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Cardiovascular Therapy and Prevention

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Vol 19, No 6 (2020)
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ARTERIAL HYPERTENSION

2287 722
Abstract

Aim. To study the association  of ultrasound characteristics of carotid atherosclerotic  plaques  (ASPs) with the concentration  of tumor necrosis factor-alpha  (TNFα) and interleukin-10 (IL-10) in patients  with essential hypertension.

Material and methods. The study included 117 patients  (men, 75; women, 42) with essential hypertension aged 40 to 75 years (mean age, 55,8±7,5 years). All patients  underwent anthropometric  measurements (height, weight, body mass index, waist circumference),  assessment of blood pressure  and heart rate, blood tests (levels of glucose, creatinine with the calculation of glomerular filtration rate using CKD-EPI equation, lipid profile), duplex ultrasound of the carotid arteries.  Also, the blood concentration  of TNFα and IL-10 by the enzyme-linked immunosorbent assay using CYTOKIN-STIMUL-BEST (Novosibirsk,Russia) kit was determined.

Results.  According to the  results  of carotid  duplex ultrasound,  3 groups of patients  were identified. Group 1 included 48 patients  with homogeneous hyperechoic ASPs; group 2 — 56 patients with dominant hyperechoic  ASPs (>50% of areas);  group 3 — 13 patients  with anechoic, unstable,  low-density ASPs. TNFα concentration  in group 3 patients, amounting to 10,51±2.23 pg/ml, was significantly higher than in patients of group 1 (7,26±0,64 pg/ml (p<0,001)) and group 2 (8,93±0,98 pg/ml (p<0,001)).  Similar results were obtained for IL-10. The logistic regression  showed that the TNFα concentration  is an independent  factor associated with unstable  ASsP (relative risk, 2,72; 95% confidence interval 1,44-5,15  (p<0,02)). It was also revealed that TNFα >10 pg/ml increased the risk of ASP instability by ~8 times.

Conclusion.  An increase  in TNFα >10 pg/ml with a high specificity (95%) was associated with vulnerable unstable carotid ASPs.

2707 768
Abstract

Obesity is a progressing epidemic, the prevalence of which has doubled over the past 30 years. The distribution of adipose tissue is an important factor in predicting the risk of cardiovascular events. The most significant inflammatory activity is characteristic of epicardial adipose tissue (EAT), the role of which in the development of atrial fibrillation (AF) remains a subject of discussion.

Aim. To study the effect of EAT size on the development of AF in hypertensive (HTN) patients.

Material and methods. The study included 95 patients with HTN aged 38-72 years (mean age, 61,5±1,8 years), including 45 patients with paroxysmal AF (group I) and 50 patients in the comparison group (group II). In order to assess the severity of visceral obesity, all patients underwent a general examination and echocardiography. To determine the EAT volume, cardiac multislice computed tomography was performed.

Results. Echocardiography revealed that the EAT thickness was significantly greater in hypertensive patients with paroxysmal AF than in the comparison group: 11,6±0,8 and 8,6±0,4 mm, respectively (p<0,001). According to cardiac multislice computed tomography, a significant increase in EAT volume was revealed in patients of group I (4,6±0,4 ml) compared with group II (3,5±0,25 ml) (p=0,019). In hypertensive patients with paroxysmal AF, a positive moderate relationship between the EAT volume and left atrial volume was revealed (r=0,7, p=0,022). Multivariate analysis showed that in hypertensive patients, EAT thickness >10 mm and volume >6 ml can serve as integral markers of the onset of paroxysmal AF.

Conclusion. Integral markers of AF in hypertensive patients are an increase in the EAT thickness >10 mm (odds ratio, 4,1; 95% confidence interval, 1,1-5,6) and volume >6 ml (odds ratio 3,7; 95%, confidence interval 1,0-4,2).

CORONARY HEART DISEASE

2546 586
Abstract

Aim. Using PC-based medical information technologies, analyze and evaluate inpatient and outpatient care for patients with coronary artery disease (CAD) with the development and testing of machine learning algorithms.

Material and methods. In 2017, 586 patients with myocardial infarction (MI) under the age of 70 years were identified according to the electronic database of the Uniform State Health Information System. Of these, 349 patients received reperfusion therapy, and 237 did not. In all 586 patients, lethal outcomes, hospital and ICU length of stay were determined. In 342 out of 586 patients after MI, using PC-based medical data, number of completed outpatient treatment cases, ambulance calls, and emergency hospitalizations for CAD were identified. According to the Uniform State Health Information System, the dynamics of heart failure (HF) and angina class was determined in patients at the end of the year.

