National Scientific Center "M.D. Strazhesko Institute of Cardiology"

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Despite major advances in therapy, the treatment of ALL remains a significant challenge. Therapeutic protocols are based on the use of combinations of chemotherapeutic drugs. While such combinations increase treatment efficacy, they also complicate the assessment of toxicity. It should be noted that the variability in the occurrence of toxic responses to ALL therapy in children may be determined by the presence of gene variants that influence both the pharmacokinetics and pharmacodynamics of chemotherapeutic drugs. This review summarized and analyzed the most significant and well-studied pharmacogenetic markers to date associated with the toxicity and response to chemotherapeutic agents used in the treatment of pediatric ALL. In particular, pharmacogenetic markers for the following drugs were analyzed: anthracyclines (doxorubicin, daunorubicin), vincristine, glucocorticoids (prednisone, dexamethasone), L-asparaginase, methotrexate, alkylating agents (cyclophosphamide, ifosfamide), 6-mercaptopurine, cytarabine, and etoposide. At present, only a few genes, TPMT and NUDT15, have well-established clinical utility, whereas the clinical relevance of pharmacogenetic markers for other drugs used in pediatric ALL therapy remains under investigation. The review also highlights the main knowledge gaps in current research and outlines promising directions for future studies aimed at integrating pharmacogenetic testing into clinical practice for personalized treatment of ALL.

Multiple studies have been conducted to investigate the factors that influence on the course of the disease and prognosis in patients after acute myocardial infarction (AMI). Particular attention is drawn to cholestasis-associated changes, which may contribute to the development of lipid metabolism disorders and a decrease in endothelial reserve – the important determinants of increased cardiovascular risk. The objective: to determine the relationship between parameters of cholestasis, the De Ritis (DR) ratio, lipid metabolism, and the number of endothelial progenitor cells (EPCs) in patients after AMI during one year of follow-up. To evaluate the effectiveness of adding ursodeoxycholic acid (UDCA) to standard treatment in patients with manifestations of cholestasis. Materials and methods. A total of 88 men after AMI were examined, with a mean age of 57.5 years. During one year of followup, three visits were performed to assess disease progression, including the determination of biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, proprotein convertase subtilisin/kexin type 9 (PCSK9) and EPC count before and after a graded exercise test. Group distribution was performed according to the DR ratio: group D included patients with DR < 1, group C – with DR > 2, and group B – with 1 ≤ DR ≤ 2. Results. Among the study participants, elevated ALT was observed in 47.7%, of them 40% were patients from group D with clinical and laboratory signs of cholestasis, and they had higher ALT levels at the first visit (Me = 44.0 U/L), which stabilized during subsequent visits, presumably due to the addition of UDCA to standard therapy. At the second visit, patients in group D showed a decreased TC level (from 4.6 to 3.3 mmol/L; p = 0.003) and LDL-C level (from 2.6 to 1.54 mmol/L; p = 0.008). At the third visit, group D demonstrated a statistically significant reduction in EPC count after physical exercises (Me from 3618 to 2618 cells/mL; p = 0.05), indicating a decreased endothelial reserve in this group. A positive correlation was established between PCSK9 levels and EPC count (r = 0.36; p = 0.03), and an inverse correlation between EPC increase after exercise and TC (r = –0.24; p = 0.04). Conclusions. A reduced DR ratio is a marker of cholestasis-associated liver dysfunction after AMI, and is associated with disturbances in cholesterol metabolism and impairment of endothelial reserve. The addition of UDCA improves the lipid profile and statin therapy tolerance, promoting the restoration of endothelial function. Comprehensive therapy after AMI is essential one to form a favorable long-term prognosis.

