Cerebral and systemic near infrared spectroscopy patterns in preterm infants treated by caffeine.

AIM: To investigate the effects of caffeine loading/maintenance administration on near-infrared spectroscopy cerebral, kidney and splanchnic patterns in preterm infants. METHODS: We conducted a multicentre case-control prospective study in 40 preterm infants (gestational age 29 ± 2 weeks) where each case acted as its own control. A caffeine loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg after 24 h were administered intravenously. Near infrared spectroscopy monitoring parameters were monitored 30 min before, 30 min during and 180 min after caffeine therapy administration. RESULTS: A significant increase (p < 0.05) in splanchnic regional oxygenation and tissue function and a decrease (p < 0.05) in cerebral tissue function after loading dose was shown. A preferential hemodynamic redistribution from cerebral to splanchnic bloodstream was also observed. After caffeine maintenance dose regional oxygenation did not change in the monitored districts, while tissue function increased in kidney and splanchnic bloodstream. CONCLUSION: Different caffeine administration modalities affect cerebral/systemic oxygenation status, tissue function and hemodynamic pattern in preterm infants. Future studies correlating near infrared spectroscopy parameters and caffeine therapy are needed to determine the short/long-term effect of caffeine in preterm infants.

Kidney function and renal resistive index in children with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a common pediatric rheumatic disease. Renal manifestations have been rarely observed in JIA, although amyloidosis could be a renal complication in systemic JIA (sJIA). To investigate renal damage in JIA children and to establish the relationship with treatment. Blood urea nitrogen (BUN), creatinine, cystatin C (CysC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urinary albumin excretion (UAE), estimated glomerular filtration rate (eGFR), and renal resistive index (RRI) were assessed in 49 JIA children (9 boys/40 girls, mean age 10.3 ± 3.8 years) and in 49 healthy controls (24 boys/25 girls, mean age 11.3 ± 3.4 years). Twenty-two JIA patients were on methotrexate (MTX) therapy (group A) and 27 on biologic drugs (group B). CysC and BUN (respectively, 0.8 ± 0.1 vs. 0.7 ± 0.1 mg/dl; 13.3 ± 2.9 vs. 11.7 ± 1.4 mg/dl) were higher (p ≤ 0.001) whereas creatinine and eGFR (respectively, 0.5 ± 0.1 vs. 0.6 ± 0.1 mg/dl; 99.2 ± 10.5 vs. 122.5 ± 19.8 ml/min/1.73 m2) were lower in JIA children as compared to controls (p < 0.001). UAE resulted higher in patients than in controls (p = 0.003). Mean RRI was higher in JIA children than controls (0.7 ± 0.04 vs. 0.6 ± 0.04; p < 0.001). Group B showed higher mean RRI than group A (0.7 ± 0.1 vs. 0.7 ± 0.04; p < 0.001). Associations were found between RRI and ESR, JADAS-27, disease state, BMI-SDS (p < 0.001), CRP (p = 0.003) and eGFR (p = 0.001). JIA children had reduced eGFR, increased UAE and higher RRI values, than controls. RRIs were higher in patients on biologic drugs than MTX group and were associated with inflammation indexes and disease state, suggesting a direct effect of the disease.

Early predictors of abnormal MRI patterns in asphyxiated infants: S100B protein urine levels.

OBJECTIVES: The early detection and stratification of asphyxiated infants at higher risk for impaired neurodevelopment is challenging. S100B protein is a well-established biomarker of brain damage, but lacks conclusive validation according to the "gold standard" methodology for hypoxic-ischemic encephalopathy (HIE) prognostication, i.e. brain MRI. The aim of the present study was to investigate the predictive role of urinary S100B concentrations, assessed in a cohort of HIE infants receiving therapeutic hypothermia (TH), compared to brain MRI. METHODS: Assessment of urine S100B concentrations was performed by immunoluminometric assay at first void and at 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120-h after birth. Neurologic evaluation, routine laboratory parameters, amplitude-integrated electroencephalography, and cerebral ultrasound were performed according to standard protocols. Brain MRI was performed at 7-10 days of life. RESULTS: Overall, 74 HIE neonates receiving TH were included in the study. S100B correlated, already at first void, with the MRI patterns with higher concentrations in infants with the most severe MRI lesions. CONCLUSIONS: High S100B urine levels soon after birth constitute trustable predictors of brain injury as confirmed by MRI. Results support the reliability of S100B in clinical daily practice and open the way to its inclusion in the panel of parameters used for the selection of cases suitable for TH treatment.

