Thromboembolic risk factors and predictors of left atrial appendage thrombosis in Far North patients with nonvalvular atrial fibrillation

Aim. To analyze thromboembolic risk factors and identify additional predictors of left atrial appendage (LAA) thrombosis, which are not included in the CHA2DS2VASc scale, in long-term Far North residents with nonvalvular atrial fibrillation (AF).Material and methods. The study included 162 patients (men, 108; women, 54; mean age, 55,3±8,7 years) with non-valvular AF, living in the Far North, and 684 patients (men, 408; women, 276; mean age, 56,9±9,3 years), living in the temperate latitudes, hospitalized for catheter ablation. All patients underwent transthoracic and transesophageal echocardiography. According to transesophageal echocardiography, Far North patients were divided into two groups: group 1 — 21 patients with LAA thrombosis, group 2 — 141 patients without LAA thrombosis.Results. Compared to patients living in the temperate latitudes, Far North patients were younger (p=0,021) and were more likely to have type 2 diabetes (14,2% vs 8,3%, p=0,022), class ³II obesity (29,6% vs 21,1%, p=0,019), persistent AF(47,5% vs 33,2%, p=0,0019), LAA thrombosis (13% vs 6,6%, p=0,006), and severe structural and functional cardiac abnormalities (biatrial and right ventricular enlargement, lower left ventricular ejection fraction). In Far North patients, using logistic regression, independent predictors of LAA thrombosis were identified: an increase in left ventricular mass index (odds ratio (OR), 1,029; 95% confidence interval (CI), 1,011-1,048; p=0,001), persistent AF (OR, 3,521; 95% CI, 1,050-11,800; p=0,041).Conclusion. In Far North patients with nonvalvular AF, scheduled for catheter ablation, compared with patients from temperate latitudes, with a similar profile of cardiovascular diseases at a younger age, type 2 diabetes, grade ³II obesity, persistent AF, and LAA thrombosis were more common. The presence of persistent AF and an increase in left ventricular mass index are independent predictors of LAA thrombosis in Far North patients with nonvalvular AF

Echocardiographic characteristics of COVID-19 pneumonia survivors three months after hospital discharge

Coronavirus disease 2019 (COVID-19) is an infectious disease that affects almost all organs and systems. The main target is the respiratory system, but cardiovascular involvement is also common. Today, it is relevant to study the effect of complicated COVID-19 course on the patient’s cardiovascular system after hospital discharge — in particular, echocardiographic parameters.Aim. To study the echocardiographic parameters of patients with COVID-19 pneumonia 3 months after discharge from the hospital.Material and methods. The study included 106 patients with documented COVID-19 pneumonia. Patients underwent a comprehensive examination during hospitalization and 3 months ± 2 weeks after hospital discharge. The mean age of participants was 47±16 years (from 19 to 84 years), while 49% were women.Results. Three months after discharge, the average body mass index of the subjects was 28,2±5,7 kg/m2. Obesity was noted in 37,1%, cardiovascular diseases — in 52%. According to echocardiography, the prevalence of right ventricular (RV) dilatation was 2,9%, a decrease in tricuspid annular plane systolic excursion (TAPSE) — 9,5%, grade ≥2 tricuspid regurgitation — 1,9%, pulmonary hypertension (pulmonary artery systolic pressure >36 mm Hg) — 3,8%. The mean value of RV global longitudinal myocardial strain (GLMS RV) and global longitudinal myocardial strain (GLES RV) was 19,6±4,5 and 20,6±4,6, respectively. We found moderate correlations between GLMS RV and blood flow time through the left ventricular outflow tract (OT) (r=-0,436), through the mitral valve (r=-0,390; both p<0,0001) and through the RVOT (r=-0,348; р=0,004), with cardiac index (CI) (r=0,316; p=0,009), as well as between GLES RV and blood flow time through the LVOT (r=-0,411; p<0,0001) and RVOT (r=-0,300; p=0,005), and with CI (r=0,302; p=0,004). At the same time, the correlation of GLES RV with RV fractional area change (FAC) was weak (r=-0,283; p=0,007), while there was no correlation with the TAPSE. In addition, correlation of GLMS RV with these parameters were not defined.Conclusion. Three months after COVID-19 pneumonia, RV strain parameters were shown to have stronger relationships with time characteristics of flows in LVOT and RVOT, as well as with CI, than with such generally accepted characteristics of RV function as FAC and TAPSE

