (P-SEP) seems to be a promising new biomarker since its plasma levels increase earlier than other sepsis-related proteins and its measurement is faster. We enrolled 157 minors who presented to the Pediatric Emergency Department of Agostino Gemelli Hospital with fever and suspected sepsis. Biochemical, anamnestic, and clinical data were collected. Viral agents were identified as the causative factor in 64 patients, who had an average P-SEP value of 309.04 pg/mL (SD ± 273.2), versus an average P-SEP value of 526.09 pg/mL (SD ± 657) found in 27 bacterial cases (p value: 0.0398). Four cases of overt sepsis had an average P-SEP value of 3328.5 pg/mL (SD ± 1586.6). The difference in P-SEP levels in viral versus bacterial infections was found to be statistically significant; therefore, P-SEP may have a central role in the evaluation of febrile children, helping clinicians distinguish between these two etiologies. Furthermore, amongst the cases of confirmed sepsis, P-SEP was always greater than 2000 pg/mL, while C-reactive protein and procalcitonin values appeared lower than what was considered significant.

The dawn of Artificial intelligence (AI) in healthcare stands as a milestone in medical innovation. Different medical fields are heavily involved, and pediatric emergency medicine is no exception. We conducted a narrative review structured in two parts. The first part explores the theoretical principles of AI, providing all the necessary background to feel confident with these new state-of-the-art tools. The second part presents an informative analysis of AI models in pediatric emergencies. We examined PubMed and Cochrane Library from inception up to April 2024. Key applications include triage optimization, predictive models for traumatic brain injury assessment, and computerized sepsis prediction systems. In each of these domains, AI models outperformed standard methods. The main barriers to a widespread adoption include technological challenges, but also ethical issues, age-related differences in data interpretation, and the paucity of comprehensive datasets in the pediatric context. Future feasible research directions should address the validation of models through prospective datasets with more numerous sample sizes of patients. Furthermore, our analysis shows that it is essential to tailor AI algorithms to specific medical needs. This requires a close partnership between clinicians and developers. Building a shared knowledge platform is therefore a key step.

Intense changes in mineral and bone metabolism are frequent in chronic kidney disease (CKD) and represent an important cause of morbidity and reduced quality of life. These disorders have conventionally been defined as renal osteodystrophy and classified based on bone biopsy, but due to a lack of bone biopsy data and validated radiological methods to evaluate bone morphology in children, it has been challenging to effectively assess renal osteodystrophy in pediatric CKD; the consequence has been the suboptimal management of bone disorders in children. CKD–mineral and bone disorder (CKD-MBD) is a new expression used to describe a systemic disorder of mineral and bone metabolism as a result of CKD. CKD-MBD is a triad of biochemical imbalances in calcium, phosphate, parathyroid hormone, and vitamin D; bone deformities and soft tissue calcification. This literature review aims to explore the pathogenesis, diagnostic approach, and treatment of CKD-MBD in children and the effects of renal osteodystrophy on growing skeleton, with a specific focus on the biological basis of this peculiar condition.

Abstract 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.

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.

Abstract 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

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.

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.

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.

Objective Understanding how paediatric emergency departments (PEDs) across Europe adapted their healthcare pathways in response to COVID-19 will help guide responses to ongoing waves of COVID-19 and potential future pandemics. This study aimed to evaluate service reconfiguration across European PEDs during the initial COVID-19 wave.Design This cross-sectional survey included 39 PEDs in 17 countries. The online questionnaire captured (1) study site characteristics, (2) departmental changes and (3) pathways for children with acute illness pre and during the first wave of COVID-19 pandemic (January–May 2020). Number of changes to health services, as a percentage of total possible changes encompassed by the survey, was compared with peak national SARS-CoV-2 incidence rates, and for both mixed and standalone paediatric centres.Results Overall, 97% (n=38) of centres remained open as usual during the pandemic. The capacity of 18 out of 28 (68%) short-stay units decreased; in contrast, 2 units (7%) increased their capacity. In 12 (31%) PEDs, they reported acting as receiving centres for diverted children during the pandemic.There was minimal change to the availability of paediatric consultant telephone advice services, consultant supervision of juniors or presence of responsible specialists within the PEDs.There was no relationship between percentage of possible change at each site and the peak national SARS-CoV-2 incidence rate. Mixed paediatric and adult hospitals made 8% of possible changes and standalone paediatric centres made 6% of possible changes (p=0.086).Conclusion Overall, there was limited change to the organisation or delivery of services across surveyed PEDs during the first wave of the COVID-19 pandemic.

