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The main aim was to evaluate the prevalence of sleep-disordered breathing (SDB) in patients with Chiari II malformation (CM-II). The secondary objectives were to evaluate the association between SDB, morphological abnormalities, and neurological symptoms and to review the literature on patients with SDB and CM-II.The study has a cross-sectional, case-control design. Patients with CM-II (patients) were compared to control patients referred for clinical polysomnography in the Sleep Medicine Unit, matched for age and sex. All patients underwent brain and spinal cord magnetic resonance imaging, and polysomnography was conducted for all participants. A review of the literature about SDB in patients with CM-II was performed.Forty patients were included (20 patients vs 20 control patients). SDB was identified in 45% of patients, a significantly higher prevalence compared to control patients. Three patients presented with purely obstructive SDB, 3 patients with purely central SDB, and 3 patients with both obstructive and central SDB. Compared with control patients, patients with CM-II showed a higher oxygen desaturation index (median: CM-II, 3.7; interquartile range, 1.6-19.5; control patients: 1.1; interquartile range, 0.3-3.2) and obstructive apnea-hypopnea index (median: CM-II, 1.5; interquartile range, 0.5-5.1; control patients, 0.1; interquartile range, 0.0-0.7). A logistic regression showed that the risk of developing SDB in patients affected by CM-II was 14.7 times higher than in the control population.Our study and literature review showed a high prevalence of SDB in patients with CM-II. These patients are often asymptomatic at diagnosis, suggesting that PSG should be routinely provided in this population.Lazzareschi I, Curatola A, Massimi L, et al. Sleep-disordered breathing in patients with Chiari malformation type II: a case-control study and review of the literature.

Introduction Spinal dysraphism (SD) is a general term used to refer to developmental abnormalities of the spine that involves many clinical conditions including myelomeningocele (MMC). In these patients, neurogenic bladder (NB) is a common and predisposing factor for renal damage; the most frequently used approach to manage this situation is based on clean intermittent catheterization (CIC) and anticholinergic drugs. Urinary tract infections (UTIs) are a significant concern for these patients, and antibiotic prophylaxis is frequently used even if it is still a debated topic of literature. The purpose of this paper is to investigate the role and the real effectiveness of antibiotic prophylaxis in the reduction of incidence of UTIs in patients with spina bifida performing CIC. Methods We collected data of all patients performing CIC, who did their last follow-up visit in the period between January 2019 and January 2021, followed at the children multidisciplinary Spina Bifida Center of A. Gemelli Hospital in Rome. Data collected included age at referral, gender, type of SD lesion, serum creatinine and cystatin C levels, the use of anticholinergic medications, antibiotic prophylaxis and type of prophylaxis (oral/endovesical), age of starting prophylaxis with its duration/adherence, number of CIC/day and its duration, episodes of UTIs in the 2 years prior to the last follow-up, and presence and grade of vesical-ureteric reflux (VUR) on cystourethrogram. Results A total of 121 patients with SD performing CIC was included in the study; 66 (54%) presented ≥ 1 episode of UTIs in the last two years and 55 (46%) none. During the study period, 85 (70%) patients received antibiotic prophylaxis (ABP group) and 36 (30%) did not (NABP group): no statistically significative difference in terms of UTI development was observed between the two groups (p = 0.17). We also evaluated compliance to the therapy; 71 patients (59%) took antibiotic prophylaxis constantly (CABP group) and 50 (41%) did not do antibiotic prophylaxis constantly or did not do antibiotic prophylaxis at all (NCABP group): we observed a statistically significative difference in terms of UTIs with a 2.2 times higher risk of development at least one episode of UTIs in NCABP group. Conclusion In conclusion, antibiotic prophylaxis performed constantly, without interruption, is associated with a lower risk of developing urinary tract infections and consequently to develop renal failure in adulthood.

This review aimed to evaluate and summarize the current knowledge about the non-pharmacological neurological stimulation (NPNS) in patients with severe brain injuries (SBI). The approaches we analyzed included sensory stimulation, music therapy, virtual reality, transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS).We performed a review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standards. The key words used for the search across electronic databases such as PubMed and the Cochrane Library were "brain injury" or "coma" or "vegetative state" and "neurological stimulation" or "sensory stimulation" or "music therapy" or "virtual reality" or "transcranial direct current stimulation" or "transcranial magnetic stimulation".38 studies matched the inclusion criteria. These articles were categorized into five clusters: sensory stimulation, music therapy, virtual reality, transcranial direct current stimulation and transcranial magnetic stimulation. Hence, a concise summary of each study was made up, including study population characteristics, type of non-pharmacological neurological stimulation, neurological clinical outcomes or neuroimaging outcomes.Overall, all the non-pharmacological approaches to neurological stimulation in patients with SBI seem to be innovative and promising. Further randomized clinical trials, including a wide range of patients, will be necessary to definitely validate these methods and develop standardized protocols shared in the scientific community.

