Multifaceted Roles of Nerve Growth Factor: A Comprehensive Review with a Special Insight into Pediatric Perspectives.

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.

Epidemiological and clinical features of bronchiolitis after the COVID-19 outbreak: comparison of two epidemic seasons.

BACKGROUND: The first aim of this study was to compare Pediatric Emergency Department (PED) admissions for acute bronchiolitis during the 2022-2023 season to those of the season 2021-2022. The secondary aim was to assess the difference in the recurrence of bronchiolitis episodes in the same patient between the two seasons. METHODS: This is a retrospective, observational, cross-sectional study conducted at the PED of IRCCS A. Gemelli University Polyclinic Foundation (Rome, Italy). We included all children aged between 0 and 2 years admitted to PED with the diagnosis of bronchiolitis. We compared features of seasons 2021-2022 and 2022-2023. RESULTS: The median age of children enrolled during the 2022-23 season was 5 months (IQR: 2-8) compared to 7 months (IQR: 2-14) in the previous one (P=0.02). We observed in the last season a higher number of children admitted to PED with a high priority code and an increased therapeutic use of high-flow nasal cannula and inhaled adrenaline. During the 2022-23 season we found 31 (12.8%) children presenting more than one episode of bronchiolitis in the same epidemic season, compared to 16 (7.6%) children in the previous season (P=0.048). CONCLUSIONS: Our data emphasize that the epidemiological features of bronchiolitis after COVID-19 outbreak have changed and are still evolving.

Diagnosis and Treatment of Group A Streptococcal Pharyngitis in Children.

The purpose of this review is to summarize the current evidence regarding the management of streptococcal pharyngitis in children. This article aims to provide a valid support to discriminate streptococcal pharyngitis from viral cases and treat it appropriately to avoid the development of complications. Differential diagnosis based only on clinical features is not always easy. For this reason, different clinical scores were created to provide an accurate diagnosis. Microbiological tests are valuable tools as well, but their use is not recommended unanimously. Concerning treatment, all guidelines agree on the drug to be used. However, doubts remain about the optimal duration of antibiotic therapy, especially in this specific historical moment as we are experiencing a peak in streptococcal infections. [Pediatr Ann. 2024;53(6):e234-e238.].

Use of multimedia devices in pediatric age: risks or advantages? A survey in an Italian center.

BACKGROUND: Nowadays children live in a digital world, exposed to relevant risks for their health and safety. The aim of this study is to investigate the use of multimedia devices in a sample of children and adolescents. METHODS: The study was performed between November 2018 and June 2019 in a third-level University Hospital, recruiting children and adolescents during general or specialistic follow-up visits. Anonymous, age-specific, questionnaires were distributed to 500 children and adolescents and 370 parents. RESULTS: Among children, 25 (17.1%) had their own mobile device, of which 84% Italian. The 54.1% of them uses multimedia devices half an hour/an hour per day and many of them (37.5% of Italian and 40% of foreign) use it without their parents' control. Most of adolescents had a mobile phone since the age of 10-12 years old. WhatsApp (Meta Inc., Cambridge, MA, USA) is the most used social network, followed by Instagram and Facebook. The use of multimedia devices was widespread between teenagers during classroom hours, meals and before sleeping and they are an important mean for cyberbullying. In addition, in the 29.9% of cases there is no correspondence between information given by parents and respective sons/daughters. CONCLUSIONS: This study shows more risks than advantages derived from the use of multimedia devices in children and adolescents. Therefore, it is essential to educate them about their correct and responsible use.

Artificial Intelligence in Pediatric Emergency Medicine: Applications, Challenges, and Future Perspectives.

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.

Presepsin Levels in Pediatric Patients with Fever and Suspected Sepsis: A Pilot Study in an Emergency Department.

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.

Traditional and innovative interventions in the management of enuresis.

