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Aim      To identify metabolomic and structure and function markers of remote left ventricular (LV) remodeling in patients with chronic heart failure (CHF) of ischemic etiology and LV ejection fraction (EF) <50%.Material and methods  This prospective study included 56 patients with 3-4 NYHA functional class CHF of ischemic etiology (mean age, 66±7 years) and 50 patients with ischemic heart disease (IHD) without signs of CHF (69 [64; 73.7] years). Concentration of 19 amino acids, 11 products of kynurenine catabolism of tryptophan, 30 acylcarnitines with different chain lengths were measured in all participants. The metabolites that showed statistical differences between the comparison groups were then used for the analysis. Echocardiography was used to assess LV cavity remodeling at the time of the CHF patient inclusion in the study and after 6 months of follow-up. Predictors of long-term LV cavity remodeling were assessed for this cohort taking into account statistically significant echocardiographic parameters and metabolites.Results Patients with CHF of ischemic etiology, predominantly (81%) had pathological calculated types of LV remodeling (concentric and eccentric hypertrophy, 46 and 35%, respectively). However, this classification had limitations in describing this cohort. In addition, in this group, the concentrations of alanine, proline, asparagine, glycine, arginine, histidine, lysine, valine, indolyl-3-acetic acid, indolyl-3-propionic acid, C16-1-OH, and C16-OH were significantly (p<0.05) lower, and the concentrations of most medium- and long-chain acylcarnitines were higher than in patients with IHD without signs of CHF. The long-term (6 months) reverse remodeling of the LV cavity in CHF of ischemic etiology was influenced by changes in the interventricular septum thickness (hazard ratio, HR, 19.07; 95% confidence interval, CI, 1.76-206.8; p=0.006) and concentrations of anthranilic acid (HR 19.8; 95% CI 1.01-387.8; p=0.019) and asparagine (HR 8.76; 95% CI 1.07-71.4; p=0.031).Conclusion      The presence of an interventricular septum thickness of more than 13.5 mm, anthranilic acid concentrations of higher than 0.235 μM/l, or an asparagine concentration of less than 135.2 μM/l in patients with CHF of ischemic etiology after 6 months of follow-up affects their achievement of LV cavity reverse remodeling.

Aim    To evaluate the risks of all-cause death (ACD), cardiovascular death (CVD), death from recurrent acute decompensated heart failure (ADHF), and a composite index of CVD and death from recurrent ADHF in patients with chronic heart failure (CHF) after the first hospitalization for ADHF during a long-term, five-year follow-up in the conditions of specialized medical care and in real clinical practice.Material and methods    This prospective cohort observational study included 942 patients after ADHF. Group 1 consisted of 510 patients who continued the outpatient follow-up at a specialized center for the treatment of CHF (cCHF); group 2 consisted of 432 patients followed up at outpatient and polyclinic institutions (OPI) at the place of residence. During the five-year follow-up, the causes of death were determined based on the medical records of inpatients, postmortem examinations, or the conclusion in the medical records of outpatients. Rates of ACD, CVD, death from recurrent ADHF, and the composite index (CVD and death from ADHF) were analyzed. Statistical analysis was performed with a R statistical package.Results    ACD was 32.3% and 53.5% in groups 1 and 2, respectively (p<0.001). Based on the results of Cox proportional hazards models, it was shown that the follow-up in group 1, regardless of other factors, was associated with a decrease in the ACD risk (HR 2.07; 95% CI 1.68-2.54; p<0.001), CVD (HR 1.94; 95% CI 1.26-2.97; p=0.002), death from recurrent ADHF (HR 2.4; 95% CI 1.66-3.42; p<0.001) and the composite mortality index (HR 2.2; 95% CI 1.65-2.85; p<0.001) compared to group 2. The risks of death in CHF patients with moderately reduced left ventricular ejection fraction (LVEF) (HFmrEF) were consistent with the death rates in CHF patients with low LVEF (HFrEF) and were significantly higher than in CHF patients with preserved LVEF (HFpEF). The prognosis of life worsened with an increase in the Clinical Condition Assessment Scale score and age. The prognosis of life was better in women, as well as with higher values of systolic blood pressure (BP) and 6-minute walk test. In the structure of death in both groups, death from ADHF and sudden cardiac death (SCD) prevailed.Conclusion    The absence of specialized follow-up at an outpatient CHF center increases the risks of ACD, CVD, death from recurrent ADHF, and the composite endpoint at a depth of five-year observation. The leading causes of death were recurrent ADHF and SCD.

Introduction: The most reliable method for bladder catheterization when necessary is to put a urethral catheter under visual control. However, this requires endoscopic equipment and transportation of patient to a cystoscopy unit or operating room, which is not always possible. To solve these problems, we have developed the optical urethral catheter Visus MG., Aim: To evaluate the safety and efficacy of a new optical urethral catheter with a portable endoscopic complex., Materials and Methods: The prospective single-center clinical study included men, in whom the first bladder catheterization with a soft urethral catheter was impossible. They underwent insertion of the optical urethral Visus MG catheter under visual control., Results: A total of 60 men were included in the study. The median age was 70 years, the average prostate volume was 40 cc. Successful repeated catheterization was performed in 57/60 (95%) patients. In 5% cases (n=3), bladder catheterization was unsuccessful due to urethral obliteration. In 53 (88.3%) men, various surgical methods or manipulations were previously performed, including temporary bladder catheterization in most cases (n=16; 30.7%). The cause of failure of primary catheterization were urethral strictures in 19 (31.7%), benign prostatic hyperplasia in 9 (15%), false passage in 10 (16.7%), bladder neck sclerosis in 10 (16.7%), urethal obliteration in 3 (5%), and the foreign body in the urethra in 1 case (1.7%). In 6 (10%) men, there were signs of iatrogenic urethral trauma with urethrorrhagia due to previous attempts of catheterization, which, however, did not prevent a placement of the urethral catheter under vision control in safe manner., Conclusion: Bladder catheterization with an optical urethral catheter Visus MG with a portable endoscopic complex was successful in 57/60 (95%) patients after failed primary catheterization, which indicates the high efficiency of the method. The advantages of the technology are its portability, mobility and direct visualization of the urethra.

Aim: To evaluate the automated medical decision support system "Sechenov.AI_nephro" in the treatment of patients with renal parenchymal tumors., Materials and Methods: The beta version of the web-platform "Sechenov.AI_nephro" consists of a neural network based on MONAI (Medical open network for AI) and a web interface, with algorithms classified based on segmentation data in manual mode using the 3D modeling program "Amira". A total of 441 patients with renal parenchymal tumors were included in the multicenter prospective study. Testing was carried out over 12 months in 3 urological centers: 358 (81.2%) patients from I.M. Sechenov First Moscow State Medical University, Moscow; 73 (16.6%) patients from Bashkir State Medical University; and 10 (2.3%) patients from Saratov State Medical University named after V.I. Razumovsky. In all cases, contrast-enhanced computed tomography (CT) was performed preoperatively. DICOM (Digital Imaging and Communications in Medicine) data of each patient's CT was uploaded to the web-platform "Sechenov.AI_nephro" for automatic construction of a 3D model of the tumor. The work of the web-platform "Sechenov.AI_nephro" was evaluated based on a questionnaire completed by surgeons who performed the surgical intervention. The questionnaire consisted of 14 questions, with a scoring system from 1 to 10 points. It was divided into 3 main sections, including first for assessment of the quality of work of the web-platform "Sechenov.AI_nephro"; second for evaluation of the use of the 3D model in communication with the patient, for surgical planning and intraoperative navigation; and third for analysis of the choice of useful data display mode, errors in constructing the 3D model., Results: The questionnaire was completed in 253 (57.37% of 441) cases. The quality of 3D models was rated 7.8-9.4 points, and the use of the 3D model in communication with the patient, for surgical planning and intraoperative navigation was rated 7.8-9.4 points. The 3D models were constructed correctly in 70% of cases. The area of interest was the useful mode of 3D models display in surgical planning. Incorrectly constructed anatomical elements were veins in 25.5% and the tumor in 26.4% of cases, respectively., Conclusion: The automated medical decision support system in the treatment of patients with renal parenchymal tumors "Sechenov.AI_nephro" demonstrated satisfactory quality of 3D reconstruction of pathological process. 3D models allow for personalized determination of the surgical tactic for treating patients with renal tumors.

Aim: To study the factors that influence the occurrence of postoperative atrial fibrillation (POAF) in patients with chronic ischemic heart disease (IHD) after coronary artery bypass grafting (CABG)., Material and Methods: This single-center prospective observational non-randomized study included 152 patients with chronic IHD. Mean age of patients was 64.4±5.9 years. All patients after CABG were divided into two groups based on the occurrence of atrial fibrillation (AF) in the early postoperative period: group 1, with POAF (n=43; 28.3%) and group 2, without POAF (n=109; 71.7%). The primary study endpoint was new-onset POAF in the early postoperative (hospital) period after CABG. The secondary study endpoint was in-hospital postoperative complications (non-fatal/fatal acute coronary syndrome (ACS), non-fatal/fatal stroke, major bleeding, death)., Results: Patients with POAF had significantly more pronounced structural and functional changes in the heart than patients with preserved sinus rhythm after CABG: larger left ventricular (LV) volume, greater LV myocardial mass, lower LV systolic function parameters and impaired diastolic function, and an enlarged left atrial (LA) cavity. Analysis of in-hospital complications did not show any differences between the groups associated with the development of POAF. The following risk factors for POAF were identified: age older than 65 years (p=0.022), body mass index ≥30.5 kg/m2 (p=0.020), epicardial adipose tissue thickness >10.5 mm (p=0.015), indexed LA volume >33 ml/m2 (p<0.001), LV myocardial mass index >115 g/m2 (p=0.042), left main coronary artery disease >50% (p=0.043), duration of cardiopulmonary bypass during CABG >60 min (p=0.019), blood potassium concentration in the early postoperative period after CABG (on the first day) <3.6 mmol/l (p<0.001), and pericardial effusion volume in the early postoperative period >88 ml (p<0.001)., Conclusion: Determining the risk of developing POAF is important and necessary for the closest monitoring of a patient with chronic IHD in the postoperative period.

