Lung ultrasound evaluation in people with cystic fibrosis: A new approach in the pulmonology outpatient clinic.

BACKGROUND: Cystic fibrosis (CF) is a genetic disease that causes progressive lung disease with major impact on the quality of life. Lung ultrasound (LUS) allows to assess the lung involvement through the artefacts analysis and is increasingly used in children but is not yet used to monitor people with CF(pwCF). The main aim of this study was to describe the LUS pattern of pwCF during their routinary check-up visit. The secondary objective was to correlate the LUS findings with pulmonary function indices. METHODS: We performed a cross-sectional observational study, enrolling adolescents and young adults with CF. Each patient underwent clinical assessment, measurement of SpO2, assessment of lung function by spirometry and LUS. RESULTS: Twenty-nine subjects with CF were included. The most frequent alterations were consolidations (72.4%) located in the left apical anterior and right apical posterior regions followed by interstitial syndrome (65.5%). The 41.4% of cases presented the lingula involvement, characterized by a consolidation with static air bronchogram, and 55.2% showed pleural irregularity mainly in the posterior apical regions. A significant correlation was found between the LUS total score and spirometric indices: FEV1 (p = .003), FVC (p = .002), Tiffenau Index <80% (p = .014), and FEF 25-75 (p = .004). CONCLUSIONS: Our study describes LUS findings in pwCF. It also showed a correlation between LUS score and the patients' lung function measured by spirometric indices. We conclude that LUS may be useful in routine monitoring of pwCF in combination with clinical and spirometric assessment.

Use of POCUS for the assessment of dehydration in pediatric patients-a narrative review.

In pediatric practice, POCUS (point-of-care ultrasound) has been mostly implemented to recognize lung conditions and pleural and pericardial effusions, but less to evaluate fluid depletion. The main aim of this review is to analyze the current literature on the assessment of dehydration in pediatric patients by using POCUS. The size of the inferior vena cava (IVC) and its change in diameter in response to respiration have been investigated as a tool to screen for hypovolemia. A dilated IVC with decreased collapsibility (< 50%) is a sign of increased right atrial pressure. On the contrary, a collapsed IVC may be indicative of hypovolemia. The IVC collapsibility index (cIVC) reflects the decrease in the diameter upon inspiration. Altogether the IVC diameter and collapsibility index can be easily determined, but their role in children has not been fully demonstrated, and an estimation of volume status solely by assessing the IVC should thus be interpreted with caution. The inferior vena cava/abdominal aorta (IVC/AO) ratio may be a suitable parameter to assess the volume status in pediatric patients even though there is a need to define age-based thresholds. A combination of vascular, lung, and cardiac POCUS could be a valuable supplementary tool in the assessment of dehydration in several clinical scenarios, enabling rapid identification of life-threatening primary etiologies and helping physicians avoid inappropriate therapeutic interventions.   Conclusion: POCUS can provide important information in the assessment of intravascular fluid status in emergency scenarios, but measurements may be confounded by a number of other clinical variables. The inclusion of lung and cardiac views may assist in better understanding the patient's physiology and etiology regarding volume status. What is Known: • In pediatric practice, POCUS (point-of-care ultrasound) has been mostly implemented to recognize lung conditions (like pneumonia and bronchiolitis) and pleural and pericardial effusions, but less to evaluate fluid depletion. • The size of the IVC (inferior vena cava) and its change in diameter in response to respiration have been studied as a possible screening tool to assess the volume status, predict fluid responsiveness, and assess potential intolerance to fluid loading. What is New: • The IVC diameter and collapsibility index can be easily assessed, but their role in predicting dehydration in pediatric age has not been fully demonstrated, and an estimation of volume status only by assessing the IVC should be interpreted carefully. • The IVC /AO(inferior vena cava/abdominal aorta) ratio may be a suitable parameter to assess the volume status in pediatric patients even though there is a need to define age-based thresholds. A combination of vascular, lung, and cardiac POCUS can be a valuable supplementary tool in the assessment of intravascular volume in several clinical scenarios.

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.

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.

Sleep Disorders in Low-Risk Preterm Infants and Toddlers.

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.

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.

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.

Diagnosing acute mastoiditis in a Pediatric Emergency Department: a retrospective review.

Background and aim Acute mastoiditis (AM) is a common complication of acute otitis media in children. There is currently no consensus on criteria for diagnosis. Head CT is the most frequent diagnostic tool used in the ED although the increasing awareness on the use of ionized radiations in children has questioned the use of CT imaging versus solely using clinical criteria. Our research aimed to understand if CT imaging was essential in making a diagnosis of AM. Methods We retrospectively analyzed medical records from pediatric patients who accessed our Pediatric Emergency Department (ED) between January 2014 and December 2020, with a clinical suspicion of AM. We reviewed clinical symptoms upon presentation, head CT and lab values (white blood cell count or WBC, C-Reactive Protein or CRP) when done, presence of complications and discharge diagnosis. A multilogistic regression model was specified to establish the role of clinical features and of CT in the diagnosis of AM based on 77 patients. Results Otalgia (OR= 5.01; 95% CI= 1.52-16.51), protrusion of the auricle (OR= 8.42; 95% CI= 1.37-51.64) and hyperemia (OR= 4.07; 95% CI= 1.09-15.23) of the mastoid were the symptoms strongly associated with a higher probability of AM. In addition to clinical features, the adjusted OR conferred by head CT was 3.09 (95% CI = 0.92-10.34). Conclusions Clinical signs were most likely predictive of AM in our sample when compared to Head CT. Most common symptoms were protrusion of the auricle, hyperemia or swelling behind the ear and otalgia.

Acute intranasal treatment with nerve growth factor limits the onset of traumatic brain injury in young rats.

