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Numerous studies have shown that critically ill infants and toddlers admitted to paediatric intensive care units (PICUs) have a lower mortality than those admitted to adult ICUs. In 2014, there were only 23 registered PICUs in Italy, most of which were located in the north. For this reason, in Italy and elsewhere in Europe, some neonatal ICUs (NICUs) have begun managing critically ill infants and toddlers. Our proposal for healthcare organization is to establish “extended NICUs” in areas where paediatric intensive care beds are lacking. While some countries have opted for a strict division between neonatal and paediatric intensive care units, the model of “extended NICUs” has already been set up in Italy and in Europe. In this instance, the management of critically ill infants and toddlers undoubtedly falls upon neonatologists, who, however, must gain specific knowledge and technical skills in paediatric critical care medicine (PCCM). Postgraduate residencies in paediatrics need to include periods of specific training in neonatology and PCCM. The Italian Society of Neonatology’s Early Childhood Intensive Care Study Group is supporting certified training courses for its members involving both theory and practice.Conclusion: Scientific societies should promote awareness of the issues involved in the intensive management of infants and toddlers in NICUs and the training of all health workers involved. These societies include the Italian Society of Neonatology, the European Society of Paediatric and Neonatal Intensive Care, and the Union of European Neonatal and Perinatal Societies. They should also act in concert with the governmental institutional bodies to establish the standards for the “extended NICUs.” What is Known:• The mortality of critically ill infants and toddlers admitted to PICUs is lower than that for those admitted to adult ICUs.• In Italy, there are only a handful of PICUs, located mainly in the north. What is New:• Critically ill infants and small toddlers can be managed in “extended NICUs” in areas with a lack of paediatric intensive care beds.• “Extended NICUs” is our proposal for healthcare organization to compensate for the paucity of paediatric intensive care beds, but neonatologists must be trained to provide them with specific knowledge and technical skills in PCCM.

Bronchiolitis is one of the most frequent acute diseases of the lower respiratory tract in infants worldwide, and Respiratory Syncytial Virus remains the most common and aggressive viral disease. The course of the disease is usually benign, but its severity may change by evolving into parenchymal disease. In the more severe cases, its clinical and radiological characteristics may be consistent with acute respiratory distress syndrome. Management of these cases includes admission to paediatric intensive care and invasive mechanical ventilation. This paper reviews the definition of paediatric and neonatal acute respiratory distress syndrome, which was primarily designed and validated for adults. The article investigates the pathophysiology of paediatric acute respiratory distress syndrome further, describing how damage to the alveolar-capillary units, surfactant inactivation and inflammation occurs. Mechanisms that contribute to acute lung injury, such as volutrauma, barotrauma, stress and strain, are illustrated in detail, and an overview of the strategies that may help minimize neonatal lung injury and optimize ventilatory support is provided. These strategies include lung-protective mechanical ventilation, surfactant treatment, inhaled nitric oxide, high frequency oscillatory ventilation, recruiting manoeuvres, prone position and neuromuscular blocking agents. The objective is to help clinicians understand the peculiar pathophysiology of severe bronchiolitis and so guide them in preventing or attenuating lung injury during treatment. As such, this paper aims to contribute to defining optimal treatment of severe cases of bronchiolitis.

Avoiding MV is a critical goal in neonatal respiratory care. Different modes of noninvasive respiratory support beyond nasal CPAP, such as nasal intermittent positive pressure ventilation (NIPPV) and synchronized NIPPV (SNIPPV), may further reduce intubation rates. SNIPPV offers consistent benefits over nonsynchronized techniques such as a more efficient positive pressure transmission to the lung, an effective increase in transpulmonary pressure during ventilation, and a better stabilization of the chest wall during inspiration. This review discusses mechanisms of action, benefits and limitations of synchronized noninvasive ventilation, describes the different modes of synchronization, and analyzes properties and clinical results.

