Comprehensive assessment of frailty for elderly high-risk patients undergoing cardiac surgery

Objective: Cardiosurgical operative risk can be assessed using the logistic European system for cardiac operative risk evaluation (EuroSCORE) and the Society of Thoracic Surgeons (STS) score. Factors other than medical diagnoses and laboratory values such as the ‘biological age' are not included in these scores. The aim of the study was to evaluate an additional assessment of frailty in routine cardiac surgical practice. Methods: ‘The comprehensive assessment of frailty' test was applied to 400 patients ≥74 years who were admitted to our centre between September 2008 and January 2010. For comparison, the STS score and the EuroSCORE were calculated. The primary end point was the correlation of Frailty score to 30-day mortality. A total of 206 female and 194 male patients were included. Results: Median Frailty score was 11 [7,15]. Median of logistic EuroSCORE was 8.5% [5.8%; 13.9%]. Median of STS score was 3.3% [2.1%; 5.1%]. There were low-to-moderate albeit significant correlations of Frailty score with STS score and EuroSCORE (p≪0.05). There was also a significant correlation between Frailty score and observed 30-day mortality (p≪0.05). Patients received isolated coronary artery bypass grafting (CABG) (n=90), isolated valve surgery (n=128), trans-catheter valve implantation (n=59) or combined procedures (n=123). Conclusions: The comprehensive assessment of frailty is an additional tool to evaluate elderly patients adequately before cardiac surgical interventions. The Frailty score combines characteristics of the Fried criteria [1], of patient phenotype, of his physical performance and laboratory results. Further analysis on a larger patient population is warranted. A combination of the new Frailty score and the traditional scoring systems may facilitate a more accurate risk scoring in elderly high-risk patients scheduled for conventional cardiac surgery or trans-catheter aortic valve replacemen

Adaptive FEM with quasi-optimal overall cost for nonsymmetric linear elliptic PDEs

We consider a general nonsymmetric second-order linear elliptic PDE in the framework of the Lax-Milgram lemma. We formulate and analyze an adaptive finite element algorithm with arbitrary polynomial degree that steers the adaptive mesh-refinement and the inexact iterative solution of the arising linear systems. More precisely, the iterative solver employs, as an outer loop, the so-called Zarantonello iteration to symmetrize the system and, as an inner loop, a uniformly contractive algebraic solver, e.g., an optimally preconditioned conjugate gradient method or an optimal geometric multigrid algorithm. We prove that the proposed inexact adaptive iteratively symmetrized finite element method (AISFEM) leads to full linear convergence and, for sufficiently small adaptivity parameters, to optimal convergence rates with respect to the overall computational cost, i.e., the total computational time. Numerical experiments underline the theory

Imaging exocytosis of ATP-containing vesicles with TIRF microscopy in lung epithelial A549 cells

Nucleotide release constitutes the first step of the purinergic signaling cascade, but its underlying mechanisms remain incompletely understood. In alveolar A549 cells much of the experimental data is consistent with Ca2+-regulated vesicular exocytosis, but definitive evidence for such a release mechanism is missing, and alternative pathways have been proposed. In this study, we examined ATP secretion from A549 cells by total internal reflection fluorescence microscopy to directly visualize ATP-loaded vesicles and their fusion with the plasma membrane. A549 cells were labeled with quinacrine or Bodipy-ATP, fluorescent markers of intracellular ATP storage sites, and time-lapse imaging of vesicles present in the evanescent field was undertaken. Under basal conditions, individual vesicles showed occasional quasi-instantaneous loss of fluorescence, as expected from spontaneous vesicle fusion with the plasma membrane and dispersal of its fluorescent cargo. Hypo-osmotic stress stimulation (osmolality reduction from 316 to 160 mOsm) resulted in a transient, several-fold increment of exocytotic event frequency. Lowering the temperature from 37°C to 20°C dramatically diminished the fraction of vesicles that underwent exocytosis during the 2-min stimulation, from ~40% to ≤1%, respectively. Parallel ATP efflux experiments with luciferase bioluminescence assay revealed that pharmacological interference with vesicular transport (brefeldin, monensin), or disruption of the cytoskeleton (nocodazole, cytochalasin), significantly suppressed ATP release (by up to ~80%), whereas it was completely blocked by N-ethylmaleimide. Collectively, our data demonstrate that regulated exocytosis of ATP-loaded vesicles likely constitutes a major pathway of hypotonic stress-induced ATP secretion from A549 cells