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Background: Nasopharyngeal tubes are useful in pediatric anesthesia for insufflating oxygen and anesthetics. During nasopharyngeal tube‐anesthesia, gas insufflation provides some positive oropharyngeal pressure that differs from the proximal airway pressure owing to the flow‐dependent pressure drop across the nasopharyngeal tube (ΔPNPT). Aims: This study aimed to investigate whether ΔPNPT could be used for calculating oropharyngeal pressure during nasopharyngeal tube‐assisted anesthesia. Methods: In a physical model of nasopharyngeal tube‐anesthesia, using Rohrer's equation, we calculated ΔPNPT for three nasopharyngeal tubes (3.5, 4.0, and 5.0 mm inner diameter) under oxygen and several sevoflurane in oxygen combinations in two ventilatory scenarios (continuous positive airway pressure and intermittent positive pressure ventilation). We then calculated oropharyngeal pressure as proximal airway pressure minus ΔPNPT. Calculated and measured oropharyngeal pressure couples of values were compared with the root mean square deviation to assess accuracy. We also investigated whether oropharyngeal pressure accuracy depends on the nasopharyngeal tube diameter, flow rate, gas composition, and leak size. Using ΔPNPT charts, we tested whether ΔPNPT calculation was feasible in clinical practice. Results: When we tested small‐diameter nasopharyngeal tubes at high‐flow or high‐peak inspiratory pressure, proximal airway pressure measurements markedly overestimated oropharyngeal pressure. Comparing measured and calculated maximum and minimum oropharyngeal pressure couples yielded root mean square deviations less than 0.5 cmH2O regardless of ventilatory modality, nasopharyngeal tube diameter, flow rate, gas composition, and leak size. Conclusion: During nasopharyngeal tube‐assisted anesthesia, proximal airway pressure readings on the anesthetic monitoring machine overestimate oropharyngeal pressure especially for smaller‐diameter nasopharyngeal tubes and higher flow, and to a lesser extent for large leaks. Given the importance of calculating oropharyngeal pressure in guiding nasopharyngeal tube ventilation in clinical practice, we propose an accurate calculation using Rohrer's equation method, or approximating oropharyngeal pressure from flow and pressure readings on the anesthetic machine using the ΔPNPT charts. [ABSTRACT FROM AUTHOR]

Summary: We describe a nonsurgical technique for managing gastric distention in infants with type C esophageal atresia, involving intubating the trachea with an umbilical catheter and entering the stomach through the fistula as soon as a flexible bronchoscope found its wide‐open orifice. This technique might have a special role when gastric distention precedes other commonly used preventive measures. [ABSTRACT FROM AUTHOR]

Advances in neonatal intensive care have markedly improved survival rates for infants born at a very early lung development stage (<26 weeks gestation). In these premature infants, even low inspired oxygen concentrations and gentle ventilatory methods may disrupt distal lung growth, a condition described as 'new' bronchopulmonary dysplasia (BPD). BPD usually develops into a mild form, with only few infants requiring ventilator support and oxygen supplementation at 36 weeks post-conception. No magic bullets exist for treating infants with established severe BPD. Current management of the disease aims at maintaining an adequate gas exchange while promoting optimal lung growth. Prolonged oxygen therapy and ventilator support through nasal cannulae or a tracheotomy are often required to maintain blood gases. Short-course, low-dose corticosteroids may improve lung function and accelerate weaning from oxygen and mechanical ventilation. Pulmonary hypertension is a major complication in infants with severe BPD. Pulmonary vasodilators, such as sildenafil followed by bosentan, may improve the oxygenation and pulmonary outcome. [ABSTRACT FROM AUTHOR]

Bacterial translocation as a direct cause of sepsis is an attractive hypothesis that presupposes that in specific situations bacteria cross the intestinal barrier, enter the systemic circulation, and cause a systemic inflammatory response syndrome. Critically ill children are at increased risk for bacterial translocation, particularly in the early postnatal age. Predisposing factors include intestinal obstruction, obstructive jaundice, intra-abdominal hypertension, intestinal ischemia/reperfusion injury and secondary ileus, and immaturity of the intestinal barrier per se. Despite good evidence from experimental studies to support the theory of bacterial translocation as a cause of sepsis, there is little evidence in human studies to confirm that translocation is directly correlated to bloodstream infections in critically ill children. This paper provides an overview of the gut microflora and its significance, a focus on the mechanisms employed by bacteria to gain access to the systemic circulation, and how critical illness creates a hostile environment in the gut and alters the microflora favoring the growth of pathogens that promote bacterial translocation. It also covers treatment with pre- and pro biotics during critical illness to restore the balance of microbial communities in a beneficial way with positive effects on intestinal permeability and bacterial translocation. [ABSTRACT FROM AUTHOR]