BACKGROUND AND PURPOSE: Traumatic 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 APPROACH: We 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 µg·kg-1 ), and motor behavioural test, morphometric and biochemical assays were carried out 24 h later. KEY RESULTS: Acute intranasal NGF prevented the onset of TBI-induced motor disabilities, and decreased reactive astrogliosis, microglial activation and IL-1ß content, which after TBI develops to the same extent in the impact zone and the hypothalamus. CONCLUSION AND IMPLICATIONS: Intranasal 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.

The acute bronchiolitis rebound in children after COVID-19 restrictions: a retrospective, observational analysis.

BACKGROUND AND AIM: Bronchiolitis represents the main cause of illness and hospitalization in infants and young children. The aim of this study was to compare the Pediatric Emergency Department (PED) admissions for bronchiolitis during the post-COVID (Coronavirus disease) period to those of previous seasons and to analyze their etiology during COVID and post-COVID period. METHODS: We compared demographics, clinical and microbiological data of children admitted to PED with bronchiolitis between September 2021 and March 2022 (post-COVID period) to the previous seasons (COVID and pre-COVID period). RESULTS: During the post-COVID period the bronchiolitis season started earlier than usual, with a peak reached in November 2021; a gradual reduction was subsequently observed between December 2021 and January 2022. Our data showed a prevalence of High Priority code in children admitted to the PED with bronchiolitis during the post-COVID period (61.4%) compared the pre-COVID period (34.8%) (p=0.00). Also regarding the hospitalization of these patients, we found a major rate of hospitalization during this epidemic season (p=0.035). In addition, only 4 (1.5%) of the tested children resulted positive for SARS-CoV-2 and all of them were admitted to PED during the post-COVID period. The search for the other respiratory viruses showed during the current season a prevalence of respiratory syncytial virus (RSV) (60.2%), followed by Human Rhinovirus (30.1%). CONCLUSIONS: The post-COVID period was characterized by an early and short-term peak in acute bronchiolitis, with an increased rate of hospitalization. In addition, SARS-CoV-2 infection was rarely cause of bronchiolitis in children under 2 years old.

COVID-19 increased in Italian children in the autumn and winter 2021-2022 period when Omicron was the dominant variant.

AIM: We examined the prevalence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children during the autumn and winter season from 1 September 2021 to 30 January 2022 and compared it with the same period in 2020-2021. METHODS: This study was carried out int the paediatric emergency department (PED) of a tertiary Italian hospital. We compared the clinical and demographical features of all children who presented during the two study periods and tested positive for SARS-CoV-2. RESULTS: During the 2021-2022 autumn and winter season 5813 children presented to the PED, 19.0% were tested for SARS-CoV-2 and 133 (12.0%) of those tested positive. In 2020-2021, 2914 presented to the PED, 12.3% were tested, and 30 (8.3%) of those tested positive. There were no statistically significant differences in clinical severity during the two study periods, despite a higher percentage of neurological symptoms in 2020-2021. Of the SARS-CoV-2-positive cases, 29/133 (21.8%) were hospitalised during the 2021-2022 season and 10/30 (33.3%) during the previous one. Only 3/163 children required intensive care. CONCLUSION: The greater spread of SARS-CoV-2 was probably due to the greater transmissibility of the Omicron variant, but the symptoms were mild and only 3 children required intensive care.

Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system.

BACKGROUND: Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries. METHODS: We conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling. RESULTS: In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI -100- -54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from -97% (95% CI -100- -47%; p=0.0005) to -36% (95% CI -79-7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14-0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20-0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25-0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31-0.97); p=0.038) were independently associated with reducing bronchiolitis. CONCLUSIONS: Several NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.

Intranasal nerve growth factor for prevention and recovery of the outcomes of traumatic brain injury.

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.

A scoping review of the management of acute mastoiditis in children: What is the best approach?

BACKGROUND: Acute mastoiditis (AM) is a severe infection of the mastoid air cells that occurs in cases of acute, sub-acute, or chronic middle ear infections. No definitive consensus regarding the management of AM has been identified. The current guidelines include a conservative approach (parenteral antibiotics alone, antibiotics plus minor surgical procedures such as myringotomy with a ventilation tube inserted or drainage of the subperiosteal abscess through retro-auricolar incision or needle aspiration) or surgical treatment (mastoidectomy). The main aim of this review was to evaluate and summarize the current knowledge about the management of pediatric AM by analyzing the current evidence in the literature. METHODS: We examined the following bibliographic electronic databases: Pubmed and the Cochrane Library, from the inception date until February 2023. The search was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISM). The key words used for the search across electronic databases were: `mastoiditis` and `management`; `mastoiditis` and `surgery`; `mastoiditis` and `conservative`; `mastoiditis` and `antibiotics`; `mastoiditis` and `myringotomy`; `mastoiditis` and `grommet`; `mastoiditis` and `drainage`; and `mastoiditis` and `mastoidectomy`. RESULTS: We selected 12 articles involving 1124 episodes of mastoiditis. Some of these studies considered medical therapy alone as a valid first step, whereas others considered a minor surgical intervention as an initial approach along with antibiotic therapy. Considering the studies that evaluated medical therapy as the initial sole treatment option, the success rate of antibiotics alone was 24.6%. Overall, the success rate of minor surgical procedures, excluding mastoidectomy, was 87.7%, whereas the mastoidectomy success rate was 97%. CONCLUSIONS: Overall, there is no shared consensus on the diagnostic or therapeutic approach to mastoiditis. Conservative therapy has gained considerable ground in recent times, quite limiting the predominant role of mastoidectomy. Further studies will be necessary to definitely develop standardized protocols shared in the scientific community.

COVID-19 review shows that benefits of vaccinating children and adolescents appear to outweigh risks of post-vaccination myopericarditis.

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.