In patients with established acute respiratory distress syndrome, open lung approach improved oxygenation and driving pressure, without detrimental effects on mortality, ventilator-free days, or barotrauma. This pilot study supports the need for a large, multicenter trial using recruitment maneuvers and a decremental positive end-expiratory pressure trial in persistent acute respiratory distress syndrome.
Mechanical ventilation consistent with clinical practice did not generate excessive regional strain in heterogeneously aerated supine lungs. However, it allowed worsening of spatial strain distribution in these lungs, associated with increased inflammation. Our results support the implementation of early aeration homogenization in normal lungs.
In the late 19th century, Otto Frank published the first description of a ventricular pressurevolume diagram, thus laid the foundation for modern cardiovascular physiology. Since then, the analysis of the pressure-volume loops became a reference tool for the study of the ventricular pump properties.However, understanding cardiovascular performance requires both the evaluation of ventricular properties and the modulating effects of the arterial system, since the heart and the arterial tree are anatomically and functionally related structures. The study of the coupling between the cardiac function and the properties of the arterial system, or ventriculo-arterial (VA) coupling, provides then a comprehensive characterization of the performance of the cardiovascular system in both health and disease. The assessment of cardiovascular function is an essential element of the hemodynamic evaluation of critically ill patients. Both left and right ventricular dysfunction and arterial system disturbances are frequent in these patients. Since VA coupling ultimately defines de performance and efficiency of the cardiovascular system, the analysis of the interaction between the heart and the arterial system could offer a broader perspective of the hemodynamic disorders associated with common conditions, such as septic shock, heart failure, or right ventricular dysfunction.Moreover, this analysis could also provide valuable information about their pathophysiological mechanisms and may help to determine the best therapeutic strategy to correct them. In this review, we will describe the basic principles of the VA coupling assessment, its limitations, and the most common methods for its estimation at the bedside. Then, we will summarize the current knowledge of the application of VA coupling in critically ill patients and suggest some recommendations for further research.
Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).
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