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

Sex-dependent differences in left ventricular function and structure in chronic pressure overload

To evaluate gender-related differences in left ventricular (LV) structure and function in aortic stenosis, LV biplane cineangiography, micromanometry and endomyocardial biopsies were carried out in 56 patients with aortic stenosis and normal coronary arteries. Patients were divided into males (M: n= θ35), and females (F: n= θ21). Sixteen normal subjects 8 M, 8 F) served as haemodynamic controls. Control biopsy data were obtained from six pre-transplantation donor hearts (3 M and 3 F). LV systolic function was evaluated by ejection fraction and its relationship to mean systolic circumferential wall stress, diastolic function by the time constant of LV pressure decay, peak filling rates and passive myocardial stiffness constant. Biopsy samples were evaluated for interstitial fibrosis, muscle fibre diameter and volume fraction of myofibrils. In a subset of 27 consecutive patients, biopsy samples were evaluated with a morphometric-morphological method, for total collagen volume fraction, endocardial fibrosis and the extension and thickness of orthogonal collagen fibres (cross-hatching). In patients with aortic stenosis, aortic valve area, aortic valve resistance and mean aortic pressure gradient were comparable in males and females, whereas end-systolic and end-diastolic volumes were larger in males than females. Ejection fraction was lower (56%) in males than females (64%) (P 1.5 grade) was present in 11 males and four females with aortic stenosis (P<0.0I). An abnormal collagen architecture was present in 13114 males and 5113 females (V<0.002). In aortic stenosis, males have a depressed systolic function and abnormal passive elastic properties when compared to females with valve lesions of similar severity. Changes in collagen architecture may account, at least in part, for these difference

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

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

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

Thrombosis of the left anterior descending artery due to compression from giant pseudoaneurysm late after a bentall operation.

BACKGROUND: A postoperative pseudoaneurysm may develop and gradually expand in the mediastinal space even late following Bentall operation for aortic root replacement, particularly in patients with dissection of the aorta. METHODS: A very large (148 mm) pseudoaneurysm originating of the right coronary ostium suture line was observed in a patient admitted with unstable angina 6 years after Bentall procedure for type A aortic dissection. Angiograms showed reduced flow in the right coronary and thrombotic subocclusion of the left anterior descending (LAD) coronary artery due to extrinsic compression from the expanding mediastinal mass. RESULTS: Reoperation was performed during femoro-femoral cardiopulmonary bypass and brief period of circulatory arrest to clamp the tubular graft. After closure of the detected right coronary ostium in the tubular graft double bypass, grafting to the right coronary and LAD arteries was required. Postoperative course was uneventful. CONCLUSIONS: Close long-term follow-up after a Bentall procedure is required to minimize the risk of developing a large pseudoaneurysmal mass, in particular, after dissection of the aorta

MAPK15 protects from oxidative stress-dependent cellular senescence by inducing the mitophagic process

Mitochondria are the major source of reactive oxygen species (ROS), whose aberrant production by dysfunctional mitochondria leads to oxidative stress, thus contributing to aging as well as neurodegenerative disorders and cancer. Cells efficiently eliminate damaged mitochondria through a selective type of autophagy, named mitophagy. Here, we demonstrate the involvement of the atypical MAP kinase family member MAPK15 in cellular senescence, by preserving mitochondrial quality, thanks to its ability to control mitophagy and, therefore, prevent oxidative stress. We indeed demonstrate that reduced MAPK15 expression strongly decreases mitochondrial respiration and ATP production, while increasing mitochondrial ROS levels. We show that MAPK15 controls the mitophagic process by stimulating ULK1-dependent PRKN Ser108 phosphorylation and inducing the recruitment of damaged mitochondria to autophagosomal and lysosomal compartments, thus leading to a reduction of their mass, but also by participating in the reorganization of the mitochondrial network that usually anticipates their disposal. Consequently, MAPK15-dependent mitophagy protects cells from accumulating nuclear DNA damage due to mitochondrial ROS and, consequently, from senescence deriving from this chronic DNA insult. Indeed, we ultimately demonstrate that MAPK15 protects primary human airway epithelial cells from senescence, establishing a new specific role for MAPK15 in controlling mitochondrial fitness by efficient disposal of old and damaged organelles and suggesting this kinase as a new potential therapeutic target in diverse age-associated human diseases

Fostering Functional Occupation and Mobility in People with Intellectual Disability and Visual Impairment Through Technology-Aided Support

Objectives: The study assessed a smartphone-based technology system, which was designed to support functional occupation and mobility in people with severe to profound intellectual disability and visual impairment. Methods: The technology system provided (a) verbal orientation cues to guide the participants to a desk with two containers (and two groups of 10 objects that were to be transported to two different destinations), (b) verbal instructions to take the objects (one at a time), (c) verbal orientation cues to reach the destinations where the objects taken had to be transported, (d) instructions to put away the objects at the destinations, and (e) praise and brief periods of preferred stimulation. Seven participants were involved in the study, which was carried out according to a nonconcurrent multiple baseline across participants design. Results: During the baseline (when the technology system was not available), the participants produced few or no correct responses (i.e., failed to collect, transport, and deposit objects at the right destinations). During the intervention phase (i.e., with the support of the technology system), their mean frequency of correct responses per session was between close to 19 and close to 20 (out of a maximum possible of 20) and their mean session duration varied between about 16 and 29&nbsp;min. Conclusions: The data suggest that the technology system used in this study may be a viable resource to support activity and mobility in people with intellectual and visual disabilities

Physical mechanisms of chromatin spatial organization

In higher eukaryotes, chromosomes have a complex three-dimensional (3D) conformation in the cell nucleus serving vital functional purposes, yet their folding principles remain poorly understood at the single-molecule level. Here, we summarize recent approaches from polymer physics to comprehend the physical mechanisms underlying chromatin architecture. In particular, we focus on two models that have been supported by recent, growing experimental evidence, the Loop Extrusion model and the Strings&Binders phase separation model. We discuss their key ingredients, how they compare to experimental data and some insight they provide on chromatin architecture and gene regulation. Progresses in that research field are opening the possibility to predict how genomic mutations alter the network of contacts between genes and their regulators and how that is linked to genetic diseases, such as congenital disorders and cancer

Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding

Loop-extrusion and phase-separation have been proposed as mechanisms that shape chromosome spatial organization. It is unclear, however, how they perform relative to each other in explaining chromatin architecture data and whether they compete or co-exist at the single-molecule level. Here, we compare models of polymer physics based on loop-extrusion and phase-separation, as well as models where both mechanisms act simultaneously in a single molecule, against multiplexed FISH data available in human loci in IMR90 and HCT116 cells. We find that the different models recapitulate bulk Hi-C and average multiplexed microscopy data. Single-molecule chromatin conformations are also well captured, especially by phase-separation based models that better reflect the experimentally reported segregation in globules of the considered genomic loci and their cell-to-cell structural variability. Such a variability is consistent with two main concurrent causes: single-cell epigenetic heterogeneity and an intrinsic thermodynamic conformational degeneracy of folding. Overall, the model combining loop-extrusion and polymer phase-separation provides a very good description of the data, particularly higher-order contacts, showing that the two mechanisms can co-exist in shaping chromatin architecture in single cells