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Aims: To analyze all evidence on the possible increase in morbidity and mortality determined by the use of inhibitors of gastric acid secretion (IGAS) drugs. Materials and Methods: We review all evidence exploring the adverse events associated with IGAS use in neonates. Results: Despite being prescribed in an off-label manner because of the perceived safety and potential benefit demonstrated for older populations, IGAS are being increasingly used in the neonatal period with much evidence derived from adults and children. Few data are available for neonates and indicate an association between IGAS use with infections and necrotizing enterocolitis (NEC), and with an increased mortality. Delayed gastric emptying, increased gastric mucus viscosity, modification in microbiota, and impairment of neutrophils functions are possible mechanisms of adverse events associated with IGAS use. Conclusions: A careful prescription of IGAS is crucial in order to reduce iatrogenic damage in neonates.

INTRODUCTION: Variation of respiratory care is described between centers around the world. The Italian Neonatal Network (INN), as a national group of the Vermont-Oxford Network (VON) allows to perform a wide analysis of respiratory care in very low birth weight infants. METHODS: We analyzed the dataset of infants enrolled in the INN in 2009 and 2010 and, for surfactant administration only, from 2006 to 2010 from 83 participating centers. All definitions are those of the (VON). A questionnaire analysis was also performed with a questionnaire on centers practices. RESULTS: We report data for 8297 infants. Data on ventilator practices and outcomes are outlined. Variation for both practices and outcome is found. Trend in surfactant administration is also analyzed. CONCLUSIONS. The great variation across hospitals in all the surveyed techniques points to the possibility of implementing potentially better practices with the aim of reducing unwanted variation. These data also show the power of large neonatal networks in identifying areas for potential improvement.

This study was undertaken to assess to what extent estimated energy content of 13 infant formulas was related to gross energy measured by bomb calorimetry. Measured gross energy exceeded significantly metabolizable energy as claimed by the manufacturers by applying the classical Atwater's factors by about 12% (range, 6-17%). Measured gross energy also exceeded significantly gross energy calculated by applying either FAO/WHO or our own values of heat combustion of nutrient by 6% (range, 3-9%) and 3.5% (range, 1-6%), respectively. It is concluded that for reasons of symmetry and simplicity, the labeling of the energy content of infant formulas should continue to be calculated by applying the classical Atwater's factors to the nutrient composition. However, when accurate energy balance studies are carried out, the energy content of the diet should be measured by bomb calorimetry rather than be estimated by applying conversion factors to claimed or determined nutrient composition.

Vain et al1 have recently reported that the use of the exchange transfusion (ET) with fresh blood in addition to antibiotics and other supportive care therapies, had brought about a decreased mortality in a series of ten newborn infants suffering from severe septicemia with sclerema. They ascribe this effect more to the removal of endotoxins and the improvement of perfusion and tissue oxygenation than to the enhancement of an inflammatory response on the basis of two factors. First, although fresh blood transfusions are postulated to increase humoral immunity depending on the opsonic activity of blood from the donors, many patients had failed to show a significant clinical response after receiving large fresh blood transfusions; but after ET with blood from the same donors a clear improvement had been obtained.

Epilepsy is a pathologic condition with high prevalence and devastating consequences for the patient and its entourage. Means for accurate diagnosis of type, patient monitoring for predicting seizures and follow up, and efficacious treatment are desperately needed. To improve this adverse outcome, miRNAs and the chaperone system (CS) are promising targets to understand pathogenic mechanisms and for developing theranostics applications. miRNAs implicated in conditions known or suspected to favor seizures such as neuroinflammation, to promote epileptic tolerance and neuronal survival, to regulate seizures, and others showing variations in expression levels related to seizures are promising candidates as useful biomarkers for diagnosis and patient monitoring, and as targets for developing novel therapies. Components of the CS are also promising as biomarkers and as therapeutic targets, since they participate in epileptogenic pathways and in cytoprotective mechanisms in various epileptogenic brain areas, even if what they do and how is not yet clear. The data in this review should help in the identification of molecular targets among the discussed miRNAs and CS components for research aiming at understanding epileptogenic mechanisms and, subsequently, develop means for predicting/preventing seizures and treating the disease.

Objective Clinical care of rare and complex epilepsies is challenging, because evidence‐based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies. Methods Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web‐based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht‐like diseases. A consensus‐based questionnaire was generated for each disease. Results Twenty‐six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht‐like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers. Significance The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers.

Statins have since long been reported to exert acute neuroprotection in experimental stroke models. However, crucial questions still need to be addressed as far as the timing of their cerebral effects after intravascular administration and the role played by the blood brain barrier (BBB) crossing properties. We tested the effects of an hydrophilic statin (pravastatin, 100 nM), which poorly crosses BBB under physiological conditions. Pravastatin was administered either 90 min before or immediately after transient middle cerebral artery occlusion in the in vitro isolated Guinea pig brain preparation. A multi-modal outcome assessment was performed, through electrophysiological and cerebral vascular tone recordings, MAP-2 immunohistochemistry, BBB evaluation via ZO-1/FITC-albumin analysis, AKT and ERK activation and whole-cell antioxidant capacity. Pravastatin pre-ischemic administration did not produce any significant effect. Pravastatin post-ischemic administration significantly prevented MAP-2 immunoreactivity loss in ischemic areas, increased ERK phosphorylation in the ischemic hemisphere and enhanced whole-cell antioxidant capacity. Electrophysiological parameters, vascular tone and AKT signaling were unchanged. In all tested ischemic brains, ZO-1 fragmentation and FITC albumin extravasation was observed, starting 30 min from ischemia onset, indicating loss of BBB integrity. Our findings indicate that the rapid anti-ischemic effects of intravascular pravastatin are highly dependent on BBB increased permeability after stroke.

