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

Early and long-term results of pectoralis muscle flap reconstruction vs sternal rewiring following failed sternal closure.

OBJECTIVES: The aim of the study was to compare early and long-term results of pectoralis muscle flap reconstruction with those of sternal rewiring following failed sternal closure. Primary outcomes of the study were survival and failure rate. Respiratory function, chronic pain and quality of life were also evaluated. METHODS: In a propensity-score matching analysis, of 94 patients who underwent sternal reconstruction, 40 were selected; 20 underwent sternal reconstruction with bilateral pectoralis muscle flaps (Group 1) and 20 underwent sternal rewiring (Group 2). Survival and failure rates were evaluated by in-hospital records and at follow-up. Respiratory function measures, including vital capacity (VC), were evaluated both by spirometry and computed tomography (CT) volumetry. Chronic pain was evaluated by the visual analogue pain scale. RESULTS: At 85 ± 24 months of follow-up, survival and procedure failure were 95 and 90% in Group 1 and 60 and 55% in Group 2, respectively (P < 0.01, for both comparisons). Based on CT-scan volumetry, in Group 1, severe non-union and hemisternal paradoxical movement occurred less frequently (2 vs 7, P = 0.01). At spirometry assessment, postoperative VC was greater in Group 1 (3220 ± 290 vs 3070 ± 290 ml, P = 0.04). The same trend was detected by CT-scan in-expiratory measures (4034 ± 1800 vs 3182 ± 862 mm3, P < 0.05). Correspondingly, in Group 1, less patients presented in NYHA Class III (P < 0.05), and both chronic persistent pain score and physical health quality-of-life score were significantly better in the same group. CONCLUSIONS: In our study, muscle flap reconstruction guaranteed better early and late-term results as shown by lower rates of mortality, procedure failure and hemisternum stability. Moreover, Group 1 patients had greater postoperative VC, lower NYHA class and better quality of life. These results suggest that, in patients with multiple bone fracture, the rewiring approach does not promote physiological bone consolidation, whereas the muscle flap reconstruction can assure more physiological ventilatory dynamics

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

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

Superhydrophobic coatings as anti-icing systems for small aircraft

Traditional anti-icing/de-icing systems, i.e., thermal and pneumatic, in most cases require a power consumption not always allowable in small aircraft. Therefore, the use of passive systems, able to delay the ice formation, or reduce the ice adhesion strength once formed, with no additional energy consumption, can be considered as the most promising solution to solve the problem of the ice formation, most of all, for small aircraft. In some cases, the combination of a traditional icing protection system (electrical, pneumatic, and thermal) and the passive coatings can be considered as a strategic instrument to reduce the energy consumption. The effort of the present work was to develop a superhydrophobic coating, able to reduce the surface free energy (SFE) and the work of adhesion (WA) of substrates, by a simplified and non-expensive method. The developed coating, applied as a common paint with an aerograph, is able to reduce the SFE of substrates by 99% and the WA by 94%. The effects of both chemistry and surface morphology on the wettability of surfaces were also studied. In the reference samples, the higher the roughness, the lower the SFE and the WA. In coated samples with roughness ranging from 0.4 and 3 μm no relevant variations in water contact angle, nor in SFE andWA were observed

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&lt;0.0001), left ventricular ejection fraction (LVEF) &lt;0.45 (P&lt;0.0001), and more diseased coronary vessels per patient (P&lt;0.0001). Five-year all-cause mortality was 18% (20/111). Independent predictors of mortality were older age at operation (P=0.0008), LVEF&lt;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

Heart rate, pr, and qt intervals in normal children: A 24‐hour holter monitoring study