Results. In patients with reperfusion therapy, in comparison with MI patients without it, significantly shorter hospital (13,17±0,17 vs 15,35±0,46 days) and ICU (1,73±0,06 vs 2,56±0,29 days) length of stay, as well as significantly lower (2,9 times) mortality. In the post-infarction period, there were no differences between these groups in the number of completed cases of outpatient CAD treatment and ambulance calls due to CAD. The number of emergency hospitalizations was significantly (1,4 times) more in the group of patients who did not receive reperfusion therapy. In both groups of patients, there was a positive dynamic in angina class and HF stage.

Conclusion. PC-based personalized medical services are informative material for assessing the results of inpatient and outpatient care for patients with CAD. It is rational to consider assessing deaths, hospital and ICU length of stay, ambulance calls, emergency hospitalizations, angina class and HF stage changes after MI as an algorithm for machine learning and computer analysis of the treatment results in patients with CAD.
2697 1773
Abstract

The main reason  for incomplete myocardial revascularization is the presence of chronic coronary total occlusion (CTO), which is detected in every fourth patient during coronary angiography. At the same time, a generally accepted approach  to the treatment of CTO has not yet been developed.

Aim. To assess the rationale of complete myocardial revascularization in patients with multivessel coronary artery disease  (CAD) with chronic total occlusion and high surgical risk.

Material and methods. This retrospective,  open-label,  non-randomized clinical trial was carried out included 180 patients multivessel CAD and CTO. The patients  underwent endovascular  surgery for complete myocardial revascularization. Depending on the success of surgery, the patients were divided into groups of complete and incomplete myocardial revascularization. Endpoints were death, acute coronary syndrome, re-revascularization after 1-year follow-up. Left ventricular (LV) contractility and clinical status  of patients  in the study groups after 1 year of observation was assessed.

Results. The median follow-up was 12,1 months. The successful  rate of revascularization was 79,4%. The incidence of main composite endpoint in the group of complete myocardial revascularization was 5,59%, while in the group of incomplete revascularizations — 21,6% (p=0,005).

Conclusion. The study showed  that low incidence  of intraoperative complications and a high successful  rate of revascularization are characteristic of complete myocardial revascularization in patients at high surgical risk with multivessel CAD and CTO. Complete myocardial revascularization leads to a significant decrease in the incidence of major coronary events.

CHRONIC HEART FAILURE

2464 802
Abstract

Aim. To study the effects  of spironolactone  and eplerenone on left ventricular diastolic function and neurohumoral factors in patients with heart failure (HF).

Material and methods. We examined 131 patients  with coronary artery disease  and NYHA class  I-III HF. Patients  were randomized  into groups depending  on HF class: class I (n=31), class II (n=51) and class III (n=49).

Results. The study revealed that the clinical course  of HF and LV diastolic dysfunction are associated with an increased  level of neurohormones  and are characterized by significantly high levels of aldosterone  and norepinephrine  in patients  with a restrictiveLV diastolic dysfunction. A correlation was found between  the level of neurohormones  (aldosterone  and norepinephrine)  and heart  remodeling parameters:  an inverse correlation with an ejection fraction (r=-0,68, r=-0,61,  respectively) and a direct correlation with LV  end-diastolic volume (r=0,58, r=0,66, respectively). Long-term treatment  with spironolactone  and eplerenone had a positive effect, reducing the level of mentioned neurohormones. In patients with class II HF, both drugs had a positive effect on the level of aldosterone  and norepinephrine, reducing them by 26,6% and 20,2% in the spironolactone  group and by 28,4% and  24,6% in the eplerenone group,  respectively.  In patients with class  III  HF, the decrease in aldosterone  level was more pronounced  in those taking eplerenone than spironolactone:  32,1% vs 20,2%, respectively.

Conclusion. In patients  with HF, combination therapy with the inclusion of spironolactone  significantly reduced  the level of neurohormones mainly in patients with class II HF and, to a lesser extent, in those with class III HF. This suggests that combination therapy with spironolactone is less effective than with eplerenone in relation to neurohormones’  levels. 

