Trial of aerosolised surfactant for preterm infants with respiratory distress syndrome

Objective To evaluate the safety of an aerosolised surfactant, SF-RI 1, administered via nasal continuous positive airway pressure (nCPAP) and a prototype breath synchronisation device (AeroFact), to preterm infants with respiratory distress syndrome (RDS). Design Multicentre, open-label, dose-escalation study with historical controls. Setting Newborn intensive care units at Mater Mothers' Hospital, Brisbane, and Royal Hospital for Women, Sydney, Australia. Patients Infants 26 weeks through 30 weeks gestation who required nCPAP 6-8 cmH 2 O and fraction of inspired oxygen (FiO 2) 2.4, nCPAP >8 cmH 2 O, arterial carbon dioxide >65 mm Hg, pH <7.20 or three severe apnoeas within 6 hours during the first 72 hours of life. Other outcomes included tolerance of the AeroFact treatment and complications of prematurity. Results 10 infants were enrolled in part 1 and 21 in part 2 and were compared with 93 historical controls. No safety issues were identified. In part 2, 6 of 21 (29%) AeroFact-treated infants compared with 30 of 63 (48%) control infants met failure criteria. Kaplan-Meier analysis of patients in part 2 showed a trend towards decreased rate of study failure in the AeroFact-treated infants compared with historical controls (p=0.10). Conclusion The AeroFact system can safely deliver aerosolised surfactant to preterm infants with RDS who are on nCPAP. Trial registration number ACTRN12617001458325

2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research

Integrin-dependent control of inositol lipid synthesis in vascular endothelial cells and smooth muscle cells

Extracellular matrix (ECM) molecules, such as fibronectin (FN), regulate fibroblast sensitivity to soluble growth factors, in part, by controlling cellular level of phosphatidylinositol bis-phosphate (PIP2), the substrate for phospholipase C-gamma (McNamee et al., 1993, J. Cell Biol. 121, 873-678). In the present study, we extended these investigations by exploring whether cells of the vascular wall also exhibit this response and analyzing the mechanism by which adhesion to ECM regulates intracellular PIP2 mass. Capillary endothelial cells, pulmonary vascular smooth muscle cells, and C3H 101/2 fibroblasts were all found to exhibit a similar two- to threefold increase in PIP2 mass within 3 h after binding to dishes coated with FN. Furthermore, similar effects were observed using dishes coated with a variety of different ECM molecules, including collagen types I and IV as well as a synthetic RGD-containing peptide. An increase in PTP2 mass also was produced when suspended cells bound to microbeads (4.5 mu m diameter; coated with RGD-peptide or anti-integrin beta 1 antibody) that induce local integrin clustering and focal adhesion formation, independently of cell spreading. In contrast, neither binding of soluble FN nor binding of microbeads coated with ligands for other transmembrane surface receptors (e.g., acetylated low-density lipoprotein, antibodies against heparan sulfate) had any effect on PIP2 mass. While these results suggest that integrin clustering stimulates PIP2 synthesis, no change in total cellular or cytoskeletal-associated phosphatidylinositol-4-phosphate kinase (PIP kinase) activity could be detected when cells bound to immobilized integrin ligands. However, when focal. adhesion complexes were isolated from these cells using a magnetic procedure (G. Plopper and D. E. Ingber, 1993, Biochem. Biophys. Res. Commun. 193, 571-578), this subfraction of the cytoskeleton was found to be enriched for PIP kinase activity by more than twofold relative to the whole cytoskeleton. These data suggest that ECM binding may increase PIP2 mass in vascular cells by clustering cell surface integrin receptors and activating cytoskeletal-associated PIP kinases locally within the focal adhesion complex. (C) 1996 Academic Press, Inc