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.

Fever is the most common problem of children admitted to emergency department (ED). The management of febrile patients ≤ 60 d old admitted to the Pediatric Emergency Department in the last 5 y was evaluated, applying the invasive bacterial infection (IBI) score proposed to evaluate the reliability and safety of this score in the authors' setting. Medical records of 280 patients with fever reported and/or detected in ED were retrospectively analyzed. A total of 166 patients were enrolled, whose average IBI score was 2.98 IBI score

Lung ultrasound (US) in the evaluation of suspected pediatric pneumonia is increasingly used and has a recognized role in evaluating pleural effusions, although there are no detailed studies specifically addressing its use in the pediatric population. To define lung US findings of severe pediatric community-acquired pneumonia that required surgical procedures during admission. Our prospective case-control study compared lung US findings in patients ages 1 month to 17 years admitted with community-acquired pneumonia that required surgical procedures from findings those who did not. Lung US was performed at admission and always before surgical procedures. Medical treatment, laboratory and microbiological findings, chest X-ray, computed tomography scan and surgical procedures are described. One hundred twenty-one children with community-acquired pneumonia were included; of these, 23 underwent surgical intervention. Compared with the control group, children requiring a surgical procedure had a significantly higher rate of large consolidations (52.2%; 95% confidence interval [CI]: 30.6% to 73.2%), larger and complicated pleural effusions (100%; 95% CI: 85.2% to 100%), and both liquid and air bronchograms (73.9%; 95% CI: 51.6% to 89.8%). Larger consolidations, larger and more complicated pleural effusions, and liquid and air bronchograms were associated with surgical treatment.

OBJECTIVES Lung ultrasound (LUS) has gained a primary role in the diagnosis and management of pleuropulmonary disorders in pediatric practice. However, normal and pathologic patterns are translated from adult studies and have never been specifically studied in children, particularly in infants. This was a prospective observational pilot study aiming to define the normal LUS pattern in healthy infants during the first 6 months of life. METHODS We recruited healthy neonates at 7 to 10 days of life, and these were followed until the sixth month of life (times: 7-10 days, 1 month, 3 months, and 6 months). We excluded neonates with a gestational age before 33 weeks and neonates with cardiac or lung abnormalities or diseases, immune deficiencies, metabolic or genetic conditions, and acute or chronic respiratory diseases. A LUS evaluation was performed by a single certified pediatrician. The chest wall was examined in 18 areas, addressing A-lines, short and long B-lines, pleural abnormalities, and subpleural consolidations. RESULTS Thirty-seven neonates were enrolled and followed until the sixth month of life, 27 (73%) of whom were born at term (≥37 weeks) and 10 (27%) of whom were born preterm (33-36 weeks). Most of the patients at 7 to 10 days showed multiple B-lines (long and short) with a progressive normalization toward a normal A pattern at 6 months (P

Objective To investigate ultrasound features of diaphragm motion and function in type 1 spinal muscular atrophy (SMA-1) patients. Design Prospective study. Patients The study cohort included SMA-1 children younger than 18-year-old. Control subjects included type 2 and type 3 SMA and other neuromuscular disorders younger than 18-year-old. Methodology Diaphragm ultrasound evaluating diaphragmatic excursion, speed of diaphragmatic contraction, duration of the respiratory cycle, inspiratory/expiratory relationship, end-inspiratory and -expiratory thickness, thickening fraction, and pattern of contractility. The interrater reliability for each variable was established by calculation of Cohen's k coefficient. Results Twenty-three SMA-1 patients and 12 controls were evaluated. Diaphragm ultrasound values were within normal ranges in all study cohort patients and no difference was found with controls. There was a gradient of diaphragm function with SMA 1.9 subgroup having the best and SMA 1.1 having the worst parameters, particularly in end-inspiratory thickness and diaphragmatic excursion (P = .031 and P = .041, respectively). Seventy-four percent of SMA-1 patients had a dysmotility pattern of diaphragm contraction, mostly represented in SMA 1.9 subgroup (P = .001). This pattern was observed in 92.8% of children on noninvasive ventilation (NIV) for less than 16 hours/d of and in 20% patients with invasive ventilation or NIV for more than 16 hours/d (P = .027). The dysmotility pattern was never observed in the control group. The levels of interobserver agreement were high for "diaphragm irregularities," "inspiratory/expiratory relationship," and "diaphragm thickness," and good for the other variables. Conclusions Ultrasound can be used to evaluate diaphragm function and contractility in SMA-1 children, providing additional information to the clinical examination and functional respiratory tests, describing a characteristic contractility pattern in these patients. Longitudinal studies are needed to understand the impact of diaphragm dysmotility and other parameters on long-term outcome in SMA-1 patients.