ПРИВЕРЖЕННОСТЬ ЛЕЧЕНИЮ

2665 684
Abstract

Aim. To study the quantitative parameters of adherence to lifestyle modification, medical support,  and therapy in patients with cardiovascular diseases (CVD).

Material and methods. This cross-sectional study included 683 respondents: 168 patients  with hypertension  (HTN); 196 patients  with stable angina; 141 patients with atrial fibrillation (AF); 178 patients with heart failure (HF). We used N. A. Nikolaev  questionnaire  for adherence assessment. For all adherence parameters, the level ≤75% was regarded as insufficient. The study was carried out in accordance with Good Clinical Practice and Declaration ofHelsinki. The study protocol was approved by the Ethics Committees of all participating clinical centers. All patients signed written informed consent.

Results. Approximately 1/3 of respondents agreed  to receive therapy. The adherence level was >75%. Patients with angina and AF were more likely to receive therapy. It turned out that that approximately 2/3 of patients  were not ready for medical support.  Patients  with angina were less ready for medical support, while those with HTN and HF hadhigher values of adherence. Adherence to lifestyle modification was owest among analyzed parameters. Only 18,5% of hypertensive patients, 25,5% of patients with angina, 26,2% of AF patients and 23,1% of patients with HF were ready to change the lifestyle.

Conclusion. The study revealed a significant number (~2/3) of CVD patients with insufficient adherence, which specifies the need  to assess the effectiveness  of therapy and course of the disease  in conditions of low adherence and to develop individualized therapeutic strategies.

ФАКТОРЫ РИСКА

2724 844
Abstract

Aim. To study the associations of cardiovascular (CVR) and fracture risks using electronic versions of the SCORE (Systematic Coronary Risk Evaluation) and FRAX (Fracture Risk Assessment Tool) scores in women without clinical manifestations of atherosclerosis.

Material and methods. This cross-sectional study included 200 female outpatients aged 45-69. All patients signed informed consent. The 10-year CVR was assessed using the high-risk SCORE charts. The 10-year risk of major osteoporotic fractures (MOF) and hip fractures was assessed using the Russian FRAX model. Bone mineral density (BMD) of the bones of the spine, femoral neck and proximal femur was measured using dual-energy X-ray absorptiometry. Statistical analysis was carried out using the Statistica.12.0, SPSS Statistics 26.0 and Excel 2016 software packages.

Results. L ow CVR (SCORЕ <1%) was detected in 72 (36%) women, moderate (SCORЕ ≥1% and <5%) – in 124 (62%), and high (SCORЕ ≥ 5% and <10%) – in 4 (2%). Depending on the CVR degree, the patients were divided into 2 groups: group I – patients with SCORE <1 (low risk); group II – SCORE ≥1 (increased risk). Since bone mass is not the only but the main risk factor for fractures, the association between BMD and CVR was assessed. The SCORE ≥1 was identified in 128 women, of whom osteoporosis was diagnosed in 33 (26%), osteopenia – in 43 (34%) patients. The combination of increased CVR and absolute risk (AR) of major MOF was noted in 7 (5,5%) people. An inverse correlation was noted between CVR and BMD of the proximal femur and femoral neck. A positive correlation was also demonstrated between CVR (SCORE) and AR of MOFI and femoral neck fractures (FRAX). Multivariate regression (adjusted for age, body mass index, hypercholesterolemia) confirmed the reliability of a negative relationship between CVR and BMD of the lumbar vertebra.

Conclusion. The data obtained confirm the hypothesis of multifaceted relationships of cardiovascular diseases caused by atherosclerosis with osteoporosis, manifested both at the clinical and preclinical levels, and at the level of risk formation, which makes it possible to recommend the cross-use of CVR and fracture AR scores for early primary prevention. This strategy will contribute to the early detection of combined pathology and timely preventive measures.
2524 704
Abstract

Aim. To study the main risk factors and signs of connective tissue dysplasia (CTD) in young people according  to quartile analysis of cardioankle vascular index (CAVI).

Material and methods. The study involved 243 young people (men, 81; women, 162) aged 18-25 years. All subjects were divided into quartile groups  depending  on CAVI on both sides,  or CAVI-R and CAVI-L, determined  using the VaSera-1500 system (Fucuda Denshia,Japan). According to the latest guidelines, the 4th  quartile of this distribution among persons  of the same sex and age corresponds to early vascular aging (EVA) syndrome.  The 1st  quartile corresponds to favorable vascular aging. We analyzed the main RFs and CTD signs in each  of the 4 CAVI quartiles. Data processing  was carried out using the Statistica 10.0 software package (StatSoft Inc,USA).

