Predictive scoring model of mortality after surgical or endovascular revascularization in patients with critical limb ischemia

ObjectiveThe latest guideline points to life expectancy of <2 years as the main determinant in revascularization modality selection (bypass surgery [BSX] or endovascular therapy [EVT]) in patients with critical limb ischemia (CLI). This study examined predictors and a predictive scoring model of 2-year mortality after revascularization.MethodsWe performed Cox proportional hazards regression analysis of data in a retrospective database, the Bypass and Endovascular therapy Against Critical limb ischemia from Hyogo (BEACH) registry, of 459 consecutive CLI patients who underwent revascularization (396 EVT and 63 BSX cases between January 2007 and December 2011) to determine predictors of 2-year mortality. The predictive performance of the score was assessed with the area under the time-dependent receiver operating characteristic curve.ResultsOf 459 CLI patients (mean age, 72 ± 10 years; 64% male; 49% nonambulatory status, 68% diabetes mellitus, 47% on regular dialysis, and 18% rest pain and 82% tissue loss as treatment indication), 84 died within 2 years after revascularization. In a multivariate model, age >75 years (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.10-2.85), nonambulatory status (HR, 5.32; 95% CI, 2.96-9.56), regular dialysis (HR, 1.90; 95% CI, 1.10-3.26), and ejection fraction <50% (HR, 2.49; 95% CI, 1.48-4.20) were independent predictors of 2-year mortality. The area under the time-dependent receiver operating characteristic curve for the developed predictive BEACH score was 0.81 (95% CI, 0.76-0.86).ConclusionsPredictors of 2-year mortality after EVT or BSX in CLI patients included age >75 years, nonambulatory status, regular dialysis, and ejection fraction <50%. The BEACH score derived from these predictors allows risk stratification of CLI patients undergoing revascularization

Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE)

Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs. This led to failure of deletion of autoreactive T cells together with dramatically reduced production of regulatory T cells in the thymus. In peripheral APCs, expression of costimulatory molecules was augmented. We suggest that levels of Aire expression need to be tightly controlled for maintenance of immunological tolerance. Our results also highlight the importance of coordinated action between central tolerance and peripheral tolerance under the common control of Aire

Regulation of the Liquid–liquid Phase-Separated Droplets of Biomacromolecules by Butterfly-Shaped Gold Nanomaterials

Liquid–liquid phase-separated (LLPS) droplets play key roles in regulating protein behaviors, such as enzyme compart-mentalization, stress response, and disease pathogenesis, in living cells. The manipulation of the droplet for-mation/deformation dynamics is the next target of nano-biotechnology, although the required nanodevices for controlling the dynamics of liquid–liquid phase separation, LLPS, have not been invented. Here, we propose a butterfly-shaped gold nanobutterfly (GNB) as a nanodevice for manipulating the droplet-formation/deformation dynamics of LLPS. GNBs are moderate, symmetrical gold nanomaterials (average diameter = ~30 nm) bearing two concaves and resembling a butter-fly. Their growth process is analyzed via their time-lapse electroscopic images and time-lapse ultraviolet/visible/near-infrared (NIR) spectroscopy, as well as the application of solution additives in protein science. These nanomaterials are synthesized via the seed-mediated method with an efficiency of ~70%. Interestingly, the GNBs stabilized the LLPS droplet of adenosine triphosphate (ATP)/poly-L-lysine, whereas other two gold nanoparticles with different shapes (spherical and rod-shaped) did not, indicating that the concave of the GNBs interacts with the precursor of the droplets. The NIR-laser irradiation of the GNBs facilitates the on-demand deformation of the droplets via the localized-heat effect. This but-terfly-shaped nanodevice represents a future strategy for manipulating the dynamics of LLPS