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1.
J Am Coll Cardiol ; 74(6): 729-740, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31395122

RESUMO

BACKGROUND: Concerns remain for a greater risk of incomplete revascularization and reduced survival with off-pump coronary artery bypass grafting (CABG) surgery compared with on-pump surgery particularly in patients with left main disease and extensive underlying myocardial ischemia. OBJECTIVES: This study sought to compare outcomes following off-pump versus on-pump surgery for left main disease by performing a post hoc analysis from the multicenter, randomized EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial. METHODS: The EXCEL trial was designed to compare percutaneous coronary intervention with everolimus-eluting stents versus CABG in patients with left main disease. CABG was performed with or without cardiopulmonary bypass (on-pump vs. off-pump surgery) according to the discretion of the operator. The 3-year outcomes in the off-pump and on-pump groups were compared using inverse probability of treatment weighting (IPTW) for treatment effect estimation. RESULTS: Among 923 CABG patients, 652 and 271 patients underwent on-pump and off-pump surgery, respectively. Despite a similar extent of disease, off-pump surgery was associated with a lower rate of revascularization of the left circumflex coronary artery (84.1% vs. 90.0%; p = 0.01) and right coronary artery (31.1% vs. 40.6%; p = 0.007). After IPTW adjustment for baseline differences, off-pump surgery was associated with a significantly increased risk of 3-year all-cause death (8.8% vs. 4.5%; hazard ratio: 1.94; 95% confidence interval: 1.10 to 3.41; p = 0.02) and a nonsignificant difference in the risk for the composite endpoint of death, myocardial infarction, or stroke (11.8% vs. 9.2%; hazard ratio: 1.28; 95% confidence interval: 0.82 to 2.00; p = 0.28). CONCLUSIONS: Among patients with left main disease treated with CABG in the EXCEL trial, off-pump surgery was associated with a lower rate of revascularization of the coronary arteries supplying the inferolateral wall and an increased risk of 3-year all-cause death compared with on-pump surgery.

2.
Soft Matter ; 15(20): 4153-4161, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31062008

RESUMO

Measurements are reported on the effect of monovalent and divalent salts on the swelling behavior and supramolecular structure of sodium polyacrylate gels (NaPA) made by osmotic swelling pressure and small angle neutron scattering measurements. The swelling response of the gels in solutions of ten different monovalent salts is found to be practically identical indicating that the principal effect of monovalent ions is screening the electrostatic repulsion among the charged groups on the polyelectrolyte chains; i.e., chemical differences between the monovalent ions do not play a significant role. Introducing Ca2+ ions into the equilibrium NaCl solution results in a sharp volume transition of the gels. The threshold Ca2+ ion concentration at which the transition occurs increases with increasing NaCl concentration in the surrounding bath. It is demonstrated that the swelling behavior of NaPA gels exhibits universal properties in solutions containing both NaCl and CaCl2. Osmotic swelling pressure measurements reveal that both the second and third virial coefficients decrease with increasing CaCl2 concentration until the volume transition is reached. The macroscopic measurements are complemented by small angle neutron scattering that reveals the variation of the thermodynamic length scales as the volume transition is approached. The thermodynamic correlation length L increases with increasing CaCl2 concentration.