Results. The minimum and maximum CAVI in the sample were 3,2 and 7,9. The overwhelming majority of studied risk factors in both sexes were not associated with the stiffness. Only body mass and body mass index increasedwith a decrease in vascular stiffness and vice versa. The average number of external stigmas of dysembryogenesis in young people increased from the 1st  to the 4th  CAVI quartile, with significant differences in the extreme groups. Such CTD signs as a carpal tunnel syndrome and thumb sign also significantly differed between the 1st  and 4th quartiles.

Conclusion. The presented results can be used for prevention among young people to form more individualized programs taking into account a comprehensive assessment of vascular aging phenotype and the level of external stigmatization of each young person.

OPINION ON A PROBLEM

2693 1793
Abstract

The article is devoted to the influence of sympathetic  nervous system (SNS) on the cardiovascular  system.  Influence of SNS activity on the blood pressure  level and the pathogenesis of hypertension  development, as well as the effect of SNS on many biochemical and metabolic parameters playing a key role in the development  of metabolic syndrome and hypertension  are considered. Possible mechanisms  of action of various methods that reduce  the SNS activity, restore  the function of autonomic nervous system  and normalize the cardiovascular system and blood pressure  are considered.

CLINICAL TRIALS AND REGISTRIES

2739 1150
Abstract

Aim. To assess the secondary prevention in Russian patients with coronary artery disease in the long-term period after acute myocardial infarction, acute coronary syndrome (ACS), percutaneous coronary intervention and/or coronary artery bypass grafting, obtained in the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE V) survey in comparison with the general population of the study.

Material and methods. EUROASPIRE V is a cross-sectional study with 27 countries, including Russia, which involved patients with ACS or indications for myocardial revascularization. At participating centers, patients admitted to hospital due to ACS or for percutaneous coronary intervention or coronary artery bypass grafting were identified. After 6 months and <2 years after discharge, patients were examined.

Results. In total, 699 patients were identified in Russia, 399 of which visit an interview (women, 27,1%; mean age, 62,8±8,7 years). In the general population of the study, 16,208 patients were identified, 8,261 of which were interviewed (women, 25,8%; mean age, 63,6±9.6 years). At the time of the interview, 18,5% of Russian patients continued to smoke (16,8% in the general study population), the prevalence of overweight or obesity – 85,4 and 81,7%, abdominal obesity – 60,4 and 58,5%, diabetes – 21,9 and 29,3% of patients, respectively. In 19,7 and 16,4% of patients, respectively, diabetes was first diagnosed with a glucose tolerance test in the study. The target glycated hemoglobin was achieved in 47,1 and 54,4%, blood pressure – in 64,0 and 53,7%, low-density lipoprotein cholesterol – in 27,6 and 29,0% of patients, respectively.

Conclusion. There were significant differences between the Russian cohort and the general study population. Some key secondary prevention parameters were more favorable in the Russian cohort, and some parameters – in the general group. In both compared populations, significant reserves are retained for further optimization.
2727 1075
Abstract

Aim. To characterize patients admitted to hospital with suspected or documented COVID-19 infection and community-acquired pneumonia (CAP) and to assess the prevalence of concomitant cardiovascular, non-cardiac diseases, prehospital cardiovascular therapy and outcomes of in-hospital treatment.

Material and methods. The TARGET-VIP registry includes patients admitted to the N. I. Pirogov National Medical and Surgical Center with suspected or documented COVID-19 infection and/or CAP for the period from April 6, 2020 to July 2, 2020. COVID-19 infection was diagnosed using polymerase chain reaction (PCR) tests and chest computed tomography (CT). Comorbid conditions and pre-hospital therapy were assessed.