Introduction During the first year of the COVID-19 pandemic, international recommendations and guidelines regarding breastfeeding-supportive hospital practices changed frequently. For example, some recommended separation of mothers and infants; others, feeding pumped milk instead of milk fed directly from the breast. Many recommendations were inconsistent or in direct conflict with each other. Guidance from UENPS (the Union of European Neonatal and Perinatal Societies) published in April 2020 recommended rooming in and direct breastfeeding where feasible, under strict measures of infection control, for women who were COVID-19 positive or under investigation for COVID-19. Key findings Our study assessed data from respondents from 124 hospitals in 22 nations, with over 1000 births per year, who completed a survey on practices during the COVID-19 epidemic, as they related to the World Health Organization (WHO) Ten Steps to Successful Breastfeeding, considered to be the gold standard for breastfeeding support. The survey was conducted in the fall of 2020/winter of 2021. Overall 88% of responding hospitals had managed COVID positive mothers, and 7% had treated over 50 birthing women with confirmed COVID-19. The biggest change to hospital policy related to visitation policies, with 38% of hospitals disallowing all visitors for birthing women, and 19% shortening the postpartum stay. Eight hospitals (6%) recommended formula feeding instead of breastfeeding for women who tested positive for COVID-19 or were under investigation, whereas 73% continued to recommend direct, exclusive breastfeeding, but with some form of protection such as a mask or hand sanitizer for the mother or cleaning the breast before the feed. While 6% of hospitals discontinued rooming in, 31% strengthened their rooming in policy (keeping mothers and their babies together in the same room) to protect infants against possible exposure to the virus elsewhere in the hospital . Overall, 72% of hospitals used their country's national guidelines when making policy, 31% used WHO guidelines and 22% UENPS/SIN guidelines. Many European hospitals relied on more than one accredited source. Discussion Our most concerning finding was that 6% of hospitals recommended formula feeding for COVID positive mothers, a measure that was later shown to be potentially harmful, as protection against the virus is transmitted through human milk. It is encouraging to note that a third of hospitals strengthened rooming in measures. Especially given the emergence of the highly transmissible Delta variant, the situation around postnatal care in maternity hospitals requires ongoing monitoring and may require proactive investment to regain pre-COVID era practices.

Background Providing appropriate care at birth remains a crucial strategy for reducing neonatal mortality and morbidity. We aimed to evaluate the consistency of practice and the adherence to the international guidelines on neonatal resuscitation in level-I and level-II Italian birth hospitals. Methods This was a cross-sectional electronic survey. A 91-item questionnaire focusing on current delivery room practices in neonatal resuscitation was sent to the directors of 418 Italian neonatal facilities. Results The response rate was 61.7% (258/418), comprising 95.6% (110/115) from level-II and 49.0% (148/303) from level-I centres. In 2018, approximately 300,000 births occurred at the participating hospitals, with a median of 1664 births/centre in level-II and 737 births/centre in level-I hospitals. Participating level-II hospitals provided nasal-CPAP and/or high-flow nasal cannulae (100%), mechanical ventilation (99.1%), HFOV (71.0%), inhaled nitric oxide (80.0%), therapeutic hypothermia (76.4%), and extracorporeal membrane oxygenation ECMO (8.2%). Nasal-CPAP and/or high-flow nasal cannulae and mechanical ventilation were available in 77.7 and 21.6% of the level-I centres, respectively. Multidisciplinary antenatal counselling was routinely offered to parents at 90.0% (90) of level-II hospitals, and 57.4% (85) of level-I hospitals (p 2 detector was available in only 20%. Significant differences between level-II and level-I centres were found in the composition of resuscitation teams for high-risk deliveries, team briefings before resuscitation, providers qualified with full resuscitation skills, self-confidence, and use of sodium bicarbonate. Conclusions This survey provides insight into neonatal resuscitation practices in a large sample of Italian hospitals. Overall, adherence to international guidelines on neonatal resuscitation was high, but differences in practice between the participating centres and the guidelines exist. Clinicians and stakeholders should consider this information when allocating resources and planning perinatal programs in Italy.