To determine the incidence and predisposing factors for severe bronchiolitis in previously healthy term infants <12 months of age experiencing their first episode of bronchiolitis. Epidemiological, clinical and virological data were prospectively collected. Severity was assessed by the need for ventilatory support. Of the 310 infants enrolled, 16 (5.1%) presented with severe bronchiolitis requiring ventilatory support (11 since admission). Compared with infants with less severe bronchiolitis, infants with severe disease presented with lower birth weight, gestational age, postnatal weight and postnatal age, and were more likely to be born by cesarian section. C-reactive protein positive results (>0.8 mg/dL) and pulmonary consolidation on chest X-ray were more common among infants with severe disease. Severity was independently associated with younger age on admission <30 days, respiratory syncytial virus (RSV) infection and lymphocyte counts <3200/μL. No significant differences were found between epidemiologic variables. Severe bronchiolitis is uncommon in previously healthy term infants <12 months of age and when present develops soon after disease onset. Severity is predicted by young age and RSV carriage, whereas epidemiologic variables seem less likely to intervene. [ABSTRACT FROM AUTHOR]

Exogenous surfactant has been the primary life-saving therapy for respiratory distress syndrome (RDS) of preterm infants for many years. More recently, early surfactant treatment administered less invasively by transient endotracheal intubation and combined to nasal ventilation has been shown to further improve neonatal outcome by reducing the need of mechanical ventilation. In addition to RDS, other neonatal and pediatric respiratory disorders characterized by surfactant inactivation or dysfunction, such as pulmonary hemorrhage, aspiration pneumonia, and viral lower respiratory tract infection, might also be amenable to surfactant replacement therapy. However, the nature of lung injury and the influence of co-morbidities may reduce the efficacy of surfactant in these conditions. Currently under investigation are new syntethic surfactant formulations which may be more effective and resistant to inactivation than natural ones and could be produced at a lower cost. The use of surfactants to deliver drugs directly to the lung also seems to be a promising technique worthy of study. [ABSTRACT FROM AUTHOR]

Introduction: Anastomotic stricture is a common complication following esophageal atresia (EA) repair, substantially affecting the patient's quality of life (QoL). Multiple dilations are often required to maintain the appropriate diameter of the esophagus, leading to ongoing challenges. The aim of this study is to assess the efficacy of oral viscous budesonide (OVB) in prolonging the time between symptom recurrence and subsequent dilation. Methods: We carried out a retrospective single-center study for pediatric patients (0-18 years) who had undergone recurrent esophageal dilations (=3) following EA repair and initiated treatment with OVB (1 mg/day <10 years, otherwise 2 mg/day). Efficacy of treatment was determined by assessing a dysphagia symptom score (DSS) =1 for at least 3 months. Recurrence time to dysphagia and dilation were analyzed according to Kaplan-Meier method. Results: Of 29 patients screened, 19 were enrolled: 19/19 were responsive to OVB and 13/19 (68%) didn't required further dilations. The median time between dilations was significantly prolonged compared to the pre-treatment period [30 months vs 2months; p<0.01] as well as the time to dysphagia relapse [18months vs 1 month; p<0.01]. Conclusion: Topical budesonide has proven to be an effective treatment for recurrent esophageal stricture in repaired EA. Further investigation is required to assess the long-term sustained response of symptoms to topical steroids. [ABSTRACT FROM AUTHOR]

Shock is a clinical disorder that challenges caregivers in the neonatal intensive care unit. The predominant cause of shock in neonates is sepsis. This article provides an overview of the current treatment of septic shock with particular emphasis on newer vasoactive drugs (milrinone, levosimendan and vasopressin) to support cardiovascular dysfunction. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Use of High-Flow Nasal Cannula Oxygen Therapy to Prevent Desaturation During Tracheal Intubation of Intensive Care Patients With Mild-to-Moderate Hypoxemia," by Romain Miguel-Montanes and colleagues in the 2015 issue.