3.
J Am Coll Cardiol ; 73(13): 1616-1628, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30947913

RESUMO

BACKGROUND: The randomized EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial reported a similar rate of the 3-year composite primary endpoint of death, myocardial infarction (MI), or stroke in patients with left main coronary artery disease (LMCAD) and site-assessed low or intermediate SYNTAX scores treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Whether these results are consistent in high-risk patients with diabetes, who have fared relatively better with CABG in most prior trials, is unknown. OBJECTIVES: In this pre-specified subgroup analysis from the EXCEL trial, the authors sought to examine the effect of diabetes in patients with LMCAD treated with PCI versus CABG. METHODS: Patients (N = 1,905) with LMCAD and site-assessed low or intermediate CAD complexity (SYNTAX scores ≤32) were randomized 1:1 to PCI with everolimus-eluting stents versus CABG, stratified by the presence of diabetes. The primary endpoint was the rate of a composite of all-cause death, stroke, or MI at 3 years. Outcomes were examined in patients with (n = 554) and without (n = 1,350) diabetes. RESULTS: The 3-year composite primary endpoint was significantly higher in diabetic compared with nondiabetic patients (20.0% vs. 12.9%; p < 0.001). The rate of the 3-year primary endpoint was similar after treatment with PCI and CABG in diabetic patients (20.7% vs. 19.3%, respectively; hazard ratio: 1.03; 95% confidence interval: 0.71 to 1.50; p = 0.87) and nondiabetic patients (12.9% vs. 12.9%, respectively; hazard ratio: 0.98; 95% confidence interval: 0.73 to 1.32; p = 0.89). All-cause death at 3 years occurred in 13.6% of PCI and 9.0% of CABG patients (p = 0.046), although no significant interaction was present between diabetes status and treatment for all-cause death (p = 0.22) or other endpoints, including the 3-year primary endpoint (p = 0.82) or the major secondary endpoints of death, MI, or stroke at 30 days (p = 0.61) or death, MI, stroke, or ischemia-driven revascularization at 3 years (p = 0.65). CONCLUSIONS: In the EXCEL trial, the relative 30-day and 3-year outcomes of PCI with everolimus-eluting stents versus CABG were consistent in diabetic and nondiabetic patients with LMCAD and site-assessed low or intermediate SYNTAX scores.(Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776).

4.
Eur J Cardiothorac Surg ; 55(6): 1144-1151, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30596978

RESUMO

OBJECTIVES: Percutaneous coronary intervention (PCI) is often favoured over coronary artery bypass grafting (CABG) surgery for revascularization in patients with chronic obstructive pulmonary disease (COPD). We studied whether COPD affected clinical outcomes according to revascularization in the Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial, in which PCI with everolimus-eluting stents was non-inferior to CABG for the treatment of patients with left main coronary artery disease and low or intermediate SYNTAX scores. METHODS: Patients with a history of COPD were propensity score matched to those without COPD. Outcomes at 30 days and 3 years in both groups were compared in patients randomized to PCI versus CABG. RESULTS: COPD status was available for 1901 of 1905 randomized patients (99.8%), 148 of whom had COPD (7.8%). Propensity score matching yielded 135 patients with COPD and 675 patients without COPD. Patients with COPD had higher 3-year rates of the primary composite end point of death, myocardial infarction or stroke (31.7% vs 14.5%, P < 0.0001), death (17.1% vs 7.5%, P = 0.0005) and myocardial infarction (18.3% vs 7.3%, P < 0.0001), but not stroke (3.3% vs 2.9%, P = 0.84). There were no statistically significant interactions in the relative risks of PCI versus CABG for the primary composite end point in patients with and without COPD at 30 days [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.12-1.21 vs HR 0.55, 95% CI 0.29-1.06; Pinteraction = 0.61] or at 3 years (HR 0.85, 95% CI 0.46-1.56 vs HR 1.28, 95% CI 0.84-1.94; Pinteraction = 0.27). CONCLUSIONS: In the EXCEL trial, COPD was independently associated with poor prognosis after left main coronary artery disease revascularization. The relative risks of PCI versus CABG at 30 days and 3 years were consistent in patients with and without COPD. CLINICAL TRIAL REGISTRATION NUMBER: http://www.clinicaltrials.gov; NCT01205776.

