Rationale and design of a prospective, randomised study of retrograde application of bone marrow aspirate concentrate (BMAC) through coronary sinus in patients with congestive heart failure of ischemic etiology (the RETRO study).

BACKGROUND: Heart failure (HF) is a major chronic illness and results in high morbidity and mortality. The most frequent cause of HF with reduced ejection fraction (HFREF) is coronary artery disease (CAD). Although revascularisation of ischemic myocardium lead to improvements in myocardial contractility and systolic function, it cannnot restore the viability of the already necrotic myocardium. METHODS/DESIGN: The aim of our prospective randomised study is to assess the efficacy of the retrograde application of non-selected bone marrow autologous cells concentrate (BMAC) in patients with HFREF of ischemic aetiology. The evaluated preparation is concentrated BMAC, obtained using Harvest SmartPReP2 (Harvest Technologies, Plymouth, MA, USA). The study population will be a total of 40 patients with established CAD, systolic dysfunction with LV EF of ≤40% and HF in the NYHA class 3. Patients have been on standard HF therapy for 3 months and in a stabilised state for at least 1 month, before enrolling in the clinical study. Patients will be randomised 1:1 to either retrograde BMAC administration via coronary sinus or standard HF therapy. The primary end-points (left ventricular end-systolic and end-diastolic diameters [LVESd/EDd] and volumes [LVESV/EDV] and left ventricular ejection fraction [LV EF]) will be assessed by magnetic resonance imaging. The follow-up period will be 12 month. DISCUSSION: The application of bone marrow stem cells into affected areas of the myocardium seems to be a promising treatment of ischemic cardiomyopathy. The Harvest BMAC contains the entire population of nuclear cells from bone marrow aspirates together with platelets. The presence of both platelets and additional granulocytes can have a positive effect on the neovascularisation potential of the resulting concentrate. Our assumption is that retrograde administration on non-selected BMAC via coronary sinus, due to the content of platelets and growth factors, might improve left ventricular function and parameters compared to standard HF therapy. Furthermore, it will be associated with improved exercise tolerance in the six-minute corridor walk test and an improvement in the life quality of patients without increasing the incidence of severe ventricular arrythmias. TRIAL REGISTRATION: (ClinicalTrials.gov; https://clinicaltrials.gov ; NCT03372954).

The rs1803274 polymorphism of the BCHE gene is associated with an increased risk of coronary in-stent restenosis.

BACKGROUND: We sought to identify gene polymorphisms that confer susceptibility to in-stent restenosis after coronary artery bare-metal stenting in a Central European population. METHODS: 160 controls without post-percutaneous coronary intervention in-stent restenosis were matched for age, sex, vessel diameter, and diabetes to 160 consecutive cases involving in-stent restenosis of the target lesion within 12 months. Using real time polymerase chain reaction and melting-curve analysis, we detected 13 single-nucleotide polymorphisms in 11 candidate genes - rs1803274 (BCHE gene), rs529038 (ROS1), rs1050450 (GPX1), rs1800849 (UCP3), rs17216473 (ALOX5AP), rs7412, rs429358 (ApoE), rs2228570 (VDR), rs7041, rs4588 (GC), rs1799986 (LRP1) and rs2228671 (LDLR). Multivariable logistic regression was used to test for associations. RESULTS: The rs1803274 polymorphism of BCHE was significantly associated with in-stent restenosis (OR 1.934; 95 % CI: 1.181-3.166; p = 0.009). No association was found with the other studied SNPs. CONCLUSIONS: The A allele of rs1803274 represents a risk factor for in-stent restenosis in Central European patients after percutaneous coronary intervention with bare-metal stent implantation.

Argon broad ion beam tomography in a cryogenic scanning electron microscope: a novel tool for the investigation of representative microstructures in sedimentary rocks containing pore fluid.

The contribution describes the implementation of a broad ion beam (BIB) polisher into a scanning electron microscope (SEM) functioning at cryogenic temperature (cryo). The whole system (BIB-cryo-SEM) provides a first generation of a novel multibeam electron microscope that combines broad ion beam with cryogenic facilities in a conventional SEM to produce large, high-quality cross-sections (up to 2 mm(2)) at cryogenic temperature to be imaged at the state-of-the-art SEM resolution. Cryogenic method allows detecting fluids in their natural environment and preserves samples against desiccation and dehydration, which may damage natural microstructures. The investigation of microstructures in the third dimension is enabled by serial cross-sectioning, providing broad ion beam tomography with slices down to 350 nm thick. The functionalities of the BIB-cryo-SEM are demonstrated by the investigation of rock salts (synthetic coarse-grained sodium chloride synthesized from halite-brine mush cold pressed at 150 MPa and 4.5 GPa, and natural rock salt mylonite from a salt glacier at Qom Kuh, central Iran). In addition, results from BIB-cryo-SEM on a gas shale and Boom Clay are also presented to show that the instrument is suitable for a large range of sedimentary rocks. For the first time, pore and grain fabrics of preserved host and reservoir rocks can be investigated at nm-scale range over a representative elementary area. In comparison with the complementary and overlapping performances of the BIB-SEM method with focused ion beam-SEM and X-ray tomography methods, the BIB cross-sectioning enables detailed insights about morphologies of pores at greater resolution than X-ray tomography and allows the production of large representative surfaces suitable for FIB-SEM investigations of a specific representative site within the BIB cross-section.

The effect of regular physical activity on the left ventricle systolic function in patients with chronic coronary artery disease.

The purpose of this study was to assess the influence of aerobic training on the left ventricular (LV) systolic function. Thirty patients with stable coronary artery disease, who had participated in the conducted 3-month physical training, were retrospectively divided into 2 cohorts. While patients in the cohort I (n=14) had continued training individually for 12 months, patients in the cohort II (n=16) had stopped training after finishing the conducted program. Rest and stress dobutamine/atropine echocardiography was performed in all patients before the training program and 1 year later. The peak systolic velocities of mitral annulus (Sa) were assessed by tissue Doppler imaging for individual LV walls. In addition, to determine global LV systolic longitudinal function, the four-site mean systolic velocity was calculated (Sa glob). According to the blood supply, left ventricular walls were divided into 5 groups: A- walls supplied by nonstenotic artery; B- walls supplied by coronary artery with stenosis ≤50 %; C- walls supplied by coronary artery with stenosis 51-70 %; D- walls with stenosis of supplying artery 71-99 %; and E- walls with totally occluded supplying artery. In global systolic function, the follow-up values of Sa glob in cohort I were improved by 0.23±0.36 as compared with baseline values at rest, and by 1.26±0.65 cm/s at the maximal load, while the values of Sa glob in cohort II were diminished by 0.53±0.22 (p=NS), and by 1.25±0.45 cm/s (p<0.05), respectively. Concerning the resting regional function, the only significant difference between cohorts in follow-up changes was found in walls E: 0.37±0.60 versus -1.76±0.40 cm/s (p<0.05). At the maximal load, the significant difference was found only in walls A (0.16±0.84 versus -2.67±0.87 cm/s; p<0.05). Patients with regular 12-month physical activity improved their global left ventricle systolic function mainly due to improvement of contractility in walls supplied by a totally occluded coronary artery.

[Basic information system of a stomatological department]. / Základní informcní systém stomatologického a oddelení.

The authors presents an account on a computer system by means of which it is possible to follow up therapeutic and preventive activities of a stomatological department. They describe the "Basic Information System" which has the following aim: to create a qualitatively new background for the evaluation and management of dental therapeutic and preventive care, to support dispensary care and to reduce administrative work to a minimum. An integral part of the information system is also an innovated "Daily working records of doctors".