The review is devoted to the influence of central sleep apnea and Cheyne-Stokes breathing on the prognosis of patients with chronic heart failure. The connection between sleep breathing disorders and an increased risk of ventricular arrhythmias and the mechanisms of these interactions are discussed, and options for approaches to therapy are considered.

The purpose of this review is to provide clinicians with information and a concise interpretation of the results of pharmacogenetic testing for the cytochrome P450 2C19 (CYP2C19) genotype when choosing a proton pump inhibitor (PPI) dosage. PPIs are widely used for the treatment and prevention of common gastrointestinal diseases, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, and other hypersecretory conditions. Most PPIs are metabolized predominantly by cytochrome P450 2C19 (CYP2C19) to form inactive metabolites, and the CYP2C19 genotype determines the action of PPIs, their efficacy and possible side effects. In clinical practice, a gastroenterologist or therapist is faced with problems of insufficient effectiveness or the development of adverse reactions when prescribing PPIs. Thus, consideration of CYP2C19 genotype appears to be necessary to determine the optimal PPI dosing regimen. The above served as a reason for generalizing in the presented review of literature data on the prescription of PPIs depending on the CYP2C19 genotype.

This review presents the relevance of mandatory assessment of the function of the lower urinary tract in multiple sclerosis to identify the lower urinary tract symptoms, the nature and severity of disability in patients regarding urinary disorders. Lower urinary tract symptoms in multiple sclerosis are diverse and correlate with the phases of the urination cycle. lower urinary tract symptoms in multiple sclerosis include urinary urgency or sporadic episodes of urinary retention. As the disease progresses, along with urgency and sensory disturbances, urinary incontinence develops, resulting in total urinary incontinence in the most severe cases. Chronic urine retention may also form, which determines the need to urine diversion from the bladder through urethral drainage. In turn, the risk of developing urinary tract infections, including catheter-associated ones, increases significantly.

Objective: to study the prognostic impact of the level of fibroblast growth factors 23 on coronary heart disease depending on the stage of chronic kidney disease. Materials and methods:  the study included 108 patients with coronary heart disease (CHD), stable angina (stress), functional class 1–3, chronic kidney disease (CKD) C1–C4, average age was 67,62±12,51 years (55 men and 53 women). The level of fibroblast growth factor 23 was assessed using the Biomedica FGF 23 multimatrix enzyme-linked immunosorbent assay. After 12 months of follow-up, the presence of a cumulative endpoint including the occurrence of acute coronary syndrome, stroke, transient ischemic attack, heart failure and death. Differences in data and correlations between them were considered statistically significant at p<0.05. Results: the developed prognostic model to determine the likelihood of cardiovascular complications in patients with coronary artery disease and CKD found that the FGF 23 level is equal to 27.9 with a sensitivity of 62.7% and specificity of 62.5% to distinguish patients with ischemic heart disease and CKD in whom a cumulative endpoint will occur over 12 months of follow-up. Conclusions: to identify patients at high risk of cardiovascular complications in coronary artery disease and CKD, it is advisable to use determination of FGF 23 level.

Objective: to evaluate the features of cardiac and vascular remodeling in patients with arterial hypertension (AH) and atherosclerosis of the arteries of the lower extremities (LAA) of varying severity. Materials and methods: the study involved 120 patients with hypertension. Depending on the presence of AANC, all patients were divided into 3 groups: group 1 — 46 patients with hypertension and clinically manifested AANC, group 2 — 39 patients with hypertension and asymptomatic AANC, group 3 — 35 patients with hypertension without AANC. The characteristics of cardiac and vascular remodeling were assessed based on the results of 24-hour blood pressure monitoring (ABPM) using Vasotens technology, triplex ultrasound scanning (UTS) of the arteries of the lower extremities (LEA), and echocardiographic examination (EchoCG). Statistical data processing was carried out using Microsoft Office Excel 16 (2015, Microsoft, USA), Statistica 10.0 (StatSoft, USA) and IBM SPSS Statistica 26.0 (IBM, USA). Results: in the group of patients with severe circulatory disorders of the lower extremities, compared with patients with asymptomatic AANK, significantly lower values of the indicator — reflected wave propagation time (RWTT, ms) (p = 0.006) and significantly higher values of the indicator — augmentation index (AIX) were revealed) and augmentation index in the aorta (AIXao) (p<0.05). A direct statistically significant correlation of moderate strength was revealed between the degree of stenosis (%) of the ANC and the values of the AIX and AIXao indicators (r = 0.345, p = 0.001). Higher values of the dimensions of the walls of the left ventricle (LV) were determined: the thickness of the interventricular septum (IVS) and the posterior wall of the left ventricle (PLW) in patients of the 1st and 2nd groups in comparison with the indicators in patients of the 3rd group (p<0 .05). Patients of all three groups had thickening of the left ventricle and intraventricular septum (>11 mm) and an increase in LVMI. In patients with hypertension and severe AANC, the maximum values of LVMI were determined, which were significantly higher than the corresponding values in patients of the 2nd (p = 0.004) and 3rd (p = 0.0001) groups. LV systolic function in all patients included in the study was assessed as intact. However, the highest ejection fraction (EF) values were recorded in patients with hypertension without AANC, and were significantly higher than those in patients with hypertension and concomitant asymptomatic AANC (p = 0.02), as well as in patients with hypertension and clinically manifested AANC (p =0.001). Conclusions: the progression of AANK was associated with an increase in the stiffness of both peripheral and main arteries, which was accompanied by an increase in the load on the myocardium, which in 97.8% of cases led to more pronounced myocardial remodeling of the concentric hypertrophy type.