Introduction: Enuresis (NE) is a socially stigmatising and stressful condition affecting children's and parent's quality of life. The aim of this review was to evaluate and summarize the current knowledge about the pharmacological and non-pharmacological traditional and innovative treatments in children with NE. Material and methods: We examined the following bibliographic electronic databases: PubMed and the Cochrane Library, from January 2000 until July 2023. The search was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) (8) and was limited to English-language papers that focused on enuresis in patients under 18 years old. Each paper that met the eligibility criteria was reviewed and analyzed in full text by three authors and any discrepancies among them were solved by debate. Due to the heterogeneity of the articles examined, we focused on a qualitative analysis. Results: Overall, we identified 560 records through database searching. As first step, we excluded 46 articles in non-English language, 6 records whose related articles were not available, 8 articles concerning ongoing trials and 210 duplicated papers. As second step, we eliminated 215 records by evaluating only title and abstract because they did not match the inclusive criteria we mentioned before. Of the remaining 75 studies, we excluded 34 through a further discussion among authors upon the reliability of data. Thus, 41 selected articles were included in the review. Conclusions: Multiple treatment approaches, both pharmacological and non pharmacological, have been established and validated to reduce signs and symptoms of NE and improve quality of life and the social and emotional discomfort experienced by children. The aim of pediatrician is to identify the right therapy protocol for very single child, evaluating the best approach for him and the family.

Sharenting: hidden pitfalls of a new increasing trend- suggestions on an appropriate use of social media.

BACKGROUND: The term "sharenting", defining the practice of sharing children's photos on social media, has become widespread globally. This phenomenon introduces new risks for children, often overlooked by parents lacking experience or caution in protecting their children from potential harms. MAIN BODY: Parents share multimedia contents with positive intentions, but the lack of immediate risk perception prevails. An Italian study revealed that a significant percentage of parents (68%) frequently share their children's photos on social platforms, often without considering potential risks. Pediatricians play a crucial role in raising awareness among parents regarding the dangers associated with online sharing and must empower families with defensive strategies to safeguard children's privacy. CONCLUSIONS: The commentary emphasizes the need for increased parental assistance in comprehending the risks of sharenting and using social media prudently. Pediatricians are pivotal in guiding parents, striking a balance between the natural urge to share children's progress and an awareness of associated risks. Immediate action by scientific societies involves training and informing parents through various digital and print resources. A concrete regulation of this phenomenon is needed to protect children's rights, but prioritizing digital awareness and education seems pivotal in mitigating sharenting-related risks.

Not only enuresis: do not disregard organic disorders.

Nocturnal enuresis (NE) is a common condition in the pediatric age. NE is defined as an intermittent bedwetting with any frequency while sleeping in children. NE is classified into primary form (patient never had achieved nocturnal urinary control) or secondary form (children with a period of 6 consecutive months of night-time urinary control before incontinence, which is generally associated with organic or psychological causes). Moreover, NE could be monosymptomatic (MNE) or non-monosymptomatic (NMNE), depending on the presence of daytime incontinence or any other lower urinary tract symptoms (LUTS). We report a 7-year- old female with a history of recent onset of sphincter troubles and recurrent low urinary tract infections. She presented urinary urgency associated to daytime incontinence, bedwetting almost every night in the previous 3 months and sometimes encopresis. The physical and neurological examination was silent, no psychological or social problem intercurred. As first approach, she was treated with deamino-delta-D-arginine vasopressin (dDAVP) 120 mcg associated with oxybutynin 5 mg and educational therapy, for 3 months without benefits. So, she underwent a magnetic resonance imaging (MRI) of the spinal cord, that highlighted the presence of hydrosyringomyelia from D6 to D10, lipoma of the terminal filum and the presence of synovial cyst between L5-S1. This case remarks that in secondary NMNE, any possible organic cause must be investigated.

Antibiotic treatment for streptococcal pharyngitis: time for a new approach?

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Bone Disorders in Pediatric Chronic Kidney Disease: A Literature Review.

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.

Intranasal human-recombinant NGF administration improves outcome in children with post-traumatic unresponsive wakefulness syndrome.

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.

Do Sleep Disorders Influence the Prognosis and the Response to the Therapy in Enuretic Children?