Background: A new prepared oral viscous budesonide (PVB) has been effective in inducing clinical and histological remission in pediatric eosinophilic esophagitis (EoE).Aims: To evaluate the efficacy of a 12-week maintenance therapy on clinical, endoscopic, and histological remission using half of the dose used in the induction therapy.Methods: We prospectively enrolled pediatric patients with active EoE. After 12 weeks of induction therapy with PVB (< 150 cm: 2 mg/day; ≥ 150 cm: 4 mg/day) patients received a maintenance dose of half of the dose used in the induction therapy (1 mg or 2 mg) for another 12 weeks. A 12-week follow-up was then performed in all patients after the end of therapy. Endoscopy was performed at weeks 0, 12, 24, and 36. Symptoms, endoscopy, and histology scores were also calculated. Serum cortisol was evaluated during the treatment period.Results: We enrolled 20 children (15 males; median age 10 years; range 4-17). After the 12-week induction therapy 18 patients (90%) were in remission, with a significant decrease in the median peak of eosinophil count/HPF as well as a marked reduction in clinical, endoscopic, and histological scores (p < 0.01). At the end of the maintenance therapy (week 24), 17 patients (85%) were still in remission, while there were only 9 at week 36 (45%). No significant changes in cortisol levels were observed during the study period.Conclusions: The 12-week maintenance treatment with the half the dose of PVB was effective in sustaining remission at week 24; however, no reduction in the rate of relapse after suspension of treatment occurred. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the role of terlipressin in the management of severe pulmonary hypertension in congenital diaphragmatic hernia in children.

The article presents a study that describes an unusual association of long QT syndrome and Torsade de pointes (TdP) with hypertensive encephalopathy. A 9-year old child was diagnosed with posterior reversible encephalopathy using magnetic resonance imaging (MRI) of the brain, with laboratory test that suggests poststreptococcal glomerulonephritis. Moreover, the authors conclude that the study extends the severe neurologic complications of hypertensive encephalopathy to cardiac disorders.

A letter to the editor is presented in response to the article "Propofol Compared With the Morphine, Atrophine and Suxamethonium Regimen as Induction Agents for Neonatal Endotracheal Intubation: A Randomized, Controlled Trial," by S. Ghanta and colleagues.

A letter to the editor is presented about a case study analyzing hypoglycaemia in an infant with severe pulmonary hypertension.

Measuring work of breathing (WOB) is an intricate task during high-flow nasal cannula (HFNC) therapy because the continuous unidirectional flow toward the patient makes pneumotachography technically difficult to use. We implemented a new method for measuring WOB based on a differential pneumotachography (DP) system, equipped with one pneumotachograph inserted in the HFNC circuit and another connected to a monitoring facemask, combined with a leak correction algorithm (LCA) that corrects flow measurement errors arising from leakage around the monitoring facemask. To test this system, we used a mechanical lung model that provided data to compare LCA-corrected respiratory flow, volume and time values with effective values obtained with a third pneumotachograph used instead of the LCA to measure mask flow leaks directly. Effective and corrected volume and time data showed high agreement (Bland–Altman plots) even at the highest leak. Studies on two healthy adult volunteers confirmed that corrected respiratory flow combined with esophageal pressure measurements can accurately determine WOB (relative error < 1%). We conclude that during HFNC therapy, a DP system combined with a facemask and an algorithm that corrects errors due to flow leakages allows pneumotachography to measure reliably the respiratory flow and volume data needed for calculating WOB. [ABSTRACT FROM AUTHOR]

