Luca Pierantoni

Changes in cerebral hemodynamics and amplitude integrated EEG in an asphyxiated newborn during and after cool cap treatment

Amplitude integrated EEG (aEEG) and Near Infrared Spectroscopy (NIRS) were applied in a newborn with a moderate hypoxic-ischemic encephalopathy before, during and after brain cooling. At 2h of life a selective head cooling with mild systemic hypothermia was started and maintained for 72h. aEEG background pattern improved from severely abnormal to normal during the first 17h of life. NIRS revealed a reduction in cerebral blood volume (CBV) during hypothermia that recovered during the rewarming period, whereas brain oxygenation remained stable. As brain cooling is supposed to reduce delayed hyperemia and help to maintain neuronal metabolism following cerebral insults, aEEG and NIRS monitoring may be useful during hypothermic treatment in order to document changes in CBV and brain oxygenation possibly reflecting the efficacy of hypothermia.

Effect of Posture on Brain Hemodynamics in Preterm Newborns Not Mechanically Ventilated

Background: Changes in head posture influence brain hemodynamics. Optimal positioning has been recommended as 1 of 10 potentially better practices to reduce the incidence of brain injury in preterm newborns. Objectives: The aim of this study was to evaluate by near-infrared spectroscopy (NIRS) the effect of different head and body positions and the influence of gestational age (GA) and nasal continuous positive airway pressure on brain hemodynamics in very preterm newborns. Methods: 24 stable preterm newborns were studied by NIRS in 6 different postures including head rotation and head inclination in both supine and prone positions. Changes in normalized tissue hemoglobin index (nTHI) and tissue oxygenation index (TOI) were measured after posture variations. Results: No statistically significant changes in nTHI and in TOI were found in the 6 postures. nTHI variations, expression of cerebral blood volume variations, were influenced by GA. A reduction in nTHI, with a stable TOI, in the less mature infants (with GA ≤26 weeks), occurred on head rotation; nTHI increased again when the head was derotated. Conclusions: Hemodynamic changes after posture variations depend on GA. Head rotation in newborns with GA ≤26 weeks produced a reduction in nTHI with stable TOI. Possible physiopathological mechanisms are discussed.

Role of bilevel positive airway pressure in the management of preterm newborns who have received surfactant

Aim:  Surfactant given during brief intubation followed by immediate extubation on nasal continuous positive airway pressure [Intubation‐Surfactant‐Extubation (InSurE) approach] is used to treat respiratory distress syndrome in newborns. Our aim was to evaluate whether bilevel positive airway pressure (BiPAP) after InSurE failure is able to prevent the need for mechanical ventilation (MV).

Cloning and mapping multiple S-locus F-box genes in European pear ( Pyrus communis L.)

European pear, as well as its close relatives Japanese pear and apple, exhibits S-RNase-based gametophytic self-incompatibility. The male determinant of this self-incompatibility mechanism is a pollen-expressed protein containing an F-box domain; in the genera Petunia (Solanaceae), Antirrhinum (Plantaginaceae), and Prunus (Rosaceae), a single F-box gene determines the pollen S. In apple and Japanese pear, however, multiple S-locus F-box genes were recently identified as candidates for the pollen S, and they were named S-locus F-Box Brothers. These genes were considered good candidates for the pollen S determinant since they exhibit S-haplotype-specific polymorphisms, pollen-specific expression, and linkage to the S-RNase. In the present study, S-locus F-Box Brothers homologs have been cloned from two of the most agronomically important European pear varieties, “Abbé Fétel” (S104-2/S105) and “Max Red Bartlett” (S101/S102), and they have been mapped on a genetic linkage map developed on their progeny. Our results suggest that the number of F-box genes linked to the S-locus of the European pear is higher than expected according with previous reports for apple and Japanese pear, since up to five genes were found to be linked to a single S-haplotype. Moreover, two of these genes exhibited an incomplete linkage to the S-RNase, allowing the identification of low-frequency recombinant haplotypes, generated by a crossing-over event between the two genes. These F-box genes are most likely placed in close proximity of the S-locus but do not belong to it, and they can thus be excluded from being responsible for the determination of pollen S function.

Evaluation of candidate F-box genes for the pollen S of gametophytic self-incompatibility in the Pyrinae (Rosaceae) on the basis of their phylogenomic context

The recent analysis of the S-locus region of apple and Japanese pear, two species of Pyrinae (Rosaceae), suggested multiple and different F-box genes (called SFBBs) as candidates for the male determinant (pollen S) of RNase-based gametophytic self-incompatibility in these two species. Here, we followed a phylogenetic approach to take advantage of the pattern of molecular evolution of the S-locus of Pyrinae in characterizing SFBB homologs belonging to S-haplotypes of apple and three species of Pyrus (European, Japanese, and Chinese pears). Our results suggested that the S-locus region of Pyrinae contains no less than six SFBB members and that its structure seems to be rather conserved between apple and pear species. In accordance with the prevailing theory on S-haplotype evolution, the pollen S is expected to have coevolved with the S-RNase and to show some common features derived from the long-term evolution under frequency-dependent balancing selection, i.e., high sequence diversity, evidence of positive selection, and shared ancestral polymorphisms. Using this conceptual framework, we present evidence that some SFBB genes may be better candidates for pollen S in Pyrinae than others. Overall, the SFBB genes analyzed exhibited much lower sequence diversity than their associated S-RNases; likewise, they showed little or no evidence of positive selection. However, evidence of coevolution with the S-RNase clearly emerged for two of them. Altogether our results suggested different evolutionary histories for different SFBBs putatively derived from their distinct involvement in self-incompatibility.