Non-pharmacological treatments for pediatric refractory epilepsies.

INTRODUCTION: Antiseizure medications (ASMs) are the primary treatment option for epilepsies of wide etiologies, however, about 10-20% of children do not gain sustained seizure control and in this case, it is worth investigating 'alternative' therapeutic approaches aside from ASMs. Nowadays, non-pharmacological strategies for epilepsy treatment encompass dietary interventions, neurostimulation-based techniques, and biobehavioral approaches. AREAS COVERED: A search on PubMed database was conducted. Experimental and clinical studies, as well as meta-analysis and structured reviews on the latest non-pharmacological treatments for drug-resistant epilepsy (DRE) in children, were included. Special attention is given to the efficacy and tolerability outcomes, trying to infer the role novel approaches may have in the future. EXPERT OPINION: The large heterogeneity of primary clinical outcomes and the unavoidable subjective response of each patient to treatments prevents Researchers from the identification of a single, reliable, approach to treat DRE. The understanding of fine pathophysiologic processes is giving the way to the use of alternative therapies, such as the well-known ketogenic diet, in a 'personalized' view of treatment. The goal is to apply the non-pharmacological treatment most suitable for the patients sake.

Parents' Perspective of Antibiotic Usage in Children: A Nationwide Survey in Italy.

BACKGROUND: Antibiotics represent the most widely prescribed drugs in children worldwide, both in hospital and community settings. A comprehensive approach to understanding the reasons and determinants of antibiotic prescription in the pediatric age is needed. This study aimed to assess parents' attitudes and perspectives about antibiotic use. METHODS: Prospective observational study was conducted in all Italian Regions between February 1 and April 30, 2020, using a standardized questionnaire. RESULTS: Six thousand six hundred twenty-five parents from all Italian regions completed the survey. Seventy-six percent of parents were aware that only bacteria are the target of antibiotics, but 92.9% knew that the antibiotic has no direct effect on fever. Antibiotic self-prescription (10.4%) or by remote consultation by phone call (19.9%) or message (9.6%) were relatively common. Ninety-three percent of parents were aware that excessive use of antibiotics could select resistant bacteria and 84.7% of them knew that they could actively fight antibiotic resistance. About two thirds of participants (66.1%) received information on antibiotic resistance from their family pediatrician. Parents born of Italy or those with lower income had a higher probability of having less information from pediatricians or knowledge of proper antibiotic use. DISCUSSION: Our study suggests that parents' knowledge and attitudes toward antibiotic use and prescription are improving compared with previous studies, while there is still a gap regarding antibiotic resistance, particularly on practices that can reduce its burden. Our study's negative finding is that families from low-income settings or those born abroad have significantly more misconceptions about important antibiotic practices.

Perioperative GABA Blood Concentrations in Infants with Cyanotic and Non-Cyanotic Congenital Heart Diseases.

Perioperative stress detection in children with congenital heart disease (CHD), particularly in the brain, is still limited. Among biomarkers, γ-amino-aminobutyric acid (GABA) assessment in biological fluids appears to be promising for its regulatory action on the cardiovascular and cerebral systems. We aimed to investigate cyanotic (C) or non-cyanotic (N) CHD children for GABA blood level changes in the perioperative period. We conducted an observational study in 68 CHD infants (C: n = 33; N: n = 35) who underwent perioperative clinical, standard laboratory and monitoring parameter recordings and GABA assessment. Blood samples were drawn at five predetermined time-points before, during and after surgery. No significant perioperative differences were observed between groups in clinical and laboratory parameters. In C, perioperative GABA levels were significantly lower than N. Arterial oxygen saturation and blood concentration significantly differed between C and N children and correlated at cardiopulmonary by-pass (CPB) time-point with GABA levels. The present data showing higher hypoxia/hyperoxia-mediated GABA concentrations in C children suggest that they are more prone to perioperative cardiovascular and brain stress/damage. The findings suggest the usefulness of further investigations to detect the "optimal" oxygen concentration target in order to avoid the side effects associated with re-oxygenation during CPB.

S100B protein, cerebral ultrasound and magnetic resonance imaging patterns in brain injured preterm infants.