Objective: to study the indicators of lipid peroxidation and the antioxidant system in the blood and moisture condensate of exhaled air in patients with AD combined with type 2 diabetes, and in the blood of these patients — total metabolites of nitric oxide. Materials and methods: the study involved 215 patients with persistent BA of moderate severity aged (38.6±2.4) years, including 88 men (40.9%), 127 women (59.1%). Among the examined patients with BA there were 64 — group I, persons with BA combined with type 2 diabetes — 151 (group II). The parameters of the lipid peroxidation system (LPS) in the blood serum were studied: malondialdehyde (MDA), diene conjugates (DC), and the antioxidant system (AOS) according to the activity of catalase and superoxide dismutase (SOD), the amount of total metabolites of nitric oxide (NOx), in the condensate of exhaled air moisture (KEAM) was determined general oxidant (GOA) and antioxidant (AOA) activity. Results: in patients with BA combined with type 2 diabetes, an increase in the concentration of POL products in the blood was revealed: MDA was 2.6 times (p<0.05) compared with the control group and 1.3 times (p<0.05) compared with the indicator in patients with AD, DC, respectively, 2.0 times (p<0.05) compared with the control group and 1.2 times (p<0.05) compared with I group. The activity of the enzymes AOS catalase and SOD in patients with comorbidity of BA and type 2 diabetes was found to be lower than in patients of group I. In the KEAM of patients with comorbidity of BA and type 2 diabetes, a significant increase in OOA and a decrease in OAA were noted. The concentration of NOx in the blood serum of group II patients was 1.6 times higher than in the control group (p<0.05), but 1.4 times lower than in patients with AD without comorbidity with type 2 diabetes (p<0.05). The direction of the revealed correlations between the products of POL in blood serum and KEAM confirmed the systemic nature of metabolic changes in the body of patients with AD, and their strength in group II patients — the negative effect of comorbid type 2 diabetes on the greater severity of these metabolic changes. Conclusions: the resulting changes in the state of LPS and AOS in the blood and KEAM of patients with BA combined with type 2 diabetes can be characterized as systemic metabolic stress, both components of which: oxidative and nitrosive are supported by insufficient stress-limiting mechanisms  — low activity of AOS enzymes and possible depletion of nitric oxide production, which should be reflected in the means of correcting metabolic disorders in patients with this comorbidity.

Objective: to investigate the state of сеntral and peripheral hemodynamics in patients with out-of–hospital pneumonia (OHP) combined with subclinical hypothyroidism (SH). Materials and methods: the study was conducted in 132 patients with OHP of clinical groups II-III, including 64 with OHP combined with SН — the main group, and 68 with OHP without SН (comparison group). The average age of the patients was 37.4±3.3 years, including 74 women among the studied, 58 men. The state of microcirculation in patients was studied by biomicroscopy of the bulbar conjunctiva using a slit lamp with the calculation of conjunctival indices, intravascular aggregation of shaped blood elements was observed in the presence of a sludge phenomenon according to N. Knisely (1965), and central cardiohemodynamics parameters were determined. Results: in patients with OHP, along with small clinical signs of hypertension, laboratory data were revealed: TSH — (6,4±0,6) мIU/ml, free T4 — (13,2±1,1) pmol/L, the level of ATP — 53,7±2,3 IU/ml — microcirculatory disorders with changes in the microvascular wall, sludge in them, perivascular changes, as well as dysfunction of the right and left ventricles of the heart. Conclusions: the combination of OHP and SH in patients is accompanied by significant microvascular shifts, which are associated with disorders of central cardiohemodynamics in the form of dysfunction of the right and left ventricles of the heart. The found correlations between the parameters of cardiohemodynamics and microcirculation in patients with OHP combined with SH and TSH levels confirm the negative effect of subclinical hypothyroidism on the state of central and peripheral hemodynamics in patients.