5.
J Chem Phys ; 149(16): 163312, 2018 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-30384682

RESUMO

Systematic investigations using neutron and X-ray small angle scattering in near-physiological salt solutions were made to reveal the effect of polymer concentration, pH, and calcium ion concentration on the structure of semi-dilute solutions of four model biopolymers [polyaspartic acid, DNA, chondroitin sulfate, and hyaluronic acid (HA)] representing typical backbone structures. In the low q range (<0.01 Å-1), the scattering response I(q) is dominated by scattering from large clusters. In the intermediate q range, I(q) varies approximately as q -1, exposing the linear nature of the scatterers. In these polyelectrolyte solutions, the correlation length L displays a power law dependence on the polymer concentration c that resembles that of neutral polymer solutions. L increases with increasing calcium chloride concentration and with decreasing pH. The effect of the different divalent cations, Ba, Mg, Ca, Sr, and Mn, on the structure of DNA solutions is practically identical. However, in mixed salt conditions at the same ionic strength, the combined effect of mono- and divalent counter-ions on the structure of the polymer solutions deviates significantly from additivity. Anomalous small angle X-ray scattering observations on both DNA and HA solutions reveal that the divalent strontium counter-ions form a tight sheath around the polymer chain. The shape of the divalent ion cloud is similar in these two systems.


Assuntos
Biopolímeros/química , Modelos Químicos , Íons , Concentração Osmolar , Peptídeos/química , Proteínas/química , Espalhamento a Baixo Ângulo , Soluções
6.
Orv Hetil ; 159(46): 1869-1875, 2018 Nov.
Artigo em Húngaro | MEDLINE | ID: mdl-30450939

RESUMO

The authors give a short introduction of the Hungarian and the international history of adult heart transplantation, and highlight the similarities in the evolution of the two programs. Their aim was to show how the Hungarian post-transplant survival changed in the last five years. They wanted to investigate how all the changes they had made in the program affected the post-transplant results. They investigated 496 heart transplantation data and compared to international data. Orv Hetil. 2018; 159(46): 1869-1875.

7.
Orv Hetil ; 159(46): 1876-1881, 2018 Nov.
Artigo em Húngaro | MEDLINE | ID: mdl-30450938

RESUMO

The mechanical circulatory support (MCS) program of the Semmelweis University Heart and Vascular Centre has become established over the last five years. The main requirements of our MCS program to be developed first were the Heart Transplantation and Heart Failure Intensive Care Unit and a well trained medical team. The wide range of mechanical circulatory support devices provides suitable background for the adequate treatment of our patients in all indications. In this review, we present our results related to extracorporeal membrane oxygenation (ECMO) supports performed in the last five years. Between 2012 and 2017, we applied MCS support in 140 cases, among them 111 patients received ECMO support. The leading indications of ECMO support were the following: primary graft failure after heart transplantation (33 cases), postcardiotomy cardiogenic shock (18 patients), acute decompensation of end-stage heart failure (14 patients), acute myocardial infarction complicated with refractory cardiogenic shock (37 patients), cardiogenic shock developed after transcatheter aortic valve implantation (3 patients), malignant arrhythmia due to drug intoxication (1 patient) and acute respiratory distress syndrome (4 cases). The mortality of patients receiving ECMO support was 46%. The analysis of the results of ECMO support needs to change our approach. The mortality results show that we lost the half of our patients. However, the mortality in the conventionally treated patients would have been 100% without ECMO. In fact, we could save the life of half of these patients. Orv Hetil. 2018; 159(46): 1876-1881.