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinical radiological syndrome with good prognosis that affects mainly children or young adults. We describe two cases of MERS, associated with echovirus 6 and influenza A infection, in two twin sisters, at the age of 4 years. Genetic analysis was performed; next exome sequencing was performed on twins to disclose the eventual causative gene. Two different frameshift mutations in the CD36 gene [NM_000072] were found in both twins and confirmed by Sanger sequencing. To best of our knowledge, we report an association between CD36 mutation and MERS. We think that this relation between CD36 and inflammation has had a crucial role in the same callosal alteration during viral disease in the twin sister with the same gene mutation.

Acute wheezing is a common clinical presentation of viral respiratory infections in children, which can also be caused by exposure to allergens and, rarely, by foreign body inhalation. Since the beginning of the COVID-19 (coronavirus disease 2019) outbreak, several public health interventions have been adopted to reduce viral spread. The aim of this study was to analyze the impact of the COVID-19 pandemic and lockdown measures on Pediatric Emergency Department (ED) admission for acute wheezing.We compared demographics and clinical data of patients admitted to the ED for acute wheezing during the COVID-19 outbreak and in the 5 previous years through a retrospective cross-sectional study.During the COVID-19 outbreak we observed an average drop of 83% in pediatric ED admission for acute wheezing, compared to the 5 previous years. In this period, 121 (80.7%) children presented with wheezing and 29 (19.3%) with bronchiolitis. The mean age of the sample was higher compared to the 5 previous years. We also noted an increased number of children presenting with higher acuity color codes during the COVID-19 period, while no differences emerged as for the hospitalizations. During the pandemic we recorded a decrease in the number of viral infections detected. Only two cases of wheezing associated with SARS-CoV-2 were identified.The COVID-19 outbreak and the national lockdown led to a drop of the number of admission to the ED for wheezing in children. This could be due to a reduction in the circulation of common respiratory viruses and partially to a reduced exposure to aeroallergens during the COVID-19 period. Future epidemiological surveillance studies will be needed to support these prelimianry findings.

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.

to identify most frequent risk factors and to propose prevention strategies for the children admitted to Pediatric Emergency Department (PED) with acute poisoning.We performed a retrospective study in a tertiary care hospital, describing the frequency and nature of pediatric poisoning, clinical management and outcome.We collected data of 436 children admitted for acute poisoning. The mean age was 30 months and 51.1% were male. Most poisoning incidents (90.1%) were unintentional and drug ingestion (39.4%) was the leading cause of poisoning. Acute poisoning happened at home in 83,7% of cases and the mother was the most frequent caregiver during the event in 61.5%. No died were reported.Our study showed that the two categories of patients at greatest risk for acute poisoning are children under 3 years and adolescents over 12 years. Adequate information campaigns about toxic substances are essential for children, adolescents and their parents.

Pupillometry has been used to assess pain intensity and response to analgesic drugs in adults. The aim of this study was to verify the usefulness and effectiveness of the pupillometer to assess pain and depth of sedation in pediatric patients undergoing painful procedures and to optimize pain management by observing pupillary variations induced by opioids.This is a prospective, monocentric study conducted in the sedation room of the Pediatric Intensive Care Unit of Fondazione Policlinico A. Gemelli in Rome. A population of 22 pediatric patients who underwent painful procedures was enrolled. Eleven children were sedated by opioid drugs. Heart rate, systolic blood pressure, diastolic blood pressure, bispectral index, maximum pupil size (Size), pupil change (CH), Neurological Pupil Index (NPi) were collected over four times: before starting the procedure; before the painful stimulus (when the patient was sedated); when the painful stimulus was applied; at the end of the procedure. A NeurOptics NPi-200 pupillometer was used for the study.Statistical significance in the variation of haemodynamic parameters was less significant than the variation obtained by analyzing the pupillary parameters: a significant change in NPi and CH in the transition from wakefulness to sedation and from the application of the painful stimulus to awakening was found in both study populations, patients who have received opioids and patients who have not received opioids. Changes in the mean CH of the pupil diameter correlate with the depth of sedation, and the size values vary in relation to the administration of opioids.Our findings highlight the potential role of pupillometry as a non-invasive method to objectively quantitate pain response in children to reach an efficient analgesic approach.

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 &lt, 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.

