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Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce the risk of major adverse cardiovascular events (MACE) and heart failure in patients with type 2 diabetes mellitus (T2DM). However, these outcomes are not similarly demonstrated in those with prior heart failure in subgroup analyses of several randomized controlled trials (RCTs). We evaluated the effect of GLP-1RAs on MACE and heart failure admissions for T2DM patients with a previous history of heart failure.We searched PubMed and EMBASE through March 2022 to identify RCTs examining the effects of GLP-1RAs compared with placebo on MACE and heart failure admission in T2DM patients with a history of heart failure. MACE were mainly defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. We performed a meta-analysis with a random-effects model.Our analysis included subgroup analyses of 7 RCTs enrolling a total of 8,965 patients with T2DM and heart failure. Pooled analysis demonstrated a significantly decreased MACE (hazard ratio, 0.88; 95% confidence interval, 0.78-0.99; P = 0.039; I2 = 18.1%) in the GLP-1RAs group. In contrast, the rate of heart failure admission was not significantly different between the two groups (hazard ratio, 1.03; 95% confidence interval, 0.91-1.16; P = 0.67; I2 = 0.0%).GLP-1RAs significantly reduced MACE in T2DM patients with prior heart failure compared with the placebo group but did not affect the risk of heart failure admission.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has demonstrated high efficacy at preventing coronavirus disease 2019 (COVID-19) and a favorable safety profile, however it has also been reported that COVID-19 vaccines may put increase of immune-mediated disease. We herein report a case of MPO-anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis following the mRNA vaccine BNT162b2 (Pfizer/BioNTech) for COVID-19. Although the causal relationship between vaccine and ANCA-associated vasculitis is uncertain, environmental and genetic factors may have set the stage for the development of vasculitis, and the vaccine may have triggered a domino effect.

Many experimental techniques have been reported to provide knowledge of the mechanical behavior of cells from biomechanical viewpoints, however, it is unclear how the intercellular structural differences influence macroscopic and microscopic mechanical properties of cells. The aim of our study is to clarify the comprehensive mechanical properties and cell-substrate adhesion strength of cells, and the correlation with intracellular structure in different cell types. We developed an originally designed micro tensile tester, and performed a single cell tensile test to estimate whole cell tensile stiffness and adhesion strength of normal vascular smooth muscle cells (VSMCs) and cervical cancer HeLa cells: one half side of the specimen cell was lifted up by a glass microneedle, then stretched until the cell detached from the substrate, while force was simultaneously measured. The tensile stiffness and adhesion strength were 49 ± 10 nN/% and 870 ± 430 nN, respectively, in VSMCs (mean ± SD, n = 8), and 19 ± 17 nN/% and 320 ± 160 nN, respectively, in HeLa cells (n = 9). The difference was more definite in the surface elastic modulus map obtained by atomic force microscopy, indicating that the internal tension of the actin cytoskeleton was significantly higher in VSMCs than in HeLa cells. Structural analysis with confocal microscopy revealed that VSMCs had a significant alignment of F-actin cytoskeleton with mature focal adhesion, contrary to the randomly oriented F-actin with smaller focal adhesion of HeLa cells, indicating that structural arrangement of the actin cytoskeleton and their mechanical tension generated the differences in cell mechanical properties and adhesion forces. The finding strongly suggests that the mechanical and structural differences in each cell type are deeply involved with their physiological functions.