Filtering in Stochastic Systems: Analysis for the case of continuous observations with memory of arbitrary multiplicity

We consider stochastic systems with continuous time over observations with memory in the presence of an anomalous noise. The paper is devoted to analysis of some properties of an optimal unbiased in mean-square sense filter. In the case of anomalous noises action in the observation channel with memory, we have proved insensitivity of the filter to inaccurate knowledge of the matrix of anomalous noise intensity and its equivalence to a truncated filter constructed only over non-anomalous components of an observation vector

Ultrasound Atherosclerosis Burden Score as a tool for predicting adverse cardiovascular events in patients with various cardiovascular risks aged 40-64 years

Aim. To investigate the prognostic significance of the Atherosclerosis Burden Score (ABS) in relation to the development of major adverse cardiovascular events in patients of different cardiovascular risks (CVR) aged 40 to 64 years.Material and methods. Men and women aged 40 to 64 years were included in the study. All the patients underwent duplex scanning of the carotid arteries and lower limb arteries. The total ABS was calculated by assessing the presence of plaque in the carotid and femoral bifurcations on both sides. The combined endpoint was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or peripheral artery revascularization.Results. The study included 232 patients who met the inclusion criteria, with a median age of 55,0 years. Very high CVR was established in 94 (40,5%) patients, while high CVR — in 48 (20,7%) patients, and low and intermediate CVR — in 90 (38,8%) patients. The follow-up period lasted 23,6 (15,5; 51,2) months, providing 632,6 patient-years of follow-up. Events within composite endpoint occurred in 28 (12,1%) patients. Increased cumulative risk of adverse cardiovascular events was observed for ABS ≥2, with a significant increase in relative risk (RR) for ABS ≥3. According to Cox regression analysis, ABS 3 was associated with a 3,71-fold (95% CI 1,18-11,6; p=0,025) increase in the RR of adverse cardiovascular events after adjustment for sex, age, baseline CVR, obesity, smoking, diabetes, CAD, a history of myocardial revascularization, type 2 diabetes, drug therapy, and levels of non-high density lipoprotein cholesterol, highly sensitive C-reactive protein, and glomerular filtration rate.Conclusion. In patients of various CVR aged 40-64 years, an ABS ≥3 was associated with a 3,71-fold (95% CI, 1,18-11,6; p=0,025) increase in relative risk of adverse cardiovascular events after adjusting for potential confounders, including sex, age, baseline CVR, CAD, and type 2 diabetes

Peripheral arterial disease and indicators of low-grade inflammation in patients with coronary artery disease and type 2 diabetes mellitus

BACKGROUND: The study of low-grade inflammation in patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular diseases is a pressing problem. A deeper understanding of the cascade of inflammatory reactions, possibly mediating the severe atherosclerotic lesions of various vascular pools in patients with diabetes, has the potential to introduce more sophisticated diagnostic and therapeutic approaches into practice. AIM: To study the interrelation of low-grade inflammation and atherosclerosis of peripheral arteries in patients with coronary artery disease (CAD) and T2DM. MATERIALS AND METHODS: The study included 137 patients (77 men and 60 women) with CAD. The average age of patients was 62.0 (57.066.0) years. The first group included 67 patients with CAD and T2DM, and the second group included 70 patients with CAD. Low-grade inflammation was assessed by the levels of high-sensitivity C-reactive protein, interleukin (IL)-1, IL-6, IL-8, IL-10 and TNF-. All patients underwent duplex scanning of carotid arteries and lower extremity arteries (LEAs). RESULTS: Patients with CAD and T2DM showed significantly greater values of stenosis of carotid arteries and LEAs. Direct correlation was revealed between markers of inflammation and the degree of stenosis of the femoral and tibial arteries, as well as the intima-media thickness of the carotid and femoral arteries. In the group of patients with T2DM, the value of IL-1 was 2.04 (0.982.52) pg/mL, which was significantly less than 2.43 (1.843.19) pg/mL for patients in the second group (p = 0.010). The values of IL-6 were also significantly lower in the first group of patients, at 1.84 (0.734.41) pg/mL vs. 3.73 (2.2710.2) pg/mL in the first and second groups, respectively (p = 0.008). The dose of metformin was inversely correlated with the level of IL-6 (r = 0.314, p = 0.003). CONCLUSIONS: Patients with CAD and T2DM compared with patients without diabetes had significantly greater values of stenosis of peripheral arteries. The levels of IL-1 and IL-6 in the group of patients with CAD and T2DM were significantly lower in comparison with patients without diabetes. The dose of metformin was inversely correlated with the level of IL-6