Hypoxic-ischemic encephalopathy (HIE) is an important cause of acute neurological damage in newborns at (or near) term. Several trials in recent years have shown that moderate hypothermia by total body cooling or selective head is an effective intervention to reduce mortality and major disability in infants survived a perinatal hypoxic-ischemic attack. Follow-up in these patients is very important to establish neurodevelopmental outcome, and specific markers can lead us to detect predicting sign for good or poor outcome. We reported a few cases of newborn with HIE treated with hypothermia, in whom the comparison between electroencephalogram (EEG) and magnetic resonance imaging (MRI) represents the first marker for neurodevelopment outcome prediction. The continuous EEG monitoring showed a depressed EEG activity with diffuse burst depression in 7 patients. No epileptic abnormalities were registered. In 10 out of 20 patients no abnormalities of the background activity and no epileptic abnormalities were observed. We found that a depressed EEG activity during the first 72 h of life and a diffused alteration of basal ganglia at MRI were correlated with a poor neurodevelopmental outcome at 18 months of follow-up. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study is to assess tumor response, treatment-related toxicities, progression-free survival (PFS), and overall survival (OS) in patients with relapsed/refractory brain tumors treated with bevacizumab-containing regimen. Methods: Patients that had received I and II line treatments with or without megatherapy were included. Doses and schedule were as follows: bevacizumab (BVZ) 10 mg/kg i.v. with irinotecan (IRI) 150 mg/m2 i.v. every 2 weeks ± temozolamide (TMZ) 200 mg/m2 p.o. daily for 5 days every 4 weeks. TMZ was omitted in heavily pretreated cases. Results: Between 2013 and 2018, 12 patients (3F/9M), median age 161 months (range 66–348), affected with medulloblastoma (n 7), or low-grade glioma (n 2), or high-grade glioma (n 3), received BVZ/IRI association (median courses 20, range 4–67); 3 of them continued single-agent BVZ (median courses 23, range 8–39). TMZ (median courses 8, range 2–26) was administered in eight patients and then stopped in three of them because of myelotoxicity or lack of compliance. Treatment was well tolerated. After 3 months, two complete responses, two partial responses, seven stable diseases, and one progressive disease were observed. Nine cases experienced an improvement in neurological symptoms. Median time to progression was 11 months (95% confidence interval, 4–18 months). Six-month and 2-year PFS were 75% and 42%, respectively. The OS is 33%; interestingly, two cases (one medulloblastoma and one high-grade glioma) are progression-free off-therapy since 30 and 48 months, respectively. Conclusions: BVZ/IRI association ± TMZ showed encouraging therapeutic activity and low toxicity in this series of relapsed/refractory brain tumors. [ABSTRACT FROM AUTHOR]

Background In this study we sought to evaluate the association between viral bronchiolitis, weather conditions, and air pollution in an urban area in Italy. Methods We included infants hospitalized for acute bronchiolitis from 2004 to 2014. All infants underwent a nasal washing for virus detection. A regional agency network collected meteorological data (mean temperature, relative humidity and wind velocity) and the following air pollutants: sulfur dioxide, nitrogen oxide, carbon monoxide, ozone, benzene and suspended particulate matter measuring less than 10 µm (PM 10 ) and less than 2.5 µm (PM 2.5 ) in aerodynamic diameter. We obtained mean weekly concentration data for the day of admission, from the urban background monitoring sites nearest to each child's home address. Overdispersed Poisson regression model was fitted and adjusted for seasonality of the respiratory syncytial virus (RSV) infection, to evaluate the impact of individual characteristics and environmental factors on the probability of a being positive RSV. Results Of the 723 nasal washings from the infants enrolled, 266 (68%) contained RSV, 63 (16.1%) rhinovirus, 26 (6.6%) human bocavirus, 20 (5.1%) human metapneumovirus, and 16 (2.2%) other viruses. The number of RSV-positive infants correlated negatively with temperature (p < 0.001), and positively with relative humidity (p < 0.001). Air pollutant concentrations differed significantly during the peak RSV months and the other months. Benzene concentration was independently associated with RSV incidence (p = 0.0124). Conclusions Seasonal weather conditions and concentration of air pollutants seem to influence RSV-related bronchiolitis epidemics in an Italian urban area. [ABSTRACT FROM AUTHOR]

Post-operative pediatric cerebellar mutism syndrome (PPCMS) is a clinical syndrome arising from cerebellar injury and characterized by absence of speech and other possible symptoms and signs. Rare reports described some benefit after administration of dopamine agonist therapy, but no treatment has proven efficacy. In this paper, we report on the dramatic, sudden resolution of PPCMS induced by midazolam administration in a boy who underwent posterior fossa surgery for choroid plexus papilloma of the fourth ventricle. In addition to clinical improvement, post-midazolam single-photon emission computed tomography also demonstrated amelioration of brain perfusion. [ABSTRACT FROM AUTHOR]

Although mechanical ventilation via an endotracheal tube has undoubtedly led to improvement in neonatal survival in the last 40 years, the prolonged use of this technique may predispose the infant to development of many possible complications including bronchopulmonary dysplasia. Avoiding mechanical ventilation is thought to be a critical goal, and different modes of noninvasive respiratory support beyond nasal continuous positive airway pressure, such as nasal intermittent positive pressure ventilation and synchronized nasal intermittent positive pressure ventilation, are also available and may reduce intubation rate. Several trials have demonstrated that the newer modes of noninvasive ventilation are more effective than nasal continuous positive airway pressure in reducing extubation failure and may also be more helpful as modes of primary support to treat respiratory distress syndrome after surfactant and for treatment of apnea of prematurity. With synchronized noninvasive ventilation, these benefits are more consistent, and different modes of synchronization have been reported. Although flow-triggering is the most common mode of synchronization, this technique is not reliable for noninvasive ventilation in neonates because it is affected by variable leaks at the mouth and nose. This review discusses the mechanisms of action, benefits and limitations of noninvasive ventilation, describes the different modes of synchronization and analyzes the technical characteristics, properties and clinical results of a flow-sensor expressly developed for synchronized noninvasive ventilation. [ABSTRACT FROM AUTHOR]

Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder characterized by early onset encephalopathy, chronic diarrhoea, petechiae, orthostatic acrocyanosis and defective cytochrome c oxidase (COX) in muscle and brain. High levels of lactic, ethylmalonic and methylsuccinic acids are detected in body fluids. EE is caused by mutations in ETHE1 gene, a mitochondrial sulfur dioxygenase. Neurologic signs and symptoms include progressively delayed development, hypotonia, seizures, and abnormal movements. We report on the clinical, electroencephalographic and MRI findings of a baby with a severe early onset encephalopathy associated with novel ETHE1 gene mutation. This is the first case described in literature with an early pure epileptic onset, presenting with West syndrome. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter baumannii has been associated with high morbidity and mortality rates, even in pediatric patients. Therapeutic options are limited, especially when the strain is multidrug resistant.Methods: Clinical and microbiological analyses of 4 cases of systemic infections caused by multi drug resistant A. baumannii treated with colistin/vancomycin combination at a Pediatric Intensive Care Unit were performed in order to explore the potential synergistic activity of colistin plus vancomycin. All the patients were treated with colistin, meropenem and vancomycin.Results: Four severe infections due to MDR A. baumannii were observed. All patients treated with colistin/vancomycin combination had a positive outcome with no infection relapses. Most importantly, no significant adverse events related to the simultaneous administration of COL plus VAN were observed. In our in-vitro experiments, the synergistic effect of the combination COL plus VAN showed an early bactericidal activity even at VAN concentration of 16 mg/L, which reflects the serum trough concentrations obtained in patients.Discussion: An antimicrobial strategy based on the activity of colistin plus vancomycin was in-vitro and in-vivo effective in life-threatening infections caused by multidrug-resistant A. baumannii in a Pediatric Intensive Care Unit, in the absence of adverse effects. Colistin plus vancomycin were highly synergic and bactericidal against carbapenem-resistant, colistin sensitive A. baumannii whereas the addition of meropenem did not enhance the in-vitro activity of colistin plus vancomycin.Conclusions: Our results confirm existing data on the potential synergistic activity of a therapeutic strategy including colistin plus vancomycin and provide important new clinical information for its potential use as a therapeutic option against MDR A. baumannii infections, especially in the pediatric population. [ABSTRACT FROM AUTHOR]

We report a case of EBV encephalitis in a seven-yr-old child with Ph+ ALL. Two months after an allogeneic HSCT from his HLA mismatched mother, the patient showed an altered sensorium, generalized seizures, and a left hemiparesis. Brain MRI demonstrated multiple lesions highly suggestive for viral encephalitis. Blood and CSF PCR analyses were negative for the most common viruses involved in immunocompromised patients including EBV. A cerebral biopsy was performed, which showed intense gliosis and perivascular lymphocytic cuffing. PCR analysis performed on brain tissue was positive only for the EBV genome, while extensive investigations for other viral infections were negative. The patient's neurological symptoms rapidly worsened and he died two months later. This case report suggests that in patients presenting neurological and radiological signs of encephalitis after an HSCT, an EBV involvement should be considered, even in the absence of CSF and blood PCR virus detection. [ABSTRACT FROM AUTHOR]

