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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.

Abstract Background Endocan is a soluble dermatan sulfate proteoglycan (50 kDa) secreted by endothelial cells and expressed by dermal, coronary, pulmonary and adipose tissue microvasculature. It plays an important role in the pathogenesis of vascular disorders, inflammatory state, endothelium dysfunction and neoangiogenesis. Aims of the study were to compare fasting serum endocan levels between children with obesity and healthy controls and to investigate the relationships between endocan, body mass index (BMI) and other indices of cardiometabolic risk. Methods This single-center, observational, retrospective study included 19 pediatric patients with obesity aged 11.94 ± 0.52 years and 19 lean matched controls. Each patient underwent clinical and auxological examination and laboratory investigations including routine organs function tests and lipid profile. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Fasting endocan serum levels were measured using an enzyme-linked immunosorbent assay (ELISA). Results Compared to healthy subjects, serum endocan levels were found to be significantly upraised in children with obesity. Endocan resulted significantly correlated with insulin levels (rho 0.47; p = 0.04); in addition, an association with HOMA-IR values with a trend toward the statistical significance (rho 0.43; p = 0.07) was found. No significant correlation with fasting blood glucose values and lipid serum levels was demonstrated. Although not statistically significant, a correlation between endocan and the presence and grading of liver steatosis on ultrasound (rho 0.51; p = 0.08 and rho 0.51; p = 0.08, respectively) was found. Conclusions These findings confirm the association between endothelial damage and insulin resistance in children with obesity. Endocan could be used as a biomarker of early endothelial dysfunction in children with obesity and could be a valid predictor of future cardiovascular risk in adulthood.

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.

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.

The aim of this study was to evaluate a potential correlation between results of the oral glucose tolerance test (OGTT) and the auxological/metabolic parameters in a cohort of overweight patients assessed for suspicion of hyperinsulinism. We analyzed 206 patients, comparing those with insulin peak below (nonhyperinsulinemic) and over 100 uIU/mL (hyperinsulinemic) at the OGTT. We found a significant difference in weight (p = 0.037), body mass index (BMI, p < 0.001) and BMI standard deviations (SD, p < 0.001), waist circumference (p = 0.001), hip circumference (p = 0.001), and waist-to-height ratio (WHtR, p = 0.016) between the two groups. Analyzing the median insulin value during OGTT in the whole population, a weakly positive correlation emerged with weight SD (p < 0.001; rho = 0.292) and a moderate positive correlation with BMI SD (p < 0.001; rho = 0.323). We also found a weakly positive correlation with waist circumference (p = 0.001; rho = 0.214), hip circumference (p = 0.001; rho = 0.217), and WHTR (p = 0.016; rho = 0.209) and a moderate positive correlation with the HOMA index (p < 0.001; rho = 0.683). The median insulin value correlates with high triglyceride (p < 0.001; rho = 0.266) and triiodothyronine values (p = 0.003; rho = 0.193) and with low HDL values (p < 0.001; rho = −0.272). In clinical practice the interpretation of laboratory and anthropometric parameters could predict the level of insulin, highlighting also a possible underlying diagnosis of insulin resistance and/or hyperinsulinemia without performing an OGTT.

Tricho-rhino-phalangeal syndrome (TRPS) is a genetic disease characterized by craniofacial and skeletal malformations including short stature, brachydactyly, with ulnar or radial deviation of the fingers, clinodactyly and early joint dysplasia, especially of the hips. The most remarkable craniofacial features are slow growing, sparse and brittle hair, pear-shaped nose with a bulbous tip, flat philtrum with thin upper lip, micrognatia and large low-set ears. The radiological hallmarks include cone-shaped phalangeal epiphyses, typical of all TRPS patients, but usually not present until 2 years of age, while bone exostoses appear only in TRPS II individuals. Management is primarily supportive. We describe a case of a male child with disharmonious short stature, affected by TRPS I. The diagnosis was established on the basis of clinical features and genetic testing