Results. A total of 1,130 patients were included in the registry (mean age, 57,5±12,8 years; men, 579 (51,2%)). Using PCR test, COVID-19 infection was established in 686 (60,7%) patients; using chest CT − 334 (29,6%) patients. The most numerous were the group with a combination of COVID-19 and CAP (n=662; 58,6%) and the group with CAP without positive PCR (n=402; 35,6%). The group of patients with COVID-19 without CAP was the smallest (n=24; 2,1%); in 3,7% of patients (n=42), CAP was not confirmed and PCR were negative. The proportion of people with cardiovascular diseases (CVD) according to the survey, in comparison with data of medical records, was higher by 2% (52,2 vs 50,2%); the proportion of persons with chronic non-cardiac diseases − higher by 6,7% (50,8 vs 44,1%). Among patients with CVD (n=598), compared with patients without CVD (n=532), following diseases was diagnosed significantly more often: diabetes (odds ratio (OR), 5,66; 95% confidence interval (CI), 3,52-9,12), respiratory disease  (OR, 2.,7; 95% CI, 1,43-4,27), chronic kidney disease (OR, 3,32; 95% CI, 1,97-5,59), obesity (OR, 15,35; 95% CI, 6,62-35,59). Hospital mortality was 4,2% and significantly differs (4,7 times) in patients with and without COVID-19 according to PCR (6,6 vs 1,4%, p=0,0001), including among patients with CAP and positive or negative PCR (6,0 vs 1,2%, p=0,0002).

Conclusion. COVID-19 infection was diagnosed in 60,7% of patients according to PCR and in 90,3% of patients according to the combination of PCR and chest CT. Among patients with CVD, the proportion of people with chronic noncardiac diseases was significantly higher (regardless of age and sex), in particular, with diabetes, chronic kidney disease and obesity. Questionnaires provided important data on the history of noncommunicable diseases and prehospital cardiovascular therapy. The mortality rate of patients with documented COVID-19 infection was 4,7 times higher than with undocumented.

CLINICAL CASE

2418 522
Abstract

The article discusses a case of episodes of asymptomatic ST-T depression during exercise in a 37-year-old patient with complaints of irregular heartbeat, tachycardia up to 100 bpm, not related to exercise. According to contrast-enhanced multislice computed tomography, in the middle third, a muscle bridge with stenosis of up to 30% was found. The diagnosis was made: Congenital coronary artery anomaly: transmyocardial muscular bridge of the middle third of left anterior descending artery with stenosis up to 30%. Class 1 silent myocardial ischemia. Stage 0, class 0 chronic heart failure. Using non-invasive coronary imaging, it was possible to identify the cause of transient ST-T depression and to choose the appropriate therapy.

REVIEW ARTICLES

2632 1321
Abstract

The pathophysiology of obesity is complex and includes changes in eating behavior, genetic, epigenetic, environmental factors, and much more. To date, ~40 genetic polymorphisms are associated with obesity and fat distribution. However, since these options do not fully explain the inheritance of obesity, other options, such as epigenetic changes, need to be considered. Epigenetic modifications affect gene expression without changing the deoxyribonucleic acid sequence. In addition, environmental exposure during critical periods of development can affect the epigenetic tags and lead to obesity. A deeper understanding of the epigenetic mechanisms underlying obesity can aid in prevention based on lifestyle changes. This review focuses on the role of epigenetic modifications in the development of obesity and related conditions.

2649 768
Abstract

The review discusses the participation of patients with coronary artery disease after acute myocardial infarction and revascularization surgeries in cardiac rehabilitation (CR) and secondary prevention programs. The problems of patients not being included in rehabilitation programs and the reasons for low adherence to these programs are considered. The contribution of non-drug therapy to achievement of CR and secondary prevention goals is discussed. Various strategies are proposed for involving and increasing adherence of patients to CR programs.

2460 2663
Abstract

The six-minute walk test (6MWT) is a well-known exercise test used in medical practice to assess the functional status of patients with various chronic cardiovascular and respiratory diseases. The results of modern research describe new potential of 6MWT, which allow a more accurate interpretation and predict the course of diseases. Heart failure (HF) is the outcome of many structural and functional heart disorders. To improve the prognosis of patients with HF, early diagnosis, appropriate therapy and effective control of the disease course are important components. This review describes the diagnostic, prognostic and therapeutic potential of 6MWT in patients with HF.

2647 1007
Abstract

Current prophylactic actions prevent or significantly delay the majority of cardiovascular diseases (CVD). Various factors are interconnected and affect a person throughout his life, determining the risk of CVD. This indicates the need for preventive measures at all stages of life and even before birth. The beneficial effects of CVD prevention are realized through various genetic, epigenetic and metabolic mechanisms. Due to the fact that many risk factors for CVD have a cumulative effect, the introduction of preventive measures from the earliest life stages will be most effective. The purpose of the article is to consider various aspects of CVD prevention in the preconceptional, prenatal and infant periods.