8.
Magy Seb ; 71(3): 117-125, 2018 09.
Artigo em Húngaro | MEDLINE | ID: mdl-30231635

RESUMO

INTRODUCTION: Although surgical specialties utilize static models for preoperative planning, the evolution of dynamic planning methods and computer simulations created the opportunity for the introduction of dynamic parameters in cardiac surgery. Our aim was to apply 3D models in cardiac surgical practice, predicting fluid dynamic results, ventricular shape, volume and function before the operation. METHODS: Using a script developed by us, the raw DICOM files were imported, the dilated left ventricle was modeled and fluid dynamic parameters were simulated, such as flow kinematic and profile analysis, turbulence calculation and myocardial response to shear stress. Then step-by-step simulation of the surgical ventricle restoration procedure was accomplished and the calculated variables were imbedded in silico model. The length of resection lines was modified based on the previous computer simulation and applied during the operation, if feasible. RESULTS: The sphericity and conicity indexes were improved significantly in postoperative period (0.42 vs. 0.67 and 0.36 vs. 0.72, p < 0.05). The occurred shear stress at endocardium decreased 83% due to the normalization of flow kinematic pattern of the ventricle in postoperative period (132.21 ± 29.5 dyne/cm2 vs. 22.92 ± 10.3 p < 0.05 dyne/|cm2). The postoperative turbulent flow pattern significantly decreased, according to our computational method (2712 vs. 1823, p < 0.0001). CONCLUSION: With our method, the standardization of the surgical ventricle reconstruction was achievable and the surgical steps were predictable. Therefore, a new decision making support system was established in cardiac surgery for high risk patients. A personalized surgical technique was offered to our patients, improving their life expectancy and quality of life.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Tomada de Decisão Clínica , Cardiopatias/diagnóstico por imagem , Cardiopatias/cirurgia , Imagem Tridimensional/métodos , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos , Cuidados Pré-Operatórios
9.
Artigo em Inglês | MEDLINE | ID: mdl-30165487

RESUMO

OBJECTIVES: Observational data suggest that the use of a single internal thoracic artery (SITA) may result in inferior outcomes compared with bilateral internal thoracic artery (BITA) use for coronary artery bypass grafting (CABG)-a finding not yet supported by randomized trial outcomes. However, the optimal number of internal thoracic artery grafts in patients with left main coronary artery disease has not been investigated. METHODS: The EXCEL trial randomized 1905 patients with left main coronary artery disease to percutaneous coronary intervention with everolimus-eluting stents versus CABG. Among the 905 patients undergoing CABG, 688 (76.0%) received SITA and 217 (24.0%) received BITA. Differences in clinical event rates were estimated using the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox regression was used to adjust for differences in baseline covariates. RESULTS: Compared to SITA, patients treated with BITA were younger (66.1 ± 9.5 vs 64.5 ± 9.3 years, P = 0.020), were less likely female (24.3% vs 14.3%, P = 0.002) and diabetic (28.8% vs 15.2%, P < 0.001), and had a lower prevalence of peripheral vessel disease (10.2% vs 5.5%, P = 0.040). The unadjusted 3-year composite primary endpoint of death, stroke or myocardial infarction (MI) occurred in 15.6% of SITA vs 11.6% of BITA patients (P = 0.17). The SITA group tended to have a higher 3-year rate of all-cause death compared with the BITA group (6.7% vs 3.3%; P = 0.070). Stroke, MI and ischaemia-driven revascularization outcomes were not significantly different between groups. After adjusting for baseline differences, neither the composite of death, stroke or MI [hazard ratio (HR) 1.12, 95% confidence interval (CI) 0.71-1.78; P = 0.62] nor mortality (HR 1.36, 95% CI 0.60-3.12; P = 0.46) was significantly higher with SITA. The rehospitalization rate after 3 years was higher in the SITA group (35.8% vs 26.0%, P = 0.008), a difference which was no longer present after multivariable adjustment (HR 1.27, 95% CI 0.93-1.74; P = 0.13). Sternal wound dehiscence within 30 days did not occur more often in the BITA group compared to the SITA group (1.8% vs 2.2%, P > 0.99). CONCLUSIONS: In the EXCEL trial, there were no clinical differences at 3 years between SITA or BITA revascularization in patients with left main coronary artery disease.