It is widely reported in the literature that CD4, CD8 and total T cell count are significantly reduced in critically ill patients with COVID‐19. Few weeks ago, we suggested natural killer (NK) cell count as a marker of severity in 34 hospitalized COVID‐19 patients. On this topic, our research group firstly described a novel potential COVID19 severity marker, Krebs von den Lungen‐6. This study aimed to investigate how a combination of COVID19 severity markers could be helpful in the clinical management of these patients. The combination of these validated, reproducible and non‐expensive bioindicators showed a good accuracy in discriminating between severe and non‐severe patients, suggesting a promising value of this approach in the early prediction of a more aggressive disease phenotype. Despite its monocentric design, our study confirms the reliable dysregulation of innate immune responses, particularly involving NK cells, and suggests that surveillance of a peripheral biomarkers’ panel, including lymphocyte cell counts and KL‐6, may be useful in the clinical management of severe COVID‐19 patients. This article is protected by copyright. All rights reserved.

Congenital lung malformations (CLMs) include a group of different disorders. With widespread use of antenatal ultrasonography (aUS) and increased use of pre-natal magnetic resonance imaging (MRI), CLMs are increasingly detected, nevertheless the best postnatal imaging approach is not yet well defined: newborns usually undergo several chest X-rays and eventually computed tomography to confirm the diagnosis. In this case series, we show lung ultrasound features of three different cases of congenital lung malformations, describing prenatal and postnatal images comparing different imaging techniques.

Hereditary spherocytosis is the most common inherited hemolytic anemia characterized by the presence of spherical-shaped erythrocytes on peripheral blood smear. The clinical manifestations of HS are highly variable, from severe forms to asymptomatic forms. HS is caused by defects in red blood cell membrane proteins, encoded by the ANK1, EPB42, SLC4A1, SPTA1 and SPTB genes. Mutation of the ANK 1 gene is the most common and inheritance is autosomal dominant in 75% of cases. In our case, heterozygous an ANK1 c.4123C > T mutation was identified in a 4-year-old girl, using targeted next-generation sequencing and Sanger sequencing.

Iron deficiency anaemia is a common disorder in the paediatric age-group. The association between iron deficiency and venous thrombosis in children without an underlying illness is rare. Two cases are described. A 17-year-old girl had been taking oestrogen-progestogen therapy for contraception for about 2 years and developed a lower-limb deep vein thrombosis associated with pulmonary embolism. A 3-year-old girl was admitted to the paediatric emergency department with pallor, weakness and vomiting, and a cerebral CT showed a recent cerebral venous thrombosis. Both cases had severe iron-deficiency anaemia which increases a thrombotic tendency and could be a further crucial trigger of venous thrombosis in patients at low risk; therefore, in cases of unexplained thrombosis, it must always be considered to be a risk factor.Abbreviations APCR: activated protein C resistance; CMV: cytomegalovirus; CT: computerised tomography; CVST: cerebral venous sinus thrombosis; CVT: cerebral venous thrombosis; DVT: deep vein thrombosis; DOACs: direct oral anticoagulants; EBV: Epstein-Barr virus; ID: iron deficiency; IDA: iron deficiency anaemia; LMWH: low molecular weight heparin; PE: pulmonary embolism; RDW: red blood cell distribution width; VT: venous thrombosis.

BAL cellularity and lymphocyte immunophenotyping offer insights into lung inflammatory status. Natural killer (NK) cells are efficient effector cells, producing pro-inflammatory cytokines. A better understanding of the biology of NK cells in BAL in the lungs is necessary to improve the pathogenesis of fibrotic ILD and develop prospective targeted treatments. Our aim was to analyse NK and NKT-like cell percentages in BAL from 159 patients with different ILD: f-HP, f-NSIP, IPF and CTD-ILD, to evaluate their potential diagnostic/prognostic role. BAL NK cell percentages showed significantly higher values in IPF than in f-HP and f-NSIP, while BAL NKT-like cells showed significantly lower values in the f-NSIP than the f-HP and IPF. A cut-off of 4%NK cells in BAL of IPF showed a significant difference in survival rate. It suggests a possible new marker of survival and raises the possibility of new targeted approach in treatment and management of IPF.