Background. Studies consistently demonstrate that involvement of pharmacists, all healthcare providers, and nurses in identifying and treating patients with hypertension can significantly improve blood pressure control. The purpose of this study was to evaluate the effectiveness of identifying hypertensive patients using the program for active diagnosis and of providing medical assistance using various information services. Materials and methods. The study included a total of 1425 participants, 61.75 % of women and 38.25 % of men who agreed to participate in the program for active diagnosis of hypertension. The largest proportion was made up of participants aged 30 to 59 years — 67.30 %. 1261 (88.49 %) of the examined underwent laboratory examination, and 11.51 % of the respondents refused to undergo a free laboratory examination. 85.54 % of the examined visited a specialist, and 14.46 % refused a consultation. Drugs and all examinations were free of charge. Less than half (48.49 %) of the patients agreed to treatment. Results. 54.32 % of the patients were diagnosed with hypertension. The drugs were dispensed through pharmacy chains. 493 patients (71.35 %) turned to pharmacies to receive free drugs within the 2nd visit. At the 3rd visit, 387 patients (56.00 %) received medication, at the 4th — 307 (44.43 %), at the 5th — 193 (27.93 %), and at the 6th visit — 88 patients (12.73 %). All participants of the program, both healthy and with detected hypertension, showed an increase in adherence to a healthy lifestyle, with improved nutrition, increased physical activity, and a decrease in harmful habits. Constant communication between healthcare providers and program participants had a positive impact on patients, which met their main wish — more live communication and caring calls. Conclusions. This program is a result of developing a system for active detection, control, and long-term observation of hypertensive patients in an organized population. It has been proven that the involvement of a wide range of healthcare providers in these processes plays a positive role in improving the identification of patients with hypertension and increasing their adherence to treatment.

ObjectiveThe aim is to compare immune status in patients (pts) with atrial fibrillation (AF) and atrial flutter (AFl) associated with hypertension and pts without rhythm disturbances and almost healthy people.Design and methodThe study involved 103 patients with hypertension and arrhythmias who were divided into three groups: 1 (n = 35) - with paroxysmal atrial fibrillation (AF), 2 (n = 38) - with persistent form of AF, 3 (n = 30) - with persistent form of atrial flutter (AFl). Control groups were formed: 4 (n = 23) - patients with hypertension, but without arrhythmias and 5 (n = 21) - almost healthy people. The immune status was assessed by the level of monocytes (Mc), lymphocytes subpopulations and T-regulatory cells (T-reg) in the peripheral blood using flow cytometry.ResultsThe number of classical CD14++CD16- and intermediate CD14++CD16+ Mc was significantly higher in pts with persistent AF and AFl comparing with patients without arrhythmias and healthy people (p<0.005). Amount of non-classical CD14+CD16++ Mc was lower in the 2 group (p<0.005). The count of T cells with natural killer (TNK) activity was higher in all groups comparing to normal value, so significance was observed only compared to the 5 group. The highest quantity of T-reg cells was found in healthy people comparing to other groups.ConclusionsAn increased activity of proinflammatory subpopulation of monocytes, higher amount of T-cells with natural killer activity and reduced T-regulatory cells was determined, whose main function is to control the immune response.

In recent years, many studies have been aimed at exploring the possibilities of cardiac rehabilitation as a tool to improve the prognosis in patients after acute coronary syndrome (ACS). Endothelial dysfunction is one of the initiating mechanisms of cardiovascular diseases, and myocardial infarction in particular, so it is important to assess the dynamics of changes in the number of endothelial progenitor cells (EPCs) in patients during cardiac rehabilitation with the increase in physical activity. The aim. To establish the relationship between the level of recovery of exercise tolerance and the recovery of endothelial function by determining the number of EPCs in patients undergoing cardiac rehabilitation after ACS. Materials and methods. The study included 44 patients with ST-elevation myocardial infarction who underwent urgent stenting of the infarct-related artery, with a mean age of 59 years (Q1-Q3; 51-64). All the study participants underwent laboratory tests (CD45+/CD34+ cell count before and after the exercise test) and instrumental tests (echocardiography, bicycle ergometry, coronary angiography). Statistical processing was carried out using SPSS Statistics 23 (trial version). Results. According to the results of the exercise test at the first examination, the patients were divided into 2 groups: group 1 with low exercise tolerance (≤50 W) and group 2 with high exercise tolerance (&gt;50 W). The data obtained indicate a link between better recovery of exercise tolerance after ACS and recovery of endothelial func-tion in patients with high exercise tolerance during follow-up compared to the patients whose exercise tolerance did not exceed 50 W, as evidenced by a statistically higher number of EPCs after exercise in patients with a favor-able course and high exercise tolerance (3633 vs. 2400 cells/ml) (p=0.006). Patients with low exercise tolerance were more likely to be diagnosed with lesions of left anterior descending coronary artery (96% vs. 70%, p=0.02). More severe coronary vascular lesions with stenosis of 75% of two or more arteries showed lower pre-exercise EPCs, but increased post-exercise EPCs (+228 cells/ml), whereas in the group with stenosis of more than 75% of one vessel, a decrease in post-exercise EPCs (–604 cells/ml) was observed (p=0.004). If patients have more than one stent, there is a 2.5-fold increased risk of decreased exercise tolerance to values of 25-50 W (relative risk = 1.8; 95% confidence interval: 1.3-2.4). Conclusions. The data obtained indicate that there is an association between a better recovery of exercise tolerance after ACS and recovery of endothelial function in patients with a favorable course at repeated examination, compared to patients whose level of exercise tolerance did not exceed 50 W (low exercise tolerance), as evidenced by a statistically greater number of EPCs after exercise test in patients with favorable course and high exercise tolerance compared with patients with unfavorable course and low exercise tolerance.

