Osteopontin in relation to Prognosis following Coronary Artery Bypass Graft Surgery

Cardiovascular events may occur even after complete revascularization in patients with coronary artery disease. We measured preoperative osteopontin (OPN) levels in 131 consecutive patients (66.5 ± 10 years old, 117 men and 14 women) with left ventricular ejection fraction of 50.7 ± 9.2 % and low logistic EuroScore (3.5 ± 3.2 %) undergoing elective Coronary Artery Bypass Grafting (CABG) surgery. Patients were prospectively followed up for a median of 12 months (range 11-24). The primary study endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, need for repeat revascularization, and hospitalization for cardiovascular events. Pre-op OPN plasma levels were 77.9 (49.5, 150.9). Patients with prior acute myocardial infarction (AMI) had significantly higher OPN levels compared to those without [131.5 (52.2, 219) versus 73.3 (45.1, 125), p = 0.007 ]. OPN levels were positively related to EuroScore (r = 0.2, p = 0.031). Pre-op OPN levels did not differ between patients who had a major adverse event during follow-up compared to those with no event (p = 0.209) and had no effect on the hazard of future adverse cardiac events [HR (95% CI): 1.48 (0.43-4.99), p = 0.527 ]. The history of AMI was associated with increased risk of subsequent cardiovascular events at follow-up (p = 0.02). OPN is associated with preoperative risk assessment prior to low-risk CABG but did not independently predict outcome. © 2016 Eftihia Sbarouni et al

The industrialization of ablation: a highly standardized and reproducible workflow for radiofrequency ablation of atrial fibrillation

Background or Purpose: The purpose of this analysis was to report on efficacy of a standardized workflow for atrial fibrillation (AF) ablation using technology advances such as 3D imaging and contact force sensing in a real-world setting. Methods: Consecutive AF ablations from 2014 to 2015 at a high-volume site in Belgium were included. The workflow consisted of a pre-specified procedure sequence including 3D modeling followed by radiofrequency encircling of the pulmonary veins (25 W posterior wall, 35 W anterior wall) with a THERMOCOOL SMARTTOUCH® Catheter guided by CARTO VISITAG™ Module (2.5 mm/5 s stability, 50% > 7 g) and ablation index (targets: 550 anterior wall, 400 posterior wall). Efficiency endpoints were procedure time, fluoroscopy time, and radiation dose. The primary effectiveness endpoint was freedom from atrial arrhythmia recurrence. Results: A total of 605 paroxysmal AF (PAF) and 182 persistent AF (PsAF) patients were followed for 436 ± 199 days. Mean procedure times were short (PAF: 96.1 ± 26.2 min; PsAF: 109.2 ± 35.6 min) with most procedures (90.6% PAF; 81.3% PsAF) completed in ≤ 120 min. Minimal fluoroscopy was utilized (PAF: 6.1 ± 3.8 min, 5.9 ± 3.4 Gy*cm2; PsAF: 6.9 ± 4.7 min, 7.4 ± 4.9 Gy*cm2). Freedom from atrial arrhythmia recurrence was higher for PAF than PsAF patients (OR: 2.0, 95% CI: 1.4–2.9, p = 0.0003), but adjusted mean rates were high in both groups (81.0% vs. 67.9%). Rates were adjusted for prior ablation and age (at 65 years). Conclusion: AF ablation using a standardized workflow resulted in low procedure times and variability, with minimal fluoroscopy exposure. Long-term freedom from atrial arrhythmia recurrence was high in both PAF and PsAF populations

Patients with triple-negative, JAK2V617F- A nd CALR-mutated essential thrombocythemia share a unique gene expression signature

Approximately 10% to 15% of patients with essential thrombocythemia (ET) lack the common driver mutations, so-called "triple-negative"(TN) disease. We undertook a systematic approach to investigate for somatic mutations and delineate gene expression signatures in 46 TN patients and compared the results to those with known driver mutations and healthy volunteers. Deep, error-corrected, next-generation sequencing of peripheral blood mononuclear cells using the HaloPlexHS platform and whole-exome sequencing was performed. Using this platform, 10 (22%) of 46 patients had detectable mutations (MPL, n 5 6; JAK2V617F, n 5 4) with 3 of 10 cases harboring germline MPL mutations. RNA-sequencing and DNA methylation analysis were also performed by using peripheral blood mononuclear cells. Pathway analysis comparing healthy volunteers and ET patients (regardless of mutational status) identified significant enrichment for genes in the tumor necrosis factor, NFkB, and MAPK pathways and upregulation of platelet proliferative drivers such as ITGA2B and ITGB3. Correlation with DNA methylation showed a consistent pattern of hypomethylation at upregulated gene promoters. Interrogation of these promoter regions highlighted enrichment of transcriptional regulators, which were significantly upregulated in patients with ET regardless of mutation status, including CEBPb and NFkB. For "true"TN ET, patterns of gene expression and DNA methylation were similar to those in ET patients with known driver mutations. These observations suggest that the resultant ET phenotype may, at least in part and regardless of mutation type, be driven by transcriptional misregulation and may propagate downstream via the MAPK, tumor necrosis factor, and NFkB pathways with resultant JAK-STAT activation. These findings identify potential novel mechanisms of disease initiation that require further evaluation

Semiconductor-based electron flying qubits: review on recent progress accelerated by numerical modelling

The progress of charge manipulation in semiconductor-based nanoscale devices opened up a novel route to realise a flying qubit with a single electron. In the present review, we introduce the concept of these electron flying qubits, discuss their most promising realisations and show how numerical simulations are applicable to accelerate experimental development cycles. Addressing the technological challenges of flying qubits that are currently faced by academia and quantum enterprises, we underline the relevance of interdisciplinary cooperation to move emerging quantum industry forward. The review consists of two main sections: Pathways towards the electron flying qubit: We address three routes of single-electron transport in GaAs-based devices focusing on surface acoustic waves, hot-electron emission from quantum dot pumps and Levitons. For each approach, we discuss latest experimental results and point out how numerical simulations facilitate engineering the electron flying qubit. Numerical modelling of quantum devices: We review the full stack of numerical simulations needed for fabrication of the flying qubits. Choosing appropriate models, examples of basic quantum mechanical simulations are explained in detail. We discuss applications of open-source (KWANT) and the commercial (nextnano) platforms for modelling the flying qubits. The discussion points out the large relevance of software tools to design quantum devices tailored for efficient operation