Genetic diversity and its impact on disease severity in respiratory syncytial virus subtype-A and -B bronchiolitis before and after pandemic restrictions in Rome.

OBJECTIVES: To scrutinize whether the high circulation of respiratory syncytial virus (RSV) observed in 2021-2022 and 2022-2023 was due to viral diversity, we characterized RSV-A and -B strains causing bronchiolitis in Rome, before and after the COVID-19 pandemic. METHODS: RSV-positive samples, prospectively collected from infants hospitalized for bronchiolitis from 2017-2018 to 2022-2023, were sequenced in the G gene; phylogenetic results and amino acid substitutions were analyzed. Subtype-specific data were compared among seasons. RESULTS: Predominance of RSV-A and -B alternated in the pre-pandemic seasons; RSV-A dominated in 2021-2022 whereas RSV-B was predominant in 2022-2023. RSV-A sequences were ON1 genotype but quite distant from the ancestor; two divergent clades included sequences from pre- and post-pandemic seasons. Nearly all RSV-B were BA10 genotype; a divergent clade included only strains from 2021-2022 to 2022-2023. RSV-A cases had lower need of O2 therapy and of intensive care during 2021-2022 with respect to all other seasons. RSV-B infected infants were more frequently admitted to intensive care units and needed O2 in 2022-2023. CONCLUSIONS: The intense RSV peak in 2021-2022, driven by RSV-A phylogenetically related to pre-pandemic strains is attributable to the immune debt created by pandemic restrictions. The RSV-B genetic divergence observed in post-pandemic strains may have increased the RSV-B specific immune debt, being a possible contributor to bronchiolitis severity in 2022-2023.

Difficult diagnosis of atypical kawasaki disease in an infant younger than six months: a case report.

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.

Surfactant therapy for acute respiratory distress in children.

In children with acute lung injury the endogenous surfactant system is altered via a variety of different mechanisms, including inflammation, vascular dysfunction, oxidant injury, cellular injury and oedema. This article examines the pathophysiology of acute lung injury and surfactant use for treatment of acute respiratory failure in infants and children.

Outcomes after tongue-lip adhesion or mandibular distraction osteogenesis in infants with Pierre Robin sequence and severe airway obstruction.

The objective was to review and compare outcomes after tongue-lip adhesion (TLA) and mandibular distraction osteogenesis (MDO) in infants with severe breathing difficulties related to Pierre Robin sequence (PRS). A single-centre retrospective (2002-2012) study was carried out; 18 infants with severe breathing difficulties related to PRS resistant to conservative treatment, who underwent TLA or MDO to correct airway obstruction, were enrolled. The primary outcome measures were successful weaning from respiratory support and resumption of full oral feeding. Nine underwent TLA and nine MDO. Eight of the nine infants who underwent MDO and all those treated with TLA were successfully weaned from respiratory support. After discharge, residual respiratory distress was diagnosed more commonly after TLA than after MDO (6/9 vs 1/9, P=0.050). Infants resumed oral feeding sooner after MDO than after TLA (mean days after surgery to full oral feeds 44±24 vs 217±134, P<0.003). The length of hospital stay was longer for infants treated with MDO than for those treated with TLA. The rate of complications was similar. Infants with severe airway obstruction related to PRS can benefit safely from either TLA or MDO. Although MDO lengthens the time to discharge, this option stabilizes airway patency of infants with PRS more efficiently and achieves full oral feeding more rapidly than TLA.

Flow-synchronized nasal intermittent positive pressure ventilation for infants <32 weeks' gestation with respiratory distress syndrome.

Aim. To evaluate whether synchronized-NIPPV (SNIPPV) used after the INSURE procedure can reduce mechanical ventilation (MV) need in preterm infants with RDS more effectively than NCPAP and to compare the clinical course and the incidence of short-term outcomes of infants managed with SNIPPV or NCPAP. Methods. Chart data of inborn infants <32 weeks undergoing INSURE approach in the period January 2009-December 2010 were reviewed. After INSURE, newborns born January -December 2009 received NCPAP, whereas those born January-December 2010 received SNIPPV. INSURE failure was defined as FiO(2) need >0.4, respiratory acidosis, or intractable apnoea that occurred within 72 hours of surfactant administration. Results. Eleven out of 31 (35.5%) infants in the NCPAP group and 2 out of 33 (6.1%) infants in the SNIPPV group failed the INSURE approach and underwent MV (P < 0.004). Fewer infants in the INSURE/SNIPPV group needed a second dose of surfactant, a high caffeine maintenance dose, and pharmacological treatment for PDA. Differences in O(2) dependency at 28 days and 36 weeks of postmenstrual age were at the limit of significance in favor of SNIPPV treated infants. Conclusions. SNIPPV use after INSURE technique in our NICU reduced MV need and favorably affected short-term morbidities of our premature infants.