Background. Oxidative stress and immune cell (T-lymphocytes, macrophages) products are important for the development of morpho-functional disorders of the nervous system in Parkinson’s disease. Connection of Parkinson’s disease with age and functioning of the major histocompatibility complex genes are also shown. The purpose was to assess changes in the brain of T-lymphocytes, macrophages, malondialdehyde (MDA) contents, the activity of antioxidant enzymes, the structure of brain and spinal cord neurons, as well as behavior in adult and aging mice with different H-2 haplotypes and toxic model of parkinsonism. Materials and methods. Adult and aging female mice of FVB/N (genotype H-2q) and 129/Sv (genotype H-2b) strains were once injected with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at the dose of 30 mg/kg. Contents of CD3+, CD3–CD11b+, CD3+CD11b+ cells, MDA and the activity of antioxidant enzymes in the brain were evaluated. The structure of neurons of the substantia nigra, lumbar spine, behavior in the open field test, as well as in rigidity and rotarod performance tests were studied. Results. In adult mice of both strains, motor and non-motor (spatial-exploratory, emotional) activity is impaired under the influence of MPTP. At the same time, linear differences in behavior changes were revealed in their directions and expressiveness. In aging FVB/N experimental mice, motor behavior disorders prevailed and were combined with non-motor changes in 129/Sv mice. Violations in the structure of substantia nigra neurons after MPTP administration were more severe in FVB/N mice while those in the lumbar spinal cord neurons were more pronounced in the 129/Sv mice. In aging experimental mice of both strains, the percentage of damaged neurons in the brain and spinal cord was significantly lower than in adult animals. After MPTP administration to adult mice, the direction of changes in the brain T-lymphocytes and macrophages (increase or decrease) depended on their strains. In aging experimental mice, the linear heterogeneity of changes was preserved for the T-lymphocyte content, while the macrophage level was increased regardless of the animal strains. Under MPTP influence, the MDA content increased in the brain of mice of all experimental groups. The direction of changes in superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities (decrease or increase) depended on the strains of animals and their age. Conclusions. MPTP-induced changes (directions, expressiveness) in T-lymphocyte, macrophage contents, antioxidant enzymes activity, the structure of neurons of the substantia nigra and lumbar spine, as well as behavioral reactions largely depended on the adult mice H-2 haplotype. There were age-related effects of the neurotoxin on changes in the studied indicators in mice of different strains. At the same time, dependence of changes in most above indicators on the H-2 haplotype preserved.

Background. Vitamin D deficiency (VDD) is widespread in the world; its proportion varies considerably in different populations and depends on many causes. Up to now, there were no National recommendations for the diagnosis, prevention, and treatment of VDD in adults in Ukraine. Their creation became the purpose of this work. Methodology. Consensus was created using the Delphi method, voting was conducted using the SurveyMonkey® platform. After approval of the composition of the Consensus Group, agreement on the order of formation and structure of the Consensus, creation and correction of the main statements, and two voting rounds, the main Consensus statements were formed and were successfully voted on. The 15 authors of the article are 15 experts who participated in the voting. The final 14 Consensus statements are presented in this article. Each statement is preceded by a justification based on high-quality evidence available in the current literature. Results. Despite the reduction of VDD in the Ukrainian population in recent years, experts have recommen­ded increasing the awareness of the medical community and the Ukrainian population about the problem and ways to overcome it, with a screening of the total serum level of 25-hydroxyvitamin D (25(OH)D) in subjects from the groups of risk to achieve the target concentration of 30–50 ng/ml (75–125 nmol/l). To ensure it, we recommend the individual selection of a prophylactic dose of vitamin D (800–2000 IU/d for young healthy persons and 3000–5000 IU/d for patients with diseases and conditions that affect the metabolism of vitamin D). For the treatment of VDD, we recommend short-term intake of higher doses (4000–10,000 IU/d) of vitamin D with control of the 25(OH)D level after 4–12 weeks of treatment and subsequent use of maintenance doses. Also, we re­commend the determination of serum 25(OH)D level before the initiation of antiosteoporotic therapy in patients with osteoporosis and its complications to prevent its ineffectiveness and increase the safety profile.

