Aortic valve replacement reduces mortality in moderate aortic stenosis:a systematic review and meta-analysis

BACKGROUND With the introduction of transcatheter aortic valve replacement and an evolving understanding of the natural progression and history of aortic stenosis,the potential for earlier intervention in appropriate patients is promising;however,the benefit of aortic valve replacement in moderate aortic stenosis remains unclear.METHODS Pubmed,Embase,and the Cochrane Library databases were searched up until 30th of December 2021 using keywords including moderate aortic stenosis and aortic valve replacement.Studies reporting all-cause mortality and outcomes in early aortic valve replacement(AVR)compared to conservative management in patients with moderate aortic stenosis were included.Hazard ratios were generated using random-effects meta-analysis to determine effect estimates.RESULTS 3470 publications were screened with title and abstract review,which left 169 articles for full-text review.Of these studies,7 met inclusion criteria and were included,totalling 4,827 patients.All studies treated AVR as a time-dependent co-variable in cox-regression multivariate analysis of all-cause mortality.Intervention with surgical or transcatheter AVR was associated with a 45% decreased risk of all-cause mortality(HR=0.55[0.42-0.68],I2=51.5%,P<0.001).All studies were representative of the overall cohort with appropriate sample sizes,with no evidence of publication,detection,or information biases in any of the studies.CONCLUSION In this systematic review and meta-analysis,we report a 45% reduction in all-cause mortality in patients with moderate aortic stenosis who were treated with early aortic valve replacement compared to a strategy of conservative management.Randomised control trials are awaited to determine the utility of AVR in moderate aortic stenosis.

The mTORC1 complex in pre-osteoblasts regulates whole-body energy metabolism independently of osteocalcin

Overnutrition causes hyperactivation of mTORC1-dependent negative feedback loops leading to the downregulation of insulin signaling and development of insulin resistance.In osteoblasts(OBs),insulin signaling plays a crucial role in the control of systemic glucose homeostasis.We utilized mice with conditional deletion of Rptor to investigate how the loss of mTORC1 function in OB affects glucose metabolism under normal and overnutrition dietary states.Compared to the controls,chow-fed Rptorob−/−mice had substantially less fat mass and exhibited adipocyte hyperplasia.Remarkably,upon feeding with high-fat diet,mice with pre-and post-natal deletion of Rptor in OBs were protected from diet-induced obesity and exhibited improved glucose metabolism with lower fasting glucose and insulin levels,increased glucose tolerance and insulin sensitivity.This leanness and resistance to weight gain was not attributable to changes in food intake,physical activity or lipid absorption but instead was due to increased energy expenditure and greater whole-body substrate flexibility.RNA-seq revealed an increase in glycolysis and skeletal insulin signaling pathways,which correlated with the potentiation of insulin signaling and increased insulin-dependent glucose uptake in Rptorknockout osteoblasts.Collectively,these findings point to a critical role for the mTORC1 complex in the skeletal regulation of wholebody glucose metabolism and the skeletal development of insulin resistance.

Pathophysiology of obesity and its associated diseases

The occurrence of obesity has increased across the whole world. Many epidemiological studies have indicated that obesity strongly contributes to the development of cancer, cardiovascular diseases, type 2 diabetes, liver diseases and other disorders, accounting for a heavy burden on the public and on health-care systems every year. Excess energy uptake induces adipocyte hypertrophy, hyperplasia and formation of visceral fat in other non-adipose tissues to evoke cardiovascular disease, liver diseases. Adipose tissue can also secrete adipokines and inflammatory cytokines to affect the local microenvironment,induce insulin resistance, hyperglycemia, and activate associated inflammatory signaling pathways. This further exacerbates the development and progression of obesity-associated diseases. Although some progress in the treatment of obesity has been achieved in preclinical and clinical studies, the progression and pathogenesis of obesity-induced diseases are complex and unclear. We still need to understand their links to better guide the treatment of obesity and associated diseases. In this review, we review the links between obesity and other diseases, with a view to improve the future management and treatment of obesity and its co-morbidities.

Effect of coronary artery dynamics on the wall shear stress vector field topological skeleton in fluid–structure interaction analyses

In this paper,we investigate the impact of coronary artery dynamics on the wall shear stress(WSS)vector field topology by comparing fluid–structure interaction(FSI)and computational fluid dynamics(CFD)techniques.As one of the most common causes of death globally,coronary artery disease(CAD)is a significant economic burden;however,novel approaches are still needed to improve our ability to predict its progression.FSI can include the unique dynamical factors present in the coronary vasculature.To investigate the impact of these dynamical factors,we study an idealized artery model with sequential stenosis.The transient simulations made use of the hyperelastic artery and lipid constitutive equations,non‐Newtonian blood viscosity,and the characteristic out‐of‐phase pressure and velocity distribution of the left anterior descending coronary artery.We compare changes to established metrics of time‐averaged WSS(TAWSS)and the oscillatory shear index(OSI)to changes in the emerging WSS divergence,calculated here in a modified version to handle the deforming mesh of FSI simulations.Results suggest that the motion of the artery can impact downstream patterns in both divergence and OSI.WSS magnitude is also decreased by up to 57%due to motion in some regions.WSS divergence patterns varied most significantly between simulations over the systolic period,the time of the largest displacements.This investigation highlights that coronary dynamics could impact markers of potential CAD progression and warrants further detailed investigations in more diverse geometries and patient cases.