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

Introduction: Reye syndrome is a rare acquired metabolic disorder appearing almost always during childhood. Its etiopathogenesis, although controversial, is partially understood. The classical disease is typically anticipated by a viral infection with 3-5 days of well-being before the onset of symptoms, while the biochemical explanation of the clinical picture is a mitochondrial metabolism disorder, which leads to a metabolic failure of different tissues, especially the liver. Hypothetically, an atypical response to the preceding viral infection may cause the syndrome and host genetic factors and different exogenous agents, such as toxic substances and drugs, may play a critical role in this process. Reye syndrome occurs with vomiting, liver dysfunction and acute encephalopathy, characterized by lack of inflammatory signs, but associated with increase of intracranial pressure and brain swelling. Moreover, renal, and cardiac dysfunction can occur. Metabolic acidosis is always detected, but diagnostic criteria are not specific. Therapeutic strategies are predominantly symptomatic, to manage the clinical and metabolic dysfunctions. Case reports: We describe three cases of children affected by Reye syndrome with some atypical features, characterized by no intake of potentially trigger substances, transient hematological changes and dissociation between hepatic metabolic impairment, severe electroencephalographic slowdown and slightly altered neurological examination. Conclusions: The syndrome prognosis is related to the stage of the syndrome and the rapidity and the adequateness of intensive care treatments. The analysis of the patients leads to a greater awareness of the difficult diagnosis of this not well completely known syndrome.

Introduction: Ischemic stroke is an important cause of death and long-term morbidity in children. Viral respiratory infections are emerging as important risk factors for ischemic stroke in this age group of patients. Direct action of virus against cerebral vessels, autoimmune reactivity, and an increased production of cytokines have all been advocated as main factors in determining ischemic stroke. Case Report: We report the case of an EBV-induced ischemic stroke in a caucasian 2-year-old female. The cerebrospinal fluid samples showed positivity of polymerase chain reaction for EBV infection, also confirmed by pharyngeal swab culture. Increased levels of interleukin 6 and interleukin 1β were also detected in the cerebrospinal fluid. Discussion: EBV infection has been identified as an important cause of neurological involvement in children. Findings of increased levels of interleukin 6 and interleukin 1β in the cerebrospinal fluid of the child with EBV induced-ischemic stroke seems to validate the role of pro-inflammatory cytokines as crucial mediators of cerebral thrombus formation. Conclusions: We believe that this report can be useful to clarify some pathophysiological mechanisms related to ischemic stroke related to Epstein-Barr Virus (EBV) infection in children. (www.actabiomedica.it)

Objective Metabolic syndrome is a cluster of cardio-metabolic risk factors associated with an increased risk of cardiovascular disease and type 2 diabetes. In the last two decades, several definitions of metabolic syndrome have been proposed for the pediatric population; all of them agree on the defining components but differ in the suggested criteria for diagnosis. This review aims to analyze the current diagnostic criteria of metabolic syndrome in pediatrics with reference to their feasibility and reliability in clinical practice. Methods The systematic research was conducted from January 2003 to June 2020 through MEDLINE via PubMed, Cochrane Library and EMBASE databases. Results After the selection phase, a total of 15 studies (182 screened) met the inclusion criteria and are reported in the present review. Twelve studies were cross-sectional, two were longitudinal and one was a consensus report. The sample population consisted of multiethnic group or single ethnic group, including Turkish, European, Asian and Hispanic subjects. Conclusions To date, there is not a univocal, internationally accepted pediatric definition of metabolic syndrome, which guarantees a high sensitivity and stability of the diagnosis. The definition proposed by IDF results the most straightforward and easy to use in clinical practice, having the unquestionable advantage of requiring measurements quickly accessible in clinical practice, without the adoption of multiple reference tables. Further research is needed to validate a new version of such definition which includes the diagnostic cut-off points recently suggested by published guidelines.

This study aims to evaluate the efficacy of the PECARN Rule (PR) in reducing radiological investigations in children with mild traumatic head injury in comparison with current clinical practice. A retrospective study was performed in our hospital between July 2015 and June 2020. Data of all children Conclusion: We demonstrated the safety and validity of the PR in our setting with 100% sensitivity in both age groups in identifying patients with ciTBI and theoretically in reducing performed CT scans by 29%. Therefore, in patients classified in the low-risk category, it is a duty not to expose the child to ionizing radiation. What is Known:• CT is the gold standard to identify intracranial pathology in children with head injury but CT imaging of head-injured children expose them to higher carcinogenic risk.• PECARN Rules support doctors in identifying children with ciTBI in order to reduce exposure to ionizing radiation. What is New:• We demonstrate the safety and validity of the PR with 100% sensitivity in both age groups in identifying patients with ciTBI.• In our setting, the application of PECARN Rule would theoretically have allowed us to reduce the CT scan by 29%.