10.
JACC Cardiovasc Interv ; 11(13): 1224-1233, 2018 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-29976358

RESUMO

OBJECTIVES: The authors sought to determine the extent to which the site of the left main coronary artery (LM) lesion (distal bifurcation versus ostial/shaft) influences the outcomes of revascularization with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). BACKGROUND: Among 1,905 patients with LM disease and site-assessed SYNTAX scores of <32 randomized in the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, revascularization with PCI and CABG resulted in similar rates of the composite primary endpoint of death, myocardial infarction (MI), or stroke at 3 years. METHODS: Outcomes from the randomized EXCEL trial were analyzed according to the presence of angiographic core laboratory-determined diameter stenosis ≥50% involving the distal LM bifurcation (n = 1,559; 84.2%) versus disease isolated to the LM ostium or shaft (n = 293; 15.8%). RESULTS: At 3 years, there were no significant differences between PCI and CABG for the primary composite endpoint of death, MI, or stroke for treatment of both distal LM bifurcation disease (15.6% vs. 14.9%, odds ratio [OR]: 1.08, 95% confidence interval [CI]: 0.81 to 1.42; p = 0.61) and isolated LM ostial/shaft disease (12.4% vs. 13.5%, OR: 0.90, 95% CI: 0.45 to 1.81; p = 0.77) (pinteraction = 0.65). However, at 3 years, ischemia-driven revascularization occurred more frequently after PCI than CABG in patients with LM distal bifurcation disease (13.0% vs. 7.2%, OR: 2.00, 95% CI: 1.41 to 2.85; p = 0.0001), but were not significantly different in patients with disease only at the LM ostium or shaft (9.7% vs. 8.4%, OR: 1.18, 95% CI: 0.52 to 2.69; p = 0.68) (pinteraction = 0.25). CONCLUSIONS: In the EXCEL trial, PCI and CABG resulted in comparable rates of death, MI, or stroke at 3 years for treatment of LM disease, including those with distal LM bifurcation disease. Repeat revascularization rates during follow-up after PCI compared with CABG were greater for lesions in the distal LM bifurcation but were similar for disease isolated to the LM ostium or shaft.

11.
Soft Matter ; 14(15): 2879-2892, 2018 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-29582024

RESUMO

Cartilage is composed of cells and an extracellular matrix, the latter being a composite of a collagen mesh interpenetrated by proteoglycans responsible for tissue osmotic swelling. The matrix composition and structure vary through the tissue depth. Mapping such variability requires tissue sectioning to gain access. The resulting surface roughness, and concomitant proteoglycan loss contribute to large uncertainties in elastic modulus estimates. To extract elasticity values for the bulk matrix which are not obfuscated by the indeterminate surface layer, we developed a novel experimental and data analysis methodology. We analyzed the surface roughness to optimize the probe size, and performed high-resolution (1 µm) elasticity mapping on thin (∼12 µm), epiphyseal newborn mouse cartilage sections cut parallel to the bone longitudinal axis or normal to the articular surface. Mild fixation prevented the major proteoglycan loss observed in unfixed specimens but not the stress release that resulted in thickness changes in the sectioned matrix. Our novel data analysis method introduces a virtual contact point as a fitting parameter for the Hertz model, to minimize the effects of surface roughness and corrects for the finite section thickness. Our estimates of cartilage elasticity converge with increasing indentation depth and, unlike previous data interpretations, are consistent with linearly elastic material. A high cell density that leaves narrow matrix septa between cells may cause the underestimation of elastic moduli, whereas fixation probably causes an overestimation. The proposed methodology has broader relevance to nano- and micro-indentation of soft materials with multiple length scales of organization and whenever surface effects (including roughness, electrostatics, van der Waals forces, etc.) become significant.

12.
J Chem Phys ; 146(16): 164905, 2017 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-28456212

RESUMO

The objective of this work is to investigate the thermodynamic and scattering behavior of tetra-poly(ethylene glycol) (PEG) gels. Complementary measurements, including osmotic swelling pressure, elastic modulus, and small angle neutron scattering (SANS), are reported for a series of tetra-PEG gels made from different molecular weight precursor chains at different concentrations. Analysis of the osmotic swelling pressure vs polymer volume fraction curves makes it possible to separate the elastic and mixing contributions of the network free energy. It is shown that in tetra-PEG gels these free energy components are additive. The elastic term varies with the one-third power of the polymer volume fraction and its numerical value is equal to the shear modulus obtained from independent mechanical measurements. The mixing pressure of the cross-linked polymer is slightly smaller than that of the corresponding solution of the uncross-linked polymer of infinite molecular weight but it exhibits similar dependence on the polymer concentration. The observed deviation between the osmotic mixing pressures of the gel and the solution can be attributed to the presence of small amount of structural inhomogeneities frozen-in by the cross-links. SANS reveals that the scattering response of tetra-PEG gel is mainly governed by the thermodynamic concentration fluctuations of the network, i.e., the contribution from static inhomogeneities to the SANS signal is small.