BACKGROUND Although short binasal prongs (SBP) are the most common interface for noninvasive ventilation, the "double-inspiratory loop cannulas" (DILC) have recently been introduced into many neonatal intensive care units. DILC show advantages over SBP, including reduced nasal trauma and increased comfort. However, their higher intrinsic resistance may compromise ventilation. Our aim was to test a new, low resistance DILC interface. METHODS A test lung was programmed to simulate preterm neonates (500-2000 g BW) with moderate-to-severe respiratory distress syndrome. The artificial nose was designed to keep prongs-to-nares leaks to around 30%. Giulia® ventilator (GINEVRI srl) was used to provide nasal continuous positive airway pressure (NCPAP) and flow synchronized nasal intermittent positive pressure ventilation (NIPPV). NCPAP was set at 4-10 cmH2 O and synchronized-NIPPV (SNIPPV) at peak inspiratory pressure, 15-20-25 cmH2 O; inspiratory time, 0.3-0.5 s; and positive end-expiratory pressure, 5-8 cmH2 O. Four sizes of Sync-flow Cannula® (GINEVRI srl) were tested. The Sync-flow Cannula® was compared with Neotech RAM® cannula and Ginevri SBP®. The outcome measures were the flow/pressure relationship through the four Sync-flow Cannula® sizes, the difference in resistance, the drop in ventilator-alveoli pressure measured by the test lung and the system response time during flow-SNIPPV. RESULTS The smaller DILC sizes had the lowest flow-pressure ratio. The resistance of the RAM® cannula was significantly higher compared to the other interfaces (p

The recent COVID‐19 pandemic has spread to Italy with heavy consequences on public health and economics. Besides the possible consequences of COVID‐19 infection on a pregnant woman and the fetus, a major concern is related to the potential effect on neonatal outcome, the appropriate management of the mother–newborn dyad, and finally the compatibility of maternal COVID‐19 infection with breastfeeding. The Italian Society on Neonatology (SIN) after reviewing the limited scientific knowledge on the compatibility of breastfeeding in the COVID‐19 mother and the available statements from Health Care Organizations has issued the following indications that have been endorsed by the Union of European Neonatal & Perinatal Societies (UENPS). If a mother previously identified as COVID‐19 positive or under investigation for COVID‐19 is asymptomatic or paucisymptomatic at delivery, rooming‐in is feasible, and direct breastfeeding is advisable, under strict measures of infection control. On the contrary, when a mother with COVID‐19 is too sick to care for the newborn, the neonate will be managed separately and fed fresh expressed breast milk, with no need to pasteurize it, as human milk is not believed to be a vehicle of COVID‐19. We recognize that this guidance might be subject to change in the future when further knowledge will be acquired about the COVID‐19 pandemic, the perinatal transmission of SARS‐CoV‐2, and clinical characteristics of cases of neonatal COVID‐19.

Aim To test the hypothesis that the balance of type-1/type-2 immune response differs between infants hospitalized with respiratory syncytial virus (RSV) bronchiolitis during the peak months and those during the nonpeak months. Methods We prospectively enrolled 90 unrelated full-term previously healthy infants hospitalized during the first year of life for RSV sole bronchiolitis over 2 epidemics (November 2016 to April 2017 and October 2017 to April 2018). We stratified infants as follows: hospitalized during the peak months (n: 71) and during the nonpeak months (n: 19). The frequencies of CD4+ producing interferon (IFN)-γ and interleukin (IL)-4 and of CD8+ producing IFN-γ T cells were measured by flow cytometry from infant peripheral whole blood. The T-helper cell (Th2) polarization index was calculated as the ratio between CD4+ T cells producing IL-4 and CD4+ T cells producing IFN-γ. Results Infants hospitalized during nonpeak months were significantly less frequently breast-fed, had a higher eosinophils count, a significantly higher percentage of CD4+ T cells producing IL-4 and higher Th2 polarization index than infants hospitalized during the peak months. Conclusions We elucidated the presence of different endotypes in infants with RSV sole bronchiolitis. Previously healthy full-term infants hospitalized during the nonpeak months seem to be more likely those with a possible predisposition to atopy.

Bronchiolitis is the first lower respiratory tract viral infection manifesting in infants younger than 12 months of age. Our aim was to evaluate clinical and serological differences in infants with bronchiolitis from a single or from multiple viruses. Our secondary aim was to investigate differences in recurrent wheezing episodes after 12‐24‐36 months of follow‐up. We reviewed the clinical records for 486 full‐term infants hospitalized for bronchiolitis with at least one virus detected in the nasopharyngeal aspirate. In 431 (88.7%) patients one virus was detected and in 55 (11.3%) infants more than one virus was found. No differences were observed in the length of hospitalization, clinical severity score, O2 supplementation or admission to the intensive care unit. Single virus was associated with higher serum C‐reactive protein (C‐RP) than infants with multiple viruses and higher blood neutrophil counts. Respiratory syncytial virus (RSV) was the most frequently detected virus. RSV alone was associated with higher C‐RP (P = 0.007), compared to RSV coinfection. Infants with human rhinovirus (hRV) alone had higher white blood cell counts, higher blood neutrophils, and higher serum C‐RP levels than hRV co‐infection (P = 0.029, P = 0.008, P = 0.008). RSV + hRV, the most frequent co‐infection, was associated with lower neutrophil count and lower C‐RP levels (P = 0.008, P = 0.016) and less fever (P = 0.012), when comparing RSV versus hRV versus RSV + hRV. No differences were found in the frequency of recurrent wheezing between single versus multiple viruses after bronchiolitis. Our findings suggest that in infants with bronchiolitis multiple viral co‐infections can occur, without influence in the clinical severity of the disease. Infants with co‐infection seems to mount a lower inflammatory response.