Neonatal molding in deformational auricolar anomalies.

INTRODUCTION: Congenital auricular anomalies can be categorized either as malformational or deformational. The first are characterized by a partial absence of the skin or cartilage resulting in a constricted or underdeveloped pinna and require surgical correction. Deformations are characterized by a misshaped but fully developed pinna and are best treated by auricular molding. AIM: Authors want to present their case load in treatment of infants affected by deformational auricolar anomalies and describe their techniques using early splinting for congenital auricular deformities, like prominent ear, lop ear, constricted ear, Stahl's ear. PATIENTS AND METHODS: Between 2009 to 2011, in Maxillo and Oral Surgery Unit, a nonsurgical technique was used to treat 22 ears affected by deformational anomalies in 12 patients soon after birth. Four patients were female. This kind of nonsurgical correction of the deformed auricle was performed on lop ears (n=6), constricted ears (n=8), prominent ears (n= 4), Stahl's ear (n=4). Children more than two months old were also excluded. The mean of treatment time was 5.5 weeks. RESULTS: according to the Authors and the parents 100% of treated auricles improved. Improving at the end of the molding treatment was observed in 18% of the auricles, but recurrence to one year of stopping treatment. There were not complications caused by this procedure. CONCLUSIONS: The nonsurgical molding has the advantage to correct at a very early age a cosmetic abnormality, giving a natural and in the most of the time a satisfactory results, with a prevalence rate of complications of much less than surgical corrections.

Surfactant and non invasive ventilation for preterm infants.

Mechanical ventilation, although life-saving, predisposes preterm infants to BPD. NCPAP emerged as an alternative to invasive ventilation, but it fails in about 30% of infants even when coupled with surfactant therapy. Alternative modes of non invasive ventilation are currently used in neonatology in order to prevent mechanical ventilation. Among these, Synchronized Nasal Intermittent Positive Ventilation (SNIPPV) seems to ensure better results. (www.actabiomedica.it).

Sevoflurane inhalation for severe bronchial obstruction in infants with bronchiolitis.

Bronchiolitis is a lower respiratory tract viral infection which may result in severe bronchial obstruction and respiratory failure despite treatment with beta-adrenergic agonists and glucocorticoids. Here we describe two otherwise healthy infants with severe bronchiolitis whose clinical course was complicated by marked bronchial obstruction and respiratory acidosis refractory to conventional medications (ß-stimulants, anticholinergics and corticosteroids) and non-invasive positive pressure ventilation. Sevoflurane inhalation allowed both infants to attain a sustained, clinical improvement in ventilation and one patient to avoid mechanical ventilation. We suggest that sevoflurane inhalation may be a therapeutic option in the treatment of young infants with severe bronchiolitis who respond poorly to conventional therapy.

Rhinovirus bronchiolitis and recurrent wheezing: 1-year follow-up.

The association between bronchiolitis and recurrent wheezing remains controversial. In this prospective study, we assessed risk factors for recurrent wheezing during a 12-month follow-up in 313 infants aged <12 months hospitalised for their first episode of bronchiolitis. Demographic, clinical and laboratory data were obtained with a questionnaire and from medical files. A total of 14 respiratory viruses were concurrently assayed in nasal washings. Parents were interviewed 12 months after hospitalisation to check whether their infants experienced recurrent wheezing. The rate of recurrent wheezing was higher in infants with bronchiolitis than in controls (52.7 versus 10.3%; p<0.001). Multivariate analysis identified rhinovirus (RV) infection (OR 3.3, 95% CI 1.0-11.1) followed by a positive family history for asthma (OR 2.5, 95% CI 1.2-4.9) as major independent risk factors for recurrent wheezing. In conclusion, the virus most likely to be associated with recurrent wheezing at 12 months after initial bronchiolitis is RV, a viral agent that could predict infants prone to the development of recurrent wheezing.