Background Apnoea, desaturations and bradycardias are common problems in preterm infants which can be treated with nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive pressure ventilation (NIPPV). It is unclear whether synchronised NIPPV (SNIPPV) would be even more effective. Objective To assess the effects of flow-SNIPPV, NIPPV and NCPAP on the rate of desaturations and bradycardias in preterm infants and, secondarily, to evaluate their influence on pattern of breathing and gas exchange. Patients and methods Nineteen infants (mean gestational age at study 30 weeks, 9 boys) with apnoeic spells were enrolled in a randomised controlled trial with a cross-over design. They received flow-SNIPPV, NIPPV and NCPAP for 4 h each. All modes were provided by a nasal conventional ventilator able to provide synchronisation by a pneumotachograph. The primary outcome was the event rate of desaturations (≤80% arterial oxygen saturation) and bradycardias (≤80 bpm) per hour, obtained from cardiorespiratory recordings. The incidence of central apnoeas (≥10 s) as well as baseline heart rate, FiO2, SpO2, transcutaneous blood gases and respiratory rate were also evaluated. Results The median event rate per hour during flow-SNIPPV, NIPPV and NCPAP was 2.9, 6.1 and 5.9, respectively (p<0.001 and 0.009, compared with flow-SNIPPV). Central apnoeas per hour were 2.4, 6.3 and 5.4, respectively (p=0.001, for both compared with flow-SNIPPV), while no differences in any other parameter studied were recorded. Conclusions Flow-SNIPPV seems more effective than NIPPV and NCPAP in reducing the incidence of desaturations, bradycardias and central apnoea episodes in preterm infants. [ABSTRACT FROM AUTHOR]

Objective: Bronchopulmonary dysplasia (BPD) or chronic lung disease is one of the principal causes of mortality and morbidity in preterm infants. Early identification of infants at the greater risk of developing BPD may allow a targeted approach for reducing disease severity and complications. The trigger cause of the disease comprehends the impairment of the alveolar development and the increased angiogenesis. Nevertheless, the molecular pathways characterizing the disease are still unclear. Therefore, the use of the metabolomics technique, due to the capability of identifying instantaneous metabolic perturbation, might help to recognize metabolic patterns associated with the condition. Methods: The purpose of this study is to compare urinary metabolomics at birth in 36 newborns with a gestational age below 29 weeks and birth weight <1500 g (very low birth weight - VLBW), admitted in Neonatal Intensive Care Unit (NICU) divided into two groups: the first group (18 cases) consisting of newborns who have not yet developed the disease, but who will subsequently develop it and the second group (18 controls) consisting of newborns not affected by BPD. Urine samples were collected within 24-36 h of life and immediately frozen at −80 °C. Results: The 1H-NMR spectra were analyzed using a partial least squares discriminant analysis (PLS-DA) model coupled with orthogonal Signal Correction. Using this approach it was possible with urine at birth to discriminate newborns that will be later have a diagnosis of BPD with a high statistics power. In particular, we found five important discriminant metabolites in urine in BPD newborns: lactate, taurine, TMAO, myoinositol (which increased) and gluconate (which decreased). Conclusion: These preliminary results seem to be promising for the identification of predictor's biomarkers characterizing the BPD condition. These data may suggest that BPD is probably the result of an abnormal development (respiratory bud, vascular tree, hypodysplasia of pneumocytes) and could be considered a congenital disease (genetics plus intrauterine epigenetics). Early identification of infants at the greater risk of developing BPD may allow a targeted approach for reducing disease severity and complications. [ABSTRACT FROM AUTHOR]

Objective: A supervised multivariate model to classify the metabolome alterations between autistic spectrum disorders (ASD) patients and controls, siblings of autistic patients, has been realized and used to realize a network model of the ASD patients' metabolome. Methods: In our experiment we propose a quantification of urinary metabolites with the Mass Spectroscopy technique couple to Gas Chromatography. A multivariate model has been used to extrapolate the variables of importance for a network model of interaction between metabolites. In this way we are able to propose a network-based approach to ASD description. Results: Children with autistic disease composing our studied population showed elevated concentration of several organic acids and sugars. Interactions among diet, intestinal flora and genes may explain such findings. Among them, the 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid has been previously described as altered in autistic subjects. Other metabolites increased are 3,4-dihydroxybutyric acid, glycolic acid and glycine, cis-aconitic acid; phenylalanine, tyrosine, p-hydroxyphenylacetic acid, and homovanillic acid are all involved in the tyrosine pathway leading to neurotransmitter cathecolamine. Conclusion: GC-MS-based metabolomic analysis of the urinary metabolome suggests to have the required sensitivity and specificity to gain insight into ASD phenotypes and aid a personalized network-based medicine approach. [ABSTRACT FROM AUTHOR]