Bronchiolitis is the leading cause of hospitalization in infants under 12 months. Our aims were to analyze epidemiological characteristics of infants with bronchiolitis over 10 consecutive seasons and to evaluate whether there are any clinical differences between infants hospitalized for bronchiolitis during epidemic peak months and infants in non-peak months. We enrolled consecutive enrolled 723 previously healthy term infants hospitalized at the Paediatric Emergency Department, "Sapienza" University of Rome over the period 2004-2014. Fourteen respiratory viruses were detected from nasopharyngeal aspirates by molecular methods. Clinical and demographic data were extracted from clinical charts. Viruses were detected in 351 infants (48.5%): RSV in 234 (32.4%), RV in 44 (6.1%), hBoV in 11 (1.5%), hMPV in 12 (1.6%), co-infections in 39 (5.4%), and other viruses in 11 (1.5%). Analyzing the 10 epidemic seasons, we found higher incidence for bronchiolitis every 4 years with a peak during the months December-January. Infants hospitalized during peak months had lower family history for asthma (P = 0.003), more smoking mothers during pregnancy (P = 0.036), were slightly higher breastfed (0.056), had lower number of blood eosinophils (P = 0.015) and had a higher clinical severity score (P = 0.017). RSV was detected mostly during peak months, while RV was equally distributed during the seasons. We found some variations in bronchiolitis incidence during epidemics, and discriminative characteristics in infants hospitalized for bronchiolitis during peak months and in non-peak months, that might reflect two different populations of children. Pediatr Pulmonol. 2016;51:1330-1335. © 2016 Wiley Periodicals, Inc.

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 (PM10) and less than 2.5 µm (PM2.5) 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., Highlights • Peak RSV activity correlates with cold temperatures and higher relative humidity. • RSV-positive cases correlates positively with BZ, NOx, SO2, PM10 and PM2.5. • The most predictive pollutant for RSV cases (constant temperature and humidity)is BZ.

Background Kawasaki disease (KD) is an acute inflammatory vasculitis of unknown origin. Case presentation We report the case of a 5-month-old child with an atypical form of KD, characterized by undulating symptoms, who developed an aneurysm of the right coronary artery and an ectasia of the left anterior descending coronary artery. Conclusion This case report underlines the difficulties in recognizing incomplete forms of the illness in young infants, who are at higher risk of cardiac complications.

Summary. Objectives: Our study was aimed to evaluate the efficacy of 7% hypertonic saline and 0.1%hyaluronicacid (7% HS‐HA)given by inhalation, in infantshospitalized for mild-to-moderate bronchiolitis. Methods: In a double-blind controlled study, 39 infants (23 boys)

Oncology is a branch of medicine in rapid evolution in the attempt to find innovative methods for early diagnosis and a better understanding of tumoral processes leading to the development of new therapies. Metabolomics is the emerging discipline among the "omics" sciences which makes it possible to further expand our knowledge concerning cancer biology. Different studies have revealed the potential role of metabolomics in gaining an understanding of pathophysiological processes in cancer, improving tumor staging, characterizing tumors and searching for biomarkers predictive of therapeutic responses. However, to date there are few works aimed at gaining deeper insights into infantile oncology through metabolomics.

International audience; 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.

