New developments in the treatment of hyperammonemia: emerging use of carglumic acid

Hyperammonemia is a true neonatal emergency with high toxicity for the central nervous system and developmental delay. The causes of neonatal hyperammonemia are genetic defects of urea cycle enzymes, organic acidemias, lysinuric protein intolerance, hyperammonemia–hyperornithinemia– homocitrullinemia syndrome, transient hyperammonemia of the newborn, and congenital hyperinsulinism with hyperammonemia. In some of these conditions the high blood ammonia levels are due to the reduction of N-acetylglutamate, an essential cofactor necessary for the function of the urea cycle, or to the reduction of carbamoyl-phosphate synthase-I activity. In these cases, N-carbamylglutamate (carglumic acid) can be administered together with the conventional therapy. Carglumic acid is an analog of N-acetylglutamate that has a direct action on carbamoyl-phosphate synthase-I. Its effects are reactivation of the urea cycle and reduction of plasma ammonia levels. As a consequence it improves the traditional treatment, avoiding the need of hemodialysis and peritoneal dialysis. In this review we evaluate the possible field of application of carglumic acid and its effectiveness and safety

Role of the Adrenergic System in a Mouse Model of Oxygen-induced Retinopathy: Antiangiogenic Effects of Beta-adrenoreceptor Blockade

METHODS. Propranolol was administered subcutaneously and picropodophyllin (PPP) intraperitoneally. Intravitreal injections of vascular endothelial growth factor (VEGF) were performed. Messengers of -ARs, VEGF, its receptors, IGF-1 and IGF-1R were measured with quantitative RT-PCR. VEGF content was determined with ELISA. -ARs, hypoxia-inducible factor (HIF)-1 , occludin, and albumin were measured with Western blot. Retinal localization of 3-ARs was determined by immunohistochemistry. Retinopathy was assessed by scoring fluorescein-perfused retinas, and plasma extravasation was visualized by Evans blue dye

Dosing Penalty of Erythropoiesis-Stimulating Agents after Switching from Originator to Biosimilar Preparations in Stable Hemodialysis Patients

To the Editor: The efficacy of ESA biosimilars has been tested mainly in the few studies needed for marketing authorization,1-5 whereas data from individual self-reported clinical experience are lacking. Such information, together with pharmacovigilance data, is key to obtaining reassurance regarding the safety of these products. Of note, 2 studies of efficacy when switching from originator to biosimilar in hemodialysis patients have reported a dosing penalty (ie, requiring higher doses to maintain Hb level) of 4% to 13% for HX575 (epoetin alfa; Binocrit) and 10% to 15% for SB309 (epoetin zeta; Retacrit). 4,5 Dosing penalty for biosimilars is relevant not only for cost reasons, but also when considering the significant association of higher ESA dose with adverse outcomes.6 All manufacturers recommend using the lowest effective dose for correcting anemia

Incidence of Respiratory Disease During the First Two\ua0Years of Life in Children with Hemodynamically Significant Congenital Heart Disease in Italy: A Retrospective Study

Children affected by hemodynamically significant congenital heart disease (HSCHD) experience severe respiratory complications that can increase the frequency of hospitalizations. The aim of the SINERGY study was to describe the incidence of respiratory diseases and to collect information on active and passive immunoprophylaxis in the first 2\ua0years of life. In this retrospective, multicenter, and epidemiologic study, children with HSCHD were enrolled across 11 Italian sites. Children born between December 31, 2007, and December 31, 2012, were observed during their first 2\ua0years of life. Data were collected through hospital database searches and parent interviews. Four hundred twenty children were enrolled: 51.7\ua0% were female, 79.5\ua0% were born full-term ( 6537\ua0weeks), and 77.6\ua0% weighed >2500\ua0g at birth. The most frequent heart defects were ventricular septal defect (23.1\ua0%) and coarctation of the aorta (14.3\ua0%). The incidence of respiratory diseases was 63.1\ua0%. Frequent respiratory diseases not requiring hospitalization were upper respiratory tract infections (76.4\ua0%), acute bronchitis (43.3\ua0%), and influenza (22.1\ua0%), while those requiring hospitalization were bronchitis and bronchiolitis (8.3\ua0% each one). While active immunoprophylaxis was applied with wide compliance (diphtheria/pertussis/tetanus, 99.5\ua0%; Haemophilus influenzae type b, 72.5\ua0%; pneumococcus, 79.9\ua0%; meningococcus, 77.4\ua0%), only 54\ua0% of children received respiratory syncytial virus (RSV) passive prophylaxis (palivizumab). Of the 35 hospitalizations due to bronchiolitis, 27 (77.1\ua0%) did not receive prophylaxis against RSV, compared with 8 (22.9\ua0%) who received prophylaxis (P\ua0<\ua00.0001). Children with HSCHD are at major risk of respiratory diseases. Passive immunoprophylaxis can help to prevent hospitalizations for bronchiolitis

Early intervention at home in infants with congenital brain lesion with CareToy revised: A RCT protocol

Background: Congenital brain lesions expose infants to be at high-risk for being affected by neurodevelopmental disorders such as cerebral palsy (CP). Early interventions programs can significantly impact and improve their neurodevelopment. Recently, in the framework of the European CareToy (CT) Project ( www.caretoy.eu ), a new medical device has been created to deliver an early, intensive, customized, intervention program, carried out at home by parents but remotely managed by expert and trained clinicians. Reviewing results of previous studies on preterm infants without congenital brain lesion, the CT platform has been revised and a new system created (CT-R). This study describes the protocol of a randomised controlled trial (RCT) aimed to evaluate, in a sample of infants at high-risk for CP, the efficacy of CT-R intervention compared to the Infant Massage (IM) intervention. Methods/design: This RCT will be multi-centre, paired and evaluator-blinded. Eligible subjects will be preterm or full-term infants with brain lesions, in first year of age with predefined specific gross motor abilities. Recruited infants will be randomized into CT-R and IM groups at baseline (T0). Based on allocation, infants will perform an 8-week programme of personalized CareToy activities or Infant Massage. The primary outcome measure will be the Infant Motor Profile. On the basis of power calculation, it will require a sample size of 42 infants. Moreover, Peabody Developmental Motor Scales-Second Edition, Teller Acuity Cards, standardized video-recordings of parent-infant interaction and wearable sensors (Actigraphs) will be included as secondary outcome measures. Finally, parents will fill out questionnaires (Bayley Social-Emotional, Parents Stress Index). All outcome measures will be carried out at the beginning (T0) and at end of 8-weeks intervention period, primary endpoint (T1). Primary outcome and some secondary outcomes will be carried out also after 2 months from T1 and at 18 months of age (T2 and T3, respectively). The Bayley Cognitive subscale will be used as additional assessment at T3. Discussion: This study protocol paper is the first study aimed to test CT-R system in infants at high-risk for CP. This paper will present the scientific background and trial methodology