BIOBANKING

2710 1063
Abstract

To carry out research projects, clinical trials and other studies in the field of personalized medicine, it is necessary to have collections of high-quality biological samples of various types. With the development of biomedical technologies, the need for large collections of biological samples will grow every year, which necessitates the creation of various biobanks for standardized collection, storage and distribution of such samples. One of the goals of the National Association of Biobanks and Biobanking Specialists is the development of a network of Russian biobanks interacting with each other at various levels, as well as the development and implementation of organizational and legal tools for its regulation. It is required not only to standardize the access and exchange of biological samples and data, but also to create a unified terminology that will be used by biobanks throughout Russia. The main aim is to create an accurate, professional and legally correct tool containing information accessible and understandable to a wide range of researchers.

2736 1147
Abstract

Aim. To study the effect of standard serum long-term storage at -70О C and with a single thawing on the biochemical markers by comparing the results of studies carried out in 2013-2014 and 2020.

Material and methods. The material was the blood serum of participants in the ESSE-RF study, which was stored in a specialized biobank from 2013-2014 at -70О C either continuously (n=149) or with a single thawing (n=20). Initially and in 2020, the quantitative determination of serum biochemical parameters was carried out using same equipment and standard techniques.

Results. Long-term storage at -70О C led to mild, but significant changes in almost all analyzed parameters: low density lipoprotein cholesterol (LDL-C) and apolipoprotein A1 levels decreased; levels of highdensity lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein B, glucose, and high-sensitivity C-reactive protein increased. Insulin and thyroid-stimulating hormone levels did not change during storage. The revealed strong positive relationships between the initial concentrations and those measured in 2020 in samples that were stored continuously indicate the relevance of such storage. In samples with single thawing, changes in most parameters were more pronounced.

Conclusion. The results of a prospective cohort study aimed at studying the stability of human serum samples during storage indicate the validity of long-term storage at -70О C without thawing. Freeze-thawing cycle of samples (even once) is unacceptable, since it leads to a pronounced LDL-C decrease. Given the fact that it is the LDL-C levels that is the target of lipid-lowering therapy, continuous low-temperature (not >-70О C) storage of blood serum samples is recommended.

2708 680
Abstract

Aim. To create a collection of samples from women at different stages of pregnancy to search for early biomarkers of preterm birth.

Material and methods. In order to standardize the sample collection, standard operation procedures have been developed with a step-by-step protocol for each research member at the clinical (collection of medical data and biological material) and laboratory (transportation, sample preparation, storage, quality control) stages.

Results. As of October 1, 2020, the collection includes peripheral blood samples from 182 women. Whole blood, serum, plasma, buffy coat and urine were collected during pregnancy, and placenta and umbilical cord blood samples — during labor. Clinical and medical history data was obtained about each pregnant woman, which includes data on the woman’s health status, the course and outcome of pregnancy. An electronic catalog has been created with information on samples (data on clinical characteristics and the number of aliquots of each sample type). The quality control (assessment of DNA and microRNA) was carried out, which showed the compliance of the obtained samples with the quality criteria and the preservation of initial characteristics during long-term storage. On the basis of collection, a study has begun to assess the level of microRNA expression in various types of biomaterial, in order to search for early biomarkers of premature birth.

Conclusion. The creation of a collection of samples from pregnant women is a significant groundwork for future fundamental and applied research in various fields of biomedicine. This collection may provide an in-depth study of the pathogenesis of various pregnancy complications and the development of new methods for their diagnosis and treatment.-

2732 912
Abstract

One of the tasks of population-based biobanks is to determine the frequencies of clinically relevant genetic polymorphisms in the population. The population of Russia is very heterogeneous both ethnically and genetically. Therefore, the frequencies of genetic markers are in demand not in one sample, but in a series of samples reflecting the heterogeneity of the gene pool of different peoples and regions.

Aim. To divide the population of Russia and neighboring countries into population groups meeting certain conditions, as well as having a representative sample in existing data and biobanks.

Material and methods. We developed a method for combining populations into larger groups with maintaining intragroup homogeneity based on the principal components analysis with K-means clustering, followed by refinement of clustering for higher homogeneity and a more equal distribution of group sizes using FST distances. The technology has been adjusted using the example of the Biobank of Northern Eurasia. Therefore, the material was the genome-wide data on 4.5 million genetic markers for 1,883 samples representing 247 populations of Russia and neighboring countries from this biobank. The developed approach, the resulting set of populations and related map can be applied for other collections of biomaterials from Russian populations.