Virological and clinical characterization of respiratory infections in children attending an emergency department during the first autumn-winter circulation of pandemic A (H1N1) 2009 influenza virus.

To characterize respiratory virus infections during the first autumn-winter season of pandemic A (H1N1) 2009 influenza virus (A/H1N1/2009) 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/H1N1/2009 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/H1N1/2009 and RV. Of the hospitalized children, stratified by age, both infants and children aged >1 year with RSV were most severely affected, whereas A/H1N1/2009 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/H1N1/2009 and RSV peaks, presented with bronchiolitis, wheezing and pneumonia. Leukocytosis occurred more frequently in RV-infected and A/H1N1/2009-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.

Detection of respiratory viruses in the 2009 winter season in Rome: 2009 influenza A (H1N1) complications in children and concomitant type 1 diabetes onset.

We investigated clinical characteristics and complications, particularly type 1 diabetes onset, in children hospitalized for 2009 pandemic influenza A (H1N1) virus and compared number of consultations, rate of hospitalization and virus identification in children hospitalized for acute respiratory symptoms (ARS) during the winter season 2009-2010 and 2004-2005. Patients were tested for 2009 H1N1 virus and 14 respiratory viruses on pharyngeal brush/nasal aspirates, using a RT-PCR or nested PCR assays. Consultations and hospitalizations were extracted from operative system GIPSE. The total number of consultations increased by 12%, consultation rate for ARS by 13% and number of hospitalizations by 56% from 2004-2005 to 2009-2010. In 2004-2005, Influenza A virus was identified in only 7 percent of hospitalized children, while in 2009-2010 the 2009 H1N1 virus was identified in 21%. Three children attending the hospital for ARS and 2009 H1N1 infection had ketoacidosis as the onset manifestation of type 1 diabetes. By comparing the number of new diabetes diagnoses among the two winter seasons, we found a higher number of new diagnoses in October 2009-January 2010 than in the same period in 2004-2005 (19 vs 10). Six children (13%), all presenting with pre-existing diseases, were admitted to the pediatric intensive care unit. No children died. The outbreak of this novel virus has increased pediatric consultation rates and hospitalizations compared with previous winters without causing deaths. The children at highest risk for severe infection are those with comorbidities. The 2009 H1N1 virus seems in some way involved in the pathogenesis of type 1 diabetes.

[Ventilatory care]. / L'assistenza ventilatoria.

Mechanical ventilation is considered a supportive, nontherapeutic technology used to perform the work of breathing for patients who are unable to do so on their own. In neonatology, mechanical ventilation is often used for premature neonates who are unable to sustain ventilation because of reduced functional residual capacity due to surfactant deficiency. Mechanical ventilation is thus an attempt to mimic the respiratory system's physiological function of gas exchange until the respiratory system reaches maturation. In pediatrics, mechanical ventilation is rarely used for acute respiratory distress syndrome as shown by Dahlem et al. in 2003 who found that only 9.9% of cases of respiratory failure in PICU was caused by ARDS. For this reason, ventilatory techniques in PICU are very heterogenous from the assisted to the most aggressive controlled modes associated with ventilator maneuvers. There are no specific guidelines for the use of mechanical ventilation in children and the low number of infants with ARDS in PICU makes it difficult to run randomized controlled trials in this population. Thus the algorithms are based on the results of either adult or neonatal studies. The advantage of extrapolating data from the neonatal evidence relates mainly to the prevention of ventilator induced lung injury (e.g., CPAP, HFOV, NIV, permissive hypercapnia, surfattant), of which neonatologists are particularly expert.

The role of terlipressin in pediatric septic shock: a review of the literature and personal experience.

Vasopressin and its synthetic analog terlipressin are potent vasopressors that could be useful in vasodilatory septic shock. In septic adults, vasopressin-terlipressin have been shown to increase mean arterial pressure and to decrease the necessity for catecholamines. Moreover, low doses of vasopressin, or terlipressin, increase urine output and ameliorate oxygenation. Although pediatric septic shock is more often hypodynamic, both vasopressin and terlipressin have proved to be effective in restoring blood pressure or increasing the diuresis in this setting. The purpose of this review is to summarize the physiology of vasopressin and to report the available evidence for the use of vasopressin or terlipressin in pediatric septic shock in order to make best use in this population. We also report our experience with the continuous infusion of terlipressin in two pediatric patients who developed catecholamine refractory septic shock.

Granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor and neutrophils in the bronchoalveolar lavage fluid of premature infants with respiratory distress syndrome.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) promote clonal maturation of neutrophil and macrophage progenitors and increase functional activities of mature cells. The number and activity of neutrophils and macrophages in the lung affect healing and remodeling following respiratory distress syndrome (RDS). QUESTIONS OF THE STUDY: (1) Are G-CSF and GM-CSF present in the airways of preterm neonates with RDS? (2) Do airway G-CSF and GM-CSF concentrations correlate with neutrophil and macrophage number in the bronchoalveolar lavage (BAL) fluid? (3) Are alveolar macrophages a source of airway G-CSF and GM-CSF? (4) Is in vitro expression of G-CSF and GM-CSF by airway macrophages modified by dexamethasone, endotoxin, or hyperoxia? METHODS: Eighteen preterm neonates with RDS requiring mechanical ventilation within the first 24 h of life underwent BAL on days 1, 3, 6, 10, 12, 15, 20, and 28 if still intubated. BAL G-CSF and GM-CSF concentrations were measured by ELISA, and neutrophils and macrophages were counted. Alveolar macrophages were cultured, and G-CSF and GM-CSF expression measured in the presence and absence of dexamethasone, endotoxin, and hyperoxia. RESULTS: G-CSF and GM-CSF were present in the BAL of intubated preterm neonates. In infants who did not develop chronic lung disease (CLD) (n = 5), G-CSF and GM-CSF concentrations were highest in the first days of life, falling thereafter, while in those who did develop CLD (n = 13) these concentrations increased over time. Neutrophil concentrations in BAL fluid followed a similar pattern. Macrophages from BAL were identified as a source of G-CSF and GM-CSF mRNA and protein. G-CSF and GM-CSF expression by these macrophages was increased by endotoxin, decreased by dexamethasone, and unchanged by hyperoxia. CONCLUSIONS: G-CSF and GM-CSF are present in neonatal BAL, and may contribute significantly to the accumulation of alveolar neutrophils.

Infection, neutrophils, and hematopoietic growth factors in the pathogenesis of neonatal chronic lung disease.

Continued definition of the biochemical and molecular mechanisms underlying the development of chronic lung disease (CLD) has persuaded investigators that inflammatory cells and mediators are key factors in the pathophysiology of the disease. High numbers of inflammatory cells and their products are present in the airways of ventilated neonates with respiratory distress syndrome and precede the development of CLD. This article reviews the mechanisms underlying neutrophil recruitment in the lungs of ventilated preterm infants with respiratory distress syndrome and the injurious effects that these cells can produce on lung parenchyma with special emphasis on the development of CLD. The role of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor is stressed as a pivotal mechanism of neutrophil recruitment and activation.

Reference values for selected trace elements in serum of term newborns from the urban area of Rome.

Reference values for Al, Cd, Co, Cu, Li, Mn, Mo, Ni, Rb, Se and Zn, and indicative intervals for Sb are proposed in serum from cord blood of 143 term newborns of the urban area of Rome. On the basis of the eligibility criteria adopted, only babies with gestational age > 37 weeks and body weight at the delivery > 2500 g, i.e., "normal" term infants, were included in this study. With the exception of Cd, Li, Ni and Sb, experimental data for each of the other analytes were found to approach a normal distribution. The estimated references values (in ng/ml) were the following: Al, 1. 12-6.79; Cd, 0.10-0.52; Co, 0.20-0.43; Cu, 140-691; Li, 0.31-2.23; Mn, 0.79-3.26; Mo, 0.36-1.56; Ni, 0.20-3.15; Rb, 196-1302; Sb, 0. 10-1.48 (indicative range); Se, 20.2-69.7; and Zn, 318-1405. For several elements, the information available in the relevant literature does not allow adequate comparisons to be performed. This was actually possible only for Cu, Se and Zn. The correlations between the weights at birth (BW), gestational ages (GA) and elemental concentrations were elucidated. As expected, significant positive correlations were found for Cu and Se with GA and BW, respectively. Strong mutual associations were observed for several other elements, but their interpretation is still debatable.

Circulating thrombopoietin levels in neonates with infection.