13.
Macromol Symp ; 372(1): 43-50, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29731595

RESUMO

The most abundant cartilage proteoglycan is aggrecan, a bottlebrush shaped molecule that possesses over 100 glycosaminoglycan (chondroitin sulfate and keratan sulfate) chains. The side-chains are linear sulfated polysaccharides that are negatively charged under physiological conditions. Aggrecan interacts with hyaluronic acid (HA) to form large aggregates. Osmotic pressure measurements and rheological measurements are used to study the static and dynamic behavior of aggrecan assemblies at the macroscopic length scales. The microscopic properties of aggrecan solutions are determined by small angle neutron scattering (SANS), and static and dynamic light scattering (SLS and DLS). In dilute solutions aggrecan forms microgels with a diffuse boundary, composed of loosely connected clusters. The osmotic pressure of the aggrecan-HA system decreases with increasing HA content. DLS yields a relaxation rate that varies as q3, arising from internal modes in the microgel. The relaxation rate in the solutions of the aggrecan-HA complex is slightly greater than in the pure aggrecan solution.

14.
N Engl J Med ; 375(23): 2223-2235, 2016 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-27797291

RESUMO

BACKGROUND: Patients with obstructive left main coronary artery disease are usually treated with coronary-artery bypass grafting (CABG). Randomized trials have suggested that drug-eluting stents may be an acceptable alternative to CABG in selected patients with left main coronary disease. METHODS: We randomly assigned 1905 eligible patients with left main coronary artery disease of low or intermediate anatomical complexity to undergo either percutaneous coronary intervention (PCI) with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). Anatomic complexity was assessed at the sites and defined by a Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score of 32 or lower (the SYNTAX score reflects a comprehensive angiographic assessment of the coronary vasculature, with 0 as the lowest score and higher scores [no upper limit] indicating more complex coronary anatomy). The primary end point was the rate of a composite of death from any cause, stroke, or myocardial infarction at 3 years, and the trial was powered for noninferiority testing of the primary end point (noninferiority margin, 4.2 percentage points). Major secondary end points included the rate of a composite of death from any cause, stroke, or myocardial infarction at 30 days and the rate of a composite of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses. RESULTS: At 3 years, a primary end-point event had occurred in 15.4% of the patients in the PCI group and in 14.7% of the patients in the CABG group (difference, 0.7 percentage points; upper 97.5% confidence limit, 4.0 percentage points; P=0.02 for noninferiority; hazard ratio, 1.00; 95% confidence interval, 0.79 to 1.26; P=0.98 for superiority). The secondary end-point event of death, stroke, or myocardial infarction at 30 days occurred in 4.9% of the patients in the PCI group and in 7.9% in the CABG group (P<0.001 for noninferiority, P=0.008 for superiority). The secondary end-point event of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years occurred in 23.1% of the patients in the PCI group and in 19.1% in the CABG group (P=0.01 for noninferiority, P=0.10 for superiority). CONCLUSIONS: In patients with left main coronary artery disease and low or intermediate SYNTAX scores by site assessment, PCI with everolimus-eluting stents was noninferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776 .).


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Everolimo/administração & dosagem , Idoso , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos
15.
PLoS One ; 11(9): e0158147, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27685846

RESUMO

Linear PEI is a cationic polymer commonly used for complexing DNA into nanoparticles for cell-transfection and gene-therapy applications. The polymer has closely-spaced amines with weak-base protonation capacity, and a hydrophobic backbone that is kept unaggregated by intra-chain repulsion. As a result, in solution PEI exhibits multiple buffering mechanisms, and polyelectrolyte states that shift between aggregated and free forms. We studied the interplay between the aggregation and protonation behavior of 2.5 kDa linear PEI by pH probing, vapor pressure osmometry, dynamic light scattering, and ninhydrin assay. Our results indicate that: At neutral pH, the PEI chains are associated and the addition of NaCl initially reduces and then increases the extent of association.The aggregate form is uncollapsed and co-exists with the free chains.PEI buffering occurs due to continuous or discontinuous charging between stalled states.Ninhydrin assay tracks the number of unprotonated amines in PEI.The size of PEI-DNA complexes is not significantly affected by the free vs. aggregated state of the PEI polymer. Despite its simple chemical structure, linear PEI displays intricate solution dynamics, which can be harnessed for environment-sensitive biomaterials and for overcoming current challenges with DNA delivery.