OBJECTIVES: The early detection of preterm infants (PI) at risk for intraventricular hemorrhage (IVH) and neurological sequelae still constitutes an unsolved issue. We aimed at validating the role of S100B protein in the early diagnosis and prognosis of IVH in PI by means of cerebral ultrasound (CUS) and magnetic resonance imaging (MRI) today considered standard of care procedures. METHODS: We conducted an observational case-control study in 216 PI of whom 36 with IVH and 180 controls. Standard clinical, laboratory, radiological monitoring procedures and S100B urine measurement were performed at four time-points (first void, 24, 48, 96 h) after birth. Cerebral MRI was performed at 40-42 weeks of corrected gestational age. RESULTS: Elevated (p<0.001, for all) S100B levels were observed in the IVH group at all monitoring time-point particularly at first void when standard monitoring procedures were still silent or unavailable. S100B measured at first void correlated (p<0.001) with the grade of hemorrhage by means of CUS and with the site and extension of neurological lesion (p<0.001, for all) as assessed by MRI. CONCLUSIONS: The present results showing a correlation among S100B and CUS and MRI offer additional support to the inclusion of the protein in clinical daily management of cases at risk for IVH and adverse neurological outcome. The findings open the way to further investigations in PI aimed at validating new neurobiomarkers by means of S100B.

Clinico-diagnostic features of neuralgic amyotrophy in childhood.

Neuralgic amyotrophy (NA), even known as Personage-Turner's syndrome (PTS), is a neurologic condition, affecting the lower motor neurons of brachial plexus and/or individual nerves or nerve branches, characterized by pain, muscle weakness/atrophy, and sensory symptoms. NA has an acute/subacute onset, after an infection or vaccination; it is more common in male and is rare in the pediatric population. The etiology remains uncertain, being considered heterogeneous and multifactorial. A severe acute neurologic pain around the shoulder girdle is the classic presenting symptom at onset. As the pain subsides, weakness and paresis develop. NA is usually unilateral, but sometimes, a subclinical contralateral limb involvement could be present and bilateral affection has been described. The diagnosis is clinical, through a comprehensive history and neurological examination. However, electrophysiological testing and imaging are critical, because there is no diagnostic test for PTS and it remains a diagnosis of exclusion. Upper brachial plexus peripheral involvement with weakness of periscapular and perihumeral muscles is the classic presentation, associated with electrophysiological evidence of denervation in the affected muscles. Imaging, laboratory, and genetic testing can be useful for the differential diagnosis. NA is in most cases a self-limiting condition, and it is characterized by good recovery. Treatment of NA usually involves a combination of corticosteroids, analgesics, immobilization, and physical therapy, even if limited data are available in children. Physiotherapy is required to maintain muscle strength.

Pediatrician's approach to diagnosis and management of group A streptococcal pharyngitis.

Group A streptococcal (GAS) pharyngitis is responsible for 20-30% of pharyngitis cases in children (Shulman et al. Clin Infect Dis 55(10):e86-e102, 2012). Recommendations for the diagnosis and treatment of GAS pharyngitis have been published by the Italian National Institute of Health guidelines in 2012 (ESCMID Sore Throat Guideline Group et al. Clin Microbiol Infect 18(Suppl 1):1-28, 2012). Adherence to such guidance is relevant for primary prevention of complications of GAS pharyngitis, above all rheumatic fever (RF). The aim of our study was to evaluate the application of Italian guidelines by the family pediatricians from the Abruzzo region. A validated questionnaire was completed by the family pediatricians and used for data collection. The 154 family pediatricians from Abruzzo (88% of the total number of family pediatricians) participated in the study. Out of the 1232 answers, 455 (37%) were wrong. Only 8% of the participants answered correctly all the questions, whereas 0.6% missed all the questions. Through the Spearman's correlation, our study found an inverse significant correlation between the questions regarding primary prophylaxis (Score B) and the work experience of pediatricians (Rho = - 0.276, p = 0.048). The majority of the family pediatricians from the Abruzzo region, in line with studies from other countries, have significant knowledge gaps about the diagnosis and treatment of GAS pharyngitis. Therefore, strategies to increase the pediatricians' awareness of the guidelines are needed, in order to reduce the RF incidence.

Acute rheumatic fever prophylaxis in high-income countries: clinical observations from an Italian multicentre, retrospective study.