Objective: to study the parameters of the immune status and the spectrum of autoimmune markers of patients suffering from an autoreactive form of chronic spontaneous urticaria. Materials and methods: the study involved 67 patients with an autoreactive form of chronic spontaneous urticaria, with clinical and laboratory signs of autoimmune pathology, aged 18 to 65 years, who were observed on an outpatient or inpatient basis in the period from 2019 to 2022. Healthy donors without signs of chronic spontaneous urticaria (n=35) were considered as a control group. The results were evaluated according to the dynamics of clinical and functional, immunological examination. Results: when assessing the immune status of patients with autoreactive chronic spontaneous urticaria, a violation of the differentiation processes of immune-competent cells was revealed, with a predominance of T-lymphocytes with helper-inductive activity, entailing an inversion of the immune-regulatory index, activation of the humoral link of the immune system was noted: an increase in B-lymphocytes, immunoglobulins of classes A, M, G, increase of circulating immune complexes. The indicators of total IgE did not differ fundamentally from the level of donors. Changes in the parameters of the monocyte-macrophage link in patients with autoreactive form of chronic spontaneous urticaria indicated an increase in the functional activity of phagocytic cells and depletion of their reserves. Conclusion: in the autoimmune genesis of chronic spontaneous urticaria, there are significant changes in the autoimmune markers corresponding to the concomitant autoimmune disease (rheumatoid factor, antibodies (Ab) to nDNA, Ab to cardiolipin, Ab to β2-glycoprotein, Ab to neutrophils), there is a high percentage of correlation with a positive test result with autologous serum, there are features of immune status of patients with autoreactive form of chronic spontaneous urticaria.

Objective: to identify the relationship between the main indicators of iron metabolism and erythrocyte parameters, myeloid and lymphoid cells in patients with sleep disorders in patients with sleep disorders (obstructive sleep apnea (OSA), chronic insomnia (CI), restless legs syndrome (RLS)). Materials and methods: 118 patients, 60 men (50.8%) and 58 women (49.2%), Me age — 47 years (Q1–Q3: 35–61), Me BMI — 25.81 kg/m² (Q1–Q3: 22.72–29.40) with obstructive sleep apnea (OSA), chronic insomnia, restless legs syndrome in their various combinations.  All patients underwent a polysomnographic study, blood cell count, biochemical parameters of iron metabolism were assessed. Results: when assessing the relationship between “Ferritin” and “Hemoglobin”, “Hematocrit (%)”, “Erythrocytes”, “Lymphocytes, abs.”, a moderate direct relationship was established (p<0.001; p<0.001; p=0.001; p< 0.013, respectively).When assessing the relationship between  “RDW (%)”, “Neutrophils total, %”, “Neutrophils, abs.” and “%TS”, a moderate inverse relationship was established (p=0.026; p=0.028; p =0.01, respectively).When assessing the relationship between “RDW (%)”, “Neutrophils total, %” and “Serum iron”, a moderate inverse relationship was established (p = 0.003; p = 0.012, respectively). When assessing the relationship between “Lymphocytes, %” and “Serum iron”, a weak direct relationship was established (p = 0.049). Conclusions: in patients with sleep disorders, a statistically significant relationship was revealed between the main parameters of iron metabolism and indicators of “red” blood, the content of neutrophils and lymphocytes. It was shown for the first time that in patients with sleep disorders, changes in the content of neutrophils and lymphocytes may be associated not only with changes in sleep itself, but also with the state of iron metabolism. The complex relationships of iron metabolism, the function of erythrocytes, neutrophils and lymphocytes in patients with sleep disorders can affect the development of both infectious and non-infectious diseases through the mechanisms of maintaining chronic inflammation, hypoferemia, ferroptosis, netosis and other mechanisms.

Objective: to evaluate the effect of knee replacement on kidney function in patients with hypertension and type 2 diabetes mellitus. Materials and methods: at stage 1, 308 people suffering from hypertension (GB), stage III osteoarthritis of the knee joint (OA CS), type 2 diabetes mellitus (DM) were examined. GB occurred in 308 people, DM — in 66 people, and OA CS — in 216 people. Depending on the presence of OA CS, observation and comparison groups were identified. Within each group, subgroups are distinguished by the presence of SD: subgroup 1 (n=170)  — OA CS +GB, subgroup 2 (n=46) — OA CS+GB+SD, subgroup 3 (n=72) — GB, subgroup 4 (n=20) — GB+SD. At stage 2, the dynamics of GFR after total knee arthroplasty (TEP CS) in subgroups 1 and 2 and against the background of AGT therapy in subgroups 3 and 4 were evaluated. Results: at the 1st stage, it was found that the proportion of people with GFR 60 ml/min/1.73 m2 was significantly higher in subgroup 1 (OA CS+GB) compared with subgroup 3 of patients with GB without joint pathology (40.6% vs. 12.5%, p0.01). The presence of DM in patients with GB significantly affected renal filtration function, which is reflected in an increase in serum creatinine levels in subgroup 4 (GB+DM) by 20.02% and a decrease in GFR by 15.35%.