Aim Links between respiratory syncytial virus bronchiolitis and asthma are well known, but few studies have dealt with wheezing following bronchiolitis induced by other viruses. We assessed the risk factors for recurrent wheezing in infants hospitalised for acute viral bronchiolitis. Methods We followed 313 infants for three years after they were hospitalised for bronchiolitis, caused by 14 different viruses, to identify risk factors for recurrent wheezing. Parents provided feedback on wheezing episodes during telephone interviews 12 (n = 266), 24 (n = 242) and 36 (n = 230) months after hospitalisation. Results The frequency of wheezing episodes diminished during the follow-up period: 137 children (51.7%) at 12 months, 117 (48.3%) at 24 months and 93 (40.4%) at 36 months. The risk of wheeze after three years was OR = 7.2 (95% CI 3.9-13.3) if they had episodes of wheezing during the first year after bronchiolitis, 16.8 (8.7-32.7) if they had episodes of wheezing during the second year and 55.0 (22.7-133.2) if they wheezed during both years. Blood eosinophils >400 cells/μL ( OR 7.7; CI 1.4-41.8) and rhinovirus infections (3.1; 1.0-9.4) were the major risk factors for recurrent wheezing. Conclusion Recurrent wheezing 36 months after infant bronchiolitis was associated with rhinoviruses and blood eosinophilia. [ABSTRACT FROM AUTHOR]

Human rhinoviruses (HRV) have been re-classified into three species (A-C), but the recently discovered HRV-C strains are not fully characterized yet. This study aimed to undertake a molecular and epidemiological characterization of HRV strains infecting children hospitalized over one year in two large research hospitals in Rome. Nasal washings from single HRV infections were retrospectively subjected to phylogenetic analysis on two genomic regions: the central part of the 5′Untranslated Region (5′UTR) and the Viral Protein (VP) 4 gene with the 5′ portion of the VP2 gene (VP4/2). Forty-five different strains were identified in 73 HRV-positive children: 55 % of the cases were HRV-A, 38 % HRV-C and only 7 % HRV-B. HRV-C cases were less frequent than HRV-A during summer months and more frequent in cases presenting wheezing with respect to HRV-A. Species distribution was similar with respect to patient age, and seasonality differed during summer months with fewer HRV-C than HRV-A cases. On admission, a significantly higher number of HRV-C cases presented with wheezing with respect to HRV-A. The inter- and intra-genotype variability in VP4/2 was higher than in 5′UTR; in particular, HRV-A patient VP4/2 sequences were highly divergent (8-14 %) at the nucleotide level from those of their reference strains, but VP4 amino acid sequence was highly conserved. In HRV-C isolates, the region preceding the initiator AUG, the amino acids involved in VP4 myristoylation, the VP4-VP2 cleavage site and the cis-acting replication element were highly conserved. Differently, VP4 amino acid conservation was significantly lower in HRV-C than in HRV-A strains, especially in the transiently exposed VP4 N-terminus. This study confirmed the high number of different HRV genotypes infecting hospitalized children over one year and reveals a greater than expected variability in HRV-C VP4 protein, potentially suggestive of differences in replication. [ABSTRACT FROM AUTHOR]

The relationship between viral load, disease severity and antiviral immune activation in infants suffering from respiratory syncytial virus (RSV)-associated bronchiolitis has not been well identified. The main objective of this study was to determine the existence of a correlation between RSV load and disease severity and also between different clinical markers and mRNA levels of the interferon stimulated gene (ISG)56 in infants hospitalized for bronchiolitis. We also evaluated whether viral load tended to be persistent over the course of the RSV infection. The levels of RSV-RNA were quantified in nasopharyngeal washings, collected from 132 infants infected with RSV as a single (90.15%) or as a dual infection with other respiratory viruses (9.85%). Results indicated that viral load was positively related to the clinical severity of bronchiolitis, the length of hospital stay, the levels of glycemia and the relative gene expression of ISG56, whereas an inverse correlation was observed with the levels of hemoglobin. We also found that the RSV load significantly decreased between the first and second nasopharingeal washings sample in most subjects. These results suggest that infants with high RSV load on hospital admission are more likely to have both more severe bronchiolitis and a higher airway activation of antiviral immune response. [ABSTRACT FROM AUTHOR]

Abstract: The genetic diversity of the host is believed to be the key of the diversity in the clinical presentation of bronchiolitis. The aim of this study was to determine whether the known rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) in interleukin (IL)28B region, influence clinical features and natural history of bronchiolitis. Both SNPs showed no significant association with the risk of hospitalization for respiratory syncytial virus (RSV), viral load, disease severity, and other clinical features of patients. Interestingly infants carrying IL28B rs12979860 TT genotype had lower age at hospital admission than that of infants carrying CC/CT genotypes. Overall our results indicate that both IL28B SNPs had no impact on the clinical course of bronchiolitis with the only exception of the IL28B rs12979860 SNP which increased the risk of hospitalization for bronchiolitis at early age. [Copyright &y& Elsevier]