Background: We sought to know more about how 14 common respiratory viruses manifest clinically, and to identify risk factors for specific virus-induced acute respiratory tract infections (ARTIs) in children younger than 3 years old and for wheezing at 36-month follow-up. Methods: We retrospectively studied the clinical records for 273 full-term children (median age, 2.9 months; range, 0.26–39; boys, 61.2%) hospitalized for ARTIs, whose nasopharyngeal specimen tested positive for a respiratory virus and 101 children with no history of respiratory diseases (median age, 8 months; range, 0.5–36.5; boys, 58.4%). At 12, 24 and 36 months after children’s discharge, all parents were interviewed by telephone with a structured questionnaire on wheezing episodes. Results: The most frequently detected viruses were respiratory syncytial virus in bronchiolitis, human rhinovirus in pneumonia and human bocavirus in wheezing. Multivariate analysis identified, as risk factors for virus-induced ARTIs, the presence of siblings [odds ratio (OR): 3.0 (95% confidence interval [CI]: 1.8–5.2)], smoking cohabitants (OR: 2.3 (95% CI: 2–4.2)] and breastfeeding lasting less than 3 months [OR: 0.5 (95% CI: 0.3–0.9)]. The major risk factor for respiratory syncytial virus–induced ARTIs was exposure to tobacco smoke [OR: 1.8 (95% CI: 1.1–3.2)]. Risk factors for human rhinovirus–induced ARTIs were attending day-care [OR: 5.0 (95% CI: 2.3–10.6)] and high eosinophil blood counts [OR: 2.6 (95% CI: 1.2–5.7)]. The leading risk factor for recurrent wheezing was exposure to tobacco smoke [OR: 2.5 (95% CI: 1.1–15.6)]. Conclusions: Each respiratory virus leads to a specific clinical manifestation. Avoiding exposing children to tobacco smoke might restrict viral spread from sick parents and siblings to younger children, prevent severe respiratory diseases, and possibly limit sequelae.

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.

High-flow nasal cannula (HFNC) is frequently used to treat respiratory distress in infants and children because of its beneficial effects on alveolar ventilation and respiratory mechanics. Setting an adequate flow rate that meets a patient's peak inspiratory flow (PIF) is thus crucially important to achieve such effects. HFNC flow rate is typically set at 1 L/min/kg +1 as suggested by the manufacturer and increased to 2 L/min/kg according to the degree of respiratory distress. However, whether this empirical flow setting actually meets a patient's PIF has not yet been investigated. In this study, we implemented our previously described respiratory mechanics monitoring system (MAES) with a new spirometry function (NSS) that allows for a simultaneous visualization of the flow tracings of HFNC and the patient's spontaneous breathing. We tested the ability of NSS-MAES to determine the adequacy of empirically set flow rates of 1 L/min/kg +1 or 2 L/min/kg on 9 infants with respiratory distress receiving HFNC. HFNC flow rate was considered adequate if its tracing was just above the patient's respiratory flow. In patients in whom 1 L/kg/min +1 was inadequate, we used NSS-MAES to identify the adequate flow by raising the HFNC flow until it reached the patient's PIF (HFNC_NSS-MAES). We also investigated which flow rate was associated with the maximal decrease of respiratory effort, namely, Pressure Time Product (PTP) and Work of Breathing (WOB). We found that 1 L/min/kg +1, but not 2 L/min/kg was often unable to meet the patient's PIF. In these cases HFNC_NSS-MAES values were around 1.6 L/min/kg. Conversely, HFNC at 2 L/min/kg always exceeded the patient's PIF. All breathing effort indexes tested improved after HFNC treatment with the maximal unloading seen at 2 L/min/kg for PTP and at HFNC_NSS-MAES.

The transfer of O2 to the tissues and the removal of CO2 are guaranteed by the simultaneous activity of the respiratory apparatus and of the cardio-circulatory system which ensures that O2 reaches the tissues and that the CO2 produced by cell metabolism is removed [1].

Although micrognathia and cleft palate have been reported in patients with Lymphedema–distichiasis syndrome (LDS), the classic Robin sequence with glossoptosis and airway obstruction has not been previously described in patients with genetically confirmed LDS. Here we report on two female siblings with LDS confirmed by a FOXC2 mutation who presented at birth with severe airway obstruction related to Robin sequence. Respiratory obstruction was successfully managed by early distraction osteogenesis. Our report highlights the unusual occurrence of Robin sequence in LDS patients and advises distraction osteogenesis to resolve breathing problems in LDS patients who present with Robin related severe airway obstruction.