Influence of gestational age on the EDIN score: an observational study

Background and aim: Hospitalised neonates, particularly if preterm, may be exposed to prolonged pain. At present the only validated scale to assess prolonged pain in preterms is the EDIN (Echelle Douleur Inconfort Nouveau-Né) scale. Gestational age has been shown to influence the response of infants to acute pain but its potential effect in the setting of prolonged pain has not been investigated. The aim of the present study was to evaluate whether neonatal maturity as expressed by gestational age and/or postnatal age influences their expression of prolonged pain. Methods: In a 1 year period, 84 neonates (gestational age 25–41 weeks), referred to the authors’ neonatal intensive care unit were evaluated using the EDIN scale two to three times a day (1571 scores). The EDIN scores were categorised as indicative (>6) or not indicative (⩽6) of pain. Gestational age and postnatal age were included in a logistic regression analysis along with some painful situations and analgesic treatment to identify the impact on the EDIN scores. Results: Logistic regression analysis showed that the EDIN scores were positively associated with gestational age (odds ratio 1.166; 95% CI 1.123 to 1.211). Postnatal age, sepsis and presence of respiratory support also influenced the EDIN score. Conclusions: Gestational age influences expression of prolonged pain. Content validity of the EDIN scale could be improved by adding categories for gestational age and attributing higher basal scores to less mature newborns.

Analgesic and sedative drugs in newborns requiring respiratory support

Infants receiving respiratory assistance may feel pain due to underlying disease or ventilation itself. Pain control during neonatal respiratory care reduces morbidity. This article summarizes the main scientific evidence about the use of drugs during ventilatory assistance, and provides some practical suggestions on pain management in neonates with respiratory support.

Gastrointestinal presentation of Kawasaki disease: A red flag for severe disease?

Background Kawasaki disease (KD) is a febrile systemic vasculitis of unknown etiology and the main cause of acquired heart disease among children in the developed world. To date, abdominal involvement at presentation is not recognized as a risk factor for a more severe form of the disease. Objective To evaluate whether presenting abdominal manifestations identify a group at major risk for Intravenous immunoglobulin (IVIG)-resistance and coronary lesions. Methods Retrospective study of KD patients diagnosed between 2000 and 2015 in 13 pediatric units in Italy. Patients were divided into 2 groups according to the presence or absence of abdominal manifestations at onset. We compared their demographic and clinical data, IVIG-responsiveness, coronary ectasia/aneurysms, laboratory findings from the acute and subacute phases. Results 302 patients (181 boys) were enrolled: 106 patients with, and 196 patients without presenting abdominal features. Seasonality was different between the groups (p = 0.034). Patients with abdominal manifestations were younger (p = 0.006) and more frequently underwent delayed treatment (p = 0.014). In the acute phase, patients with abdominal presentation had higher platelet counts (PLT) (p = 0.042) and lower albuminemia (p = 0.009), while, in the subacute phase, they had higher white blood cell counts (WBC) and PLT (p = 0.002 and p < 0.005, respectively) and lower red blood cell counts (RBC) and hemoglobin (Hb) (p = 0.031 and p 0.009). Moreover, the above mentioned group was more likely to be IVIG-resistant (p < 0.005) and have coronary aneurysms (p = 0.007). In the multivariate analysis, presenting abdominal manifestations, age younger than 6 months, IVIG- resistance, delayed treatment and albumin concentration in the acute phase were independent risk factors for coronary aneurysms (respectively p<0.005, <0.005, = 0.005 and 0.009). Conclusions This is the first multicenter report demonstrating that presenting gastrointestinal features in KD identify patients at higher risk for IVIG-resistance and for the development of coronary aneurysms in a predominantly Caucasian population. Clinical trial registration 8/20014/O/OssN.

Follow-up at the corrected age of 24 months of preterm newborns receiving continuous infusion of fentanyl for pain control during mechanical ventilation

Abstract The neurodevelopmental impact of fentanyl given to preterm newborns for pain control is still unknown. The aim of this study was to assess the neurodevelopmental impact of 2 regimens of fentanyl administration by a prospective follow-up evaluation. In our previous multicenter, double-blind, randomized controlled trial, 131 mechanically ventilated newborns (gestational age ⩽32+6 weeks) were randomized to fentanyl (continuous infusion of fentanyl + open label boluses of fentanyl) or placebo (continuous infusion of placebo + open label boluses of fentanyl). Infant development was evaluated using Griffiths Mental Developmental Scales (Griffiths, 1996) until 24 months of corrected age by trained psychologists who were not aware of the group allocation. 106/131 infants survived at discharge; 3 died after discharge, 25 were lost to follow-up (12 in the fentanyl and 13 in the placebo group). Seventy-eight patients were evaluated at 2 years of corrected age. Children in the fentanyl group, compared with those in the placebo group, obtained significantly lower Griffiths general developmental quotient (mean [SD]: 89.95 [13.64] vs 97.18 [12.72], P = 0.024) together with the scores on the eye-hand coordination (mean [SD]: 89.09 [12.13] vs 99.19 [13.19], P = 0.002) and performance skills (mean [SD]: 79.71 [15.80] vs 90.09 [15.28], P = 0.009) scales. After adjustment for clinical confounders (gestational age, CRIB score, and sex) only eye-hand co-ordination was associated with fentanyl infusion. This study demonstrates that continuous infusion of fentanyl in very preterm infants, given at 1 mcg·kg−1·h−1 during mechanical ventilation, is associated with a significant decrease in eye and hand co-ordination skills. Longer follow-up is needed to evaluate the impact on future motor, cognitive, and behavioral functions.