Objective: The most common reason of arrhythmia onset nowadays is hypertensive desease. The aim of the study is to compare the subpopulations of lymphocytes (LCTs) and monocytes (MCTs) in blood of patients (pts) with paroxysmal and persistent forms of AF or atrial flutter (AFL) associated with arterial hypertension. Design and method: The study involved 103 patients with atrial fibrillation and flutter that occurred on the backdround of hypertension. Depending on the form of arrhythmia, patients were divided into three main groups: group I – with paroxysmal form of atrial fibrillation, group II – with a persistent form of atrial fibrillation, group III – with a persistent form of atrial flutter. The control groups included patients with hypertension, but without these arrhythmias and healthy individuals who entered groups IV and V, respectively. The lymphocytes and monocytes subpopulation in peripheral blood was assessed by flow cytometry. Results: Analyzing the lymphocyte subpopulations in peripheral blood of patients with atrial fibrillation and flutter (groups I, II and III), it was found that the number of cells with cytotoxic activity (NK and NKT) in both absolute count and percentage values was significantly higher than in healthy individuals. A statistically significant decrease of T-regulatory cells number was found in patients with arrhythmias compared to control groups (p &lt; 0.05). In patients with AF and AFL associated with hypertension, compared to patients with hypertension without these rhythm disturbances or healthy individuals, there is an increased number of classical and intermediate monocytes subpopulations. Conclusions: 1. In patients with atrial fibrillation or atrial flutter associated with hypertension, compared to patients with hypertension without these rhythm disturbances or healthy people, there is an increased number of classical and intermediate monocytes fraction and a decreased content of T-regulatory cells in peripheral blood, an increased number of cells with cytotoxic activity (NK and NKT) compared to healthy individuals. These changes can be one of the factors for the activation of systemic and local inflammatory processes that can lead to fibrosis in the myocardium and the associated electrical and structural remodeling typical for AF and AFL.

Objective: to evaluate the clinical consequences in hypertensive patients after 1.2 ± 0.3 years after COVID-19 recovery. Design and method: We studied 51 treated hypertensive patients, which were divided into 2 groups: 26 patients recovered from mild to moderate COVID-19 in 2020-2021 years (1st group) and 25 patients were not ill COVID-19 (2nd group). The clinical characteristics, laboratory finding, echocardiographic measurement and clinical outcomes were analyzed. Results: There were no significant differences in sex, age, duration of hypertension, frequency of family history of premature CVD and presence of concomitant obesity, DM, CAD, stroke/TIA, atrial fibrillation, heart failure, CKD, PAD and average number of antihypertensive drugs, office systolic BP between the 2 groups. Levels of office diastolic BP by 10 % (P = 0.001) and heart rate by 13 % (P = 0.01) were higher in post COVID-19 group. Low adherence was present at 81.8 % patients 1st group compared with 45 % of 2nd patients group (P = 0.03). Cognitive impairment by the MMSE scale was detected in 68.2 % of COVID-19 recovered patients and 25 % of 2nd patients group (P = 0.03). Fasting glucose by 7.5 % (P = 0.046), 24-h albuminuria in 1.8 times (P = 0.049), level of CRP by 38.5 % (P = 0.04) were higher and blood concentration of endothelial progenitor cells (CD133+CD31+CD45-/+) by 14, 9 % (P = 0.04), left ventricular ejection fraction by 10 % (P = 0.03) were lower in post COVID-19 patients than in patients of 2nd group. Conclusions: The study indicate that the changes were found in the hypertensive patients after 1.2 ± 0.3 years of recovery from COVID-19. In the future these may signal an increased risk for incidence of CV outcomes. Cognitive dysfunction and possibly as a consequence poor adherence to antihypertensive treatment contribute to negative outcomes.