Cutting Edge Geometry Effect on Plastic Deformation of Titanium Alloy

The paper presents experimental studies of ОТ4 titanium alloy machining with cutting edges of various geometry parameters. Experiments were performed at a low speed by the scheme of free cutting. Intensity of plastic shear strain was set for defining of cutting edge geometry effect on machining. Images of chip formed are shown. Estimation of strain magnitude was accomplished with digital image correlation method. Effect of rake angle and cutting edge angle has been studied. Depth of deformed layer and the area of the plastic strain is determine. Results showed that increasing the angle of the cutting edge inclination results in a change the mechanism of chip formation

Design and operation of a Rayleigh Ohnesorge Jetting Extensional Rheometer (ROJER) to study extensional properties of low viscosity polymer solutions

The Rayleigh Ohnesorge Jetting Extensional Rheometer (ROJER) enables measurement of very short relaxation times of low viscosity complex fluids such as those encountered in ink-jet printing and spraying applications. This paper focuses on the design and operation of the ROJER. The performance of two nozzle designs are compared using Newtonian fluids alongside a study using computational fluid dynamics (CFD). Subsequently a disposable nozzle is developed that overcomes issues of blockage and cleaning. The operability of this design is subject to a focused study where low viscosity polymer solutions are characterised. The test fluid materials are ethyl hydroxy-ethyl cellulose (EHEC) and poly ethylene oxide (PEO) mixed with water/glycerol solutions. Results obtained by the disposable nozzle are encouraging, paving the way for a more cost-efficient and robust ROJER setup

Antibiotic Dosing in Chronic Kidney Disease

Infectious process is an important cause of morbidity and mortality among patients with chronic kidney disease. Prescription of antibacterial drugs should take into account the pharmacokinetic parameters of the medicine and the individual characteristics of the patient. Adequate antibiotic dosing is crucial for positive treatment outcome and minimisation of side effects. The aim of the study was to analyse scientific literature on factors affecting the dosing of antibacterials in patients with chronic kidney disease. Since most antibacterial medicines are eliminated by the kidneys, a decrease in glomerular filtration rate or kidney function should be followed by the dose adjustment in order to prevent the medicine accumulation and reduce the risk of side effects. Antibiotic dosing in such patients should be accompanied by kidney function assessment and be adjusted to ensure effective and safe treatment, as well as prevention of bacterial resistance. The review provides data on the dosing of some antibiotic groups (beta-lactams, aminoglycosides, fluoroquinolones) at different creatinine clearance rates. Extrarenal excretion of medicines does not usually require the dose adjustment in patients with chronic kidney disease

Cardiovascular status and echocardiographic changes in survivors of COVID-19 pneumonia three months after hospital discharge