OBJECTIVE: The current study describes the prevalence of sleep disorders in enuretic children, playing as influencing factors in the response to treatment and risk of relapse. MATERIALS AND METHODS: Data were collected from September 2020 to February 2021 in 114 children aged between 5 and 14 years, with a diagnosis of nocturnal enuresis and concomitant sleep disorders, referred to the Pediatric Unit, Campus BioMedico University, Rome. Enuretic children were subjected to an anamnestic and clinical assessment. Sleep disorders investigated were sleep apnea, sleep talking, snoring, bruxism, restless sleep, and somnambulism. Each patient was subjected both to pharmacological and to non-pharmacological treatments and monitored for 3 months to identify the presence of relapse. Patients were divided into 2 groups according to therapy response, and statistical analysis was performed to evaluate possible variables involved in enuresis relapse. RESULTS: A high prevalence of sleep disorders was documented: 8/114 children (7%) had sleep apnea, 47/114 (41.2%) had bruxism, 66/114 (57.8%) had snoring, 54/114 (47.3%) had sleep talking, 18/114 (15.7%) had restless sleep. Forty-three of 114 children (37.7%) had relapses: 21/43 (49%) relapses occurred in children with only 1 sleep disorder, while 22/43 (51%) relapses occurred in children with 2 or more sleep disorders. Lower risk of relapses was reported in children subjected to dual therapy. CONCLUSION: Sleep disorders were widely associated with nocturnal enuresis, acting as comorbidities in the clinical course of nocturnal enuresis. Combined therapy seems to be associated with a lower rate of relapse of enuresis in a 3-month follow-up. A multidisciplinary approach is required to improve patients' management.

Pain management in pediatric age. An update.

Differently from the adult patients, in paediatric age it is more difficult to assess and treat efficaciously the pain and often this symptom is undertreated or not treated. In children, a selection of appropriate pain assessment tools should consider the age, the cognitive level, the presence of eventual disability, the type of pain and the situation in which it is occurring. Improved understanding of developmental neurobiology and paediatric analgesic drug pharmacokinetics should facilitate a better management of childhood pain. The objective of this update is to discuss the current practice and the recent advances in pediatric pain management.  Using PubMed and the Cochrane Library we conducted an extensive literature analysis on pediatric pain assessment and commonly used analgesic agents in this kind of patients. According to our results, a multimodal analgesic regimen provides a better pain control and a functional outcome in children. Cooperation and communication among the anaesthesiologist, the surgeon and the paediatrician remains essential for successful anaesthesia and pain management in childhood.

Presepsin as a diagnostic marker of sepsis in children and adolescents: a short critical update.

BACKGROUND AND AIM: Sepsis is a potentially fatal condition which strikes 1.2 million children worldwide per year. New biomarkers have been proposed in the assessment of the risk of sepsis progression and in the identification of patients with the worst outcome. This review aims to assess the diagnostic value of presepsin, a promising new biomarker, in pediatric sepsis, with particular attention to its usefulness in emergency department. METHODS: We performed a literature search of the last 10 years to find presepsin related studies and reports concerning pediatric population aged from 0 months to 18 years. We mainly focused on randomized placebo-control studies, followed by case-control studies, observational (both retrospective or prospective), and finally systematic reviews and meta-analysis. The article selection process was carried out independently by three reviewers.   Results: A total of 60 records were identified in literature, 49 were excluded according to the exclusion criteria. The highest presepsin sensitivity value was 100%, with a high cut-off (800.5 pg/mL). The highest sensitivity-specificity ratio was 94% vs 100%, with a similar considered presepsin cut-off (855 ng/L). As regards the presepsin cut-offs reported in the various studies, several authors agree on a critical threshold of about 650 ng/L to guarantee a sensitivity> 90%. The analyzed studies show a wide variability for patients' age and presepsin risk cut-offs.   Conclusions: Presepsin seems to be a new useful marker for early diagnosis of sepsis, even in a pediatric emergency setting. Being a new marker of sepsis, more studies are required to better understand its potential.

An Interesting Case of Neonatal AKI: What Is the Time to Consider Anuria Irreversible?