While the clinical impact of COVID-19 on adults has been massive, the majority of children develop pauci-symptomatic or even asymptomatic infection and only a minority of the latter develop a fatal outcome. The reasons of such differences are not yet established. We examined cytokines in sera and Th and B cell subpopulations in peripheral blood mononuclear cells (PBMC) from 40 children (+ children as compared to adult patients, the expression of other pro-inflammatory cytokines such as IFNγ and TNFα directly correlated with early age infection and symptoms. Th and B cell subsets were modified during pediatric infection differently with respect to adult patients and controls and within the pediatric group based on age. Low levels of IgD− CD27+ memory B cells correlated with absent/mild symptoms. On the contrary, high levels of FoxP3+/CD25high T-Regs associated with a moderate–severe clinical course in the childhood. These T and B cells subsets did not associate with severity in infected adults, with children showing a predominant expansion of immature B lymphocytes and natural regulatory T cells. This study shows differences in immunopathology of SARS-CoV-2 infection in children compared with adults. Moreover, these data could provide information that can drive vaccination endpoints for children.

Ingestion of foreign bodies is a frequent pediatric cause of access to the Emergency Department (ED). The aim of this study was to determine the epidemiological and clinical features of pediatric patients with a diagnosis of foreign body ingestion and to identify the factors associated with an urgent invasive procedure or hospitalization. This is a retrospective study conducted on a population of 286 pediatric patients (0–17 years) evaluated for foreign body ingestion at the Pediatric ED of “Fondazione Policlinico Universitario A. Gemelli, IRCSS” between October 2014 and June 2019. Data concerning age and gender, underlying diseases, type of foreign body, symptoms and signs, instrumental tests, specialist visits, treatment and outcome were analyzed. The majority of foreign bodies were coins (23%). Symptoms recurred in 50% of the foreign bodies with esophageal localization and between the 92 (32%) patients with symptoms the most common was vomiting (7%). X-rays was performed in 61% of patients. Among all patients, 253 patients (88.8%) had been discharged, 21 (7%) had been hospitalized, and four (1.4%) were sent to an outpatient facility. Besides, 17 (5.9%) patients had been transferred to the Observation Unit. Of the hospitalized patients (21 (7.3%)), clinical observation was performed for 57% and endoscopic procedure for 45%. Our data confirm that the ESPGHAN-ESGE guidelines application prevents interventions that are not necessary, avoiding diagnostic and therapeutic delays.

Abstract Background Pediatricians play a crucial role in the identification and management of child abuse and neglect (CAN) but they often don’t have a formal specialized training. Methods We analysed retrospectively data about patients, 0 - 18 years of age, victims of CAN between 1 April 2005 and 30 April 2015. The aim of the study was to evaluate the effect of a multidisciplinary educational program, “CAN: prevention strategies, individuation and treatment”, on the knowledge, case recognition, treatment and follow-up of physicians of Gemelli University Hospital in Rome, regarding physical, sexual abuse and neglect. This program, in 3 different editions biannually, respectively in May-July 2010, November-January 2012 and February-May 2014, was based on 4 sessions, each one of 2 days. Results Considering the number of victims of CAN between 2005 and 2015 we observed 66 cases of maltreatment. We divided the study population in 2 groups: group A, before the educational programs, patients evaluated from 1 April 2005 to 30 July 2010; group B, after the educational program from 1 August 2010 to 30 April 2015. We observed 23 children in group A and 43 children in group B with an improvement of 87%. Analyzing our data about sex, nationality, type of perpetrators, we found that: 37/66 (56%) of children were females compared to 29/66 (44%) males; 41/66 (62%) of children came from Italy compared to 25/66 (38%) of foreign children; 52/66 (79%) of the perpetrators of abuse were parents or family members compared to acquaintances 10/66 (15%) and to strangers 4/66 (6%). Conclusions Considering the prevalence of CAN, the need to develop clinically competent clinicians and the improving of residency education in child maltreatment is imperative. Improving the clinical skills of pediatricians to identify and evaluate CAN may lead to reduce morbidity and mortality of these children.

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.

Purpose This study aims to evaluate and compare the efficacy of exogenous melatonin associated with desmopressin (dDAVP) and dietary recommendations. Methods A total of 189 patients were enrolled from the Service of Pediatrics, Campus Bio-Medico University Hospital of Rome, from January 2013 to June 2015. Of the 189 original patients, 153 children, aged between 5 and 14 years (mean age, 8.7 years) were included in the study. After clinical evaluation and a 3-month period of observation without treatment, children were assigned to receive treatment in one of 3 groups: group 1, dDAVP at a dose of 120 mcg a day (Minirin); group 2, dDAVP at a dose of 120 mcg and dietary recommendations; or group 3, dDAVP at a dose of 120 mcg, dietary recommendations, and melatonin at a dose of 1 mg a day (Melamil plus). Each patient was treated for 3 months. Results After the 3 months of therapy, a desiderable response was achieved in 30 of 51 patients (58.82%) treated with dDAVP, 35 of 53 patients (66.04%) treated with dDAVP and dietary recommendations, and 35 of 49 patients (71.43%) treated with dDAVP, dietary recommendations, and melatonin. Conclusions Although not statistically significant, the results show that the association between dDAVP treatment with dietary recommendations and melatonin could be considered a safe and effective treatment of NE. Considering that the statistically insignificant results might be due to the small sample size, the study will be continued to increase the number of subjects.