Results. Application of this approach made it possible to divide the entire population of Russia and neighboring countries into 29 ethnogeographic groups, characterized by relative genetic homogeneity. This set of populations is recommended as a baseline for population screenings to identify the frequency of any genetic markers among the population of Russia. A map has been constructed showing the division of population into 29 ethnogeographic areas.

Conclusion. On the basis of a reliable genome-wide data, the zoning of gene pool of the Russian population was carried out. We identified ethnogeographic groups with intergroup contrasting allele frequencies, but at the same time with relatively homogeneous intragroup parameters. The resulting map and register of groups can be used in population genetic, medical genetic and pharmacogenetic studies.

2726 2375
Abstract

Aim. To study the effect of the shelf life of frozen whole blood samples in a biobank on the amount of released deoxyribonucleic acid (DNA).

Material and methods. The study included whole blood samples placed in tubes with the anticoagulant EDTA (ethylenediaminetetraacetic acid at a concentration of 1,8 mg/ml) from participants in the epidemiological study ESSE-RF-1 and ESSE-RF-2 and cohort studies conducted at the National Medical Research Center for Therapy and Preventive Medicine. The samples were stored in the biobank of the National Medical Research Center for Therapy and Preventive Medicine at temperature from -22О C to -32О C. The shelf life from blood collection to DNA extraction ranged from several weeks to 11 years. DNA was extracted using QIAamp DNA Blood Mini Kit (250) and 96 Blood Kit (Qiagen, Germany). Statistical analysis was performed using the R 3.6.1 software. To analyze the association of blood storage time with the logarithm of DNA concentration, a linear regression was used.

Results. The analysis included data on the DNA concentration of 5405 samples. Multivariate regression showed that the blood shelf life was significantly associated with a decrease in concentration by 3,92% (3,16-4,68) for each year of storage (p <0,0001). For 509 samples, the DNA concentration was measured twice, immediately after isolation and after 4,5 years of DNA storage at -32О C. During storage, the concentration of DNA increased by an average of 2% (p=0,046).

Conclusion. Long-term storage of whole blood samples at temperature from -22О C to -32О C is associated with a decrease in the DNA yield. Long-term storage of the isolated DNA at a temperature of -32О C is not associated with a decrease in its concentration.

2741 533
Abstract

Aim. To present the main results and changes in the work of the biobank of the National Medical Research Center of Oncology during the pandemic of coronavirus disease 2019 (COVID-19).

Material and methods. The paper presents a dynamic analysis of the delivery of fresh frozen biological samples from operated patients for three quarters of 2019 and 2020, as well as considers possible ways to implement research projects to collect and deposit materials for the biobank within the COVID-19 pandemic. The work included persons over 18 years old, with primary gastrointestinal cancers, who, upon hospitalization, gave informed consent to transfer biological material to

the biobank. One of the inclusion criteria was the presence of a negative nasopharyngeal swabs tested for SARS-CoV-2 by the polymerase chain reaction. Data calculation and comparative analysis of the results was carried out using the Microsoft Office Excel software package.

Results. It was revealed that in the first quarter of 2019, 34% of biological samples were received from the total amount for the year, while in 2020 — 50%; in the second quarter of 2019 — 35%. The second quarter of 2020 was characterized by change in the schedule of work of institutions due to the COVID-19 pandemic, which led to a 56% decrease in the number of samples compared to the same period in 2019 and amounted to 14% of material collected for the three quarters of2020. In the third quarter of 2020, the flow was restored and amounted to 65 patients, which corresponds to 36% of material collected in this year and is more than in 2019 by 23%.

Conclusion. a critical decrease in the deposited material in the second quarter of 2020 indicated the need to adapt the current biobanking rules inRussia in general and the studied biobank in particular. Possible adaptation ways may consist in the creation of joint projects between groups of scientists from different organizations, taking into account the requirements of information and biological safety. This problem and ways to solve it were widely discussed at international and Russian platforms, including the 4th meeting of the National Association of Biobanks and Biobanking Specialists, dedicated to the organization of biobanking during the COVID-19 pandemic.