Objective: To compare the tolerability and feasibility of transrectal(TR) versus transperineal (TP) routes for prostate biopsy under local anaesthesia(LA). To assess the functional outcome and the complication of both procedures., Method: s. A prospective cohort observational study was performed on patients who underwent prostate biopsy under LA. Visual Analogue Scale (VAS) was used during the procedure. International Prostate Symptoms Score (IPSS) and International Index of Erectile dysfunction (IIEF) were assessed before the procedure and in 14 days after the procedure. Complication for each procedure was recorded., Result: A total of 128 patients with 64 patients for each group underwent prostate biopsy by TP and TR under LA. TP targeted biopsy group had comparable pain scores to those who underwent the procedure using the TR routes. The median pain score for the TP group was 2 and TR was 3, (IQR=2, range 0-10 for both groups)with no significant pain difference between both groups (P=0.48). Furthermore, there was no significant difference in urinary function(p=0.68) and sexual function (p=0.19) between the two groups post-procedure. Both groups have similar rates of complications, with no significant difference observed. Urinary tract infection incidents that did occur were rare and did not significantly differ between the groups (p=0.21). None of the patients experienced sepsis postoperatively. AUR was reported in both groups, slightly higher with 9.4%(N=6) in the TP group and 6.3%(N=4) in the TR group however no significant difference(p=0.112) was noted. Haematuria is common in both groups with TP (66%) and TR (59%) but self-limiting with Clavien-Dindo grade I without significant difference (p=0.589)., Conclusion: Our results showed that both Transperineal and transrectal approaches have similar tolerability with no significant difference in functional outcome or complications. Further studies are mandatory to verify our results.

Aim: To study the dynamics of cystatin C in patients after procedures on retroperitoneal viscera using laparoscopic and retroperitoneal access., Material and Methods: A prospective study of serum and urine cystostatin C levels in 162 patients with renal cysts using laparoscopic (n=83) and retroperitoneal access (n=79) was carried out. Patients were divided into four groups depending on the duration of the procedure and the gas level. For determination of cystatin C level in serum and urine, flow cytometry was performed using Human Kidney Function Panel 2 Mix and Match Subpanel (for Serum/Plasma Samples)., Results: A significant increase in the serum and urine level of cystatin C in groups 3 and 4 was seen on the 1st day after laparoscopic procedures in case of pneumoperitoneum pressure above 12 mm Hg., regardless of its duration. For retroperitoneoscopic procedures, similar changes were found only in group 4 with a gas pressure above 12 mm Hg and duration of the intervention of more than 30 minutes. By day 3, cystatin C levels returned to baseline values in all groups., Conclusion: The most significant risk factor for acute kidney injury after laparoscopic and retroperitoneoscopic procedures is the gas pressure. The second most important factor is the duration of the intervention. Pneumoperitoneum has a greater effect on cystatin C levels compared to retropneumoperitoneum.

Introduction: Today it is urgent to introduce into clinical practice more advanced methods of kidney stone treatment with high indicators of their effectiveness and safety while minimizing the risk of repeated interventions. The goal of effective treatment of kidney stones is to completely rid the patient of stones and complaints, to eliminate organ dysfunction, using minimally invasive treatment methods that reduce the patients hospital stay and the risk of complications. However, there are only few studies comparing the clinical efficacy and safety of modern methods of surgical treatment of kidney stones 2 to 3 cm in size. Remote shockwave lithotripsy or retrograde intrarenal surgery is the treatment of choice for kidney stones up to 2 cm, and percutaneous nephrolithotomy is the treatment of choice for stones larger than 2 cm. Flexible ureterorenoscopy is not recommended as first-line treatment in patients with kidney stones >2 cm due to the high risk of reintervention, according to the RTC clinical guidelines. However, it can be performed successfully in centers with extensive experience with this technique. The advantages of retrograde intrarenal surgery are low trauma, low risk of complications such as bleeding and damage to adjacent organs, and shorter hospital stay. The efficacy of flexible ureterorenoscopy is significantly lower for stones larger than 3 cm, and for stones between 2 and 3 cm there are only a few studies, which do not allow a reliable judgment on the efficacy and safety of this technique., Purpose of the Study: To evaluate the efficacy and safety of flexible ureterorenoscopy in comparison with mini-percutaneous nephrolithotomy for kidney stones from 2 to 3 cm., Materials and Methods: A prospective randomized study to determine the efficacy of methods of surgical treatment of kidney stones from 2 to 3 cm in size using flexible ureterorenoscopy and mini-PCNL was conducted at the Institute of Urology and Human Reproductive Health of the I.M. Sechenov First Moscow State Medical University (Sechenov University) in Moscow. The study analyzed the results of the performed surgical interventions in patients with urolithiasis using flexible URS and mini-PCNL as an example from the point of view of their effectiveness and safety for kidney stones from 2 to 3 cm. The study utilized the results of 133 patients (including 64 patients after flexible URS and 69 patients after mini-PCNL). The mean size and mean density and location of the nodule between the groups were comparable and had no statistically significant differences. The effectiveness of the intervention in the form of complete absence of concretions, length of stay in the clinic, operative time, development of postoperative complications (bleeding, urinary tract infection) and Claviens surgical complication score were evaluated., Results: of the study. The duration of surgery was longer in the flexible URS group where it amounted to 69.9+/-9.3 minutes, in the mini-PCNL group the duration of surgery averaged 48.3+/-5.8 minutes (p=0.0001). The incidence of early postoperative complications in the flexible URS group was 6,2%, in the mini-PCNL group - 12,6%, which had statistically significant differences between the study groups at the level of p=0.001. The length of stay in the clinic was shorter in the flexible URS group, which averaged 2+/-1 days, while in the mini-PCNL group the length of stay was 5+/-2 days (p=0.0003). The frequency of concrement removal 3 months after the surgical intervention detected by computed tomography in the group of flexible URS was lower and amounted to 90,6%, in the group of mini-PCNL this index was at the level of 92,7% (p=0,06)., Conclusion: The results of this study demonstrate that flexible URS and mini-PCNL have a comparable success rate in removing concretions. Flexible URS reduces hospitalization time, causes fewer complications and can be used as an alternative in the treatment of kidney stones from 2 to 3 cm. Meanwhile, mini-PCNL has shown a higher percentage of effectiveness in getting rid of concretions 3 months after surgical intervention.

Purpose of the Study: Comparison of the pharmacokinetic characteristics of the drug Vildegra registered in the Russian Federation with literature data for the original drug Viagra., Materials and Methods: Study design: prospective, open-label in healthy volunteers with a single oral dose on an empty stomach. The study included 48 male volunteers aged 18 to 45 years with a verified diagnosis of "healthy." All subjects of the clinical study took 1 tablet of Vildegra once on an empty stomach. Blood samples to determine the concentrations of active substances were taken before taking the study drug and then after 0.25; 0.5; 0.75; 1; 1.5; 2; 2.5; 3; 3.5; 4; 4.5; 5; 5.5; 6; 7; 8; 10; 12; 16; 24; thirty; 36; 48 and 72 hours after taking the drug. Dynamic monitoring was carried out throughout the study, including clinical examination, measurement of vital signs, monitoring of laboratory parameters and monitoring of adverse events (AE). The concentrations of sildenafil and its active metabolite N-desmethylsildenafil in the blood plasma of volunteers were determined by high-performance liquid chromatography with tandem mass spectrometric detection. Pharmacokinetic parameters were calculated using a model-free method using the specialized program PK Solution2.0., Results: The AUC0-t, AUC0- and Cmax values for sildenafil and its active metabolite when taking the drug Vildegra are in good agreement with the literature data for the original drug Viagra. The values of tmax and t1/2 of the drug Vildegra are slightly higher than those of the original drug, which is apparently explained by the extended-release dosage form in the case of Vildegra. In 10 of 48 volunteers (21%), 20 AE were recorded, which resulted in complete recovery. No serious or unexpected AE were noted., Conclusion: The results obtained allow us to conclude that the pharmacokinetics, good tolerability and satisfactory safety profile of the drug Vildegra are comparable with the published data for the original drug Viagra.

Aim: To compare the efficacy of adding original moxonidine and its generics to previous ineffective antihypertensive therapy in patients with poorly controlled arterial hypertension (AH)., Material and Methods: This observational prospective non-randomized study included 120 patients with poorly controlled blood pressure on the previous antihypertensive therapy. All patients underwent clinical evaluation, including anthropometric and laboratory indexes, and 24-hour blood pressure monitoring (24-h BPM) at baseline and after 12 weeks of observation. Office systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) were recorded after 4 and 12 weeks of treatment. During the observation period, 4 equal groups were formed: group 1, Physiotens was added to the treatment; group 2, Moxonitex; group 3, Moxonidine SZ; and group 4, Moxonidine Canon. Statistical analysis was performed with the StatTech v.4.2.7 software (© OOO StatTech, Russia)., Results: After 4 weeks of therapy, the BP target was achieved significantly more frequently in group 1 (63% of patients) compared to groups 2 (36.7% of patients), 3 (16.7% of patients), and 4 (16.7% of patients) (p<0.05). At 12 weeks, office SBP, DBP, and HR were significantly decreased in all groups, but the decrease was significantly greater in group 1. The therapy was associated with a more pronounced decrease in all studied 24-h BPM parameters in the Physiotens group than in other groups, as well as with a significantly more frequent normalization of the 24-h BP profile, in 66.7% of patients vs. 46.7%, 33.4%, and 23.2% of patients in groups 2, 3, and 4, respectively., Conclusion: The treatment with original moxonidine demonstrated advantages over generic drugs in terms of achieving the BP goal, reducing office BP and HR, and improving 24-h BPM parameters.

Aim: To study clinical and demographic characteristics, treatment options, and clinical outcomes in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) compared with patients with myocardial infarction with obstructive coronary arteries (MIOCA)., Material and Methods: This single-center prospective observational study included 712 successive patients diagnosed with acute myocardial infarction (MI), who routinely underwent direct coronary angiography. Based on the presence of stenosing coronary atherosclerosis, the patients were divided into two groups: MIOCA (coronary stenosis ≥50%) and MINOCA (coronary stenosis <50% without other, alternative causes). Clinical outcomes included in-hospital and long-term overall mortality, and cardiovascular rehospitalization. The median follow-up was 1.5 years., Results: MINOCA was diagnosed in 73 (10.3%) patients, 37 (50%) of whom were women. The median age of patients with MINOCA was 61 years and in the MIOCA group 65 years. No significant differences in cardiovascular risk factors were found between patients with MINOCA and MIOCA. In 53.4% of cases, the cause of MINOCA was a discrepancy between the myocardial oxygen demand and supply, and in 35.6% of cases, the cause was hypertensive crisis and pulmonary edema. The factors associated with MINOCA included an age ≤58 years, female gender, absence of the ST-segment elevation, absence of areas of impaired local contractility, and presence of aortic stenosis and bronchopulmonary infection. Patients with MINOCA were less likely to be prescribed acetylsalicylic acid, P2Y12 inhibitors, dual antiplatelet therapy, beta-blockers, and statins (p<0.05). Data on long-term outcomes were available for 87.5% of patients (n=623). The prognosis of patients with MIOCA was comparable for in-hospital mortality (1.5% vs. 6.2%; p=0.161) and long-term overall mortality (6.1% vs. 14.7%; p=0.059). Cardiovascular rehospitalizations were more frequent in the MINOCA group (33.3% vs. 21.5%; p=0.042)., Conclusion: The prevalence of MINOCA in our study was 10.3% among all patients with acute MI. MINOCA patients had comparable generally recognized cardiovascular risk factors with MIOCA patients. MINOCA patients had a comparable prognosis for in-hospital and long-term mortality and more often required cardiovascular rehospitalization.