Thrombocytopenia is a commonly encountered hematologic complication in neonates with sepsis. Thrombopoietin (TPO) is the principal physiologic regulator of megakariocytopoiesis and platelet production. This study was carried out to determine whether variations in circulating TPO levels would occur in infected neonates and/or if they would correlate with platelet counts. In a prospective study of 36 sick neonates (gestational age 24-42 wk) admitted to a regional Neonatal Intensive Care Unit (NICU), blood was collected for TPO measurements and platelet counts on admission to the NICU, if infection was inferred, and at recovery before discharge. An additional group of 15 apparently healthy neonates was also studied (median postnatal age at the time of blood sampling for TPO assessment: 4 d, range 1-10) as control. TPO was measured on plasma samples using a commercially available enzyme-immunosorbent assay (ELISA). On admission, the majority (21/36) of the sick neonates had non-infectious diseases, 2 had early onset sepsis, and 13 had infection (defined as the presence of clinical signs of sepsis, abnormal leukocyte counts or C-reactive protein values, and positive results on local cultures, but negative blood culture results). During the hospital stay, 5 neonates developed sepsis (positive blood culture) and 6 had infection (as previously defined) or necrotizing enterocolitis (NEC). The median TPO level (1704 pg/ml, range 51-3912) was higher during sepsis (either early or late) than during infection (included NEC) (198 pg/ml, range 21-2504), or non-infectious disease (659 pg/ml, range 0-2533), while platelet counts (median value 37,000 cells/microl, range 15,000-486,000) were lower than during either infection (included NEC) (median value 238,000 cells/microl, range 49,000-655,000) or non-infectious disease (median value 110,000 cells/microl, range 45,000-549,000). When infants had recovered from these illnesses, TPO concentrations markedly dropped (median value 59 pg/ml, range 0-825). These values were similar to those found in the control neonates (median TPO level 85 pg/ml, range 43-620). In infected neonates (sepsis plus infection), TPO levels inversely correlated with platelet counts (r = -0.634, p = 0.001) as did those of infants with non-infectious disease (r = -0.574, p = 0.006), while there was no significant correlation between TPO levels and platelet counts in the samples obtained after recovery or in the control infants. We conclude that infected neonates have high circulating TPO levels in the face of low platelet counts. Whether larger TPO concentrations following exogenous administration of recombinant TPO would restore the number of circulating platelets warrants further investigation.

Comparing the effects of nasal synchronized intermittent positive pressure ventilation (nSIPPV) and nasal continuous positive airway pressure (nCPAP) after extubation in very low birth weight infants.

In this study we hypothesized that nasal synchronized intermittent positive pressure ventilation (nSIPPV) would provide more ventilatory support than nasal continuous positive airway pressure (nCPAP) in the immediate post-extubation period in very low birth weight (VLBW) infants. We tested this hypothesis by comparing the effects of these two ventilatory techniques on ventilation, gas exchange, and patient inspiratory effort in 11 preterm infants immediately after extubation. All neonates studied (BW: 1141+/-(SEM) 53 g; GA: 28.1+/-(SEM) 0.5 wks) had received mechanical ventilation because of respiratory distress at birth and were extubated by day 14 of life. Nasal SIPPV and nCPAP were applied in random order to each infant after extubation so that each was his/her own control. Both nCPAP and nSIPPV were delivered at end-expiratory pressures (PEEP) of 3 cm H2O. Inspiratory times (Ti) and peak inspiratory pressures set during nSIPPV were the same as those used at the time of extubation. Recordings lasted 45 min in each mode of ventilation. Tidal volume (Vt), minute volume (Ve), respiratory rate (RR), airway pressure (Paw), transcutaneous PO2 (TcPO2) and PCO2 (TcPCO2) as well as phasic esophageal pressure deflections (Pe), as an estimate of inspiratory effort, were measured. The measurements obtained during both modes of ventilation indicated significant differences between the two techniques. Indeed, application of nSIPPV was associated with a statistically significant increase in Vt and Ve. In addition, Pe decreased by 30% during nSIPPV (P<0.01). TcPCO2 was statistically significantly lower during nSIPPV than nCPAP, and RR as well. These data therefore suggest that nSIPPV may provide more ventilatory support than nCPAP in the post-extubation period with less patient inspiratory effort.