Background: Nasal flow-synchronized intermittent positive pressure ventilation (NFSIPPV) is a new non-invasive ventilatory mode that delivers synchronized mechanical breaths through the nasal prongs. An unmasked, prospective randomized controlled trial was conducted to compare the efficacy of NFSIPPV and conventional nasal continuous positive airway pressure (NCPAP) in increasing the likelihood for successful extubation in very low-birthweight infants. Methods: Consecutive infants who weighed <1251 g at birth, required endotracheal intubation within 48 h of birth and met specific predetermined criteria for extubation by day 14 of life were recruited. Each infant was randomized to receive either NFSIPPV or NCPAP soon after extubation. Extubation was deemed successful if re-intubation was not needed for at least 72 h. Criteria for re-intubation were persistent severe respiratory acidosis (arterial pH <7.20 with pCO2 >70 mmHg), severe recurrent apneic episodes not responding to increased ventilatory settings and then requiring bag ventilation, and hypoxemia (SaO2 <90% or pO2 <60 mmHg with FiO2 ≥0.70). Results: There were no significant differences in clinical characteristics between the two groups at randomization. Ninety-four percent (30/32) infants were successfully extubated to NFSIPPV but only 61% (19/31) to conventional NCPAP ( P > 0.005). Infants assigned to NCPAP failed extubation mainly because of apnea and hypercapnia, and those assigned to NFSIPPV because of hypoxia. Neither procedure induced major adverse effects. Conclusions: NFSIPPV in the post-extubation period is safe and more effective than NCPAP in preventing re-ventilation. [ABSTRACT FROM AUTHOR]

Neonates with Pierre Robin Sequence (PRS) usually present with varying degrees of upper airway obstruction and difficulty feeding. Early treatment is important for such children in order to prevent impaired cognitive development resulting from hypoxemic episodes. Various procedures aimed at widening the pharyngeal space have been proposed, including prone position, tongue-lip adhesion, mandibular traction, non-invasive ventilation and palatal plates. Mandibular distraction osteogenesis (MDO) using external or internal devices has become increasingly popular as an alternative treatment option when other medical or surgical techniques do not prove to be satisfactory. This review summarizes current evidence on the effectiveness of MDO in infants with PRS. Because of a lack of studies comparing this treatment with other procedures, general recommendations cannot be drawn and treatment of infants with PRS still requires individualization. [ABSTRACT FROM AUTHOR]

Background: Preliminary results suggest that pertussis infection might be considered in infants during a seasonal respiratory syncytial virus (RSV) outbreak.Methods: In order to analyze clinical features and laboratory findings in infants with pertussis hospitalized for acute respiratory symptoms during a seasonal RSV outbreak, we conducted a retrospective single-center study on 19 infants with pertussis (6 boys; median age 72 days) and 19 matched controls (RSV-bronchiolitis), hospitalized from October 2008 to April 2010. B. pertussis and RSV were detected from nasopharyngeal washes with Real Time-PCR.Results: Infants with pertussis were less often breastfeed than infants with RSV bronchiolitis (63.2% vs 89.5%; p <0.06). Clinically, significantly fewer infants with pertussis than controls had more episodes of whooping cough (63.2% vs 0.0%; p < 0.001) and also less frequently fever at admission (15.8% vs 68.4%; p <0.01), apnea (52.6% vs 10.5%; p <0.006), and cyanosis (52.6% vs 10.5%; p < 0.006). Infants with pertussis had more often no abnormal chest sounds on auscultation than infants with RSV bronchiolitis (0% vs 42,1%; p < 0.005). The absolute blood lymphocyte and eosinophil counts were higher in infants with B. pertussis than in controls with bronchiolitis (23886 ± 16945 vs 10725 ± 4126 cells/mm(3), p < 0.0001 and 13.653 ± 10.430 vs 4.730 ± 2.400 cells/mm(3), p < 0.001). The molecular analysis of 2 B. pertussis isolates for ptxA1, ptxP3, and prn2 genes showed the presence of gene variants.Conclusions: When infants are hospitalized for acute respiratory symptoms, physicians should suspect a pertussis infection, seek for specific clinical symptoms, investigate lymphocyte and eosinophil counts and thus diagnose infection early enough to allow treatment. [ABSTRACT FROM AUTHOR]