Functional constipation (FC) represents 95% of pediatric constipation cases. The aim of this study was to assess the prevalence of Functional Constipation in children admitted to Pediatric Emergency Department (ED) with acute abdominal pain, the demographic factors associated, the use of imaging exams and laboratory tests.A retrospective observational study was conducted on 4100 medical records of children aged 0 to 18 years.Among children with abdominal pain, 11.3% of them had a discharge diagnosis of constipation and 45.5% underwent imaging exams. Most of children (93.9%) were discharged with home therapy and 6.5% of patients needed of additional visits. In ED 6.7% of patients underwent enema, 45.2% were discharged with indication to perform it at home.FC is a medical condition that could be managed in the outpatient setting, even if we observed a significant percentage of cases in ED. We observed over-utilization of radiologic tests, whereas the diagnosis should be clinical.

The increased incidence of childhood obesity and related non-alcoholic fatty liver disease (NAFLD) has determined the need to identify a non-invasive technique to diagnose and monitor NAFLD. Two-dimensional shear wave elastography (2D-SWE) has emerged as a reliable, non-invasive, tool to evaluate liver tissue elasticity in clinical practice. Aims of this study were to longitudinally evaluate 2D-SWE changes in relation to weight loss, metabolic profile, and body composition modifications and to investigate the correlation between 2D-SWE variation and clinical and biochemical indices of cardio-metabolic risk in obese children. Thirty-three children underwent anthropometric, bioimpedenziometric, fasting biochemical assessments, ultrasound, and SWE evaluations, at baseline (V0) and after a 12-months of follow-up (V12). Diet and physical activity programs have been prescribed to all patients according to European Society of Endocrinology and Pediatric Endocrine Society recommendations. Adherence to the prescribed diet and physical activity program was checked every 3 months during the 12-month of follow-up. Variation of all parameters was evaluated in intragroup and intergroup comparison analysis in children, who had not lost weight (Group A) and those who had lost weight (Group B) at V12. Study population was also analyzed dividing it into two groups with respect to 2D-SWE liver elasticity value ≤10.6 kPa or >10.6 kPa. A significant reduction of mean 2D-SWE value was demonstrated both in the entire cohort (p = 0.002) and in Group B children (p = 0.004). Intragroup comparison analysis, between V0 and V12, documented a significant decrease of 2D-SWE and BMI SDS and a significant improvement of metabolic profile (decrease of HOMA-IR, HbA1c, oral glucose tolerance test 120-min glucose and insulin, triglycerides, triglycerides/HDL-ratio, transaminases, uric acid, and increase of Matsuda-index and HDL) in children of Group B but not in those of Group A. Intergroup comparison analysis showed significant differences for BMI, BMI SDS, transaminases and several parameters of glucose and lipid metabolism, between Group A and Group B children after 12-months of follow-up. No significant differences were documented with regard to clinical and biochemical variables by dividing the population in accordance with the 2D-SWE cut-off of 10.6 kPa. These results suggested a relation between weight loss, metabolic profile improvement and 2D-SWE value reduction. SWE could play a significant role in the non-invasive assessment of NAFLD in children and adolescents with obesity.

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

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

SARS-CoV2-induced direct cytopathic effects against type II pneumocytes are suspected to play a role in mediating and perpetuating lung damage. The aim of this study was to evaluate serum KL-6 behavior in COVID-19 patients to investigate its potential role in predicting clinical course. Sixty patients (median age IQR, 65 (52–69), 43 males), hospitalized for COVID-19 at Siena COVID Unit University Hospital, were prospectively enrolled. Twenty-six patients were selected (median age IQR, 63 (55–71), 16 males); all of them underwent follow-up evaluations, including clinical, radiological, functional, and serum KL-6 assessments, after 6 (t1) and 9 (t2) months from hospital discharge. At t0, KL-6 concentrations were significantly higher than those at t1 (760 (311–1218) vs. 309 (210–408) p = 0.0208) and t2 (760 (311–1218) vs 324 (279–458), p = 0.0365). At t0, KL-6 concentrations were increased in patients with fibrotic lung alterations than in non-fibrotic group (755 (370–1023) vs. 305 (225–608), p = 0.0225). Area under the receiver operating curve (AUROC) analysis showed that basal KL-6 levels showed good accuracy in discriminating patients with fibrotic sequelae radiologically documented (AUC 85%, p = 0.0404). KL-6 concentrations in patients with fibrotic involvement were significantly reduced at t1 (755 (370–1023) vs. 290 (197–521), p = 0.0366) and t2 (755 (370–1023) vs. 318 (173–435), p = 0.0490). Serum concentrations of KL-6 in hospitalized COVID-19 patients may contribute to identify severe patients requiring mechanical ventilation and to predict those who will develop pulmonary fibrotic sequelae in the follow-up.