CARDIAC ARRHYTHMIAS IN CERTAIN INTERNAL DISEASES (review)

Heart rhythm disorders are considered as changes in the normal frequency, regularity, and source of depolarization of the heart, as well as impulse conduction disorders. Cardiac arrhythmias can be caused by numerous reasons, as well as their combination. The review presents current data on the frequency, risk stratification and prognostic value of cardiac arrhythmias in patients with various internal diseases. The data on the increased risk of atrial fibrillation in gastroesophageal reflux disease, gastric diseases and inflammatory bowel diseases are presented. The spectrum of the most common arrhythmias in patients with chronic obstructive pulmonary disease and asthma, as well as thyroid diseases, diabetes mellitus and acromegaly is considered. The options for cardiac arrhythmias associated with the use of chemotherapeutic drugs in the treatment of hemoblastosis are considered separately. Modern ideas about the mechanisms of development of arrhythmias in various internal diseases are discussed. In most cases, cardiac arrhythmias are associated with both the direct effect of the underlying disease on the cardiovascular system and the systemic reactions that occur. However, to date, the question remains to what extent the myocardial state that precedes the underlying disease plays a role in the occurrence of cardiac arrhythmias. The significance of various congenital and genetic factors has not been clarified. These questions are essential for everyday clinical practice and require detailed scientific study

The FINDRISC scale as a risk assessment tool for liver fibrosis in patients with nonalcoholic fatty liver disease

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, which includes changes from hepatic steatosis and nonalcoholic steatohepatitis to fibrosis and cirrhosis. Attempts to find noninvasive markers of liver fibrosis have led to a variety of scales, diagnostic algorithms, and imaging techniques. Individual studies have analyzed the relationship between the FINDRISC scale and hepatic steatosis and concluded that this questionnaire can be used as part of population screening to identify individuals at risk for hepatic steatosis. However, our review of the literature did not reveal any clinical studies on the use and effectiveness of the FINDRISC in liver fibrosis screening.AIM: To evaluate diagnostic value of FINDRISC for liver fibrosis detection.MATERIALS AND METHODS: The study enrolled patients aged 40–60 years from unorganized outpatient population. The sample of patients was formed randomly according to the inclusion and noninclusion criteria. All patients were assessed with standard anthropometric parameters. The FINDRISC questionnaire was used. All patients underwent transabdominal ultrasound examination of the liver and transient liver elastometry. The degree of steatosis was evaluated using Hamaguchi ultrasound scale. RESULTS: The study included 100 patients. An increased risk of type 2 DM (≥7 points) was detected in 68% of patients using the FINDRISC scale. Liver steatosis was diagnosed in 41% of patients. Median values of hepatic elastic modulus by transient elastometry were 4.50 (4.00; 5.25) kPa. At the same time, liver elasticity modulus values ≥5.9 kPa were registered in 11 (11.0%) patients. When analyzing the array of sensitivity and specificity values using the ROC-curve, it was found that for the FINDRISC scale the maximum LR+ and the minimum LRvalues were observed when the number of points on the indicated scale exceeded 10. At this cutoff, the FINDRISC scale had a sensitivity of 81.8% and specificity of 61.8% for detecting liver fibrosis (liver modulus of elasticity ≥5.9 kPa). The scale was of good diagnostic value (AUC 0.699; 95% CI 0.530–0.815).CONCLUSION: In an unorganized sample of patients aged 40–60 years the FINDRISC can serve as a diagnostic tool for liver fibrosis and steatosis. Sum of FINDRISC scores >10 allowed to diagnose liver fibrosis (liver elastic modulus ≥5.9kPa) with sensitivity 81.8% and specificity 61.8%. The probability of absence of hepatic fibrosis with FINDRISC scale values <10 was 96.5%

Features of the upper gastrointestinal tract mucous membrane state in patients with atherosclerosis of the mesenteric arteries