OBJECTIVES: The aim of the study is to evaluate the compliance rate to secondary prophylaxis and the presence of rheumatic heart disease (RHD) in a cohort of Italian patients with acute rheumatic fever (ARF). METHODS: This is a multicentre retrospective study. The patients were divided into two groups by the presence or absence at last follow-up of RHD. Clinical features, ARF recurrences and the rate of compliance to secondary prophylaxis were evaluated. RESULTS: Two-hundred and ninety patients were enrolled (137 females; 153 males). Carditis at onset was present in 244 patients (84.7%). At the end of follow-up, 173 patients manifested RHD. Adherence to secondary prophylaxis was low in 26% of patients. The presence of RHD at follow-up was associated with the presence of carditis and its severity at onset (p=0.001), but it was not related to secondary prophylaxis adherence (p=NS). No association between prophylaxis adherence and ARF recurrence was found (p=NS) nor between ARF recurrence and RHD at the end of follow-up (p=NS). CONCLUSIONS: Poor adherence to secondary prophylaxis does not seem to be associated with increased risk of RHD in developed countries. Further studies are needed to confirm our data in a larger population.

Macrophage activation syndrome in Still's disease: analysis of clinical characteristics and survival in paediatric and adult patients.

Macrophage activation syndrome (MAS) is a reactive form of hemophagocytic lymphohistiocytosis, complicating Still's disease, both in paediatric and adult patients. In this work, we aimed to investigate clinical picture and outcome of Still's disease patients developing MAS. We performed a retrospective analysis of patients, both paediatrics and adults, affected by Still's disease attending our department. During the follow-up, each patient was investigated for MAS occurrence and possible predictors, clinical and laboratory factors, were analysed. We evaluated 50 patients affected by Still's disease, 21 paediatric and 29 adult patients. Ten patients experienced MAS (five adult and five paediatric patients) and its development significantly reduced the survival rate when compared with patients without this complication (p < 0.0001). The analysis of possible predictors showed that high-value systemic score (p = 0.03) and high levels of serum ferritin (p = 0.002) were independently associated with an increased likelihood of MAS. MAS occurrence significantly reduced survival rate in both paediatric and adult patients affected by Still's disease. The high levels of serum ferritin and an elevated systemic score, at the time of diagnosis, were significantly associated with MAS.

MBL2 and FCN2 gene polymorphisms in a cohort of Italian children with rheumatic fever: A case-control study.

BACKGROUND: Mannose-binding lectins and human ficolins are pattern-recognition proteins involved in innate immunity. A role for MBL2 and FCN2 gene polymorphisms in the pathogenesis of recurrent severe streptococcal infections and rheumatic carditis has been suggested. OBJECTIVES: The aim of this study is to evaluate the presence of MBL2 and FCN2 gene polymorphisms (SNPs) in children with a history of rheumatic fever (RF) and to investigate their possible role in RF clinical presentation and disease course. METHODS: A total of 50 Caucasian patients with RF were recruited with a control group of 52 healthy children. DNA was extracted for analysis of MBL2 gene (exon 1, codons: 52, 54, and 57) and FCN2 gene (promoter region at position -986, -602, and -4). RESULTS: The FCN2 AG genotype at the -986 position was more frequently observed in patients, as compared to healthy subjects (p = 0.006); furthermore, the A allele was identified as a possible risk factor for the development of RF (OR = 7.14, CI: 2.439-20.89). Conversely, the GG genotype at the same position was observed more frequently in the control group and can be considered a protective factor for the development of the disease (p = 0.001, OR = 8.37, 95% CI: 2.763-25.33). In addition, the FCN2 GG and AG genotypes in the -4 position were also found to be protective factors for the development of RF and for carditis respectively (OR = 3.32, CI: 1.066-10.364; OR = 0.15, 95% CI: 0.037-0.566). Finally, the AA genotype in the -602 position was associated with a late onset of RF (p = 0.006). The analysis of the MBL2 gene only resulted in a higher frequency of the AA genotype on position 57 in controls as compared to patients (p = 0.025). CONCLUSIONS: This is the first study evaluating the FCN2 gene polymorphisms in patients with RF and rheumatic carditis finding a protective effect of -986 GG and -4 GG genotypes in the development of RF and the -4 AG genotype for the development of carditis. Our data do not support a possible role for MBL2 polymorphisms in the pathogenesis and in the clinical manifestations of RF.