Influence of Bleeding Risk on Outcomes of Radial and Femoral Access for Percutaneous Coronary Intervention: An Analysis From the GLOBAL LEADERS Trial

BackgroundRadial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding.MethodsPatients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days.ResultsIn the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; P_interaction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; P_interaction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant.ConclusionsOur findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating.     

Prognostic value of angiographic markers of myocardial reperfusion in patients treated with primary coronary angioplasty for anterior wall acute myocardial infarction

BACKGROUND: Modern therapy of acute myocardial infarction (AMI) is aimed at rapid and persisting restoration of blood flow in an infarct-related artery (IRA). However, in some patients myocardial reperfusion is not achieved in spite of effective IRA recanalisation. Myocardial Blush Grade (MBG) is one of the angiographic markers useful for the detection of this phenomenon. AIM: To assess the prognostic value of MBG in patients with anterior AMI treated with primary angioplasty. METHODS: The study group consisted of 104 patients (74 males, 30 females, mean age 62+/-13 years) treated with primary angioplasty due to anterior ST-segment elevation AMI. MBG was assessed after the procedure. The mortality and major cardiovascular event (MACE) rates were analysed one and six months after AMI. RESULTS: Patients with preserved myocardial reperfusion following angioplasty (MBG 2-3, n=64 (61.5%)) had a trend towards lower one-month mortality and significantly reduced six-month mortality compared with 40 (38.5%) patients with an impaired (MBG 0-1) myocardial reperfusion (3% vs 12.5%, NS; and 6.25% vs 20%, p<0.05, respectively). The rate of MACE was significantly lower in patients with rather than without reperfusion both after one and six months of follow-up (9.4% vs 27.5%, p=0.027 and 12.5% vs 42.5%, p<0.001, respectively). Compared with patients with a high MBG score, patients with altered reperfusion more frequently had diabetes (30% vs 12.5%, p=0.04), hypertension (67.5% vs 45%, p=0.043), longer time from the onset of symptoms to balloon inflation (355.9+/-199 min vs 215.5+/-113 min, p<0.001) and lower left ventricular ejection fraction, measured 3 days after AMI (43.3%+/-8 vs 47.4%+/-9, p=0.02). CONCLUSIONS: MBG has a significant prognostic value in patients with anterior AMI treated with primary angioplasty. Diabetes, hypertension and long delay of treatment are associated with the impairment of myocardial reperfusion.     

Pharmacogenetics of the local thrombolysis in patients with deep vein thrombosis

Thrombophilia, the state of increased tendency for blood clotting, is considered the disorder of a complex etiology, caused by both environmental and genetic factors. As gene variants predisposing to thrombophilia and influencing the increased risk of vein thrombosis might influence response to local thrombolysis, the aim of the work was to characterize the pharmacogenetic conditions for local streptokinase treatment in patients with a deep vein thrombosis (DVT) of lower extremities based on the following polymorphism analyses: G1691A polymorphism of factor V (FV), G20210A polymorphism of prothrombin (PT), A4250G (Thr312Ala) polymorphism of fibrinogen-alpha (FGA), G(-455)A polymorphism of fibrinogen-beta (FGB), 4G/5G polymorphism of plasminogen activator inhibitor type 1(PAI-1) and insertion/deletion (I/D) polymorphism of tissue plasminogen activator (t-PA). The study included 40 DVT patients who underwent a local thrombolytic treatment within 14-day period from diagnosis. Full recanalization was achieved in 20 subjects (50%) [group R(+)], whereas incomplete or total lack of recanalization was identified in the remaining 20 patients [group R(-)]. No major complications of thrombolytic treatment occurred in the studied group. In the case of prothrombin gene all individuals carried homozygous wild type genotype (GG). Prevalence of the genotypes and alleles of the remaining five polymorphisms did not differ significantly between the groups R(+) and R(-). Neither sex nor age, smoking or time period from diagnosis to introduction of the thrombolytic treatment significantly influenced treatment efficacy. The results of the study suggest that a local thrombolysis with streptokinase introduced within two week period from the diagnosis is a safe and efficient method of treatment for deep vein thrombosis of lower extremities. However, size of the group is insufficient to clearly determine the association between investigated polymorphisms and efficacy of local treatment with streptokinase.     

Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?

Hepatocellular carcinoma is the main liver-related cause of death in patients with compensated cirrhosis. The early phases are asymptomatic and the prognosis is poor, which makes prevention essential. We propose that non-selective beta-blockers decrease the incidence and growth of hepatocellular carcinoma via a reduction of the inflammatory load from the gut to the liver and inhibition of angiogenesis.     