This paper examines equilibrium asset prices and leverage in an exchange economy populated with both retail and institutional investors. Institutional investors influence the price of the stocks they trade and are aware of the price impact of the opponent and, thus, interact strategically. Because of the price impact, institutional investors decrease their demand for stocks and lend money to the retail sector, thereby increasing leverage in the economy. The risk-free rate (equity premium) tends to be lower (higher) as compared to an economy populated by retail investors only. Retail investors' compensation for liquidity provision depends on the behavior of institutional investors and the state of the economy. [ABSTRACT FROM AUTHOR]

The Covid-19 pandemic drastically modified social life and lifestyle, in particular, among children and adolescents, promoting sedentary behaviors and unhealthy eating habits. The aims of this study were to assess the rate and the factors associated with outpatient drop-out in childhood obesity management, and to evaluate how the Covid-19 pandemic influenced weight status and lifestyle of children and adolescents with obesity. One hundred and forty-five children and adolescents with obesity were identified, including 80 subjects evaluated before the Covid-19 pandemic (group A) and 65 subjects in the period straddling the Covid-19 pandemic (group B). Anamnestic (family history of obesity, dietary habits, physical activity, screen time), socio-cultural (economic status, employment and schooling of parents, household composition, place of living) and clinical (weight, height, BMI, waist circumference) data were retrospectively analyzed for each subject in both groups at baseline (V0) and 12-months (V1) at in-person assessment. Glycemic and lipid profiles were assessed at V0. Drop-out rate did not differ significantly between the two groups. BMI SDS at V0 (OR=2.52; p=0.004), female sex (OR=0.41; p=0.035), and the presence of a single parent in the household (OR=5.74; p=0.033) significantly influenced drop-out in both groups. Weight loss between V0 and V1 was significantly greater among group A patients compared to group B (p=0.031). In group B, hours spent in physical activity significantly decreased from V0 to V1, being significantly lower than group A at V1; on the contrary, screen time significantly increased in the same period. The consumption of sugary drinks and snacks was significantly greater in group B than group A at V1. Our study documented that the Covid-19 pandemic, although not affecting the drop-out rate of obese children in a follow-up program, negatively influenced lifestyle and reduced the effectiveness of outpatient counseling in childhood obesity treatment.

Asprosin physiologically increases in fasting conditions and decreases with refeeding and has been implicated in glucose homeostasis. An alteration of meal-related circadian oscillation of asprosin has been suggested in adults affected by type 2 diabetes mellitus.Aims of this study were to test the hypothesis of an alteration in the meal-related variation of asprosin levels in non-diabetic children and adolescents with obesity and to assess which metabolic variables condition this variation in non-diabetic children and adolescents with obesity. This is a cross-sectional study which included 79 children and adolescents with obesity. Children underwent clinical and biochemical assessments, including oral glucose tolerance test (OGTT), and liver ultrasound evaluation. Asprosin serum levels were measured by an enzyme-linked immunosorbent assay at a fasting state and at the 120-minute OGTT timepoint (2h-postprandial asprosin). Fasting and 2h-postprandial asprosin serum levels did not significantly differ in the entire study population (374.28 ± 77.23 vs 375.27 ± 81.26;p=0.837). 55.7% of patients had a significant increase in 2h-postprandial asprosin compared with fasting levels. The asprosin level increase condition was significantly associated with HOMA-IR (OR,1.41; 95%CI,1.005-1.977; p=0.047), fasting glycaemia (OR,1.073; 95%CI,1.009-1.141;p=0.024) and HOMA-B (OR,0.99; 95%CI,0.984-0.999; p=0.035). Moreover, the IFG condition was associated with the increase in asprosin levels (OR, 3.040; 95%CI, 1.095-8.436; p=0.033), even after adjustment for HOMA-IR, BMI SDS, sex and pubertal stage. Insulin resistance and IFG influence meal-related changes of asprosin serum levels in our study population of obese, non-diabetic, children. Alteration of asprosin circadian secretion might be an early biomarker of impaired glucose regulation in obese children with insulin resistance.

A disparate group of rare hematological diseases characterized by impaired maturation of neutrophil granulocytes defines congenital neutropenias. Neutropenic patients are prone to recurrent infections beginning in the first months of life. Of interest is “cyclic neutropenia”, an ultra-rare disorder revealed by sinusoidal variations of the neutrophil count and periodically-recurring infections every 21 days. Diagnosis of these disorders is frequently obscured by the multiple causes of recurrent fevers in children. Aim of this overview is to outline the physical assessment of children presenting with early-onset symptomatic neutropenia, identify the disease between the many medical conditions and even emergencies which should enter in differential diagnosis, hint at the potential management with granulocyte-colony stimulating factor, define the risk of evolution to hematologic malignancy, and summarize inter-professional team strategies for improving care coordination and outcomes of such patients.