Objectives: The main aim of this study was to evaluate BMI changes in children and adolescent with obesity or overweight, analyzing the possible risk factors that contributed to weight gain during a pandemic-associated lockdown. Material and Methods: The study was conducted at the Pediatric Endocrinology Department of a third-level University Hospital in Rome, including children and adolescents with overweight and obesity. Personal, anthropometrics data and other information about physical activity, eating habits and psychological aspects were collected. Results: We included in our study 64 participants, of which 33 (51.6%) were patients with overweight and 31 (48.4%) with obesity. We divided patients in two groups: patients with pre-versus post-lockdown Δ-BMI > 0 (31, 48.4%) and patients with Δ-BMI < 0 (33, 51.6%). Our data showed that patients whose BMI increased were more sedentary (p=0.024 for physical activity and p=0.005 for hours spent with videogames) during the pandemic. As for the eating habits more than half of the subjects (67.2%) had increased the consumption of homemade desserts, bread, pasta and pizza, and a worse diet was found in patients with BMI gain (p=0.000). Regarding the psychic condition the 80% of patients reported psychological discomfort, and patients with an increase in BMI had episodes of emotional feeding more frequently (p=0.016). Conclusions: The COVID19 pandemic has had disastrous effects not only directly, but also indirectly through the lockdown especially on some categories, such as adolescents with overweight and obesity. The results indicate that it also causes significant changes in lifestyle, physical inactivity and psychological problems among children and adolescents with obesity/overweight. (www.actabiomedica.it)

PURPOSE: Foreign body (FB) ingestions represent a common problem in children. History and physical examination are commonly not enough to diagnose a foreign body ingestion; therefore, conventional radiography is routinely used to detect them. Point-of-care ultrasound is widely used in the emergency department for several diagnostic applications but there are few articles describing the possibility to use point-of-care ultrasound to detect ingested foreign bodies, and the necessary training to get competent in this application. The main objective of this paper is to illustrate the use of point-of-care ultrasound (POCUS) to detect ingested foreign bodies. The secondary objective is to describe a limited training, necessary for emergency pediatricians, to obtain this skill. METHODS: This is a case series of eight pediatric patients who presented to the pediatric Emergency Department (ED), with suspected ingestion of FB, and were assessed with POCUS. Physician sonographers were two pediatricians and three residents in pediatrics working in two Italian Pediatric EDs. All sonographers participated in a 2-day POCUS workshop which included the most common pediatric POCUS applications. RESULTS: POCUS, performed by emergency pediatricians who participated to a limited training, allowed to always identify the foreign bodies ingested. CONCLUSIONS: We demonstrate that an appropriate and limited training allows pediatric emergency physicians to correctly identify foreign body in the esophagus or stomach. Point-of-care ultrasound in foreign body ingestion in the Emergency Department may allow to prioritize the escalation of care in children and it can contribute to reduce the time to endoscopic management when needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40477-020-00452-z) contains supplementary material, which is available to authorized users.

PURPOSE: Point-of-care ultrasound (POCUS) has been shown to have unique potential in low-income countries. Physicians and other healthcare providers can perform effective scans after a short period of training. This study aimed to evaluate indications and utility of ultrasonography as the main imaging service in a poor rural sub-Saharan region of Africa. Second, it evaluated the effect of a short training on POCUS for non-physician health providers and their agreement with a group of Italian physicians. METHODS: This study was undertaken in Lokomasama—a chiefdom of Sierra Leone—between January and February 2019. Based on clinical indications, ultrasound findings were evaluated with respect to the initial diagnostic hypothesis. Volunteer doctors conducted a theoretical–practical training of two community health officers (CHO) on chest and abdominal POCUS and E-FAST protocol. The evaluation of the achieved technical skills was obtained with a numeric score. Inter-observer agreement concerning ultrasound diagnosis based on clinical indications was assessed. RESULTS: A total of 196 consecutive patients underwent ultrasound examination. POCUS findings were in keeping with the clinical diagnosis in the 49.5%. POCUS changed the initial diagnosis in 17% of cases. After training, E-FAST and POCUS knowledge score was 90% and 83%, respectively. An excellent inter-observer agreement (0.88) was found between CHOs and physicians. CONCLUSION: POCUS represents a powerful diagnostic tool in a low-income country that may improve the patient management. Training of non-physician health providers is doable and may improve healthcare management in resource-limited settings.