Aim: To evaluate the prognostic value of GDF-15 in relation the development of bleeding and events in stable CAD patients, receiving combined antithrombotic therapy., Materials and Methods: The data was obtained from the prospective registry REGATA, 343 CAD patients (249 males), median age 68 [IQR 62; 75] years) were enrolled. Patients with sinus rhythm and concomitant PAD received acetylsalicylic acid in combination with rivaroxaban 2.5 mg bid (31.8%) or clopidogrel (24.8%). Other 43.4% with concomitant atrial fibrillation (AF) received direct oral anticoagulants in combination with antiplatelet therapy after elective percutaneous coronary interventions. Median follow-up was 12 months [ IQR 9.0 ; 18.0]. The safety end point was major and clinically relevant bleedings (type 2-5) according to the BARC classification. Plasma samples for GDF-15 identification were taken at the inclusion and analyzed using ELISA assay., Results: Frequency of BARC 2-5 bleedings was 16% (BARC 2 - 46; BARC 3 - 9; BARC 4-5 - 0), median GDF-15 level was 1185.0 pg/ml [850.0; 1680.0]. In patients with AF and concomitant MFA, the level of GDF-15 was significantly higher than in the subgroups of patients with only AF or MFA ( p =0.0022). According to the quintile analysis, GDF-15 values in the top three quintiles of distribution (cut-off value >943 pg/ml) were associated with higher frequency of bleeding events: 23.2% versus 5.1%; p =0.0001. The multivariable logistic regression model demonstrated that bleeding events were independently associated with GDF-15 level>943 pg/ml (OR 2.65, 95% CI 1.11-6.30; p =0.0275), AF (OR 2.61, 95% CI 1.41-4.83; p =0.0023) and chronic kidney disease (OR 1.92, 95% CI 1.03-3.60; p =0.0401). Clinical factors determining the risk of bleeding events also determined a GDF-15 elevation., Conclusion: Assessment of GDF-15 level may improve bleeding risk stratification in CAD patients with concomitant AF and/or PAD receiving combined antithrombotic therapy.

Aim: Evaluation in real clinical practice of the effectiveness and safety of levilimab therapy in patients with highly and moderately active rheumatoid arthritis (RA)., Materials and Methods: A prospective observational study (6 months) involving 35 patients with RA (29 women and 6 men, mean age 53.17±13.2 years) who were treated at the Ochapovsky Regional Clinic Hospital of Krasnodar Region. All patients included in the study were prescribed the drug levilimab (Ilsira)., Results: After 1 month of observation, there was a decrease in the clinical and laboratory activity of the process in the form of a decrease in the number of painful joints - 17.0 (14.0; 20.0) vs 8.0 (6.0; 10.0); p =0.000001, number of swollen joints - 3.0 (2.0; 4.0) vs 0.0 (0.0; 0.0); p =0.000002, reduction in pain intensity according to visual analog scale - 60.0 (60.0; 70.0) mm vs 30.0 (20.0; 40.0) mm ( p =0.000001). Also, by the end of the first month of therapy, there was a decrease in clinical activity indices DAS28-ESR by 43%, SDAI by 60%, CDAI by 55%. Positive dynamics of laboratory parameters were noted - a decrease in erythrocyte sedimentation rate by 76%, a decrease in C-reactive protein level by 98%. By the 6th month of therapy, a decrease in RF by 36% and ACCP by 11% was recorded, but the dynamics of these indicators did not reach statistical significance. By the end of 4 weeks of treatment, 24 (68.6%) patients showed an increase in the level of total blood cholesterol - 5.1 (3.91; 6.0) mmol/L vs 6.1 (4.99; 7.07) mmol/L ( p =0.000006), while 11 (45.8%) patients from this group had initially elevated cholesterol levels (6.4±0.6 mmol/L). In 5 (14.3%) patients, an increase in alanine aminotransferase (ALT) was recorded in the 4th week - 17.0 (11.0; 25.0) U/L vs 32.0 (22.0; 43.0) U/L ( p =0.000062) and aspartate aminotransferase (AST) - 19.0 (14.0; 24.0) U/L vs 25.0 (18.0; 36.0) U/L ( p =0.000171), in 1 (2.85%) of the patient, an increase in ALT and AST above normal was noted (ALT 144 U/L, AST 52 U/L), which required discontinuation of levilimab. In 2 (5.7%) patients, by the end of the 4th week a decrease in the absolute number of neutrophils was registered - 3.2 (2.6; 4.0)×10E 9 /L vs 2.3 (2.0; 2.5)×10E 9 /L ( p =0.002), which did not require discontinuation of treatment, since the number of cells remained more than 1×10E 9 /L. During treatment with levilimab 162 mg subcutaneously once a week, the proportion of patients taking prednisolone decreased from 46% at the start of therapy to 11% at the end of 6 months of therapy., Conclusion: Levilimab is a highly effective drug for the treatment of patients with highly and moderately active RA and has a favorable tolerability and safety profile.

Aim: To assess the incidence of glucose metabolism disorders, administered hypoglycemic therapy and its effectiveness in a cohort of patients with previously diagnosed diabetes mellitus (DM) hospitalized for scheduled lower limb joint arthroplasty., Materials and Methods: The study included 502 patients. Medical history, information about previously diagnosed DM and prescribed hypoglycemic therapy were collected in all patients according to medical documentation, as well as according to the patients' survey. Within the preoperative examination, the glucose level was measured, and in patients with previously diagnosed diabetes, measuremaent of the HbA 1c level was recommended., Results: The study population included 180 (35.9%) males and 322 females (64.1%). Among them, 99 (19.7%) patients had disorders of glucose metabolism [type 1 diabetes - 1 (0.2%) patient, type 2 diabetes - 90 (17.9%) patients, impaired glucose tolerance (IGT) - 8 (1.6%) patients]. In 8 patients, type 2 diabetes was newly diagnosed during the preoperative examination. HbA 1c was measured before hospitalization in 26 patients with diabetes, the mean level was 7.0±1.4%. Regarding the analysis of hypoglycemic therapy, almost half of the patients with DM - 47 (47.5%) - received metformin monotherapy, 8 patients with IGT and 8 patients with newly diagnosed DM did not receive any drug therapy. Target glycemic levels during therapy were achieved in 36 (36.4%) patients, and target HbA 1c levels were achieved in 21 patients., Conclusion: The cohort of patients hospitalized for elective lower limb joint arthroplasty is characterized by a relatively high incidence of glucose metabolism disorders, and in some patients, DM was newly diagnosed during the preoperative examination. Metformin is most often used as hypoglycemic therapy, and the target values of glycemia during treatment were achieved in less than half of the patients. The monitoring of the level of glycated hemoglobin is low and requires additional population analysis in order to determine the causes and optimize the strategy of patient management.

Introduction: Several techniques are used for laser enucleation of benign prostate hyperplasia, including two- and three-lobe enucleation, enucleation of all lobes in a single block (en-bloc), and enucleation of all nodes in a single block without longitudinal incisions (total en-bloc)., Aim: A prospective and retrospective analysis of the results of two-lobe, en-bloc, and total en-bloc using thulium fiber laser enucleation of the prostate (ThuFLEP) techniques was performed., Method: s. The study included a retrospective and prospective comparative analysis of the peri- and postoperative results of ThuFLEP using several techniques. Patients with benign prostatic hyperplasia causing bladder outlet obstruction (IPSS>20, Qmax<15) were undergone to ThuFLEP from January 2015 to May 2022. All patients were examined prior to and 1, 3, and 6 months after the procedure. In the pre- and postoperative period, the age of the patients, prostate volume, level of prostate-specific antigen, functional parameters (IPSS, post-void residual, Qmax, and QoL), the stress urinary incontinence were evaluated. In addition, the following intraoperative parameters were assessed: duration of the procedure, enucleation rate, morcellation rate, and mass of enucleated tissue., Results: We found 450 patients who underwent thulium fiber laser enucleation of prostate hyperplasia (ThuFLEP). Three laser enucleation techniques were used, including two-lobe (n=148; group A), en-bloc (n=150; group B), and total en-bloc without longitudinal incision (n=152; group C). The mean prostate volume was comparable between groups. The mean operation time for the total en-bloc technique (group C) was less compared to the other two techniques (58.9+/-30.1 vs. 68.8+/-30.6 for group A and 67.4+/-30.1 min for group B, respectively; p<0.005). The mean enucleation rate in group C was higher compared to groups A and B (2.3+/-0.78 vs. 1.9+/-0.74 and 1.9+/-0.69 g/min, respectively; p<0.005). The mean morcellation rate in all three groups was comparable (2.8+/-1.7, 3.0+/-1.1, and 2.9+/-2.1 g/min; p>0.05). After 6 months, there were no differences in functional results, according to the IPSS, PVR, Qmax, and QoL., Conclusion: The two-lobe, en-bloc, and total en-bloc techniques were comparable in functional results and the complication rate. Total en-bloc enucleation showed the higher enucleation efficiency.

