American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 2019
The S52F FOXF1 Mutation Inhibits STAT3 Signaling and Causes Alveolar Capillary Dysplasia.
Rationale: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal congenital disorder causing respiratory failure and pulmonary hypertension shortly after birth. There are no effective treatments for ACDMPV other than lung transplant, and new therapeutic approaches are urgently needed. Although ACDMPV is linked to mutations in the FOXF1 gene, molecular mechanisms through which FOXF1 mutations cause ACDMPV are unknown. ⋯ Furthermore, we have developed a novel formulation of highly efficient nanoparticles and demonstrated that nanoparticle delivery of STAT3 cDNA into the neonatal circulation restored endothelial proliferation and stimulated lung angiogenesis in Foxf1WT/S52F mice. Conclusions: FOXF1 acts through STAT3 to stimulate neonatal lung angiogenesis. Nanoparticle delivery of STAT3 is a promising strategy to treat ACDMPV associated with decreased STAT3 signaling.
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Am. J. Respir. Crit. Care Med. · Oct 2019
Multicenter StudyMechanical Ventilation Management during ECMO for ARDS: An International Multicenter Prospective Cohort.
Rationale: Current practices regarding mechanical ventilation in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown. Objectives: To report current practices regarding mechanical ventilation in patients treated with ECMO for severe acute respiratory distress syndrome (ARDS) and their association with 6-month outcomes. Methods: This was an international, multicenter, prospective cohort study of patients undergoing ECMO for ARDS during a 1-year period in 23 international ICUs. ⋯ A higher Vt and lower driving pressure (likely markers of static compliance improvement) across the ECMO course were also associated with better outcomes. Conclusions: Ultraprotective lung ventilation on ECMO was largely adopted across medium- to high-case volume ECMO centers. In contrast with previous observations, mechanical ventilation settings during ECMO did not impact patients' prognosis in this context.
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Am. J. Respir. Crit. Care Med. · Oct 2019
Understanding and Enhancing Sepsis Survivorship: Priorities for Research and Practice.
An estimated 14.1 million patients survive sepsis each year. Many survivors experience poor long-term outcomes, including new or worsened neuropsychological impairment; physical disability; and vulnerability to further health deterioration, including recurrent infection, cardiovascular events, and acute renal failure. However, clinical trials and guidelines have focused on shorter-term survival, so there are few data on promoting longer-term recovery. ⋯ The top short-term priorities identified by nominal group technique culminating in formal voting were to better leverage existing databases for research, develop and disseminate educational resources on postsepsis morbidity, and partner with sepsis survivors to define and achieve research priorities. The top longer-term priorities were to study mechanisms of long-term morbidity through large cohort studies with deep phenotyping, build a harmonized global sepsis registry to facilitate enrollment in cohorts and trials, and complete detailed longitudinal follow-up to characterize the diversity of recovery experiences. This perspective reviews colloquium discussions, the identified priorities, and current initiatives to address them.