OBJECTIVE: Burns are among the most common injuries in children. In burns of more than 20% of the total body surface area, a systemic inflammatory response involving several chemical mediators occurs. Among them, nerve growth factor (NGF) regulates the inflammatory response related to wound healing and promotes keratinocyte proliferation and angiogenesis. The aim of our study was to investigate the physiological response to injury in children with moderate-severe burns, assaying proNGF, mature NGF (mNGF), interleukins (IL)- 1β, and IL-10 serum levels. PATIENTS AND METHODS: This is a prospective observational study, including twelve children hospitalized for moderate-severe burns at the Gemelli Hospital (Rome). Their laboratory features were compared to those of patients with obstructive hydrocephalus who underwent surgery. RESULTS: Our results showed an increase in proNGF and mNGF serum levels. In burn patients, proNGF levels increased before mNGF, and serum concentrations of both were not correlated with burn extension and depth. The most significant levels of mNGF and proNGF were reported in scalds involving the face. Serum IL-1β and IL-10 peak levels were reached with a timecourse pattern similar to proNGF. CONCLUSIONS: Our preliminary results validate the hypothesis that serum levels of proNGF and mNGF may represent inflammatory biomarkers useful for monitoring burn patients and defining new strategies for their treatment. [ABSTRACT FROM AUTHOR]

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.] [ABSTRACT FROM AUTHOR]

Abstract Lung ultrasound (LUS) is nowadays a fast-growing field of study since the technique has been widely acknowledged as a cost-effective, radiation free, and ready available alternative to standard X-ray imaging. However, despite extensive acoustic characterization studies and documented medical evidences, a lot is still unknown about how ultrasounds interact with lung tissue. One of the most discussed lung artifacts are the B-lines [in all ages] and the subpleural consolidations (in young infants). Recently, LUS has been claimed to be able to detect pneumonia in infants with bronchiolitis, although this can be an overestimation due to the peculiar physiology of small peripheral airways of the pediatric lung (particularly in neonate/infants). Distinguishing consolidations from atelectasis in young infants with bronchiolitis can be challenging and those criteria well defined for adults and older children (size and bronchogram) cannot easily translated in this specific subset. Therefore, if decades of studies clearly defined the low risk of SBI in bronchiolitis, we need to be careful before stating that LUS may confirm pneumonia in such a high number of cases and, importantly, new and promising techniques such as LUS should give us new insights bringing us to improvements and not back to overuse of antibiotics. More studies are surely need on this topic.

Nurses play a pivotal role during pediatric procedural sedation and their perspective is an important indicator for the quality of care. The aim of this study is to examine nurses’ satisfaction comparing four different pharmacological regimens used for pediatric sedation outside of the operating room. A prospective observational study was conducted in a third-level pediatric teaching hospital, involving all the nurses with experience in the field of pediatric procedural sedation. A 13-item survey was used to assess the level of nurses’ satisfaction for the quality of sedation with four different analgesic–sedative drugs. Fifty-one questionnaires were completed by pediatric nurses, with a median length of experience of 10 years. Regarding the overall quality of the sedation, the highest median satisfaction scores were observed for propofol (8, IQR 7–9), dexmedetomidine (8, IQR 6–8) and midazolam (8, IQR 7–9). Ketamine (5, IQR 3–7) displayed the lowest score. When asked to rate their level of perceived safety, nurses gave high scores to all the four drugs studied, with no statistically significant difference between them. Non-pharmacological techniques during procedural sedation were judged as important by 38 (74.5%) nurses. According to this sample of pediatric nurses, the best quality of procedural sedation in children outside of the operating room is obtained with propofol, dexmedetomidine and midazolam. During procedural sedation, nurses feel safe overall, regardless of the pharmacological regimen used. Moreover, they highlighted the relevance on non-pharmacological approaches in the preparation of the child for the procedure.

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.