AIMS: Developmental dysplasia of the hip is an important cause of disability in children and young adult and it also has a significant socio-economic impact in our society. The main objective of our study is to evaluate, in our hospital, the effectiveness of a universal ultrasound screening protocol and to assess the general knowledge about the theme of pediatricians and neonatologists. METHODS: Retrospective study of infants born from January 2016 to April 2019, evaluated with hip ultrasound (Graf method). Risk factors assessed were female gender, breech presentation at birth, positive family history and twin birth. For the secondary objective, an anonymous and validated questionnaire was distributed to all pediatricians and neonatologists. RESULTS: Among the 4000 hips analyzed, on ultrasound examination, 98.8% hips resulted mature or immature but appropriate for age, while 1,2% hips were pathological. Analyzing the mature or immature hips, 2,4% were positive on clinical examination and 97,6% were negative. In relation to ultrasound pathological hips, 33,3% have positive clinical examination, while 66,7% negative. From the analysis of risk factors a significant association emerged between female sex, breech presentation and family history with the ultrasound pathological findings. The results of Survey showed that inadequate training about developmental dysplasia of the hip is done during medical school. CONCLUSIONS: A universal ultrasound screening allowed us to identify developmental dysplasia of the hip in a number of children with normal clinical examination and no risk factors. Specific training courses should be implemented regarding Developmental Dysplasia of the Hip for neonatologists and pediatricians. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40477-020-00463-w) contains supplementary material, which is available to authorized users.

Anomalous origin of left coronary artery from the pulmonary artery (ALCAPA) is a life-threatening ischemic congenital cardiac disease, resulting in myocardial dysfunction and heart failure within the first year of life. The authors report the case of a 1-mo-old infant with a radiological diagnosis of pneumonia handled with point-of-care lung ultrasound (POCUS) due to the persistence of dyspnea, despite a week of antibiotic therapy. Lung ultrasound showed a non-univocal interpretation of the lesion and gave indication to the second level instrumental diagnostics that confirmed the presence of ALCAPA. There is no case of lung ultrasound aiding to the early diagnosis of ALCAPA and no indirect ecographic signs of ALCAPA that have been described in literature yet.

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.

Community-acquired pneumonia (CAP) is associated with high morbidity and mortality among children worldwide. Over the last 10 years, lung ultrasound (US) has been widely studied as an alternative diagnostic tool for adult and pediatric CAP with excellent results. In this case series, we describe clinical and laboratory results as well as detailed lung US findings in 6 children with CAP, showing the potential use of lung US in monitoring the response to antibiotic therapy.

The AU-rich element (AUUUA)n, found in the 3' noncoding region of many short-lived cytokine and proto-oncogene mRNAs, is sufficient to specifically target these mRNAs for rapid degradation in mammalian cells. The mechanism by which the AU-rich element promotes rapid mRNA decay is not known. Previous studies have shown that release of intracellular stored calcium by ionophore treatment of thymocytes and mast cells inhibits the rapid turnover of AU-rich interleukin mRNAs. Increased cytoplasmic half-life of interleukin mRNAs was linked to calcium-induced activation of the N-terminal c-Jun kinase. In this report we have characterized the calcium-induced stabilization of AU-rich mRNAs. We show that calcium induces stabilization of mRNAs with canonical AU-rich elements in all cell types tested. These results indicate that short-lived mRNA stabilization by calcium is not unique to immune cells nor interleukin mRNAs, but is a widespread default response that includes generic AU-rich mRNAs. Stabilization is shown to be rapid but transient, and to act without altering nuclear transcription or cytoplasmic translation rates. These data support the view that calcium release likely stabilizes short-lived mRNAs by altering trans-acting decay factors that promote AU-rich mRNA turnover.

The nature of the link (causal vs non-causal) between low 1,25-OH vitamin D and insulin resistance (IR) in patients with chronic kidney disease (CKD) remains elusive. We have now made a post hoc analysis of the effect of vitamin D receptor activation by paricalcitol on IR in the complete dataset of a double-blind, randomized, placebo controlled trial, the Paricalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY).Eighty-eight patients with stage 3-4 CKD were randomized (1:1) to receive 2 μg/day paricalcitol or matching placebo for 12 weeks. IR was measured by five IR indices: the homeostasis model assessment of insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), the McAuley index, the HOMA corrected for adiponectin (HOMA-AD) and the Leptin-adiponectin ratio (LAR). As compared to placebo, paricalcitol produced the expected small rise in serum calcium (+0.07 mmol/L, P = 0.01) and phosphate (+0.08 mmol/L, P = 0.034) and the expected parathyroid hormone suppression (-96 pg/ml, P 0.001). However, the drug largely failed to affect the five indices of IR which remained unchanged both in the active and the placebo arm (paricalcitol vs placebo, P ranging from 0.25 to 0.62) and no effect modification of paricalcitol on IR by vitamin D or other parameters was registered.Paricalcitol treatment for 12 weeks does not improve IR in patients with stage 3-4 CKD. Low vitamin D receptor activation is not a causal factor for IR in the CKD population.