16.
Gels ; 2(4)2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28649573

RESUMO

Hydrogels are of intense recent interest in connection with biomedical applications ranging from 3-D cell cultures and stem cell differentiation to regenerative medicine, controlled drug delivery and tissue engineering. This prototypical form of soft matter has many emerging material science applications outside the medical field. The physical processes underlying this type of solidification are incompletely understood and this limits design efforts aimed at optimizing these materials for applications. We address this general problem by applying multiple techniques (e.g., NMR, dynamic light scattering, small angle neutron scattering, rheological measurements) to the case of a peptide derivative hydrogelator (molecule 1, NapFFKYp) over a broad range of concentration and temperature to characterize both the formation of individual nanofibers and the fiber network. We believe that a better understanding of the hierarchical self-assembly process and control over the final morphology of this kind of material should have broad significance for biological and medicinal applications utilizing hydrogels.

17.
Proc Inst Mech Eng H ; 229(12): 895-904, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26614803

RESUMO

We discuss the main findings of a long-term research program exploring the consequences of sodium/calcium ion exchange on the macroscopic osmotic and elastic properties, and the microscopic structure of representative synthetic polyelectrolyte (sodium polyacrylate, (polyacrylic acid)) and biopolymer gels (DNA). A common feature of these gels is that above a threshold calcium ion concentration, they exhibit a reversible volume phase transition. At the macroscopic level, the concentration dependence of the osmotic pressure shows that calcium ions influence primarily the third-order interaction term in the Flory-Huggins model of polymer solutions. Mechanical tests reveal that the elastic modulus is practically unaffected by the presence of calcium ions, indicating that ion bridging does not create permanent cross-links. At the microscopic level, small-angle neutron scattering shows that polyacrylic acid and DNA gels exhibit qualitatively similar structural features in spite of important differences (e.g. chain flexibility and chemical composition) between the two polymers. The main effect of calcium ions is that the neutron scattering intensity increases due to the decrease in the osmotic modulus. At the level of the counterion cloud around dissolved macroions, anomalous small-angle X-ray scattering measurements made on DNA indicate that divalent ions form a cylindrical sheath enveloping the chain, but they are not localized. Small-angle neutron scattering and small-angle X-ray scattering provide complementary information on the structure and interactions in polymer solutions and gels.


Assuntos
Cálcio/química , Géis/química , Pressão Osmótica , Sódio/química , Resinas Acrílicas/química , Elasticidade , Troca Iônica , Espalhamento a Baixo Ângulo
18.
ACS Nano ; 9(10): 9517-27, 2015 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-26301492

RESUMO

Despite the effort of developing various nanodelivery systems, most of them suffer from undesired high uptakes by the reticuloendothelial system, such as liver and spleen. Herein we develop an endogenous phosphatase-triggered coassembly strategy to form tumor-specific indocyanine green (ICG)-doped nanofibers (5) for cancer theranostics. Based on coordinated intermolecular interactions, 5 significantly altered near-infrared absorbance of ICG, which improves the critical photoacoustic and photothermal properties. The phosphatase-instructed coassembly process, as well as its theranostic capability, was successfully conducted at different levels ranging from in vitro, living cell, tissue mimic, to in vivo. Specifically, the tumor uptake of ICG was markedly increased to 15.05 ± 3.78%ID/g, which was 25-fold higher than that of free ICG (0.59 ± 0.24%ID/g) at 4 h after intravenous injection. The resulting ultrahigh T/N ratios (>15) clearly differentiated tumors from the surrounding normal tissue. Complete tumor elimination with high therapeutic accuracy has been successfully achieved upon laser irradiation (0.8 W/cm(2), 5 min) within 24-48 h postinjection. As the first example, in vivo formation of tumor-specific ICG-doped nanofiber for PTT theranostics owns the immense potential for clinical translation of personalized nanomedicine with targeted drug delivery as well as for cancer theranostics.