A dynamic electrocardiographic Holter monitoring study was performed in 32 healthy children (20 males and 12 females, age range 6-11 years old), without heart disease, according to clinical and noninvasive instrumental examination. We evaluated atrioventricular conduction time (PR), heart rate (HR), and QT interval patterns defining the range of normality of these electrocardiographic parameters. The PR interval ranged from 154 +/- 10 ms (mean +/- SD) for HR less than or equal to 60 to 102 +/- 12 ms for HR greater than or equal to 120 (range 85-180). The absolute mean HR was 87 +/- 10 beats/min (range 72-104), the minimum observed HR being 61 +/- 10 (range 51-79), the maximum 160 +/- 20 beats/min (range 129-186). Daytime mean HR gave a mean value of 93 +/- 10 (range 71-148), while during night hours it was 74 +/- 11 (range 54-98). The minimum QT interval averaged 261 +/- 10 ms for HR greater than 120 and the maximum 389 +/- 9 ms for HR less than or equal to 60; the corresponding mean value of QTc (i.e., QT corrected for HR) ranged from 388 +/- 8 for HR less than or equal to 60 beats/min to 403 +/- 14 ms for HR greater than 120 beats/min. The results of the present study provide data of normal children which can be readily compared against those of subjects in whom cardiac abnormalities are suspect or patient.(ABSTRACT TRUNCATED AT 250 WORDS

The FHP01 DDX3X helicase inhibitor exerts potent anti-tumor activity in vivo in breast cancer pre-clinical models

Inhibition of DDX3X expression or activity reduces proliferation in cells from various tumor tissues, in particular in breast cancer, and its expression often correlates to tumor aggressiveness. This makes DDX3X a prominent candidate for the design of drugs for novel personalized therapeutic strategies. Starting from an in silico drug discovery approach, a group of molecules has been selected by molecular docking at the RNA binding site of DDX3X. Here, the most promising among them, FHP01, was evaluated in breast cancer preclinical models. Specifically, FHP01 exhibited very effective antiproliferative and killing activity against different breast cancer cell types, among which those from triple-negative breast cancer (TNBC). Interestingly, FHP01 also inhibited WNT signaling, a key tumorigenic pathway already correlated to DDX3X functions in breast cancer model cell lines. Ultimately, FHP01 also caused a significant reduction, in vivo, in the growth of MDA MB 231- derived TNBC xenograft models. Importantly, FHP01 showed good bioavailability and no toxicity on normal peripheral blood mononuclear cells in vitro and on several mouse tissues in vivo. Overall, our data suggest that the use of FHP01 and its related compounds may represent a novel therapeutic approach with high potential against breast cancer, including the triple-negative subtype usually correlated to the most unfavorable outcomes because of the lack of available targeted therapies

Early and long-term results of pectoralis muscle flap reconstruction versus sternal rewiring following failed sternal closure

Objectives: The aim of the study was to compare early and long-term results of pectoralis muscle flap reconstruction with those of sternal rewiring following failed sternal closure. Primary outcomes of the study were survival and failure rate. Respiratory function, chronic pain and quality of life were also evaluated. Methods: In a propensity-score matching analysis, of 94 patients who underwent sternal reconstruction, 40 were selected; 20 underwent sternal reconstruction with bilateral pectoralis muscle flaps (Group 1) and 20 underwent sternal rewiring (Group 2). Survival and failure rates were evaluated by in-hospital records and at follow-up. Respiratory function measures, including vital capacity (VC), were evaluated both by spirometry and computed tomography (CT) volumetry. Chronic pain was evaluated by the visual analogue pain scale. Results: At 85 ± 24 months of follow-up, survival and procedure failure were 95 and 90% in Group 1 and 60 and 55% in Group 2, respectively (P < 0.01, for both comparisons). Based on CT-scan volumetry, in Group 1, severe non-union and hemisternal paradoxical movement occurred less frequently (2 vs 7, P = 0.01). At spirometry assessment, postoperative VC was greater in Group 1 (3220 ± 290 vs 3070 ± 290 ml, P = 0.04). The same trend was detected by CT-scan in-expiratory measures (4034 ± 1800 vs 3182 ± 862 mm3, P < 0.05). Correspondingly, in Group 1, less patients presented in NYHA Class III (P < 0.05), and both chronic persistent pain score and physical health quality-of-life score were significantly better in the same group. Conclusions: In our study, muscle flap reconstruction guaranteed better early and late-term results as shown by lower rates of mortality, procedure failure and hemisternum stability. Moreover, Group 1 patients had greater postoperative VC, lower NYHA class and better quality of life. These results suggest that, in patients with multiple bone fracture, the rewiring approach does not promote physiological bone consolidation, whereas the muscle flap reconstruction can assure more physiological ventilatory dynamics.© The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved