Factors influencing the urokinase-type plasminogen activator system play important roles in pathogenetic processes in Ph-negative myeloproliferative neoplasms (MPNs). In addition, the JAK2V617F mutation is a key determinant of outcomes in these diseases. This study evaluated complete blood count (CBC) parameters, the plasminogen activator inhibitor 1 (PAI-1) 4G/5G polymorphism, and the JAK2V617F mutation in patients with Ph-negative MPNs, aiming to identify possible associations between them. We analyzed results from 56 patients newly diagnosed with Ph-negative MPNs— essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF)—before treatment initiation. The CBC of 475 people from a diagnostic center database served as a population sample for comparison. In patients with Ph-negative MPNs, PAI-1 genotypes 4G/4G, 4G/5G, and 5G/5G were detected in 11 (19.6%), 29 (51.8%), and 16 (28.6%) cases, respectively. No significant differences in genotypedistribution were found among ET, PV, and PMF patients. PMF patients with the 4G/5G genotype had a higher white blood cell (WBC) count compared to those with the 5G/5G genotype (P = 0.027). The JAK2V617F mutation was found in 44 (78.6%) patients. ET patients with this mutation (n = 13) exhibited significantly higher counts of platelets (PLTs), red blood cells (RBCs), and WBCs compared to those without it. The PLT/RBC ratio was significantly higher in all disease categories compared to the population sample, with the highest ratios in ET patients. The PLT/WBC ratio in ET and PV patients was also higher than in the population sample (P < 0.05). This relative thrombocytosis is likely clonal in origin, associated with genes responsible for PLT quantitative parameters, JAK-STAT signaling pathway proteins, and factors in the uPA-uPAR-PAI-1/PAI-2 system. These genes share common loci in chromosomes (1p34.1-p34.3, 7q21.1-q21.3, 9p24.1, 19p13.11-p13.2, and 19q13.31-q13.32). Due to their close spatial proximity, these genes can form genetic complexes and mutually influence their expression levels, thereby contributing to the unique pathogenesis of these diseases.
UDC 616.89-008.45/.46/.47:616.12-008.3-073.96
Background.The purpose of our work was to reveal the dependence of changes in the cognitive sphere on the peculiarities of the daily profile of blood pressure (BP) and heart activity in patients with arrhythmias.
Materials and methods. We examined 139 patients with different clinical forms of arrhythmias. All of them underwent extended neuropsychological testing, a study of the daily BP profile and heart activity. Hemodynamic status was assessed by daily BP and ECG monitoring. Average daily, average daytime and nighttime systolic (SBP), diastolic blood pressure (DBP) and heart rate (HR) were evaluated. The analysis of spectral indicators of heart rate variability was performed to assess the state of the autonomic nervous system. Correlations of hemodynamic indicators with the results of neuropsychological testing were determined.
Results. In patients with cognitive disorders (CD), there was an increase in SBP in all periods of the day, most pronounced in patients with moderate CD (p = 0.049). In patients with mild CD and without CD, there were no significant intergroup differences in the level of average daily, daytime and night SBP, DBP and pulse pressure (p > 0.05). Patients with moderate CD had significantly higher SBP and time index of SBP at the expense of average daytime and average night values of these indicators compared to those without CD (p < 0.05). During the active period of the day, time index of DBP was significantly higher in patients with moderate CD (p = 0.002) who also had an increase in average daily, daytime and night SBP variability compared to participants without CD (p = 0.041). The differences between the groups were not significant in terms of DBP variability (р = 0.07). In 61 (54 %) patients with CD, non-dipper SBP prevailed in the structure of disorders of the daily BP profile, with the highest indicators in moderate CD (55.6 %). The presence of adverse daily DBP profiles — night-peaker (6.2 %) and over-dipper (8.8 %), which prevailed in patients with moderate CD, is hidden behind normal indicators of the daily BP index. Increased average SBP24 (odds ratio (OR) = 3.26, 95% confidence interval (CI): 1.45–5.35, p < 0.001), DBP24 (OR = 3.06, 95% CI: 1.41–4.79, p < 0.001), average HR24 (OR = 2.67, 95% CI: 1.32–4.14, p < 0.001), average SBP24 variability (OR = 2.13, 95% CI: 1.11–3.32, p < 0.001) are the main factors of central hemodynamic disorders that increase the risk of developing CD in patients with arrhythmias.