Against the background of the performed TEP in the group with GB, 64.06% had a stable GFR value or its increase, and in the subgroup of GB+ DM after TEP, 72.41% of patients had an increase or stable state of renal filtration capacity. At the same time, during the same follow-up period in the comparison group (in patients with GB without comorbid conditions), only 39.13% of cases had stable GFR values, and a decrease in GFR was recorded in 60.87%. At the same time, the dynamics of GFR values manifested itself in an increase of 11.19% in patients of subgroup 5 (TEP CS + GB) and by 12.47% in the group of the described knee joint intervention with a combination of GB and DM. In patients with controlled hypertension, GFR decreased by 6.6%. Conclusion: knee replacement in patients with hypertension and type 2 diabetes mellitus can slow down the rate of GFR reduction.

Drug-induced liver damage is becoming one of the important liver diseases and a diagnostic problem for general practitioners and gastroenterologists. A case report of suspected liver damage caused by ashwagandha is described. The disease appeared 2 months after starting to take ashwagandha 1 g per day and occurred with cholestatic and cytolytic forms of liver damage, jaundice and skin itching. The therapy led to an improvement in the patient's general condition, but the jaundice tended to be protracted. It is recommended to avoid repeated use of dietary supplement (Ashwagandha).

As is known, orphan diseases, which include histiocytosis, including Erdheim-Chester disease (ECD), occur under the guise of other diseases, which complicates timely diagnosis and treatment. The presence of various symptoms in patients with an unspecified diagnosis (weight loss, fever, chills, night sweats, malaise, shortness of breath, thirst, polyuria; pain in the muscles and joints, in the long tubular bones of the upper and lower extremities, in the lower back or abdomen due to kidney damage and/or retroperitoneal fibrosis; exophthalmos; rash, xanthomas; frequent infectious diseases; nystagmus, ataxia, dysarthria) requires doctors to be wary of BEC.The variety of symptoms is due to the involvement of many organs and systems (orbits, kidneys, skin, brain, including the pituitary gland; lungs; heart; blood vessels; tubular bones), which requires a thorough examination, including morphological verification of the pathological process. Histological examination of biopsy specimens for BEC is characterized by histiocytic infiltrates (so-called “foamy histiocytosis”) with signs of inflammation and the presence of Touton giant cells; Immunohistochemistry reveals positive staining of these giant cells for CD68 antigen and factor XIIIa. Bone scintigraphy reveals a pronounced symmetrical accumulation of radiopharmaceuticals in the affected bones; with radiography in places of ossalgia — significant symmetrical bilateral osteosclerosis of the periosteum; according to CT data - “hairy” kidneys, “lined” aorta as a result of infiltration with histiocytes. The BRAF V-600E gene mutation, detected in half of the cases, in combination with one or more clinical and morphological signs allows a correct diagnosis to be made. The treatment of this disease is quite complex due to the lack of multicenter international clinical studies due to the rare occurrence of this pathology. However, clinical studies are currently being conducted on the use of drugs of various groups in the treatment of BEC. There is no doubt that due to the rarity of the disease and the low awareness of doctors, our own clinical experience in managing such patients is of great interest.

Listeriosis is a saprozoonotic infection caused in humans mainly by the species Listeria monocytogenes. Its source can be objects of the external environment (soil and water of open reservoirs with a high content of organic compounds, plants) and more than 90 species of animals. The high metabolic activity of listeria and resistance to adverse factors create the possibility of an easy transition from a saprophytic to a parasitic type of metabolism when ingested by the host. A variety of transmission routes and "entrance gates" cause the emergence of a variety of primary localized forms of infection, the most common of which is gastrointestinal. Invasive forms of listeriosis develop mainly in people with immunological insufficiency. "Risk groups" are pregnant women, newborns, people with comorbid conditions, over 60 years old, drug addicts, etc. They are characterized by polymorphism of symptoms, the absence of specific manifestations. Pathogenicity factors of L. are important in the pathogenesis of infection. monocytogenes, providing their incomplete phagocytosis, intracellular parasitism, high rate of colonization of neighboring healthy cells, the formation of antibiotic resistance. The pathological expression of changes caused by listeria in cells is the formation of small granulomas — listeriomas. The "diversity" of listeriosis, the high mortality rate (up to 50% or more) and the low alertness of doctors regarding this infection create difficulties in making a diagnosis, and therefore the improvement of microbiological diagnostic methods is of particular importance.

The article provides information about outstanding scientists who selflessly fought against the causative agents of the most dangerous infectious diseases over the centuries of human existence. The contribution to the fight against epidemics of Russian and Soviet scientists is shown, who experimented with self-infection on themselves, testing new vaccines and methods of nonspecific prevention of severe infections.