Coronavirus disease 2019 (COVID-19) affects the function of all organs and systems. Today, studying the effect of COVID-19 on cardiovascular system, including on echocardiographic characteristics, is relevant.Aim. To study the prevalence of symptoms, cardiovascular disease and changes in echocardiographic data in persons after documented COVID-19 pneumonia 3 months after discharge from the hospital.Material and methods. The study included 106 patients after documented COVID-19 pneumonia. The patients underwent a comprehensive examination during hospitalization and 3 months±2 weeks after discharge from the hospital. The mean age of participants was 47±16 years (19-84 years); 49% of subjects were women.Results. Three months after hospital discharge, the symptoms persisted in 86% of examined patients. There were significant echocardiographic changes as follows: a decrease in LV end-diastolic, end-systolic and stroke volume (113,8±26,8 ml vs 93,5±29,4 ml; 37,7±13,0 ml vs 31,3±14,2 ml; 77,2±17,8 ml vs 62,2±18,7 ml, respectively, p<0,001 for all). The right ventricular anteroposterior dimension and the pulmonary trunk diameter decreased over time (26,0 [24,0-29,3] mm vs 25,0 [23,0-27,0] mm, p=0,004; 21,7±3,6 mm vs 18,7±2,5 mm, p<0,001), the same as the pulmonary artery systolic pressure, estimated by tricuspid regurgitation gradient (28,0 [25,0-32,25] mm Hg vs 21,5 [17,0-25,0] mm Hg). The right atrial volume (42,0 [37,0-50,0] m><0,001), the same as the pulmonary artery systolic pressure, estimated by tricuspid regurgitation gradient (28,0 [25,0-32,25] mm Hg vs 21,5 [17,0-25,0] mm Hg). The right atrial volume (42,0 [37,0-50,0] ml vs 31,0 [22,0-36,5] ml, p<0,001) a><0,001) and maximum width (36,1±4,6 mm vs 34,5±6,5 mm, p=0,023) decreased, while the right atrial maximum length increased (46,7±6,8 mm vs 48,6±7,1 mm, p=0,021).Conclusion. In survivors of COVID-19 pneumonia three months after hospital discharge, complaints persisted in 86% of cases. Cardiovascular diseases were detected in 52% of participants, including hypertension in 48,1% and coronary artery disease in 15,1%. Compared with in-hospital data, the echocardiographic characteristics improved, which was expressed mainly in a decrease in right heart load

An IRAK1-PIN1 signalling axis drives intrinsic tumour resistance to radiation therapy

Drug-based strategies to overcome tumour resistance to radiotherapy (R-RT) remain limited by the single-agent toxicity of traditional radiosensitizers (for example, platinums) and a lack of targeted alternatives. In a screen for compounds that restore radiosensitivity in p53 mutant zebrafish while tolerated in non-irradiated wild-type animals, we identified the benzimidazole anthelmintic oxfendazole. Surprisingly, oxfendazole acts via the inhibition of IRAK1, a kinase thus far implicated in interleukin-1 receptor (IL-1R) and Toll-like receptor (TLR) immune responses. IRAK1 drives R-RT in a pathway involving IRAK4 and TRAF6 but not the IL-1R/TLR-IRAK adaptor MyD88. Rather than stimulating nuclear factor-κB, radiation-activated IRAK1 prevented apoptosis mediated by the PIDDosome complex (comprising PIDD, RAIDD and caspase-2). Countering this pathway with IRAK1 inhibitors suppressed R-RT in tumour models derived from cancers in which TP53 mutations predict R-RT. Moreover, IRAK1 inhibitors synergized with inhibitors of PIN1, a prolyl isomerase essential for IRAK1 activation in response to pathogens and, as shown here, in response to ionizing radiation. These data identify an IRAK1 radiation-response pathway as a rational chemoradiation therapy target

Individual quality of life: adaptive conjoint analysis as an alternative for direct weighting?

In the schedule for the evaluation of individual quality of life (SEIQoL) the weights for five individualized quality of life domains have been derived by judgment analysis and direct weighting (DW). We studied the feasibility and validity of adaptive conjoint analysis (ACA) as an alternative method to derive weights in 27 cancer patients and 20 patients with rheumatoid arthritis. Further, we assessed the convergence between direct weights and weights derived by ACA, and their correlation with global quality-of-life scores. All respondents finished the ACA task, but one in five respondents were upset about the ACA task. Further, the task was vulnerable to judgment ‘errors’, such as inconsistent answers. The agreement between the two weights was low. Both weighted index scores were strongly correlated to the unweighted index score. The relationships between the index score and scores on a visual analogue scale for global individual quality of life and global quality of life were similar whether or not the index score was calculated with DW weights, with ACA weights, or without using weights. We conclude that, because weights did not improve the correlation between the index score and global quality of life scores, it seems sufficient to use the unweighted index score as a measure for global individual quality of life