Acute kidney injury is a frequent complication for critical newborns. Its management is a significant challenge, especially in extremely low-birth-weight (ELBW) infants. Currently, peritoneal dialysis (PD) is the most manageable treatment. However, data are lacking regarding when diuresis can be declared irreversible relative to the start of PD. A female infant born at 28 + 0 weeks with a birth weight of 800 g by monochorionic diamniotic pregnancy, complicated by twin-to-twin transfusion syndrome, developed acute renal failure on the second day of life because of long-term intrauterine hypoperfusion. PD was started on day 7. The patient remained anuric until the 52nd day of dialysis, when she presented adequate urine output of 2.5 mL/kg/h and PD was suspended for 11 days. After an episode of sepsis, PD was re-started, and after 50 days of treatment, given a urine output of 1.5 mL/kg/h, it was discontinued. The patient died on day 132 after a disseminate infection, which led to multiorgan failure. In ELBW infants, PD is a valid therapeutic instrument to treat patients with renal failure. Despite the evidence of low renal functional reserve in these patients, the duration of recovery from diuresis after a period of anuria can be very long.

Early treatment with N-acetylcysteine reduces hepatotoxicity in acute acetaminophen poisoning.

During the outbreak of COVID19 measures taken to contain the spread of the virus have influenced the mental well-being of adults and adolescents. Acetaminophen overdose is the major cause of drug intoxication among children and adolescents. We reported a case of a 15-year- old girl referred to our Emergency Department 3 hours after ingestion of 10 g of paracetamol for suicidal purposes. She promptly started the administration of intravenous N-acetylcysteine (NAC) and the patient was discharged after 5 days of hospitalization in good clinical condition and with neuropsychiatric follow-up. Our case shows that the timing of the intravenous NAC administration is considered the most important factor in the prevention of acetaminophen-induced hepatic failure, despite high serum levels after acetaminophen ingestion.

Combined treatment of nerve growth factor and transcranical direct current stimulations to improve outcome in children with vegetative state after out-of-hospital cardiac arrest.

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.

SARS-CoV-2-related bronchiolitis: a multicentre international study.

BACKGROUND: Bronchiolitis is the main acute lower respiratory tract infection in infants. Data regarding SARS-CoV-2-related bronchiolitis are limited. OBJECTIVE: To describe the main clinical characteristics of infants with SARS-CoV-2-related bronchiolitis in comparison with infants with bronchiolitis associated with other viruses. SETTING, PATIENTS, INTERVENTIONS: A multicentre retrospective study was conducted in 22 paediatric emergency departments (PED) in Europe and Israel. Infants diagnosed with bronchiolitis, who had a test for SARS-CoV-2 and were kept in clinical observation in the PED or admitted to hospital from 1 May 2021 to 28 February 2022 were considered eligible for participation. Demographic and clinical data, diagnostic tests, treatments and outcomes were collected. MAIN OUTCOME MEASURES: The main outcome was the need for respiratory support in infants testing positive for SARS-CoV-2 compared with infants testing negative. RESULTS: 2004 infants with bronchiolitis were enrolled. Of these, 95 (4.7%) tested positive for SARS-CoV-2. Median age, gender, weight, history of prematurity and presence of comorbidities did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative infants. Human metapneumovirus and respiratory syncytial virus were the viruses most frequently detected in the group of infants negative for SARS-CoV-2.Infants testing positive for SARS-CoV-2 received oxygen supplementation less frequently compared with SARS-CoV-2-negative patients, 37 (39%) vs 1076 (56.4%), p=0.001, OR 0.49 (95% CI 0.32 to 0.75). They received less ventilatory support: 12 (12.6%) high flow nasal cannulae vs 468 (24.5%), p=0.01; 1 (1.0%) continuous positive airway pressure vs 125 (6.6%), p=0.03, OR 0.48 (95% CI 0.27 to 0.85). CONCLUSIONS: SARS-CoV-2 rarely causes bronchiolitis in infants. SARS-CoV-2-related bronchiolitis mostly has a mild clinical course.