Introduction: Symptoms of dysuria due to bladder inflammation associated with sexual intercourse (postcoital cystitis) negatively affect the psycho-emotional state of patients, reduce the quality of life and lead to the development of sexual dysfunction. With the advent of the possibility of antibacterial prophylaxis and improved sanitary and hygienic conditions, interest in surgical treatment of postcoital cystitis has decreased., Material and Methods: An open, prospective, non-comparative study included 56 patients with postcoital cystitis in different periods of menopause (perimenopause, menopause and postmenopause). At the time of inclusion, all women had symptoms of cystitis associated with recent (no more than 24 hours ago) sexual intercourse. Patients filled out a specially developed questionnaire and the Acute Cystitis Symptom Score (ACSS). They underwent urinalysis and urine culture with antibiogram. All patients were prescribed Superlymph suppositories in a dose of 10 units as monotherapy according to the scheme: 1 suppository rectally in the evening, 1 suppository vaginally in the morning. Patients with leukocyturia and bacteriuria were initially given antibacterial therapy, after which they were prescribed Superlymph according to the scheme described above as monotherapy. The targeted cytokine therapy was prescribed for 1 month. During treatment, the patients continued to have sexual activity as usual. The efficiency of treatment was assessed immediately after completion of the course and 3 months after its completion. The efficiency was evaluated according to the incidence of postcoital cystitis., Results: In patients included in the study, the first episode of cystitis occurred on average at the age of 33.1+/-2.4 years. In almost half of women (n=24 (42.9%)), the onset of cystitis was associated with sexual activity. During reproductive age, 42 (75%) women had postcoital cystitis, and 10 (23.8%) of them had only one episode. At the same time, every fourth woman (n=14 (25%)) suffered from first episode of postcoital cystitis during menopause. The average age of patients at which the first episode of postcoital cystitis occurred was 38.6 +/- 7.7 years. After a month of monotherapy with Superlymph, 31 patients (55.4%) did not report a single episode of postcoital cystitis, while after three months, 42 women (75.0%) achieved recurrence-free status. Of the 26 patients (46.4%) who were initially diagnosed with bacterial vaginosis, the vaginal normocenosis was found in 18 (69.2%) cases., Conclusion: Postcoital cystitis can occur in women of any age, including those with a normal anatomy of the genitourinary system. Combined rectal and vaginal use of Superlymph suppositories at a dose of 10 U for a month helps to avoid relapse of postcoital cystitis in 55.4% of patients. Targeted cytokine therapy has a prolonged effect within three months after completion therapy, and 75% of women did not report relapses of postcoital cystitis.

Objective: The purpose of this study was to evaluate the effectiveness of the drugs Solifenacin and Vesusten in relation to the treatment of neurogenic bladder overactivity in multiple sclerosis (MS)., Materials and Methods: A prospective, single-site, single-center, placebo-controlled, parallel-group, comparative clinical trial was conducted. The study included 41 MS patients of both sexes aged 18-50 years with urodynamically confirmed detrusor overactivity. Data were obtained by completing a voiding diary. Clinical data were assessed before taking the drugs, during a monthly course of therapy and after a month of observation after the end of treatment. The results were processed by nonparametric methods of statistical analysis., Results: Both drugs are effective in patients with MS to correct neurogenic bladder overactivity. At the same time, in comparison with Solifenacin, Vesusten showed better clinical efficacy in relation to clinical manifestations of overactive bladder (OAB). Pollakiuria and urgency also decreased significantly. The best profile of maintaining the therapeutic effect was observed with Vesusten in relation to the frequency of urinary incontinence and OAB syndrome. The results of the study established that Solifenacin and Vesusten can cause adverse events, the frequency and nature of which correspond to the data declared by the manufacturers., Discussion: Considering the clinical features of MS, the priority in treatment, in addition to effectiveness, is maximum conservative therapy. The currently recommended therapy for neurogenic bladder overactivity is limited to the use of M-anticholinergics and intradetrusor administration of botulinum toxin type A drugs. At the same time, multiple side effects of such treatment are observed with a high frequency. The emergence of a new effective therapeutic agent is a promising direction for the treatment of neurogenic bladder overactivity in patients with MS., Conclusions: Both Solifenacin and Vesusten are effective therapeutic options for the management of neurogenic bladder overactivity in MS. However, Vesusten has a more significant therapeutic profile, expressed in the correction of pollakiuria, urge incontinence and urgency. After completion of therapy, Vesusten, in comparison with Solifenacin, demonstrates the retention of a strong therapeutic effect. Based on the combination of various assessment parameters of a voiding diary, Vesusten is a priority therapeutic agent that determines the best quality of life profile for patients with MS.

Introduction: According to the literature of recent years, there has been an increased interest in non-oncological diseases of the bladder, between which differential diagnostics have to be carried out in order to determine a plan for the diagnosis and treatment of patients with these nosologies. There are often certain difficulties in the differential diagnosis of some forms of viral cystitis and leukoplakia OBJECTIVE: to determine pathomorphological criteria for the differential diagnosis of leukoplakia and chronic recurrent papillomavirus cystitis., Materials and Methods: The prospective study included 85 sexually active patients aged 20-45 years, who were divided into two groups depending on the etiological factor. Patients of group I (n=70) - with chronic recurrent cystitis (CRC) of papillomavirus (PV) etiology, group II (n=15) - with leukoplakia. All patients were examined in accordance with the recommendations of the European Association of Urology (EAU) and the Russian Society of Urology (ROU); an additional endoscopic examination of the bladder (cystoscopy) was performed, followed by a morphological examination of the bladder biopsy., Results: A morphological examination of biopsy tissue in all patients of group I revealed koilocytic transformation of the urothelium combined with non-keratinizing metaplasia of the urothelium, and in patients of group II, in all cases, keratinizing metaplasia of the urothelium with hyperkeratosis was detected., Conclusion: Morphological examination is the gold standard in differential leukoplakia and chronic recurrent papillomavirus cystitis.

Objective: to evaluate the effectiveness of the recommended modes of laser lithotripsy in clinical practice by analyzing the necessity of changing laser radiation parameters during percutaneous nephrolithotripsy (PCNL), ureterolithotripsy (URS) and retrograde intrarenal surgery (RIRS)., Materials and Methods: a prospective non-randomized clinical study was conducted from October 2023 to December 2023. Patients who underwent surgical procedures for urinary stones using a Thulium fiber laser at the Clinic of Urology of Sechenov University were included. Data on localization, size and radiological density of the stones, initial parameters of laser radiation, presence or absence of mode change were recorded. Statistical data was processed using IBM SPSS Statistics software, version 26.0.0.0.0., Results: 90 patients were included in the study. Laser radiation mode change was recorded in 38% of cases when performing RIRS, in 25% - during PCNL, and in 24% - during URS. A significantly higher total energy consumption at comparable volumes and radiological density of the stones was registered in the group of mode change at RIRS. In the URS group the results suggest that the laser radiation mode change depends on the volume and density of urinary stones., Discussion: the need for intraoperative change of laser radiation modes in 31% of all observations may indicate that the existing optimal modes for stone destruction in clinical practice may be suboptimal. New studies of the structure and mechanical properties of urinary stones, assessment of their porosity, hardness, size and properties of crystals, as well as the use of Artificial Intelligence for automatic set up of laser radiation parameters for higher efficiency of lithotripsy., Conclusion: In addition to linear size and radiologic density urinary stones have a whole complex of morphometric and physicochemical characteristics, so the laser lithotripsy parameters preset should be viewed only as a guideline, while effective settings are to be selected intraoperatively considering urologists knowledge of laser radiation physical properties.

Background: Non-pharmacological treatments based on collagen as a dietary supplement are emerging as a new area of interest to support preventive or therapeutic effects in patients with osteoarthritis (OA)., Aim: In a multicenter, prospective, double-blind, placebo-controlled, randomized study, to evaluate the effectiveness and safety of the use of the Artneo complex containing undenatured chicken collagen type II in patients with OA of the knee joints., Materials and Methods: The study enrolled 212 outpatients from 12 centers in the Russian Federation with knee OA, stages II and III according to the Kellgren-Lawrence classification. The participants included 171 women (80.7%) and 41 men (19.3%), with an average age of 60.2±9.0 years (range: 40 to 75 years). The study population was randomly allocated in equal proportions into two groups using an interactive web response system (IWRS). Group 1 (Artneo) consisted of 106 patients who took one capsule of the drug once daily for 180 days. Group 2 (Placebo) also had 106 patients, with the dosage form and regimen identical to Group 1. During the treatment period, the following outcomes were assessed: WOMAC index, KOOS, pain according to VAS, quality of life using the EQ-5D questionnaire, and the need for NSAIDs. All patients underwent a clinical blood test, general urine analysis, biochemical blood test, and ultrasound examination of the affected knee joint., Results: In a prospective, double-blind, placebo-controlled, randomized study, it was demonstrated that the Artneo combination, containing undenatured chicken collagen type II, has a positive effect on all clinical manifestations of OA: it effectively reduces pain, stiffness, and improves the functional state of joints and quality of life. It has a good safety profile and is superior to placebo in all parameters studied., Conclusion: The results of the study confirm the good effectiveness and safety of the Artneo combination in patients with OA of the knee joints.

Introduction: Erectile dysfunction is often a consequence of stressful situations, lack of adequate sleep and rest, and sedentary lifestyles. The profession of locomotive engineer implies the presence of these negative factors, which in addition provoke high blood pressure and the development of hypertension., Materials and Methods: A total of 85 patients of the urological and therapeutic departments of the "Clinical Hospital "Russian Railways Medicine" in the city of Barnaul", working as locomotive drivers or assistant drivers, were examined. 65 men with erectile dysfunction and hypertension of 1-2 stages (all received antihypertensive therapy) were randomly divided into 3 groups: in the group 1, an activator of endogenous nitric oxide synthase (NOS) was added to the treatment of hypertension; in group 2, a combination of an endogenous NOS activator and a phosphodiesterase-5 inhibitor (PDE-5) was used. Patients of group 3 did not receive additional treatment. The efficiency of treatment was assessed using markers of endothelial dysfunction, including plasminogen activator inhibitor type 1 (PAI-1), endothelin-1 (ET-1), homocysteine, high-selective C-reactive protein (hs-CRP). In addition, the International Index of Erectile Function and male copulatory function scores were filled out. Moreover, laser doppler flowmetry (LDF) with determination of blood flow in penile vessels was done. Follow-up examination was carried out after 2 and 4 months. Twenty of the persons were healthy and referred to the control group., Results: There were no significant changes in markers and LDF values after 2 months in groups 1 and 3. In group 2, ET-1 and hs-CRP returned to the reference limits, which indicated a decrease in ischemia. After 4 months, there was an improvement in hemodynamics and marker values in group 2. The mean blood flow increased in group 1, while hs-CRP returned to the reference limits. In patients of group 2, a higher total IIEF and male copulatory function scores was documented. In group 3, there was no improvement., Conclusion: The combination of hypotensive drugs, PDE-5 inhibitor and NOS activator showed the best effect, improving blood flow, reparative properties of endothelium with preventing of thrombus formation. Treatment with an NO synthase activator partially eliminates pathological processes in the endothelium.