Conclusions.The identified associations between cognitive dysfunction, indicators of daily BP monitoring and heart activity are important in the context of their comprehensive accounting for optimizing an individualized approach to patient management and predicting the development of CD
UDC 616.36-003.826-06-008.9:616.98:578.834.1
The combination of metabolic-associated liver disease starting with liver steatosis (MASLD) and coronavirus disease (COVID-19) in the clinic has not been sufficiently studied. We reviewed the literature on the combination of COVID-19 and liver steatosis in the Pubmed database and assessed the frequency of its manifestations in patients with COVID-19-associated community-acquired pneumonia of clinical group III by examining 22 inpatients aged 54.7±2.1 years. It was found that liver steatosis can either be a background condition or occur as a result of COVID-19 due to hepatocyte damage by the virus, excessive activation of the systemic inflammatory response, hypoxia, coagulopathy, endotheliitis, cardiac right ventricular failure, and drug-induced liver damage. Adverse effects on hepatocytes of high doses of glucocorticosteroids, azithromycin and several antiviral drugs have been described, which may be aggravated by taking them in combination with NSAIDs. Background liver disease is also important, as COVID-19 has been described to activate the persistence of hepatitis B and C viruses, and treatment of COVID-19 with massive doses of corticosteroids may affect viral replication. According to their own observations, 68% of inpatients with COVID-19-associated community-acquired pneumonia of clinical group III of mature age were diagnosed with MASLD, which was manifested by a heterogeneous structure with increased echogenicity (100%) with clear, even liver contours and non-expanded bile ducts and normal choledochus; moderate increase in liver size (92%), loss of liver vascular pattern (23%). At the same time, normal liver function tests and lipid metabolism were observed, moderate hyperglycaemia and a more pronounced inflammatory syndrome were noted. However, the course of pneumonia was more severe with lower oxygen saturation.
УДК 616.24-006.6-089.87+089.844+616.233-089.844
While the development of specific steatohepatitis-associated cardiomyopathy (SHACMP) in the context of fatty liver disease has been documented, it remains unclear whether any cardiac changes occur during the initial stage of fatty liver disease, known as metabolic-associated liver steatosis (LS).
Objective — to evaluate the characteristics of metabolism and electrical activity of the heart in patients with chronic obstructive pulmonary disease and chronic forms of coronary heart disease and concomitant liver steatosis.Materials and methods. 35 patients with chronic obstructive pulmonary disease, respiratory insufficiency stages I and II, coronary heart disease, atherosclerotic cardiosclerosis, and heart failure functional classes I and II, were examined. Their diagnosis and treatment were conducted in accordance with established protocols and international recommendations. Depending on the occurrence of LS, patients, matched for age, gender and lung function parameters, were divided into two groups: those suffering from it (n = 26) or not suffering from it (n = 9). Additionally, leptin level was determined, body mass index (BMI), leptin to BMI ratio, De Ritis ratio, hepatic steatosis index, glomerular filtration rate (according to MDRD) were calculated, and automatic ECG test was run. The results were processed statistically; the significance assumed at р < 0.05.
Results and discussion. It was established that LS was diagnosed in patients with a higher BMI and was accompanied by clear metabolic changes — higher values of leptin, leptin-to-BMI ratio, fasting blood glucose and total cholesterol levels. The criteria of LS are not only an increase in echogenicity and size of the liver, but also higher values of ALT, De Ritis ratio and hepatic steatosis index. According to the correlation analysis, the deterioration of the liver condition was accompanied by changes in the heart — tachycardia and a decrease in the angle of the QRS complex, which can be considered as signs of the development of SHACMP, characteri-zed by a prolongation of the PQ interval (р = 0.07) and a significant deviation of the angle of the QRS complex. Inflammation and endogenous intoxication are the leading mechanisms of progression of both LS and SHACMP.Conclusions. Patients with chronic obstructive pulmonary disease and chronic forms of coronary heart disease, alongside with liver steatosis, exhibit signs of steatohepatitis-associated cardiomyopathy caused by metabolic changes, inflammation and endogenous intoxication.