Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. / Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. / Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. / Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. / Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. / Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). / Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. / Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943

Feilke revisited : 60 Stellenbesuche

Weitere Hrsg.: Thorsten Pohl, Sara Rezat, Torsten Steinhoff, Martin SteinseiferAnlässlich des 60. Geburtstags des Linguisten und Sprachdidaktikers Helmuth Feilke wurden Wegbegleiterinnen und Wegbegleiter gebeten, einzelne Stellen in seinen wissenschaftlichen Schriften erneut zu besuchen. Entstanden sind pointierte Kommentare, kurze wissenschaftliche Abhandlungen und Analysen, Varianten auch des kritischen und kontroversen Nach- und Weiterdenkens und Ansätze zur Neu- oder Re-Kontextualisierung. Je nach wissenschaftlicher Vita der Autorinnen und Autoren kann es sich um Stellen handeln, deren Rezeption zeitlich weit zurückliegt, oder um Passagen, die ganz aktuelle Fragen der eigenen Forschungsarbeit tangieren. Abgesehen davon, dass ein kurzes Format für die Beiträge gewählt und die Autorinnen und Autoren gebeten wurden, die ausgewählte Stelle knapp zu verorten und zu erläutern, war die Bearbeitungsform gänzlich freigestellt. So sind Texte in einer Bandbreite von pointierten Kommentaren, kurzen wissenschaftlichen Abhandlungen und Analysen, Varianten des Nach- und Weiterdenkens, Ansätze zur Neu- oder Re-Kontextualisierung bis hin zu Formen des kritischen Hinterfragens und der kontroversen Auseinandersetzung entstanden

Chloride channel blockers suppress formation of engulfment pseudopodia in microglial cells

Background/Aims: Phagocytosis depends on the formation of engulfment pseudopodia surrounding the target. We tested in microglia, monocyte-derived cells in the brain, whether a swelling-activated Cl--current (ICl,swell), required for global cell volume (CV) regulation, also contributes to local expansion and retraction of engulfment pseudopodia. Methods: We used scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) to visualize and quantify the uptake of polystyrene microbeads (MBs) by microglial cells. Flow cytometry was used for cell volume measurments and ICl,swell was measured by whole-cell patch clamp. Results: We found that exposure of microglial BV-2 cells to MBs in Cl--free extracellular solution attenuated MB uptake and that the Cl--channel blockers DIOA, flufenamic acid, NPPB and DCPIB suppressed the uptake of MBs in BV-2 cells and in primary microglial cells. Microglial cells exposed to MBs in the presence of Cl- channel blockers failed to extend engulfment pseudopodia. We observed that cells containing at least three MBs revealed an about twofold increase in current density of ICl, swell compared to cells without MB. Osmotic challenges to stimulate global CV regulation before exposure to MBs modulated phagocytosis. Pre-conditioning of cells in hypo- or hypertonic medium for 12-16 hours caused a decrease in MB uptake. Conclusion: These findings indicate that ICl,swell contributes to formation of engulfment pseudopodia and participates in engulfment and particle uptake in microglial cells.Barbara Harl, Judith Schmölzer, Martin Jakab, Markus Ritter, Hubert H. Kerschbau

Inflammation and lung maturation from stretch injury in preterm fetal sheep

Mechanical ventilation is a risk factor for the development of bronchopulmonary dysplasia in premature infants. Fifteen minutes of high tidal volume (Vt) ventilation induces inflammatory cytokine expression in small airways and lung parenchyma within 3 h. Our objective was to describe the temporal progression of cytokine and maturation responses to lung injury in fetal sheep exposed to a defined 15-min stretch injury. After maternal anesthesia and hysterotomy, 129-day gestation fetal lambs (n = 7–8/group) had the head and chest exteriorized. Each fetus was intubated, and airway fluid was gently removed. While placental support was maintained, the fetus received ventilation with an escalating Vt to 15 ml/kg without positive end-expiratory pressure (PEEP) for 15 min using heated, humidified 100% nitrogen. The fetus was then returned to the uterus for 1, 6, or 24 h. Control lambs received a PEEP of 2 cmH2O for 15 min. Tissue samples from the lung and systemic organs were evaluated. Stretch injury increased the early response gene Egr-1 and increased expression of pro- and anti-inflammatory cytokines within 1 h. The injury induced granulocyte/macrophage colony-stimulating factor mRNA and matured monocytes to alveolar macrophages by 24 h. The mRNA for the surfactant proteins A, B, and C increased in the lungs by 24 h. The airway epithelium demonstrated dynamic changes in heat shock protein 70 (HSP70) over time. Serum cortisol levels did not increase, and induction of systemic inflammation was minimal. We conclude that a brief period of high Vt ventilation causes a proinflammatory cascade, a maturation of lung monocytic cells, and an induction of surfactant protein mRNA