Comparative analysis of prospective study data of biochemical parameters of blood serum in patients with ischemic heart disease with the presence and absence of type 2 diabetes

Purpose: to conduct a prospective comparative analysis of laboratory parameters of the lipid profile, markers of the inflammatory response and functional activity of the endothelium in groups of patients with ischemic heart disease and coronary heart disease in combination with diabetes under condition of absence of significant lesion of coronary arteries. Determine a set of laboratory parameters that determine the likelihood of developing cardiovascular complications. Materials. According to the data of selective coronary angiography, patients without significant coronary stenosis were identified. Group 1 - patients with IHD (n = 29), 2nd group - CHD with type 2 diabetes mellitus (DM), (n = 39). The study of laboratory parameters of blood serum was performed against the background of standard therapy before and after 12 ± 2.4 months of follow-up. Results. In both groups, the excess of the reference values of the parameters of the lipid profile and the markers of vascular inflammation was revealed. In the 2nd group the levels of total cholesterol, LDL, Apo-B, high-sensitivity C-reactive protein, homocysteine, interleukin 1 beta are significantly higher than in the 1st group. Prospective observation with standard therapy demonstrated the presence of negative dynamics of the lipid spectrum, the preservation of a prolonged response to the activation of the inflammatory reaction, which was indicated by interleukin 1β, homocysteine, matrix metalloproteinase 9 and the persistence of disorganization of the endothelin system in both groups of patients. Conclusion: The results of the study indicate the preservation of a prolonged inflammatory response in the endothelium in both the 1 st and 2 nd group of patients, which can become a provoking factor for the destabilization of the atherosclerotic process. The increased risk of atherothrombosis in both groups of patients requires a strict control of the effectiveness of the therapy in the conditions of real clinical practice.Цель: провести сравнительный анализ лабораторных параметров липидного профиля, маркеров воспалительной реакции и функциональной активности эндотелия в группах больных ИБС и ИБС в сочетании с СД при условии отсутствия значимого поражения коронарных артерий по данным коронароангиографии. Выделить комплекс лабораторных параметров, определяющих вероятность развития сердечно-сосудистых осложнений. Материалы: Согласно данным селективной коронарной ангиографии выделены пациенты без значимого коронарного стеноза. 1-я группа - больные ИБС (n=29), 2-я группа - ИБС с сахарным диабетом типа 2 (СД), (n=39). Исследование лабораторных параметров сыворотки крови проводилось на фоне стандартной терапии до и через 12±2,4 месяцев наблюдения. Результаты: В обеих группах выявлено превышение референсных значений параметров липидного профиля и маркеров сосудистого воспаления. Во 2-ой группе достоверно выше уровни общего холестерина, ЛПНП, Апо-В, высокочувствительного С-реактивный белка, гомоцистеина, интерлейкина 1 β по сравнению с 1-ой группой. Проспективное наблюдение на фоне стандартной терапии продемонстрировало наличие негативной динамики липидного спектра, сохранение пролонгированного ответа активации воспалительной реакции, индикатором которой явились интерлейкин 1 β, гомоцистеин, матриксная металлопротеиназа 9 и сохранение дезорганизации эндотелиновой системы в обеих группах больных. Заключение: Результаты исследования свидетельствует о сохранении как в 1-ой, так и во 2-ой группе пациентов пролонгированного воспалительного ответа в эндотелии, что может стать провоцирующим фактором для дестабилизации атеросклеротического процесса. Повышенный риск развития атеротромбоза в обеих группах пациентов требует жесткого контроля эффективности проводимой терапии в условиях реальной клинической практики