2729 716
Abstract

Aim. Using a collection of samples from the biobank ofCityHospital № 40 ofSt. Petersburg, to study the cytokine profile in patients with coronavirus disease 2019 (COVID-19) and sepsis, in comparison with patients with abdominal inflammation and septicemia.

Material and methods. The study included serum samples from 181 patients with sepsis and COVID-19 (127 patients with a diagnosis confirmed by polymerase chain reaction (PCR); 54 patients with a negative PCR test, but with a characteristic computed tomographic lung performance) and 47 patients with abdominal sepsis. The content of cytokines was determined using a multiplex immunofluorescence analysis based on the Luminex xMAP technology using the HCYTOMAG60K panel — a soluble CD40 ligand (sCD40L), interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNFα), vascular endothelial growth factor (VEGF). Other laboratory parameters (C-reactive protein (CRP), ferritin, procalcitonin) were taken from patient records. Normality of distribution was assessed by the Shapiro-Wilk test. To compare groups, the Mann-Whitney test for independent samples, Wilcoxon test for dependent samples, and the Kruskal-Wallis test with Bonferroni correction for multiple comparisons were used.

Results. In patients with sepsis and COVID-19 infection, no differences in the concentrations of cytokines, ferritin and CRP were found between the groups with detected and not detected virus by PCR test. Based on this, this group was considered homogeneous when studying the cytokine profile. It was shown that in patients with sepsis and COVID-19, significantly higher levels of sCD40L (p<0,0001) and VEGF (p=0,037) and relatively low levels of CRP (p<0,0001), IL-6 (p<0,0001), IL-8 (p<0,0001), TNFα (p<0,00058).

Conclusion. These results indicate that sepsis in patients with COVID-19 courses with less elevation in inflammatory cytokine than in abdominal sepsis. At the same time, a critically high level of sCD40L indicates the significant endothelial damage.

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Abstract

The advances of biomedicine include the new technologies, diagnosis and treatment techniques, as well as the practical use of new types of biological targets, in particular, nucleic acids. Genomic deoxyribonucleic acid (DNA), extracellular DNA (exDNA) and microbiome DNA obtained from different types of samples (tissues, blood and its derivatives, feces, etc.) are used as objects of genetic research. The use of new technologies for DNA analysis required the development of standardized methods for processing biological samples in order to obtain high-quality DNA samples. The research uses various methods for collecting, preparing samples and storing various DNA-containing biomaterials and isolated DNA, as well as methods for assessing the quality of samples and biobank standards. It is obvious that the use of uniform standards will allow large-scale genetic research on the basis of biobanks and research laboratories. Specialists from professional organizations such as International Society for Biological and Environmental Repositories (ISBER), Biobanking and BioMolecular Resources Research Infrastructure-European Research Infrastructure Consortium (BBMRI-ERIC), European, Middle Eastern & African Society for Biopreservationa and Biobanking (ESBB) and the Russian National Association of Biobanks and Biobanking Professionals.

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Abstract

Cardiovascular diseases, along with cancer, are the leading causes of death worldwide. Although modern pharmacological treatment of various cardiomyopathies can slow the development of myocardial dysfunction, they have limited effectiveness in patients with end-stage disease. Many researchers believe that heart transplantation is the only radical treatment in this case. However, the lack of donors and the high 

operation cost require careful selection of surgical candidates. With the introduction of molecular and cell biology into medical practice, today, stem cell therapy can become an alternative method of nonsurgical restoration of myocardial functions. The most studied and attractive is the use of mesenchymal stem cells (MSCs). MSCs differ from hematopoietic stem cells used as support for hematopoiesis in high-dose chemotherapy by the following features: pronounced trophic effect, immune tolerance, the ability to suppress alloreactivity and autoimmune disorders. An important stage in the implementation of cell therapy is the creation of a cell biobank of MSCs. In A.F.Tsyb Medical Radiological Research Center, this work has been carried out since1984. Asignificant number of experimental studies have been carried out, confirming the possibility of clinical implementation of this approach. A method for obtaining stable cultures of MSCs and cardiomyoblasts from bone marrow cells was developed and approvals were obtained. Experimental studies of cell therapy are also being conducted to overcome anthracycline-induced cardiotoxicity in cancer patients.

This article is devoted to practical application of MSC-based therapy, in particular, in cancer patients with cardiotoxicity, as well as to the issues of creating a cell biobank for treatment with MSCs.

 
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Abstract
Brief description of biobanks

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