Mini-extracorporeal circulation minimizes coagulation abnormalities and ameliorates pulmonary outcome in coronary artery bypass grafting surgery

Hemostasis is impaired during CABG and coagulation abnormalities often result in clinically relevant organ dysfunctions, eventually increasing morbidity and mortality rates. Fifteen consecutive patients with coronary artery disease submitted to conventional extracorporeal circulation (cECC) have been compared with 15 matched patients, using mini-ECC (MECC). Postoperative lung function was evaluated according to gas exchange, intubation time and lung injury score. In the MECC group, thrombin-antithrombin complex levels (TaTc), prothrombin fragments (PF1+2) formation and thromboelastography (TEG) clotting times were lower compared to the cECC group (p=0.002 and p<0.001, respectively) whereas postoperative blood loss was higher in the cECC group (p=0.030) and more patients required blood transfusion (p=0.020). In the MECC group, postoperative gas exchange values were better, intubation time shorter and lung injury score lower (p<0.001 for all comparisons). Our study suggests that MECC induces less coagulation disorders, leading to lower postoperative blood loss and better postoperative lung function. This approach may be advantageous in high-risk patients. © The Author(s) 2013

Polymer physics of chromosome large-scale 3D organisation

Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of di erent regions, folded in the conformational classes predicted by polymer thermodynamics. The contact matrix of the Sox9 locus, a region linked to severe human congenital diseases, is derived with high accuracy in mESCs and its molecular determinants identi ed by the theory; Sox9 self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Our approach is also applied to the Bmp7 locus. Finally, the model predictions on the e ects of mutations on folding are tested against available data on a deletion in the Xist locus. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding

Polymer physics indicates chromatin folding variability across single-cells results from state degeneracy in phase separation

The spatial organization of chromosomes has key functional roles, yet how chromosomes fold remains poorly understood at the single-molecule level. Here, we employ models of polymer physics to investigate DNA loci in human HCT116 and IMR90 wild-type and cohesin depleted cells. Model predictions on single-molecule structures are validated against single-cell imaging data, providing evidence that chromosomal architecture is controlled by a thermodynamics mechanism of polymer phase separation whereby chromatin self-assembles in segregated globules by combinatorial interactions of chromatin factors that include CTCF and cohesin. The thermodynamics degeneracy of single-molecule conformations results in broad structural and temporal variability of TAD-like contact patterns. Globules establish stable environments where specific contacts are highly favored over stochastic encounters. Cohesin depletion reverses phase separation into randomly folded states, erasing average interaction patterns. Overall, globule phase separation appears to be a robust yet reversible mechanism of chromatin organization where stochasticity and specificity coexist

Mid-Term Outcome of Mitral Valve Repair and Coronary Artery Bypass Grafting for Ischemic or Degenerative Mitral Regurgitation

Aim of the study. To verify the impact of the etiology of mitral valve regurgitation on a 5-year outcome after repair and concomitant coronary artery bypass grafting (CABG). Methods. One hundred and eleven consecutive patients (mean age of 69±8 years) who underwent mitral valve repair, 65 for ischemic and 46 for degenerative mitral regurgitation, and concomitant CABG, were retrospectively analyzed. The mean follow-up was 40±28 (9-104) months. Five-year survival (including operative mortality), and survival free from events (postoperative low output syndrome, progression of mitral regurgitation, onset or worsening of congestive heart failure, recurrence of myocardial infarction, and the need for mitral valve replacement) were analyzed. Results. Compared with degenerative, ischemic mitral regurgitation was associated with a higher incidence of previous myocardial infarction (P<0.0001), left ventricular ejection fraction (LVEF) <0.45 (P<0.0001), and more diseased coronary vessels per patient (P<0.0001). Five-year all-cause mortality was 18% (20/111). Independent predictors of mortality were older age at operation (P=0.0008), LVEF<0.45 (P=0.04), and the ischemic etiology of mitral regurgitation (P=0.03). At five years, survival was 69%±7.6% for ischemic versus 87%±6.5% for degenerative etiology (P=0.03); event-free survival was 58%±8.4% versus 75%±8% (P=0.02), and freedom from late cardiac death was 85%±6.6% versus 100% (P=0.02). Freedom from mitral valve reoperation was 97±2.4%. Conclusions. Ischemic mitral regurgitation “per se” predicted limited survival and event-free survival. Left ventricular dysfunction is frequently associated with the ischemic etiology. An early surgical indication to prevent left ventricular dysfunction could be important to improve the mid-term outcom

Effectiveness of the Chebyshev Approximation in Magnetic Field Line Tracking

The tracking of magnetic field lines can be very expensive, in terms of computational burden, when the field sources are numerous and have complex geometries, especially when accuracy is a priority, because an evaluation of the field is required in many situations. In some important applications, the computational cost can be significantly reduced by using a suitable approximation of the field in the integrated regions. This paper shows how Chebyshev polynomials are well-suited for field interpolation in magnetic field-line tracking, then discusses the conditions in which they are most appropriate, and quantifies the effectiveness of parallel computing in the approximation procedures

Clinical conundrum. Three management strategies for three-vessel coronary artery disease?

Inspired by King’s word, the goal of optimal pharmacotherapy is optimizing patient outcomes in an appropriate and consistent fashion, integrating itself with other management strategies, when and as appropriate, but this goal cannot be achieved if such therapy is not implemented in a forceful and proactive fashion. Indeed, cardiovascular pharmacotherapy for ischemic heart disease due to coronary artery disease (CAD) represents a unique case study in this sense, given the complex interplay between societal and individual preventive strategies as well as clinical treatments aimed at secondary or tertiary prevention, which may apparently challenge immediate and thorough implementation

Effects of balloon injury on neointimal hyperplasia in steptozotocin-induced diabetes and in hyperinsulinemic nondiabetic pancreatic islet-transplanted rats.

BACKGROUND: The mechanisms of increased neointimal hyperplasia after coronary interventions in diabetic patients are still unknown. METHODS AND RESULTS: Glucose and insulin effects on in vitro vascular smooth muscle cell (VSMC) proliferation and migration were assessed. The effect of balloon injury on neointimal hyperplasia was studied in streptozotocin-induced diabetic rats with or without adjunct insulin therapy. To study the effect of balloon injury in nondiabetic rats with hyperinsulinemia, pancreatic islets were transplanted under the kidney capsule in normal rats. Glucose did not increase VSMC proliferation and migration in vitro. In contrast, insulin induced a significant increase in VSMC proliferation and migration in cell cultures. Furthermore, in VSMC culture, insulin increased MAPK activation. A reduction in neointimal hyperplasia was consistently documented after vascular injury in hyperglycemic streptozotocin-induced diabetic rats. Insulin therapy significantly increased neointimal hyperplasia in these rats. This effect of hyperinsulinemia was totally abolished by transfection on the arterial wall of the N17H-ras-negative mutant gene. Finally, after experimental balloon angioplasty in hyperinsulinemic nondiabetic islet-transplanted rats, a significant increase in neointimal hyperplasia was observed. CONCLUSIONS: In rats with streptozotocin-induced diabetes, balloon injury was not associated with an increase in neointimal formation. Exogenous insulin administration in diabetic rats and islet transplantation in nondiabetic rats increased both blood insulin levels and neointimal hyperplasia after balloon injury. Hyperinsulinemia through activation of the ras/MAPK pathway, rather than hyperglycemia per se, seems to be of crucial importance in determining the exaggerated neointimal hyperplasia after balloon angioplasty in diabetic animals

Polymer models of chromatin organization

This is an invited commentary on the research field concerning the modelling of chromosome organization in the cell nucleus of eukaryotes