Early-Age-Related Changes in Proteostasis Augment Immunopathogenesis of Sepsis and Acute Lung Injury

adult) mechanisms that augment immunopathogenesis of sepsis and acute lung injury. model to standardize the efficacy of salubrinal (inhibitor of eIF2α de-phosphorylation) in controlling the accumulation of ubiquitinated proteins and the NFκB levels. Finally, we evaluated the therapeutic efficacy of salubrinal to correct proteostasis-imbalance in the adult mice based on its ability to control CLP induced IL-6 secretion or recruitment of pro-inflammatory cells.Our data demonstrate the critical role of early-age-related proteostasis-imbalance as a novel mechanism that augments the NFκB mediated inflammation in sepsis and ALI. Moreover, our data suggest the therapeutic efficacy of salubrinal in restraining NFκB mediated inflammation in the adult or older subjects

Supplementary Material for: Combination of Correctors Rescues CFTR Transmembrane-Domain Mutants by Mitigating their Interactions with Proteostasis

<i>Background/Aims:</i> Premature degradation of mutated cystic fibrosis transmembrane conductance regulator (CFTR) protein causes cystic fibrosis (CF), the commonest Mendelian disease in Caucasians. Despite recent advances in precision medicines for CF patients, many CFTR mutants have not been characterized and the effects of these new therapeutic approaches are still unclear for those mutants. <i>Methods:</i> Cells transfected or stably expressing four CFTR transmembrane-domain mutants (G85E, E92K, L1077P, and M1101K) were used to: 1) characterize the mutants according to their protein expression, thermal sensitivity, and degradation pathways; 2) evaluate the effects of correctors in rescuing them; and 3) explore the effects of correctors on CFTR interactions with proteostasis components. <i>Results:</i> All four mutants exhibited lower protein expression than did wild type-CFTR, and they were degraded by proteasomes and aggresomes. At low temperature, only cells expressing the mutants L1077P and M1101K exhibited increased CFTR maturation. Co-administration of C4 and C18 showed the greatest effect, restoring functional expression and partial stability of CFTR bearing E92K, L1077P, or M1101K at the cell surface. However, this treatment was inefficient in rectifying the defect of CFTR bearing G85E. Correctors rescued CFTR mutants by reducing their interactions with proteostasis components associated with protein retention in the endoplasmic reticulum and ubiquitination. <i>Conclusion:</i> Co-administration of C4 and C18 rescued CFTR transmembrane-domain mutants by remodeling the CFTR interactome

Current state of the art and recommendations in robotic mitral valve surgery

Thoracic Surger

Robotic Cardiac Surgery in Europe: Status 2020

BackgroundEuropean surgeons were the first worldwide to use robotic techniques in cardiac surgery and major steps in procedure development were taken in Europe. After a hype in the early 2000s case numbers decreased but due to technological improvements renewed interest can be noted. We assessed the current activities and outcomes in robotically assisted cardiac surgery on the European continent. MethodsData were collected in an international anonymized registry of 26 European centers with a robotic cardiac surgery program. ResultsDuring a 4-year period (2016-2019), 2,563 procedures were carried out [30.0% female, 58.5 (15.4) years old, EuroSCORE II 1.56 (1.74)], including robotically assisted coronary bypass grafting (n = 1266, 49.4%), robotic mitral or tricuspid valve surgery (n = 945, 36.9%), isolated atrial septal defect closure (n = 225, 8.8%), left atrial myxoma resection (n = 54, 2.1%), and other procedures (n = 73, 2.8%). The number of procedures doubled during the study period (from n = 435 in 2016 to n = 923 in 2019). The mean cardiopulmonary bypass time in pump assisted cases was 148.6 (63.5) min and the myocardial ischemic time was 88.7 (46.1) min. Conversion to larger thoracic incisions was required in 56 cases (2.2%). Perioperative rates of revision for bleeding, stroke, and mortality were 56 (2.2%), 6 (0.2 %), and 27 (1.1%), respectively. Median postoperative hospital length of stay was 6.6 (6.6) days. ConclusionRobotic cardiac surgery case numbers in Europe are growing fast, including a large spectrum of procedures. Conversion rates are low and clinical outcomes are favorable, indicating safe conduct of these high-tech minimally invasive procedures.Thoracic Surger

Robotic Cardiac Surgery in Europe: Status 2020

BackgroundEuropean surgeons were the first worldwide to use robotic techniques in cardiac surgery and major steps in procedure development were taken in Europe. After a hype in the early 2000s case numbers decreased but due to technological improvements renewed interest can be noted. We assessed the current activities and outcomes in robotically assisted cardiac surgery on the European continent. MethodsData were collected in an international anonymized registry of 26 European centers with a robotic cardiac surgery program. ResultsDuring a 4-year period (2016-2019), 2,563 procedures were carried out [30.0% female, 58.5 (15.4) years old, EuroSCORE II 1.56 (1.74)], including robotically assisted coronary bypass grafting (n = 1266, 49.4%), robotic mitral or tricuspid valve surgery (n = 945, 36.9%), isolated atrial septal defect closure (n = 225, 8.8%), left atrial myxoma resection (n = 54, 2.1%), and other procedures (n = 73, 2.8%). The number of procedures doubled during the study period (from n = 435 in 2016 to n = 923 in 2019). The mean cardiopulmonary bypass time in pump assisted cases was 148.6 (63.5) min and the myocardial ischemic time was 88.7 (46.1) min. Conversion to larger thoracic incisions was required in 56 cases (2.2%). Perioperative rates of revision for bleeding, stroke, and mortality were 56 (2.2%), 6 (0.2 %), and 27 (1.1%), respectively. Median postoperative hospital length of stay was 6.6 (6.6) days. ConclusionRobotic cardiac surgery case numbers in Europe are growing fast, including a large spectrum of procedures. Conversion rates are low and clinical outcomes are favorable, indicating safe conduct of these high-tech minimally invasive procedures

Corrigendum: Robotic Cardiac Surgery in Europe: Status 2020.

[This corrects the article DOI: 10.3389/fcvm.2021.827515.]