Hemoglobin life-threatening value (1.9 g/dl) in good general condition: a pediatric case-report

Abstract Background We report a pediatric patient presenting in good general condition despite a hemoglobin value of 1,9 g/dL, which is normally regarded as life-threatening. Case presentation An African 5 years-old girl presented to our Emergency Department (ED) for worsening asthenia, within a clinical picture of good general condition. The hemoglobin value at admission was 1,9 g/dL. The subsequent diagnostic-therapeutic pathway highlighted the presence of two different causes, both well known to be responsible for chronic anemia (with slow reduction of hemoglobin values): iron deficiency anemia (IDA) due to a very low dietary intake of iron-rich foods, and homozygous sickle cell disease (HbSS). She received transfusions of packed red blood cells (overall 15 ml/kg) and subsequently intravenous iron preparations (total amount 200 mg) followed by oral iron supplements. The Hb value at discharge, 10 days after the admission, was 9.8 g/dL. Conclusions When approaching a picture of severe anemia, we suggest pediatricians take into consideration clinical conditions rather than laboratory values and to take advantage of detailed anamnestic data in order to make the diagnosis

Ultrasound of acquired posterior fossa abnormalities in the newborn

Neonatal brain sonography is part of routine clinical practice in neonatal intensive care units, but ultrasound imaging of the posterior fossa has gained increasing attention since the burden of perinatal acquired posterior fossa abnormalities and their impact on motor and cognitive neurodevelopmental outcome have been recognized. Although magnetic resonance imaging (MRI) is often superior, posterior fossa abnormalities can be suspected or detected by optimized cranial ultrasound (CUS) scans, which allow an early and bed-side diagnosis and monitoring through sequential scans over a long period of time. Different ultrasound appearances and injury patterns of posterior fossa abnormalities are described according to gestational age at birth and characteristics of the pathogenetic insult. The aim of this review article is to describe options to improve posterior fossa sequential CUS image quality, including the use of supplemental acoustic windows, to show standard views and normal ultrasound anatomy of the posterior fossa, and to describe the ultrasound characteristics of acquired posterior fossa lesions in preterm and term infants with effect on long-term outcome. The limitations and pitfalls of CUS and the role of MRI are discussed

Modulation of microglial activation by adenosine A2a receptor in animal models of perinatal brain injury

Neuroinflammation has a key role in the pathogenesis of perinatal brain injury. Caffeine, a nonspecific antagonist of adenosine receptors (ARs), is widely used to treat apnea of prematurity and has been linked to a decrease in the incidence of cerebral palsy in premature infants. The mechanisms explaining its neuroprotective effect have not yet been elucidated. The objective of this study was to characterize the expression of adenosine and ARs in two neonatal rat models of neuroinflammation and to determine the effect of A2aR blockade on microglial activation assessed through inflammatory cytokine gene expression. We have used two rat models of microglial activation: the gestational low protein diet (LPD) model, associated with chronic brain injury, and postnatal ibotenate intracerebral injections, responsible for acute excitotoxicity injury. Adenosine blood levels have been measured by Tandem Mass Spectrometry. The expression of ARs in vivo was assessed using qPCR and immunohistochemistry. In vivo models have been replicated in vitro on primary microglial cell cultures exposed to A2aR agonist CGS-21680 or antagonist SCH-58261. The effects of these treatments have been assessed on the M1/M2 cytokine expressions measured by RT-qPCR. LPD during pregnancy was associated with higher adenosine levels in pups at postnatal day 1 and 4. A2aR mRNA expression was significantly increased in both cortex and magnetically sorted microglial cells from LPD animals compared to controls. CD73 expression, responsible for extracellular production of brain adenosine, was significantly increased in LPD cortex and sorted microglia cells. Moreover, CD73 protein level was increased in ibotenate treated animals. In vitro experiments confirmed that LPD or control microglial cells exposed to ibotenate display an increased expression, at both protein and molecular levels, of A2aR and M1 markers (IL-1\u3b2, IL-6, iNOS, TNF\u3b1). This pro-inflammatory profile was significantly reduced by SCH-58261, which reduces M1 markers in both LPD and ibotenate-exposed cells, with no effect on control cells. In the same experimental conditions, a partial increased of M1 cytokines was observed in response to A2aR agonist CGS-21680. These results support the involvement of adenosine and particularly of its receptor A2aR in the regulation of microglia in two different animal models of neuroinflammation

Cranial ultrasound findings in preterm germinal matrix haemorrhage, sequelae and outcome

Germinal matrix-intraventricular haemorrhage (GMH-IVH), periventricular haemorrhagic infarction (PHI) and its complication, post-haemorrhagic ventricular dilatation (PHVD), are still common neonatal morbidities in preterm infants that are highly associated with adverse neurodevelopmental outcome. Typical cranial ultrasound (CUS) findings of GMH-IVH, PHI and PHVD, their anatomical substrates and underlying mechanisms are discussed in this paper. Furthermore, we propose a detailed descriptive classification of GMH-IVH and PHI that may improve quality of CUS reporting and prediction of outcome in infants suffering from GMH-IVH/PHI