Risk of thromboembolic complications in patients with permanent atrial fibrillation undergoing cardioverter-defibrillator implantation

BACKGROUND: Cardioversion of atrial fibrillation (AF) carries the risk of thromboembolic complications and, therefore, anticoagulation therapy is routinely administered before and after this procedure. In patients with permanent AF who undergo implantation of cardioverter-defibrillator (ICD), anticoagulants are usually withdrawn during the perioperative period. However, in some patients sinus rhythm may be restored during defibrillation threshold (DFT) testing which potentially may increase the risk of thromboembolic complications. AIM: To assess the frequency of sinus rhythm restoration during ICD implantation in patients with permanent AF and the rate of both thromboembolic events and local bleeding complications which may occur due to temporary withdrawal of anticoagulation therapy and its re-initiation early after the procedure. METHODS: Permanent AF was present in 23 (12%) of 193 patients selected for ICD implantation. All patients received prolonged oral anticoagulation according to the generally accepted standards. Anticoagulation therapy was stopped few days before the procedure and replaced by low molecular weight heparin which was administered up to 24 hours before ICD implantation and re-initiated 12-24 hours afterwards. RESULTS: During DFT testing sinus rhythm was restored in 5 (21.7%) patients with AF. Clinical and DFT characteristics were similar in those who were converted to sinus rhythm and those who remained in AF. No thromboembolic events were noted in either group. Local haematoma at the site of ICD implantation occurred in two (8%) patients. CONCLUSIONS: Sinus rhythm was restored in 21.7% of patients with permanent AF who underwent ICD implantation. Temporary withdrawal of anticoagulation therapy did not increase the risk of thromboembolic complications, however, its early re-initiation after implantation resulted in an increase in local bleeding complication rate.     

A Pathway toward a New Era of Open-Cell Polyurethane Foams—Influence of Bio-Polyols Derived from Used Cooking Oil on Foams Properties

In order to create greener polyurethane (PUR) foams, modified used cooking oils (UCO) were applied as starting resources for the synthesis of bio-polyols. The bio-polyols were produced using transesterification of UCO with diethylene glycol (UCO_DEG) and triethanolamine (UCO_TEA). Next, open-cell PUR foams were synthesized by replacing 20, 40, 60, 80 and 100% of the petrochemical polyol with the bio-polyol UCO_DEG or UCO_TEA. It was observed that an increasing bio-polyol content (up to 60%) led to an increase of the closed cell content. However, a further increase in the bio-polyol content up to 100% resulted in foam cell opening. The bio-foams obtained in the experiment had an apparent density of 13–18 kg/m³. The coefficient of thermal conductivity was determined at three different average temperatures: 10, 0 and −10 °C. The PUR bio-foams modified with bio-polyol UCO_TEA had lower values of thermal conductivity, regardless of the average temperature (35.99–39.57 mW/m·K) than the foams modified with bio-polyol UCO_DEG (36.95–43.78 mW/m·K). The compressive strength of most of the bio-foams was characterized by a higher value than the compressive strength of the reference material (without bio-polyol). Finally, it was observed that the bio-materials exhibited dimensional stability at 70 °C.     

Development and Characterization of “Green Open-Cell Polyurethane Foams” with Reduced Flammability

This work presents the cell structure and selected properties of polyurethane (PUR) foams, based on two types of hydroxylated used cooking oil and additionally modified with three different flame retardants. Bio-polyols from municipal waste oil with different chemical structures were obtained by transesterification with triethanolamine (UCO_TEA) and diethylene glycol (UCO_DEG). Next, these bio-polyols were used to prepare open-cell polyurethane foams of very low apparent densities for thermal insulation applications. In order to obtain foams with reduced flammability, the PUR systems were modified with different amounts (10–30 parts per hundred polyol by weight—php) of flame retardants: TCPP (tris(1-chloro-2-propyl)phosphate), TEP (triethyl phosphate), and DMPP (dimethyl propylphosphonate). The flame retardants caused a decrease of the PUR formulations reactivity. The apparent densities of all the foams were comparable in the range 12–15 kg/m³. The lowest coefficients of thermal conductivity were measured for the open-cell PUR foams modified with DMPP. The lowest values of heat release rate were found for the foams based on the UCO_TEA and UCO_DEG bio-polyols that were modified with 30 php of DMPP.     

Antitumor Effects of Recombinant Antivascular Protein ABRaA-VEGF121 Combined with IL-12 Gene Therapy

Development and neoplastic progression strongly rely on tumor microenvironment cells. Various kinds of cells that form such tumor milieu play substantial roles in angiogenesis and immunosuppression. Attempts to inhibit tumor vascularization alter tumor milieu and enhance immune response against the tumor. Anticancer therapeutic strategy bringing together antiangiogenic and immunostimulating agents has emerged as a promising approach. We here investigated whether therapy directed against preexisting vessels, combined with an immunomodulatory factor would be equally effective in arresting tumor growth. To this goal, we investigated the effectiveness of ABRaA-vascular endothelial growth factor isoform 121 (VEGF₁₂₁), an antivascular drug constructed by us. It is a fusion protein composed of VEGF₁₂₁, and abrin A chain (translation-inhibiting toxin). We used it in combination with interleukin (IL-12) gene therapy and tried to inhibit B16-F10 melanoma tumor growth. ABRaA-VEGF₁₂₁ is a chimeric recombinant protein capable of destroying tumor vasculature and triggering necrosis in the vicinity of damaged vessels. IL-12 cytokine, in turn, activates both specific and non-specific immune responses. Our results demonstrate that combination of ABRaA-VEGF₁₂₁ antivascular agent with immunostimulatory cytokine IL-12 indeed inhibits tumor growth more effectively than either agent alone, leading to complete cure of ca. 20 % mice. Post-therapeutic analysis of tumors excised from mice treated with combination therapy showed decreased numbers of blood microvessels in the tumor microenvironment, lowered numbers of regulatory T lymphocytes, as well as showed higher levels of CD4⁺ and CD8⁺ as compared to control mice. It seems that bringing together antivascular strategy and the action of immunostimulating agents indeed inhibits growth of tumors.