Advances in neonatal intensive care have markedly improved survival rates for infants born at a very early lung development stage (

To characterize respiratory virus infections during the first autumn-winter season of pandemic A (HINI) 2009 influenza virus (A/HINI/2009) circulation, a prospective study in children attending a paediatric emergency department at the Sapienza University hospital, Rome, was conducted from November 2009 to March 2010. By means of both nasal washings and pharyngeal swabs, enrolled children were checked for 14 respiratory viruses. The majority of acute respiratory infections resulted from viral pathogens (135/231, 58%). Overall, the most common was respiratory syncytial virus (RSV), in 64% of positive samples; A/HINI/2009 was the only influenza virus found in 16% and rhinovirus (RV) in 15%. Virus-positive children did not differ significantly from virus-negative children in signs and symptoms at presentation; of the virus groups, RSV-infected children were younger and more frequently admitted to intensive-care units than those infected with A/HINI/2009 and RV. Of the hospitalized children, stratified by age, both infants and children aged >1 year with RSV were most severely affected, whereas A/HINI/2009 infections were the mildest overall, although with related pulmonary involvement in older children. Children with RV infections, detected in two flares partially overlapping with the A/HINI/2009 and RSV peaks, presented with bronchiolitis, wheezing and pneumonia. Leukocytosis occurred more frequently in RV-infected and A/HINI/2009-infected children, and numbers of blood eosinophils were significantly elevated in RV-infected infants. Given the fact that clinical and epidemiological criteria are not sufficient to identify viral respiratory infections, a timely virological diagnosis could allow different infections to be managed separately.

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.

Aim: To determine the incidence and predisposing factors for severe bronchiolitis in previously healthy term infants 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

In a group of children with suspected pulmonary aspiration, we aimed to describe the type and physical characteristics of gastro-oesophageal reflux (GOR) episodes, and to determine their correlation with the lipid-laden macrophage (LLM) content in bronchoalveolar lavage (BAL).Twenty-one children with a diagnosis of bronchial asthma, recurrent lung consolidations and recurrent laryngotracheitis underwent 24-h multichannel intraluminal impedance and pH (MII-pH) monitoring, fibreoptic bronchoscopy and BAL. The following parameters were evaluated: total number of reflux episodes, number of acid reflux [AR; pH4] and non-acid reflux [NAR] episodes [pH4], height of reflux episodes, LLM content and percentage of neutrophils in the BAL.The number of NAR episodes and the number of those reaching the proximal oesophagus were significantly higher in patients with recurrent lung consolidations than in those with bronchial asthma and laryngotracheitis (p0.01 and p0.01). BAL studies showed a significantly higher LLM content in children with recurrent lung consolidations than in those with bronchial asthma and laryngotracheitis (p0.01). The LLM content correlated significantly with the total number of reflux episodes (r=0.73; p0.001) and with those reaching the proximal oesophagus (r=0.67; p0.001). Finally, the LLM content correlated with the number of NAR episodes (r=0.61; p0.01), with those reaching the proximal oesophagus (r=0.64; p0.01) and with the percentage of BAL neutrophils (r=0.7; p0.01).NAR episodes reaching the proximal oesophagus correlate with diagnostic marker for pulmonary micro-aspiration. MII-pH monitoring increases the yield in identifying types and proximal extension of reflux episodes, that discriminate between patients with and without pulmonary aspiration.

Bronchiolitis is the main cause of respiratory insufficiency in infants, characterized by acute inflammation, edema, necrosis of epithelial cells and increased mucus production. Mucus is mainly purulent and consequently rich in DNA, as derived from nuclei of degenerating neutrophils and epithelial debris. The treatment is mainly supportive; bronchodilators and systemic steroids are often used but do not reduce the length of hospital stay. The aim of our study is to evaluate the efficacy of recombinant human DNase (rhDNase), in infants affected by moderate-severe bronchiolitis. In a randomized double-blind placebo-controlled study, twenty-two infants (12 males) under 6 months of age (median age 1.6 months) were enrolled and randomly assigned to receive either nebulized rhDNase or placebo (saline) at a dose of 2.5 ml once a day for three days. All infants were evaluated, based on a clinical assessment score, on admission and four times daily during the hospitalization. Placebo and study groups were sex- and age-matched and were similar in terms of clinical severity on admission. No differences were observed between the two groups of patients with regard to the length of hospitalization and clinical score during the days observed. Two out of four infants, all in the study group, presenting atelectasis on chest radiographs, showed a rapid improvement on the first day. RhDNase is not an effective routine therapy in treating infants hospitalized for bronchiolitis and it is not useful in preventing severe forms of the disease. On the contrary, it may be an effective, safe and cost-benefit treatment only in infants with bronchiolitis and massive atelectasis.