Continuous Glucose Monitoring in Preterm Infants: The Role of Nutritional Management in Minimizing Glycemic Variability

Glycemic variability (GV) is common in preterm infants. In the premature population, GV is a risk factor for morbidity and mortality. Both hypo- and hyperglycemia can impair neurodevelopment. We investigated the impact of continuous versus intermittent tube enteral feeding on GV. In our prospective observational study, 20 preterm infants with a gestational age ≤ 34 weeks at either continuous or intermittent bolus full enteral feeding. For five days, continuous glucose monitoring (CGM) was utilized, which was achieved through the subcutaneous insertion of a sensor. A total of 27,532 measurements of blood glucose were taken. The mean amplitude of glycemic excursions did not differ between the two cohorts statistically. Continuous feeding resulted in higher positive values, increasing the risk of hypo- and hyperglycemia. Subjects who were small for their gestational age had a higher standard deviation during continuous feeding (p = 0.001). Data suggest that intermittent bolus nutrition is better for glycemic control than continuous nutrition. Nutritional management optimization of preterm infants appears to be critical for long-term health. In the future, CGM may provide a better understanding of the optimal glucose targets for various clinical conditions, allowing for a more personalized approach to management

Oxidative stress as a primary risk factor for brain damage in preterm newborns

The risk of oxidative stress is high in preterm newborns. Room air exposure of an organism primed to develop in a hypoxic environment, lacking antioxidant defenses, and subjected to hyperoxia, hypoxia, and ischemia challenges the newborn with oxidative stress production. Free radicals can be generated by a multitude of other mechanisms, such as glutamate excitotoxicity, excess free iron, inflammation, and immune reactions. Free radical-induced damage caused by oxidative stress appears to be the major candidate for the pathogenesis of most of the complications of prematurity, brain being especially at risk, with short to long-term consequences. We review the role of free radical oxidative damage to the newborn brain and propose a mechanism of oxidative injury, taking into consideration the particular maturation-dependent vulnerability of the oligodendrocyte precursors. Prompted by our observation of an increase in plasma Adenosine concentrations significantly associated with brain white matter lesions in some premature infants, we discuss a possible bioenergetics hypothesis, correlated to the oxidative challenge of the premature infant. We aim at explaining both the oxidative stress generation and the mechanism promoting the myelination disturbances. Being white matter abnormalities among the most common lesions of prematurity, the use of Adenosine as a biomarker of brain damage appears promising in order to design neuroprotective strategies

Rethinking the neonatal transport ground ambulance

Objectives: This article describes the detailed project aimed to realize a dedicated ground ambulance for neonatal emergency transport service (NETS). To date, the European Community rules specify requirements for the design, testing, performance, and equipping of road ambulance used for transport and care of adult injured or ill patients, completely ignoring neonatal transport. Methods: The project consisted of electric and gas supply planning, interior design taking into account ergonomic and occupant protection principles, both during travel and during medical care performances. Results: A detailed project is presented. Main differences between European Type C ambulance and the new proposed Type D neonatal ground ambulance are the presence on board of air compressed cylinder, iNO cylinders and delivery system, phototheraphy, shock adsorbing stretcher support, cooling device, patient's placenta (refrigeration box), and transcutaneous gas analyzer. Conclusion: The European Community rules specify requirements for road ambulance used for transport and care of adult injured or ill patients, completely ignoring neonatal transport. This study describes the detailed project aimed to realize a dedicated ground ambulance for neonatal emergency transport service. This study demonstrated that it is not possible simply to adapt the currently dedicated ambulance for mobile intensive care and resuscitation services (actual type C European Community) in a modern dedicated NETS ambulance; it is of paramount importance suggesting to European Community to introduce a further ambulance type, to be identified type D, strictly reserved to neonatal transport activities

High frequency of ribosomal protein gene deletions in Italian Diamond-Blackfan anemia patients detected by multiplex ligation-dependent probe amplification assay

Diamond-Blackfan anemia is an autosomal dominant disease due to mutations in nine ribosomal protein encoding genes. Because most mutations are loss of function and detected by direct sequencing of coding exons, we reasoned that part of the approximately 50% mutation negative patients may have carried a copy number variant of ribosomal protein genes. As a proof of concept, we designed a multiplex ligation-dependent probe amplification assay targeted to screen the six genes that are most frequently mutated in Diamond-Blackfan anemia patients: RPS17, RPS19, RPS26, RPL5, RPL11, and RPL35A. Using this assay we showed that deletions represent approximately 20% of all mutations. The combination of sequencing and multiplex ligation-dependent probe amplification analysis of these six genes allows the genetic characterization of approximately 65% of patients, showing that Diamond-Blackfan anemia is indisputably a ribosomopathy