Aim: Identification of clinical and instrumental predictors for non-arrhythmic death in patients with heart failure (HF) and implantable cardioverter-defibrillator (ICD)., Material and Methods: Through a telephone survey and examination of medical records from hospital and polyclinic databases, data were obtained on the alive/dead status and causes of death for 260 patients with heart failure (HF) and ICD included in the Kuzbass Registry of Patients with ICD. The follow-up period was 1.5 years. Clinical and instrumental parameters entered into the registry before the ICD implantation were included in a univariate and multivariate step-by-step analysis using the logistic (for qualitative variables) and linear (for quantitative variables) regression with calculation of regression coefficients and construction of a prognostic regression model. The quality of the created model was assessed using a ROC analysis., Results: During the observation period, 54 (20.8%) patients died. In 21 (38.8%) patients, death occurred in the hospital and was caused by acute decompensated heart failure in 15 (71.4%) patients, myocardial infarction in 3 (14.3%) patients, stroke in 1 (4.7%) patient, and pneumonia in 2 (9.5%) patients. 33 (61.2%) patients died outside the hospital; the cause of death was stated as the underlying disease associated with acute decompensated heart failure: in 9 (27.2%) patients, dilated cardiomyopathy; in 1 (3.0%) patient, rheumatic mitral disease; and in 23 (69.7%) patients, ischemic cardiomyopathy. According to the univariate regression model, the risk of death in the long-term period was increased by the QT interval prolongation (U 2.41, p = 0.0161); elevated pulmonary artery systolic pressure (U 4.30, p=0.0000) and increased left atrial size according to echocardiography (U 2.98, p=0.0029); stage IIB HF (OR 2.41; 95% CI: 1.26-4.6), NYHA III-IV (OR 3.03; 95% CI: 1.58-5.81); chronic obstructive pulmonary disease (OR 5.24; 95% CI: 2.04-13.45); and lack of optimal drug therapy (ODT) for HF before ICD implantation (OR 2.41; 95% CI: 1.29-4.49). The multivariate analysis identified the most significant factors included in the prognostic regression model: pulmonary artery systolic pressure above 45 mm Hg, social status, chronic obstructive pulmonary disease, and lack of ODT for HF., Conclusion: To ensure a maximum benefit from ICD, the factors that increase the likelihood of non-arrhythmic death should be considered before making a decision on ICD implantation. Particular attention should be paid to mandatory ODT for HF as the main modifiable risk factor for unfavorable prognosis.

Aim: To evaluate a potential role of different patterns of intrarenal blood flow using Doppler ultrasound as a part of determining the severity of venous congestion, predicting impairment of renal function and an unfavorable prognosis in patients with acute decompensated chronic heart failure (ADCHF)., Material and Methods: This prospective observational single-site study included 75 patients admitted in the intensive care unit for ADCHF. Upon admission all patients underwent bedside renal venous Doppler ultrasound to determine the blood flow pattern (continuous, biphasic, monophasic). In one hour after the initiation of intravenous diuretic therapy, sodium concentration was measured in a urine sample. The primary endpoint was the development of acute kidney injury (AKI). The secondary endpoints were the development of diuretic resistance (a need to increase the furosemide daily dose by more than 2 times compared with the baseline), decreased natriuretic response (defined as urine sodium concentration less than 50-70 mmol/l), and in-hospital death., Results: According to the data of Doppler ultrasound, normal renal blood flow was observed in 40 (53%) patients, biphasic in 21 (28%) patients, and monophasic in 14 (19%) patients. The monophasic pattern of intrarenal blood flow was associated with the highest incidence of AKI: among 14 patients in this group, AKI developed in 100% of cases (OR 3.8, 95% CI: 2.5-5.8, p&lt;0.01), while among patients with normal and moderate impairment of renal blood flow, there was no significant increase in the risk of developing AKI. The odds of in-hospital death were increased 25.77 times in patients with monophasic renal blood flow (95% CI: 5.35-123.99, p&lt;0.001). Patients with a monophasic intrarenal blood flow pattern were also more likely to develop diuretic resistance compared to patients with other blood flow patterns (p&lt;0.001) and had a decreased sodium concentration to less than 50 mmol/l (p&lt;0.001) in a spot urine test obtained one hour after the initiation of furosemide administration., Conclusion: Patients with monophasic intrarenal blood flow are at a higher risk of developing AKI, diuretic resistance with decreased natriuretic response, and in-hospital death.

Aim: Based on data from the Russian REGION-MI registry, to characterize patients with myocardial infarction (MI) hospitalized in Russian hospitals, describe their historical, demographic, and clinical characteristics, and compare the results with the data of previous Russian and international registries of acute coronary syndrome., Material and Methods: REGION-MI is a multicenter prospective observational study. The follow-up period was divided into three stages: during the hospital stay, at 6 and 12 months after the inclusion in the registry. Demographic and historic data and information about the present case of MI were entered into the patient's individual record card., Results: The median age of all patients was 63 years; 68% of patients were men. The mean age of women was older than that of men. Among all MI cases, 70% were ST-segment elevation myocardial infarction (STEMI). Patients with non-ST-segment elevation myocardial infarction (NSTEMI) were older and had more comorbidities than patients with STEMI. The median time from the first symptoms to ECG recording was two hours, and from the first symptoms to CAG 7 hours. CAG was performed in 91% of patients with STEMI and 84% of patients with NSTEMI. Stenting was performed in 69% of patients. Although many patients had a complicated cardiovascular history, at the time of admission only 31.5% of patients were taking at least one drug from the groups of antiplatelets, oral anticoagulants, statins, and beta-blockers., Conclusion: Patients with MI in the Russian Federation are younger than patients with MI in European countries. Among the clinical and historical characteristics, conspicuous is the presence of modifiable risk factors in many patients, as well as the presence of a previous diagnosis of ischemic heart disease. Furthermore, a small proportion of patients took statins, antiplatelet agents or anticoagulants at the outpatient stage, which indicates a great reserve of both primary and secondary prevention of cardiovascular diseases in the Russian Federation. The delayed seeking medical help is also noticeable, which indicates the need for increasing the public awareness of the symptoms of MI and the importance of timely hospitalization.

Aim: To evaluate the impact of chronic obstructive pulmonary disease (COPD) on hospital outcomes of percutaneous coronary interventions (PCI) in patients with acute coronary syndrome (ACS)., Materials and Methods: A cohort prospective study of the COPD effect on mortality and coronary microvascular obstruction (CMVO, no-reflow) development after PCI in ACS was carried out. 626 patients admitted in 2019-2020 were included, 418 (67%) - men, 208 (33%) - women. Median age - 63 [56; 70] years. Myocardial infarction with ST elevation identified in 308 patients (49%), CMVO - in 59 (9%) patients (criteria: blood flow <3 grade according to TIMI flow grade; perfusion <2 points according to Myocardial blush grade; ST segment resolution <70%). 13 (2.1%) patients died. Based on the questionnaire "Chronic Airways Diseases, A Guide for Primary Care Physicians, 2005", 2 groups of patients were identified: 197 (31%) with COPD (≥17 points) and 429 (69%) without COPD (<17 points). Groups were compared on unbalanced data (÷ 2 Pearson, Fisher exact test). The propensity score was calculated, and a two-way logistic regression analysis was performed. The data were balanced by the Kernel "weighting" method, logistic regression analysis was carried out using "weighting" coefficients. Results as odds ratio (OR) and 95% confidence interval., Results: The conducted research allowed us to obtain the following results, depending on the type of analysis: 1) analysis of unbalanced data in patients with COPD: OR death 3.60 (1.16-11.12); p =0.03; OR CMVO 0.65 (0.35-1.22); p =0,18; 2) two-way analysis with propensity score: OR death 3.86 (1.09-13.74); p =0.04; OR CMVO 0.61 (0.31-1.19); p =0.15; 3) regression analysis with "weight" coefficients: OR death 12.49 (2.27-68.84); p =0.004; OR CMVO 0.63 (0.30-1.33); p =0.22., Conclusion: The presence of COPD in patients with ACS undergoing PCI increases mortality and does not affect the incidence of CMVO.

Рost-COVID-19 syndrome (PS) is one of the medical and social problem. According to WHO, 10-20% of COVID-19 patients suffer from PS. The use of medical gases - inhaled nitric oxide (iNO) and molecular hydrogen (iH 2 ) - may influence on the mechanisms of development PC., Aim: To evaluate the safety and efficacy of the combined inhalation of NO and H 2 (iNO/iH 2 ) in patients with respiratory manifestations of PS., Materials and Methods: 34 patients with PS (11 men/23 women, 60.0±11.7 years) were included in the prospective open-label controlled study in parallel groups: the main group ( n =17) received iNO/iH 2 for 90 minutes once a day for 10 days (concentration of NO 60 ppm, H 2 <4% in the gas mixture), the control group ( n =17) didn't receive inhalations. The period from the confirmation of COVID-19 to the start of the study was 641.8±230.5 days. The groups did not differ in the baseline parameters. The clinical symptoms (from the self-observation diary and mMRC questionnaires, "dyspnea language"), FAS, HADS, SF-36 scores, 6-minute walk test, the blood serum parameters of oxidative stress, the dynamics of the microcirculation in the eye bulbar conjunctiva were evaluated. The individual dose of iNO has chosen during a 15-minute test (the positive dynamics of the microcirculation have indicated that the dose was selected correctly)., Results: The decrease the symptoms severity, such as dyspnea, cough, fatigue and palpitations ( p <0.005), the increase in SF-36 questionnaire scores ( p =0.006) and a reducing of FAS score ( p =0.001), as well as the anxiety component of HADS ( p =0.02) were revealed at the end of treatment in the main group compared to the control group. We observed an improvement in distance walked ( p =0.01) and the values SpO 2 ( p =0.04) in 6-minute walk test, the increase in the volumetric blood flow velocity in venules ( p <0.001), and the date in oxidative damage ( p <0.001) and antioxidant activity ( p =0.03) parameters in the blood serum., Conclusion: The results of the study demonstrate clinical efficacy iNO/iH 2 on clinical indicators, parameters of oxidative stress and microcirculation in patients with PS.