Assuntos
Corantes/uso terapêutico , Verde de Indocianina/uso terapêutico , Nanofibras/uso terapêutico , Neoplasias/diagnóstico , Neoplasias/terapia , Nanomedicina Teranóstica/métodos , Animais , Corantes/química , Corantes/metabolismo , Corantes/farmacocinética , Sistemas de Liberação de Medicamentos , Células HeLa , Humanos , Hipotermia Induzida/métodos , Verde de Indocianina/química , Verde de Indocianina/metabolismo , Verde de Indocianina/farmacocinética , Camundongos , Modelos Moleculares , Nanofibras/química , Imagem Óptica/métodos , Monoéster Fosfórico Hidrolases/metabolismo , Técnicas Fotoacústicas/métodos , Fototerapia/métodos
19.
Orv Hetil ; 156(13): 521-7, 2015 Mar 29.
Artigo em Húngaro | MEDLINE | ID: mdl-25796280

RESUMO

INTRODUCTION: Since the celebration of the 20th anniversary of the first heart transplantation in Hungary in 2012 the emerging need for modern heart failure management via mechanical circulatory support has evolved. In May 2012 the opening of a new heart failure and transplant unit with 9 beds together with the procurement of necessary devices at Semmelweis University accomplished this need. AIM: The aim of the authors was to report their initial experience obtained in this new cardiac assist device program. METHOD: Since May, 2012, mechanical circulatory support system was applied in 89 cases in 72 patients. Indication for support were end stage heart failure refractory to medical treatment and acute left or right heart failure. RESULTS: Treatment was initiated for acute graft failure after heart transplantation in 27 cases, for end stage heart failure in 24 cases, for acute myocardial infarction in 21 cases, for acute postcardiotomy heart failure in 14 cases, for severe respiratory insufficiency in 2 cases and for drug intoxication in one case. Among the 30 survivor of the whole program 13 patients were successfully transplanted. CONCLUSIONS: The available devices can cover all modalities of current bridge therapy from short term support through medium support to heart transplantation or long term support and destination therapy. These conditions made possible the successful start of a new cardiac assist device program.


Assuntos
Insuficiência Cardíaca/terapia , Coração Auxiliar , Adulto , Idoso , Doença Crônica , Oxigenação por Membrana Extracorpórea , Feminino , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Avaliação de Programas e Projetos de Saúde , Faculdades de Medicina
20.
Soft Matter ; 10(38): 7653-60, 2014 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-25137385

RESUMO

Mannobiose-modified polyethylenimines (PEI) are used in gene therapy to generate nanoparticles of DNA that can be targeted to the antigen-presenting cells of the immune system. We report that the sugar modification alters the DNA organization within the nanoparticles from homogenous to shell-like packing. The depth-dependent packing of DNA within the nanoparticles was probed using AFM nano-indentation. Unmodified PEI-DNA nanoparticles display linear elastic properties and depth-independent mechanics, characteristic of homogenous materials. Mannobiose-modified nanoparticles, however, showed distinct force regimes that were dependent on indentation depth, with 'buckling'-like response that is reproducible and not due to particle failure. By comparison with theoretical studies of spherical shell mechanics, the structure of mannobiosylated particles was deduced to be a thin shell with wall thickness in the order of few nanometers, and a fluid-filled core. The shell-core structure is also consistent with observations of nanoparticle denting in altered solution conditions, with measurements of nanoparticle water content from AFM images, and with images of DNA distribution in Transmission Electron Microscopy.


Assuntos
DNA/química , Mananas/química , Nanopartículas/química , Nanopartículas/ultraestrutura , Polietilenoimina/química , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão
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