Background Human bocavirus (HBoV) was first discovered in Sweden in 2005 and has now been found worldwide; however its role in clinically relevant diseases has not yet been clearly defined. Objectives To gain new insight into HBoV infection among children hospitalized with acute respiratory infections in Rome. Methods Between November 2004 and May 2007, 415 nasal washings were tested for the presence of an extensive range of respiratory viruses using molecular methods. Results Viral pathogens were detected in 214 children (51·6%), 28·9% being respiratory syncytial virus (RSV) and 9·6% being rhinovirus positive. Of the 34 children (8·2%) who tested positive for HBoV, 21 (61·8%) were co-infected with another respiratory virus, mainly RSV. Human bocavirus was the only pathogen identified in four pneumonia and six bronchiolitis cases in March 2005 and January 2007, respectively. Human bocavirus was also detected in one child hospitalized with gastroenteritis and in another with erythema. Conclusions In the examined population, HBoV was the third most common virus detected but with a high rate of co-infection with other respiratory viruses. Human bocavirus appeared to be the etiological agent in some pneumonia and bronchiolitis cases in which tests for all likely respiratory pathogens were negative.

Background: Acute viral respiratory tract infections (ARTIs) are the most frequent diseases in children. Aim: To analyze risk factors for ARTIs, to evaluate clinical differences among children with different viral respiratory infection and to study virological risk factors for recurrent wheezing at 3 years follow-up. Methods: We studied 273 children (median age 2.9 months, 167M) hospitalized at the Paediatric Emergency Department, “Sapienza” University of Rome (Oct 2009-May 2014) with ARTIs (148 had RSV infection, 67 hRV, 13 hMPV, 10 hBoV, 29 co-infections and 6 other viruses) and 101 control children. We performed a follow-up after 3 years. Results: Risk factors for ARTIs were the presence of siblings (p Conclusions: Environmental and genetic factors contribute to ARTIs. Clinical entities depend on viral etiology. RSV is the virus. RSV infants had more often long lasting sequelae.

Background: Bronchiolitis is the leading cause of hospitalization in infants Methods: among 190950 children admitted to Pediatric Emergency Department, “Sapienza” University of Rome, in 3151 patients bronchiolitis was diagnosed. Out of these, we selected 724 previously healthy term infants(median age 64d;395M) hospitalized and collected nasal aspirates to detect, with RT-PCR, 14 respiratory viruses. Clinical data were extracted from clinical charts. Results: Percentage of hospitalization was stable during 10 years. Viruses were detected in 348 infants(48%): RSV in 30.8%, RV in 6.6%, hBoV in 1.8%, co-infections in 5.8%, other viruses in 3%. Analyzing the 10 seasons we found a peak of incidence for bronchiolitis every four years(Fig). RV was equally distributed during the all season while RSV was detected mostly during the colder months(Dec-Jan). No significant differences were found between infants with bronchiolitis from different viruses and clinical variables analyzed except for higher number of eosinophils in RV patients compared to other viruses (p Conclusions: incidence of bronchiolitis follows viral season and it seems to have a peak every 4 years with a significant decrease the year after. Further studies are needed to understand the role of eosinophils in HRV bronchiolitis.

Introduction: Around 40% of infants with bronchiolitis will present recurrent wheezing in the first years of life. It is still unclear whether the virus directly modifies the host immune response or it infects infants somehow prone to wheeze. Aim: To evaluate whether Respiratory Syncytial Virus(RSV)-RNA load and IFN lambda 1-3 expression correlate with wheezing 36 months after bronchiolitis. Methods: We reviewed 68 (43 males, age range: 7-277 days) infants hospitalised for RSV bronchiolitis at the Paediatric Emergency Department, “Sapienza” University of Rome. Nasopharyngeal washing was collected from each infant, and divided into two aliquots (one for nucleic acid extraction and viral detection, the second for gene expression analysis). A TaqMan-based real-time PCR technique for RSV RNA quantification was performed. The mRNA copy content of IFN lambda 1, and 2/3 was measured by a real-time 59 exonuclease RT-PCR assay using the Light Cycler 480 sequence detector. 12-24-36 months after discharge, one of the authors interviewed parents of all infants using a standardized telephone procedure with a structured questionnaire seeking information on recurrent wheezing. Results: 29/68 (42.6%) infants with bronchiolitis experienced recurrent wheezing at 36 months follow-up. Children with recurrent wheezing after bronchiolitis showed a significantly higher RSV-RNA load(p=0.015) and higher IFN lambda 2/3 levels than wheezing negative patients(p=0.047). Conclusions: A high RSV-RNA load and IFN lambda activation at the admission for bronchiolitis are associated with recurrent wheezing after 36 months. We could speculate that this viral-related inflammation might cause bronchial lumen modifications.

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.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.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.The median event rate per hour during flow-SNIPPV, NIPPV and NCPAP was 2.9, 6.1 and 5.9, respectively (p0.001 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.Flow-SNIPPV seems more effective than NIPPV and NCPAP in reducing the incidence of desaturations, bradycardias and central apnoea episodes in preterm infants.

High-flow humidified nasal cannula (HFNC) is often used to relieve respiratory distress in children with acute pulmonary disease, although its effects on respiratory mechanics have not been objectively studied. The purpose of this study was to test the feasibility of measuring pharyngeal (PP) and esophageal (Pes) pressures of young children on HFNC oxygen therapy through a specifically designed new monitoring, acquisition, and elaboration system (MAES). Through MAES we recorded and elaborated Pes and PP tracings obtained through esophageal and pharyngeal catheters in a group of young children hospitalized in a Pediatric Intensive Care Unit because of respiratory distress. All traces were recorded during spontaneous breathing and on HFNC 1 and 2 L/kg/min. To determine the onset and the end of inspiration, the Pes and PP signals were synchronized with the inspiratory flow obtained by a flow transducer placed in the HFNC circuit. Direct measurement of inspiratory flow by a face mask pneumotachograph also allowed for inspiratory tidal volume (TV) measurement which was used together with Pes curve to build Campbell's diagram as well as the static lung and chest wall recoil curves required for pressure time product (PTP) evaluation. Using MAES we were able to obtain: time interval between the beginning of inspiratory effort and inspiration (Tdelay), TV, intrinsic positive end expiratory pressure (PEEPi), total inspiratory Pes variation (ΔPes), transpulmonary pressure at end of inspiration (Ptpei), dynamic lung compliance (CLdyn), total lung resistance (RLtot) along with all the relevant components of the inspiratory work of breathing (WOB) and PTP. We believe that this new system will allow clinicians for a bedside monitoring of respiratory distress in infants treated with HFNC and to modify flow rates accordingly.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-1133-3) contains supplementary material, which is available to authorized users.

Many infants with a repaired esophageal atresia (EA) undergo fundoplication, aortopexy, or glossopexy because the mechanisms most responsible for airway obstruction and/or apparent life-threatening event (AO/ALTE) syndrome are considered to be gastroesophageal reflux (GER), tracheal compression (TC), or obstructive apnea, respectively. In the present study, we investigated whether these mechanisms are independent or interrelated. We developed a database of 120 consecutive patients with EA treated by the senior author between 1967-2002. We studied the clinical manifestations of patients with a cervical esophagostomy and/or blind lower esophageal stump, which ruled out TC and/or proximal esophageal GER as a mechanism for AO/ALTE. Of 25 neonates who underwent section/ligation of lower tracheo-esophageal fistula and/or feeding gastrostomy, 10 critically ill neonates died. Of 15 survivors, 9 infants had a feeding gastrostomy without an esophagostomy. Of these, 6 infants presented one or more episodes of AO, and 8 presented ALTE with or without AO. Subsequently, 5 of the 9 infants underwent an esophagostomy. Eventually, 11 infants had a feeding gastrostomy with an esophagostomy. Of the latter, 5 infants presented one or more episodes of AO, and 6 presented ALTE without AO. In conclusion, oral feeding, proximal esophageal GER, and TC are not essential for AO/ALTE syndrome to occur. They are probably factors which offer evidence of an underlying problem with control of upper airway patency.