Aim: To study ischemic and/or nonspecific ECG signs of metabolic changes in the myocardium and to determine their relationship with unfavorable cardiovascular prognosis in a 7-year prospective observation of young people under 45 years of age., Material and Methods: A cross-sectional population survey of a random sample aged 25-44 years (n=1363) was conducted in Novosibirsk. The survey program used the standardized epidemiological Rose questionnaire. Biochemical tests were used to measure blood concentrations of total cholesterol (C), triglycerides (TG), low- and high-density lipoprotein cholesterol (LDL-C, HDL-C), and fasting blood plasma glucose. Systolic and diastolic BP (SBP, DBP), the presence of arterial hypertension (AH), body mass index (BMI), waist circumference (WC), and smoking status were assessed. ECG was recorded at rest in 12 standard leads followed by interpretation according to the Minnesota Code. The presence of ischemic and/or nonspecific ECG signs of metabolic changes in the myocardium was determined. Subjects with ECG signs of ischemic changes in the myocardium were selected for long-term follow-up and additional examination by cardiologists. Then the whole cohort was monitored for 7 years, and cardiovascular events were recorded, including using data from the WHO Myocardial Infarction Registry in Novosibirsk. For statistical analysis of the results, cardiovascular events were combined into a composite endpoint., Results: During 7 years, 40 people (27 men and 13 women) had an unfavorable cardiovascular prognosis. Multivariate regression analysis showed that a 7-year unfavorable cardiovascular prognosis in people younger than 45 years was associated with signs of ischemic myocardial alterations identified on the background ECG (OR 5.319, 95% CI: 1.543-18.342, p=0.008) and nonspecific ECG signs of metabolic changes in the myocardium (OR 2.978, 95% CI: 1.216-7.216, p=0.017) regardless of age, gender, the presence of arterial hypertension (AH) and type 2 diabetes mellitus (DM2)., Conclusion: In young people under 45 years of age, not only ECG signs of ischemic changes in the myocardium, but also nonspecific ECG signs of metabolic changes in the myocardium are associated with an unfavorable cardiovascular prognosis, directly and independently on age and gender, in a long-term, 7-year period.

In condition of challenges from menaces to health due to COVID-19 the role of primary health care physicians increases that requires development of management decisions at the regional level. The purpose of the study. On the basis of analysis of medical demographic indicators and data concerning provision of primary health care personnel in the Russian Federation, proposals were made related to reforming of primary health care system in conditions of implementation of general medical practice with purpose to counteract menaces to population health. The analytical and statistical methods were applied. The official statistics data from the Minzdrav of the Russian Federation and Rosstat, results of original researches with content analysis and interpretation were used. The COVID-19 pandemic negatively impacted population health. The indicator of newly detected morbidity in the Russian Federation in 2020 decreased as compared to 2019 from 78024.3 to 75989.7‰oo (by 2.6%). This is the result of decreasing of dispensary and preventive activities among population. In next COVID-19 year (2021), as compared to 2020, indicator of primary morbidity increased to 85531.6‰oo that 12.6% higher than in 2020. The increase occurred in all classes of diseases that caused necessity of rehabilitation of these patients. The COVID-19 morbidity increased up to 2.4 times i.e. from 3391.1 in 2020 to 8085.7‰oo in 2021. The provision of physicians in the Russian Federation was 37.7‰o in 2021. Across the Federal Okrugs differences in indicators made up to 1.3 times and in subjects of the Russian Federation - up to 2.7 times. In conditions of COVID-19 significance of menaces to population health worsened. The situation requires both enhancement of primary health care and implementation of physicians of new formation - general practitioners responsible for patient health. The general practice (GP) widely developed in Russia in the 1990s during last ten years loses its significance in most subjects of the Russian Federation. In 2021, provision of general practitioners in the Russian Federation made up to 0.67‰o. In the Federal Okrugs, difference between indicators made up to 5.6 times. In the subjects of the Russian Federation the difference is enormous - 141.5 times. The article presents and scientifically substantiates prospective functional organizational models of general practice. The established situation with COVID-19 infection requires development of management decisions and measures at the regional level concerning improvement of organization of primary health care and implementation of general practice in conditions of counteracting risks of menaces to population health and health preservation.

Introduction: Chronic recurrent cystitis (CRC) is a complex multifaceted problem of modern uroinfectology., Objective: To study the immunological parameters of urine in patients with chronic recurrent cystitis depending on the etiological factor., Materials and Methods: The prospective study included 71 patients aged 20-45 years who had previously been diagnosed with recurrent lower urinary tract infection: chronic recurrent cystitis (CRC) during an exacerbation period. Based on the results of bacteriological and PCR studies of urine, scraping of the urethra and vagina, depending on the dominant etiological factor, the patients were divided into three groups: group 1 (n=30) - with papillomavirus CRC (PVI-CRC), group 2 (n=30) - with bacterial CRC (B - CRC), group 3 (n=11) - with candida CRC (C - CRC). Analysis of the assessment of immunological parameters of urine was carried out using an enzyme-linked immunosorbent assay (ELISA-BEST)., Results: Based on the results of an immunological study of urine in the study groups, characteristic specific changes in the level of interleukins and interferons were identified, which made it possible to determine a protocol for the differential diagnosis of CRC., Conclusions: Our study shows the advisability of testing interleukins in urine (IL-1 beta, IL-6, IL-8); these indicators can serve as scoring criteria in the differential diagnosis of CRC of various origins., Conclusions: , it is reasonable to study the level of IFN-2b and IFN; when identifying the functional inferiority of the IFN system in women with CRC, correction of the IFN system is necessary.

Aim: To evaluate the effect of antibacterial prophylaxis using oral fosfomycin during the removal of a urethral catheter after radical prostatectomy on the development of urinary tract infection, severity of leukocyturia and bacteriuria, as well as the severity of lower urinary tract symptoms., Materials and Methods: A single-center, non-blind, prospective, randomized controlled trial was carried out. The main group included 40 patients, and the control group included 37 patients. In the group 1, patients received two doses of oral fosfomycin, 3 g, namely in the evening on the day of catheter removal (the first dose) and 48 hours after catheter removal (the second dose). In the group 2, patients did not receive any antibacterial prophylaxis after urethral catheter removal. The endpoints of the study were confirmed episodes of urinary tract infection within 1 month after removal of the urethral catheter, leukocyturia and bacteriuria in urinalysis/urine culture) and severity of the lower urinary tract symptoms assessed by IPSS questionnaire., Results: In the group 2, urinary tract infection was noted in 17.1%, while in the group 2 only in 2.6% of patients (p=0.032). Leukocyturia and bacteriuria were significantly less common in the group receiving antibacterial prophylaxis with fosfomycin (18.4% vs. 48.6%, respectively; p=0.006). Positive urine culture was observed in 7.9% vs. 25.7%, respectively (p=0.035). Four weeks after removal of the urethral catheter, the average IPSS score was significantly higher in the group 2 (13.2 vs. 9.5 points; p=0.002). There were no cases of allergic reaction and pseudomembranous colitis associated with C. difficile in both groups. Diarrhea cured with sorbents was noted in 2 patients (5.2%) in fosfomycin group., Conclusion: Antibacterial prophylaxis using two oral doses of fosfomycin 3 g on the day of urethral catheter removal and 48 hours after catheter removal after radical prostatectomy appears to be an effective scheme that reduces the incidence of urinary tract infection and the severity of lower urinary tract symptoms, and is characterized by a minimal risk of adverse events. It is necessary to carried out further research and develop clear recommendations for antibacterial prevention in urological interventions requiring prolonged urethral catheterization.

Aim: To carried out a comparative analysis of the risk of complications and oncological results of repeat partial nephrectomy and radical nephrectomy in patients with local recurrence after previous organ-sparing procedures., Materials and Methods: Retrospective and prospective data of 64 patients with local recurrence of kidney cancer after nephron-sparing procedures. who underwent surgical treatment in the department of oncourology of the National Medical Research Center of Oncology named after N.N. Blokhin in the period from 2000 to 2022. A total of 37 (57.8%) patients of the main group underwent repeat partial nephrectomy, while in 27 (42.2%) patients in the control group a radical nephrectomy was done. Median follow-up was 35 (3-131; Q1-Q3: 13-57) months. Both groups were comparable in terms of demographic and clinical characteristics (p>0.05). The median time to detect relapse after previous partial nephrectomy was 24 (2-172) months., Results: Complications were noted in 8 (21.6%) patients after repeat partial nephrectomy, compared to 29.6% in the control group (n=8) (p=0.563). A comparative analysis revealed a significant advantage in overall survival in patients of the main group (p=0.042). There were no significant differences between groups in cancer-specific and disease-free survival (p=0.369 and p=0.537, respectively)., Conclusion: Repeat partial nephrectomy for local recurrence of kidney cancer leads to an increase in overall survival compared to radical nephrectomy, in the absence of significant differences in cancer-specific and relapse-free survival.

Aim: To improve treatment outcomes in patients with ureteral stones by optimizing the use of noninvasive and minimally invasive techniques., Material and Methods: A prospective analysis of 186 patients with ureteral stones who were treated at the "RSSPMCU" in the period from July 2020 to April 2023 was carried out. Among them, 84 were undergone to electromagnetic extracorporeal shock-wave lithotripsy (ESWL) using the Storz Modulith SLX-F2 device (Switzerland). A procedure was performed under ataralgesia. The mean stone size was 8.54+/-2.79 (4-16 mm). The average amount of shock waves per stone was 2436+/-247.78. The session duration was 19.37+/-1.86 minutes. Endoscopic procedures were performed in 102 patients. Among them, 49 stones were removed using the ureteroscopy (URS), while in 49 and 4 cases percutaneous access (PCNL) and a combination of PCNL and URS under spinal anesthesia were done, respectively. The mean stone size was 11.46+/-4.26 (5-26 mm). Holmium laser or pneumatic lithotripsy was performed. The duration of the procedure was 63.38+/-17.48 min., Results: The stone density of patients undergoing ESWL was 855+/-319.84 HU, while those undergoing endoscopic procedures was 943.78+/-319.48 HU (p>0.05). The absorbed dose with ESWL was 18.73+/-4.15 mGy compared to 31.42+/-1.40 mGy for endoscopic procedures (p<0.001). A length of stay was 1.0+/-0.0 and 2.75+0.1, respectively (p<0.001). After 7-10 days, the stone free rate (SFR) was 76.2% (n=64) after ESWL and 99.02% (n=101) after endoscopic interventions (p<0.05). In the ESWL group, 3 patients received second session of ESWL for residual stones and in 9 cases URS was done. The SFR was 100% on day 45. In patients after endoscopic interventions, 1 patient underwent URS and SFR was 100% on the 15th day., Conclusion: In general, the endoscopic technique is superior to ESWL in patients with ureteral stones both in terms of SFR and duration of procedure, but is inferior in safety due to invasiveness and the absorbed dose. In our opinion, the key indication for endoscopic treatment should be stone size greater than 6 mm, density more than 1000 HU, and patient preference.