Aim. To evaluate the clinical and endoscopic features of diseases of the upper gastrointestinal tract (GIT) in patients with atherosclerosis of the mesenteric arteries (MA). Materials and methods. The study included 48 patients with atherosclerosis of MA and 43 patients without atherosclerosis of MA, who were hospitalized in the department of vascular surgery of the Chelyabinsk Regional Clinical Hospital in the period from 2019 to 2021. All patients underwent multispiral computed tomoangiography of the visceral and lower limb arteries, esophagogastroduodenoscopy. Results. Assessment of lesions of the upper gastrointestinal tract revealed a higher incidence of erosive and ulcerative gastroduodenopathies among patients with atherosclerosis of MA (60.4%), compared with patients without atherosclerosis MA (39.5%); p=0.047. Signs of severe atrophy according to the data of histological examination were statistically significantly more frequent among patients with atherosclerosis of MA (29.2 and 11.6%; p=0.031). According to the results of logistic regression, the following predictors of erosions and ulcers of the upper gastrointestinal tract were revealed: the severity of stenosis of the superior mesenteric artery (SMA) is more than 35%, the body mass index (BMI) is less than 25.9 and the total score on the HADS scale is more than 6.5 points for depression (p=0.008). Conclusion. Erosive-ulcerative gastroduodenopathies and atrophy of the gastric mucosa are significantly more common in the group of patients with MA atherosclerosis. The main risk factors for erosions and ulcers of the upper gastrointestinal tract in patients with MA atherosclerosis are: the severity of SMA stenosis is more than 35%, a decrease in BMI is less than 25.9 and an increase in the HADS score is more than 6.5 points

Relationships between serum HMGB1 concentration and subpopulation composition of circulating monocytes in patients with subclinical atherosclerosis

Chronic non-infectious inflammation of low intensity is the most important mechanism of development and progression in atherosclerosis. Under the conditions of persistent non-resolving inflammation observed in the vascular wall and atherosclerotic plaque (ASB), permanent tissue damage occurs, thus leading to increased formation of endogenous danger-associated molecular patterns (DAMPs). The non-histone chromosomal protein HMGB1 may be regarded as a prototypical DAMPs. HMGB1 acts as a DAMP if entering the extracellular space, causing inflammation by its binding to pattern-recognizing receptors (TLR2, TLR4, RAGE, CD36, etc.). A number of clinical studies have revealed higher HMGB1 levels in the blood of patients with coronary heart disease and atherosclerotic disease of the lower limb arteries, as well as its interrelations with the burden of coronary artery atherosclerosis. Currently, the mechanisms of HMGB1-mediated atherosclerosis progression are studied only fragmentary. The aim of our study was to investigate relationships between the serum HMGB1 level and subsets of circulating monocyte subpopulations in patients with subclinical atherosclerosis.The study enrolled patients aged 40-64 years with subclinical atherosclerosis of peripheral arteries. Serum HMGB1 concentration was determined using enzyme immunoassay kits (Human HMGB1/HMG-1 ELISA Kit, NBP2-62766, Novus Biologicals, USA). The serum HMGB1 threshold was 18.75 pg/ml, whereas the measurement range was 31.25 to 2000 pg/ml. Phenotyping of the blood monocyte subpopulations was performed by flow cytometry using Navios 6/2 device (Beckman Coulter, USA).An increase in serum HMGB1 concentration was associated with decreased number of classical M2 monocytes, and an increase in intermediate and M1 monocytes. Moreover, an increase in HMGB1 concentration was associated with higher numbers of classical, intermediate, and non-classical monocytes expressing CD36 and TLR2. Increased HMGB1 concentration (from Q1 to Q4) correlated with higher numbers of classical (p = 0.001) and intermediate monocytes (p = 0.006) but not with non-classical phenotypes (p = 0.147). Upon increase of HMGB1 concentration (Q1 to Q4), we have found an increase in the number of classical (p < 0.0001), intermediate (p < 0.0001), and non-classical (p < 0.0001), CD36-expressing monocytes. An increased number of intermediate (p = 0.022; p1, 4 = 0.034) and non-classical, TLR2-expressing monocytes was also revealed (p = 0.002; p1, 4 = 0.035). By mean of correlation analysis, IL-1β concentrations showed direct correlation with the number of M1 monocytes (r = 0.268; p = 0.035) and inverse relation with the number of M2 monocytes (r = -0.376; p = 0.003).Increased serum HMGB1 concentration in patients with subclinical atherosclerosis was associated with decreased numbers of classical and M2 monocytes, as well as higher numbers of intermediate and M1 monocytes, like as with increased contents of intermediate and non-classical monocytes expressing CD36 and TLR2. IL-1β levels directly correlated with HMGB1 concentration and the number of Mi-monocytes

Interactions between immunosuppressor neutrophiles, innate and adaptive immunity indexes in the patients with subclinical atherosclerosis