Objectives Most children admitted to the emergency department (ED) require peripheral venous access (PVA), which is often difficult to perform or is unsuccessful. Ultrasound guidance helps with the placement of peripheral short cannulas (SC), but it has a limited cannula duration and a high risk of developing complications. The aim of this study was to compare success rates, dwell times and complications of peripheral venous long cannulas (LCs) inserted under ultrasound guidance with those of SCs in children.Methods We prospectively studied all children older than 10 years of age admitted to our paediatric ED requiring PVA for an expected therapy of more than 5 days. In children with difficult intravenous access (DIVA), after two unsuccessful attempts of ‘blind’ placement of SCs, LCs (20 G, 8 cm) were inserted in the deep veins of arms using ultrasound guidance and the direct Seldinger technique.Results LC placement (n=20) was successful in 100% of the cases. LC dwell time was 9.2±6.0 days, and most catheters were electively removed because they were no longer indicated. SC (n=20) placement showed a shorter dwell time duration, 3.2±2.1 days (p

Deoxynivalenol (DON) is a mycotoxin mainly produced by Fusarium graminearum that can contaminate cereals and cereal-based foodstuff. Urinary DON levels can be used as biomarker for exposure assessment purposes. This study assessed urinary DON concentrations in Italian volunteers recruited by age group, namely children, adolescents, adults, and the elderly. In addition, vulnerable groups, namely vegetarians and pregnant women, were included in the study. To determine the urinary DON, its glucuronide and de-epoxydated (DOM-1) forms, an indirect analytical approach was used, measuring free DON and total DON (as sum of free and glucuronides forms), before and after enzymatic treatment, respectively. Morning urine samples were collected on two consecutive days, from six different population groups, namely children, adolescent, adults, elderly, vegetarians and pregnant women. Total DON was measured in the 76% of the collected samples with the maximum incidences in children and adolescent age group. Urine samples from children and adolescent also showed the highest total DON levels, up to 17.0 ng/mgcreat. Pregnant women had the lowest positive samples per category (40% for day 1 and 43% for day 2, respectively), low mean levels of total DON (down to 2.84 ng/mgcreat) and median equal to 0 ng/mgcreat. Estimation of DON dietary intake reveals that 7.5% of the total population exceeds the TDI of 1 μg/kg bw/day set for DON, with children showing 40% of individuals surpassing this value (male, day 2).

Hypoxic-ischemic brain injuries (HIBI) in childhood are frequently associated with poor clinical and neurological outcome. Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement. Several neurotrophins, such as Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Glial Derived Neurotrophic Factor (GDNF), play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI. We report two cases of children with HIBI and prolonged comatose state who showed a significant improvement after intraventricular NGF administration characterized by amelioration of electroencephalogram (EEG) and cerebral perfusion at single-photon emission computed tomography (SPECT). The improvement in motor and cognitive functions of these children could be related to the neuroprotective role exerted by NGF in residual viable cholinergic neurons, leading to the restoration of neuronal networks in the damaged brain.

Background: To evaluate physical and mental health in children in foster care and comparison with general population.Methods: The study is carried out between September 2011 and April 2012 into nine group homes in Rome. It involved 112 children ranging in age 2-17 years, living in temporary care facilities or institutes. All data came out of clinical history and physical exams, validated by a pediatrician. Such data were being then compared with samples of general population.Results: Significant themes were high percentage of children with psychiatric disorders in foster care (22.3%); high percentage of psychiatric disorders diagnosed immediately while arriving at the foster care (56%); no significant differences in weight, height and BMI between children in foster care and general population; significant differences (P

The role of cytokines in relation to clinical manifestations, disease severity, and outcome of children with H1N1 virus infection remains thus far unclear. The aim of this study was to evaluate interleukin IL-1β and IL-6 plasma expressions and their association with clinical findings, disease severity, and outcome of children with H1N1 infection. We prospectively evaluated 15 children with H1N1 virus infection and 15 controls with lower respiratory tract infections (LRTI). Interleukin plasma levels were measured using immunoenzymatic assays. Significantly higher levels of IL-1β and IL-6 were detected in all patients with H1N1 virus infection compared to controls. It is noteworthy to mention that in H1N1 patients with more severe clinical manifestations of disease IL-1β and IL-6 expressions were significantly upregulated compared to H1N1 patients with mild clinical manifestations. In particular, IL-6 was significantly correlated with specific clinical findings, such as severity of respiratory compromise and fever. No correlation was found between interleukin expression and final outcome. In conclusion, H1N1 virus infection induces an early and significant upregulation of both interleukins IL1β and IL-6 plasma expressions. The upregulation of these cytokines is likely to play a proinflammatory role in H1N1 virus infection and may contribute to airway inflammation and bronchial hyperreactivity in these patients.