Aim: To assess the quality of life of patients with interstitial cystitis (IC) and to study effective options used to control symptoms on outpatient basis., Materials and Methods: The results of a descriptive prospective cross-sectional cohort study are presented. The medical charts of patients who were treated in the City Clinical Hospital named after Spasokukotsky from 2021 to 2023 were analyzed. Eighty inpatient medical charts of various patients with a final diagnosis of IC with Hunner's lesion were identified. Only 53 patients were interviewed due to the inclusion/exclusion criteria. Respondents were asked to complete a survey consisting of 15 questions. The survey was carried out online for patients who did not require surgical treatment at the time of the study, and offline for patients admitted for repeated surgical treatment., Results: The average age of respondents was 59.011.1 years. 58% (31) of patients noted the presence of constant pain in the pelvic area during the day, while 85% (45) of patients reported pain outside the bladder area, in the urethra and perineum. The intensity of pain in the pelvic area was 4.9 (2.3-5.6) points. Higher pain scores 6.24 (5.8-9.0) were observed in 47% (25) of patients admitted for repeat surgical treatment. 62% (33) of patients had a titer of bacteria in a urine test above 104, while 51% (27) of patients experienced relief of symptoms after taking antibacterial drugs. For the treatment and symptomatic relief, the following are most often used: pentosan sodium polysulfate (26%, n=14), antibacterial drugs of the nitrofuran group (25%, n=13), amitriptyline (15%, n=8), non-steroidal anti-inflammatory drugs (11%, n=6) patients. 23% (12) of respondents received intravesical therapy. The time from the onset of symptoms to the final diagnosis was 48 (24-96) months., Conclusions: Although infection is a criterion for excluding the diagnosis of IC, more than 62% of patients have positive urine culture. The results obtained indicate the need to improve existing approaches to the diagnosis of IC, as well as to develop treatment algorithms for painful bladder syndrome to control symptoms.

Aim: To study the prognostic significance of inflammatory biomarkers in patients with chronic heart failure (CHF) and stenotic multivessel coronary atherosclerosis, with determination of the biomarker separate set that reflects subclinical inflammation and is associated with the development of cardiovascular complications during prospective observation., Material and Methods: A prospective observational study was conducted that included 80 patients with CHF and ischemic heart disease who were scheduled for coronary artery bypass grafting (CABG) during their current hospitalization. In addition to routine clinical laboratory tests, coagulation parameters were evaluated and the following inflammatory biomarkers were determined: neutrophil gelatinase-associated lipocalin (NGAL), growth/differentiation factor 15 (GDF-15), fibroblast growth factor 23 (FGF-23), transforming growth factor beta-1 (TGF-β1), and high-sensitivity C-reactive protein. Also, the calculated neutrophil-to-lymphocyte ratio (N LR) was included in the analysis. Follow-up duration was at least 12 months (median 16 [13, 22] months). Statistical analysis of the data was performed with the IBM SPSS Statistics 21 software., Results: The study presented results of a factor analysis of 10 inflammatory biomarkers in patients who were scheduled for CABG. One of the factors identified by the analysis included the levels of NGAL and GDF-15, N LR, and the level of fibrinogen in the blood in CHF patients with stenotic coronary atherosclerosis and was significantly associated with the death rate during prospective observation. Furthermore, this association remained significant even after adjustments for age, glomerular filtration rate, severity of heart and coronary insufficiency, and the presence of diabetes mellitus., Conclusion: In patients with CHF and stenotic coronary atherosclerosis, a set of inflammatory markers, including blood NGAL, GDF-15, N LR, and fibrinogen, can be combined into one factor reflecting subclinical inflammation. The value of this factor can be used to predict cardiovascular death in the long term after surgical myocardial revascularization.

Aim: To evaluate the impact of frailty syndrome (FS) on the course of acute decompensated heart failure (ADHF) and the quality of drug therapy before discharge from the hospital in patients with reduced and moderately reduced left ventricular ejection fraction (LVEF)., Material and Methods: This open prospective study included 101 patients older than 75 years with reduced and mid-range LVEF hospitalized for decompensated chronic heart failure (CHF). FS was detected during the outpatient follow-up and identified using the Age is Not a Hindrance questionnaire, the chair rise test, and the One Leg Test. The "fragile" group consisted of 54 patients and the group without FS included 47 patients. Clinical characteristics of patients were compared, and the prescribing rate of the main drugs for the treatment of CHF was assessed upon admission to the hospital. The sacubitril/valsartan or dapagliflozin therapy was initiated in the hospital; prescribing rate of the quadruple therapy was assessed upon discharge from the hospital. Patients with reduced LVEF were followed up for 30 days, and LVEF was re-evaluated to reveal possible improvement due to optimization of therapy during hospitalization. Statistical analysis was performed with the SPSS 23.0 software., Results: The main causes for decompensation did not differ in patients of the compared groups. According to the correlation analysis, FS was associated with anemia (r=0.154; p=0.035), heart rate ≥90 bpm (r=0.185; p=0.020), shortness of breath at rest (r =0.224; p=0.002), moist rales in the lungs (r=0.153; p=0.036), ascites (r=0.223; p=0.002), increased levels of the N-terminal pro-brain natriuretic peptide (NT-proBNP) (r= 0.316; p&lt;0.001), hemoglobin concentration &lt;120 g / l (r=0.183; p=0.012), and total protein &lt;65 g / l (r=0.153; p=0.035) as measured by lab blood tests. Among patients with LVEF ≤40 % in the FS group (n=33) and without FS (n=33), the quadruple therapy was a part of the treatment regimen at discharge from the hospital in 27.3 and 3.0 % of patients, respectively (p=0.006). According to the 30-day follow-up data, improvement of LVEF was detected in 18.2% of patients with LVEF ≤40% in the FS group and 12.1% of patients with LVEF ≤40% in the FS-free group (p=0.020). In patients with LVEF 41-49 % in the FS (n=21) and FS-free (n=14) groups, the prescribing rate of the optimal therapy, including sacubitril/valsartan, sodium-glucose cotransporter 2 inhibitors, beta-blockers, and mineralocorticoid receptor antagonists, no statistically significant differences were detected (14.3 and 7.1 %, respectively; p=0.515) at discharge from the hospital., Conclusion: Patients with ADHF and FS showed more pronounced clinical manifestations of decompensation, anemia, heart rate ≥90 beats/min, and higher levels of NT-proBNP upon admission. The inpatient therapy with sacubitril/valsartan or dapagliflozin was more intensively initiated in FS patients with reduced LVEF. An individualized approach contributed to achieving a prescribing rate of sacubitril/valsartan of 39.4%, dapagliflozin of 39.4%, and quadruple therapy of 27.3% upon discharge from the hospital.

Relevance: Insulinoma is the most common hormonally active neuroendocrine tumor (NET) of the pancreas. In recent years, there has been a trend towards an increase in the incidence of NET especially insulinoma., Aim: Summarizing and analyzing current data on various approaches to the treatment of insulinoma. Our review includes a comprehensive assessment of the advantages and disadvantages of currently available insulinoma treatment methods in comparison with past experience, as well as a review of promising methods that are not currently widely used., Materials and Methods: Analysis of literature from such databases as scientific electronic library elibrary.ru, Pubmed, Google Scholar, MedLine, Scopus and Web of Science., Results: The most common treatment for insulinoma is surgery. For patients with high operative risk, alternative methods such as alcohol ablation, radiofrequency ablation, and tumor embolization may be used. Medications include the use of somatostatin analogues, diazoxide. The literature describes the potential benefit of the use of beta-blockers, phenytoin, glucagon, however, in clinical trials, these drugs have not demonstrated a significant effect. For the treatment of malignant and metastatically advanced insulinoma, targeted therapy (primarily Everolimus), chemotherapy, as well as embolization (including chemoembolization, radioembolization), radiofrequency ablation (RFA), microwave ablation and cryoablation, ultrasound ablation (HIFU), laser ablation, brachytherapy, irreversible electroporation are used., Conclusion: The study of new drugs is an important task for scientists, among medications the most promising are new generations of somatostatin analogues, targeted drugs and chemotherapy drugs. The rare frequency of insulinoma makes it difficult to conduct randomized controlled trials and prospective studies. That is why physicians and scientists need to maintain close contacts with each other and take into account the experience of treating each patient with such disease, which will help develop effective treatment algorithms in the future.

Aim: To evaluate the contribution of traditional and additional cardiovascular risk factors (CVRFs) to the development of chronic ischemic heart disease (CIHD) in liver transplant recipients during the long-term postoperative period., Material and Methods: A single-center prospective cohort study was conducted. The study included 740 patients with chronic end-stage liver disease (CESLD) and cirrhotic cardiomyopathy (CCMP). During the observation period (5.4±2.29 years), patients were divided into two groups: liver transplant recipients (n=420) and patients with CESLD on the waiting list who did not receive a donor organ (n=320). In patients enrolled to the study upon inclusion in the waiting list, CVRFs, history, clinical and laboratory and instrumental data were studied at all stages of the hepato-cardiac continuum., Results: During the long-term postoperative period, liver transplant recipients belonged to the group of high cardiovascular risk: over a 5-year observation period, 35.7% (n=150) of them developed metabolic syndrome (MS), 9.8% developed verified CIHD associated with MS. The incidence of traditional CVRFs was high (arterial hypertension, 88.6%; obesity, 36.6%; hypercholesterolemia, 77.8%; hypertriglyceridemia, 43.6%; reduced concentration of high-density lipoprotein cholesterol, 35.4%; increased concentrations of low-density lipoprotein cholesterol, 66.8% and very low-density lipoprotein cholesterol, 51.2%; increased atherogenic index, 61.5%). During the long-term postoperative period as compared to the period when patients were on the waiting list, additional CVRFs appeared: increases in body mass index, calcium index, nitric oxide metabolites, endothelin-1, homocysteine, intercellular adhesion molecules VCAM-1 and ICAM-1, and decreases in endothelium-dependent vasodilation and glomerular filtration rate to less than 60 ml/min/1.73 m2. A model for the development of CIHD was created. The model uses a complex of independent risk factors and demonstrates a predictive accuracy of 84.6%., Conclusion: The study results indicate a modification of CVRFs and a dynamic change in the cardiovascular phenotype of liver transplant recipients: progression of CCMP during their stay on the waiting list, regression of CCMP manifestations during the first 12 months after orthotopic liver transplantation, and increases in the total cardiovascular risk and likelihood of CIHD in the long-term postoperative period.