The last fifteen years have been marked by rapid progress in the study of neutrophils. The discovery of transcriptional plasticity of neutrophils, their phenotypic and functional heterogeneity contributed to launching active interdisciplinary studies on the role of neutrophils in various chronic inflammatory diseases. Increased systemic circulation of immunosuppressive neutrophils can be observed not only in sepsis, but also in chronic systemic inflammation, which, along with disorders of lipid metabolism, is the major mechanism of atherosclerosis development and progression. Monocytes, dendritic cells, Tlymphocytes and neutrophils are key participants and modulators of inflammation in atherosclerosis. Potential significance of immunosuppressive neutrophils in atherogenesis and regulation of inflammatory response in atherosclerosis has not been currently established. However, taking into account their possible effects upon T lymphocytes and innate immunity cells, the study of immunosuppressive neutrophils seems promising in the context of atherosclerosis and atherosclerotic cardiovascular diseases. The purpose of this study was to evaluate relationship between the numbers of circulating immunosuppressive neutrophils and subpopulations of T cells and monocytes in the patients with subclinical atherosclerosis. The study enrolled patients aged 40-64 years with subclinical atherosclerosis of peripheral arteries. Subpopulations of neutrophils, lymphocytes and monocytes were phenotyped by flow cytometry using “Navios 6/2” (Beckman Coulter). 133 patients, 65 (48.8%) males and 68 (51.2%) females were included into the study. Correlation analysis showed that increased number of circulating CD16hiCD11bloCD62Lbr neutrophils was associated with increased number of regulatory T lymphocytes. The patients with subclinical atherosclerosis and absolute numbers of circulating immunosuppressive neutrophils within the first quartile (<136 cells/μL) had a statistically significantly lower number of regulatory T lymphocytes compared with patients in the 2-4 quartiles. An increase in immunosuppressive neutrophils was associated with decreased number of classical monocytes expressing TLR4 (r = -0.335; p = 0.004), and a decrease in TLR2 surface expression intensity (r = -0.268; p = 0.023) on the non-classical monocytes. In patients with subclinical atherosclerosis of 40-64 years old, an increase in immunosuppressive CD16hiCD11bloCD62Lbr neutrophils was associated with increase in regulatory T lymphocytes and nonclassical monocytes, as well as decrease in classic monocytes expressing TLR4, and lower intensity of TLR2 expression on the non-classical monocytes

Screening for abdominal aortic aneurysm in the world and in Russia

Despite the global trend towards a decrease in the prevalence of abdominal aortic aneurysm (AAA), this disease remains one of the sudden death causes in the elderly. This necessitates the need to conduct screening studies, the effectiveness and feasibility of which has been proven in large studies, including population-based ones, and meta-analyses. The traditional and most optimal screening method is ultrasound examination. According to the guidelines of different countries, the indications for abdominal aorta ultrasound vary. Today in Russia there is no accurate data on the prevalence of AAA, while the target group for screening has not been defined, and therefore the country needs to conduct large population studies to study its prevalence and risk factors, as well as to calculate indicators of the clinical and economic effectiveness of implementation AAA screening programs

Mature neutrophils as a marker of hypoechoic carotid plaques and a predictor of polyvascular disease progression

Aim. To evaluate the diagnostic and prognostic value of circulating mature and aging neutrophils in relation to hypoechoic carotid plaques and short-term progression of carotid and multifocal atherosclerosis.Material and methods. The study included 200 patients (89 males and 111 fe­males), aged 40-64 years. All patients underwent duplex ultrasound of the carotid and lower extremity arteries at the first visit and at a repeat visit after 12-24 months. Ultrasound morphology of carotid plaques was assessed using greyscale median analysis. Phenotyping and differentiation of neutrophil subpopulations was carried out using flow cytometry.Results. The absolute and relative number of mature neutrophils directly correlated with ultrasound indicators of carotid atherosclerosis, while the number of aging neutrophils — with the degree of lower extremity artery stenosis. Patients with hypoechoic carotid plaques were characterized by a significantly higher absolute number of mature neutrophils (p=0,0340). An increase in the number of mature neutrophils over 3023,0 cells/μL made it possible to predict the hypoechoic carotid plaques with a sensitivity of 75,0% and a specificity of 69,5%. Patients with carotid atherosclerosis progression had a higher absolute number of mature neutrophils (p=0,0140), as did patients with progression of multifocal atherosclerosis (p=0,0162). An increase in the number of mature neutrophils more than 3223,0 cells/μL was associated with an increase in the relative risk of polyvascular disease progression by 3,09 times (95% confidence interval, 1,34-7,17; p=0,0082) after adjustment for baseline cardiovascular disease risk.Conclusion. Among patients aged 40-64 years, increased numbers of circulating mature neutrophils are associated with an increased carotid plaque burden and hypoechoic carotid plaques. An increase in the number of mature neutrophils over 3223,0 cells/μL was associated with a 3,09-fold increase in the relative risk of polyvascular disease after adjustment for baseline cardiovascular risk