Objective To describe the natural course of intestinal failure with onset in the neonatal period to provide data regarding the occurrence and to provide a population-based survey regarding the spectrum of underlying diseases. Study design We performed a retrospective chart review including infants admitted to the neonatal intensive care unit of 7 Italian tertiary care centers. Intestinal failure was defined as a primary intestinal disease that induces the need of total parenteral nutrition (PN) for more than 4 weeks or the need of partial PN for more than 3 months. Results The total number of live births during the study time within the enrolled institutions was 30 353, and the number of newborns admitted to the neonatal intensive care unit was 5088. Twenty-six patients satisfied the definition of intestinal failure; thus the occurrence rate of intestinal failure was 0.1% among live-birth newborns and 0.5% among infants at high risk. The main underlying diseases leading to intestinal failure in neonatal age were congenital intestinal defects (42.3%), necrotizing enterocolitis (30.8%), severe intestinal motility disorder (11.5%), intestinal obstruction (7.7%), structural enterocyte defects (3.8%), and meconium peritonitis (3.8%). After a follow-up of 36 months, 84.6% of patients achieved intestinal competence, 1 patient was still receiving home PN, 1 patient underwent transplantation, and 2 patients died. Cholestatic liver disease was diagnosed in 54% of observed children. Conclusion An understanding of the incidence, causes, and natural history of intestinal failure would be helpful to appropriately allocate resources and to plan clinical trials.

The incidence of inflammatory bowel disease (IBD) is progressively increasing in children in Western countries (1). At present, IBD diagnosis and staging is based on a combination of clinical, endoscopic, histological, and radiographic criteria, and there is no simple, noninvasive reliable individual marker for evaluating disease activity and topographical involvement, to predict relapses, and to select distinct treatment strategies (2, 3). Increased nitric oxide (NO) levels have been detected in the stools and plasma of children with IBD (4). This is the likely result of an upregulation of inducible NO synthase activity, which has been detected in intestinal mucosal segments of patients with active ulcerative colitis (UC) and, with lower intensity, of those with Crohn's disease (CD), suggesting a role of NO in IBD pathophysiology . The aim of this study was to determine whether rectal NO production, measured by a simple and noninvasive technique, reflects local inflammatory changes and disease activity in children with IBD. Forty children were included in the study: diagnosis, disease activity, and topographical involvement were obtained in all subjects by endoscopy and mucosal biopsy. Mean NO concentration was significantly higher in children with active UC than in control subjects. In nonactive UC patients and in active CD patients with rectal involvement, an overproduction of NO was also detected, but its magnitude was significantly lower than that observed in active UC children. On the contrary, in active CD children with rectal sparing NO production was similar to that of controls

Background: Enterai feeding for infants with birth weight1000 g (ELBWI) is still a controversial issue. The aim of the present survey was to ascertain the attitudes of Italian neonatal intensive care units (NICUs) regarding this point. Method: A questionnaire, with multiple choice answers, regarding the timing of enteral feeding, its progression, the different techniques utilised, the eventual use of fortifiers and the interrupting criteria, was mailed to 92 Italian NICUs. Results: 74 NICUs all over the country participated in the study.1153 ELBWI were hospitalised in 1996 in these Units. Enterai feeding for babies between 501 g and 750 g is started on the 1st day of life in 23.3% of the NICUs and for babies between 751 g and 1000 g in 36.5%. NICUs that start enteral feeding not later than the 3rd day of life are 75.3% and 86.5% respectively. The most frequent investigation prior to starting enterai feeding was the evaluation of gastric aspirate. Mechanical ventilation is considered a contraindication for starting enterai feeding only in 1/4 of NICUs. Enterai feeding is started most often with glucose water solution and raw human milk. The most frequent administration techniques are interminent oro- and nasogastric gavage. Pasteurization facilities are available in 31 % of NICUs, but are located mostly in the Centre and North of Italy. Conclusion: This survey shows that enterai feeding policy for ELBWI varies among different Italian NICUs. In Italy there is a common tendency to start feeding early, even in ventilated infants.

Genetic absence epilepsy rats from Strasbourg (GAERS) have non-convulsive generalized seizures associated with spike-wave (SW) discharges, which are due to a hyperexcitable state of the thalamo-cortico-thalamic circuits involving the reticular thalamic nucleus (nRt). Investigation of the primary genetically-determined defect responsible for GAERS epilepsy revealed the following abnormalities: (1) increased effectiveness of AMPA receptors dependent glutamate-mediated transmission; (2) impairment of GABA-mediated transmission in the neocortex; (3) increased amplitude of the voltage-dependent low-threshold Ca 2+ -current ( I T ) in the nRt. The maturational profile of these abnormalities supports the conclusion that the abnormality in the I T current in the nRt is the primary genetically-determined defect, which may secondarily induced the other changes found in the neocortex and thalamus of GAERS.