Hiatal hernia may be accompanied by chronic bleeding from erosions and subsequent iron deficiency anemia. This anemia is drug-resistant in 5-10% of patients with hiatal hernia. In this case, the only approach is antireflux surgery for hiatal hernia repair., Material and Methods: A prospective examination of 42 patients with hiatal hernia and concomitant iron deficiency anemia was conducted between 2023 and 2024. To identify latent iron deficiency anemia, patients underwent in-depth laboratory tests. All patients underwent original fundoplication. The results were assessed in 6 and 12 months after surgery., Results: Favorable functional results with disappearance of reflux esophagitis symptoms were obtained in 39 patients (92.8%). The follow-up laboratory tests after 6 months revealed higher hemoglobin and normal serum iron in 35 (94.5%) out of 37 available patients. Patients did not take iron supplements during the second half of the year, but hemoglobin and serum iron were normal., Conclusion: Original fundoplication demonstrates high efficiency in patients with hiatal hernia and concomitant chronic iron deficiency anemia.

The study assessed the severity of inflamaging, lipid peroxidation, as well as the state of antioxidant protection in elderly patients with chronic obstructive pulmonary disease (COPD), depending on the ischemic stroke (IS). A prospective cohort study included 138 elderly patients (mean age 68±4 years). Of these, the 1st (control) group consisted of 30 people who did not have established COPD and cardiovascular diseases comparable in gender and age to the patients of the main group. The main group included 108 patients, of which 53 people [42 (79,2%) men and 11 (20,8%) women] had COPD outside the exacerbation (2nd group), and 55 people [41 (74,5%) men and 14 (25,5%) women] with COPD outside the exacerbation who underwent IS (3rd group). It was found that elderly patients with COPD who underwent IS have more pronounced dysproteinemia, high insulin resistance index (40,4%, p<0,001), NLR (23,2%, p<0,01), MLR (22,9%, p<0,01), CRP (18,4%, p<0,01), MCP-1 (25,9%, p<0,01) compared to the COPD group. An increase in the processes of lipid peroxidation was revealed - the total oxidative capacity (15,9%, p<0,05), oxidized LDL (18,2%, p<0,01), malondialdehyde (17,4%, p<0,01) and a decrease in the body's antioxidant system - vitamin E (34,4%, p<0,01), superoxide dismutase (21,1%, p<0,01), with an increase in the homocysteine content in blood plasma by 28,3% (p<0,01). Thus, the data obtained indicate the maximum severity of inflamaging and imbalance of pro- and antioxidants in the pathogenesis of COPD comorbidity and ischemic stroke in the elderly.

Objective: To study the efficacy and safety of long-term (3 years) course Cerebrolysin therapy in an open comparative study as a means potentially capable of slowing or preventing the transition of MCI into dementia, as well as to analyze the possibility of Cerebrolysin preventive effect predicting based on clinical and biological parameters., Material and Methods: In total, 100 patients with aMCI were included in the study, randomly assigned to 2 groups: patients of group 1 ( n =50) received annual course therapy with Cerebrolysin for 3 years (20 intravenous infusions of Cerebrolysin 20 ml in 100 ml of saline solution for 4 weeks). Group 2 patients underwent annual clinical examination, but did not receive therapy. All patients were monitored on an outpatient basis and were examined once a year. Clinical and psychopathological, psychometric, immunological, catamnestic, molecular genetic, and statistical methods were used., Results: A comparative three-year prospective study conducted in a group of aMCI patients treated with annual course therapy with Cerebrolysin and those who did not receive therapy showed a lower progression of cognitive deficits and a significantly lower conversion rate to dementia in patients who received annual courses for 3 years Cerebrolysin therapy compared with the comparison group., Conclusion: The data obtained indicate the presence of a disease-modifying effect in the annual course of Cerebrolysin and the possibility of using this drug in programs of dementia preventive therapy in people with a high risk of cognitive deficits progression and the dementia development in elderly patients with aMCI.

Objective: Evaluation of the analgesic, opioid-sparing, anti-inflammatory and adverse effects of the diclofenac and orphenadrine (Neodolpasse) fixed combination for analgesia in the postoperative period of surgical cancer patients., Material and Methods: A randomized, single-center, prospective, comparative study evaluated two analgesic regimens in 40 cancer patients undergoing various open cavity surgeries, including extensive combined interventions associated with the resection of 3 or more organs. The study was conducted following the transfer from the ICU to the surgical department during the early activation period, within the first two postoperative days. In the first group N ( n =20), "Neodolpasse" (a fixed combination of 75 mg Diclofenac and 30 mg Orphenadrine) was administered as an infusion, twice daily. In the second group K ( n =20) analgesia was performed with ketoprofen as an intravenous infusion at a daily dose of 200 mg. Patients in both groups received scheduled prolonged epidural analgesia with 0.2% ropivacaine, and when the severity of pain in a visual analogue scale (VAS) increased to more than 40 mm, so an additional dose of 100 mg tramadol was administered intramuscularly. Daily measurments of blood creatinine level and C-reactive protein were taken, postoperative blood loss was accounted for, as well as postoperative complications according to the Clavien-Dindo classification., Results: The comparative analysis of the indicators of pain syndrome severity showed that the patients in group N exhibited a more pronounced analgesic effect, so on the second postoperative day 30% of patients reported moderate pain (from 50 to 60 mm on the pain scale), on the third day - 15%, and by the fourth day - all 100% of patients experienced pain of low intensity. The additional analgesia with tramadol in group N was required twice less than in the comparison group, and such adverse effects as nausea, drowsiness, and weakness were significantly more common in the ketoprofen group. In both groups, the average blood creatinine level did not exceed permissible values, and the C-reactive protein was elevated at all stages of the study but tended to decrease by the fourth day. The analysis of postoperative complications according to the Clavien-Dindo scale at the time of discharge did not reveal a direct correlation between the occurred complications and the use of NSAIDs. Adverse effects such as anastomotic failure, gastrointestinal complications, or other hemorrhagic manifestations were not recorded., Conclusion: The inclusion of Neodolpasse into multimodal analgesic regimens resulted in the most pronounced analgesic and opioid-sparing effects in surgical cancer patients using laparotomy access. Additionally, the application of short courses of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a favorable safety profile.

Objective: To evaluate the effect of Cortexin treatment on cognitive function and quality of life for young patients after ischemic stroke., Material and Methods: The open prospective observational study included 30 patients from 18 to 45 years old with confirmed ischemic stroke in the carotid blood supply who received a course of treatment with Cortexin. Before and after therapy, all patients in the study group underwent examination to assess their neuropsychological status (MoCA test), The Short Form-36 (SF-36) questionnaire was used to assess quality of life. The study results were processed using statistical analysis., Results: Based on the results of neurocognitive tests, changes in indicators of neurodynamic, visual-spatial and mnestic functions were determined. Thus, in the beginning of the study the MoCA test scores were 25.1±1.4 points. Over time, there was an improvement mainly in the areas of attention, short-term memory, and multiple aspects of executive functions. However, statistical significance for MoCA was achieved by the end of the second course of treatment with Cortexin (visit 4) - 28.4±1.3 points. Delayed neuropsychological testing showed encouraging results - the achieved level of cognitive functioning was maintained (28.0±1.1). According to SF-36 questionnaire at the stage of inclusion in the observation, low results were noted, which indicated the negative impact of the underlying disease on the daily life of the patient who had suffered a stroke. Low quality of life scores persisted until the third visit; a significant improvement in SF-36 results was recorded at visit 4 and persisted with a positive trend at the fifth visit., Conclusion: Cortexin therapy has been shown to be effective, safe and well tolerated in young people with cognitive deficits in the poststroke period.

Postmastectomy syndrome (PMS) is a complex neurovascular set of symptoms that develops in most patients after breast cancer (BC) treatment and significantly reduces the quality of life. One of the potential mechanisms of its occurrence is considered to be an endothelial dysfunction. The possible method of reducing manifestation of endothelial dysfunction is systematic aerobic dynamic training., Objective: To evaluate the influence of 12-week aerobic dynamic training program of moderate intensity on the endothelial dysfunction laboratory markers and life quality in patients with PMS., Material and Methods: Single-center prospective randomized trial included 40 patients with PMS divided into study (20 patients) and comparative (20 patients) groups, as well as 20 healthy female volunteers. The expression level of soluble intercellular adhesion molecule-1 (ICAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) were evaluated in all participants at baseline by enzyme-linked immunosorbent assay method, and additionally psychological and physical component of health by SF-36 questionnaire were assessed in patients with PMS., Patients of study group received a course of 12-week partially controlled aerobic dynamic training of moderate intensity lasting 45 minutes with frequency equal 5 times per week. Patients with PMS were re-evaluated for ICAM-1 and PECAM-1, as well as for life quality., Results: The group of patients with PMS after BC treatment had increased level of ICAM-1 in long-term period, that may indicate endothelial dysfunction. Statistically significant decrease of endothelial dysfunction laboratory markers was revealed in patients with PMS, who underwent the course of cardiorespiratory training. In the same time, the dynamics of changes in ICAM-1 was higher in the study group than in comparative group. Further, improvement of physical and psychological components of health by SF-36 questionnaire was found., Conclusions: The program of cardiorespiratory trainings of moderate intensity in patients, who had BC treatment a year ago, decreases intercellular adhesion molecules level that may show an improvement of endothelial dysfunction.

Multiple sclerosis (MS) is a chronic autoimmune-inflammatory and neurodegenerative disease., Purpose: This study explores the main structural changes in patients with MS and their relationships with the activity and type of disease course., Material and Methods: This prospective study included 159 patients (318 eyes) with an established diagnosis of MS: group (44 eyes; 13.84%) - relapsing-remitting type MS (RRMS) lasting up to 1 year without a history of optic neuritis (ON); group 2 (30 eyes; 9.43%) - RRMS up to 1 year with ON; group 3 (56 eyes; 17.61%) - RRMS lasting from 1 to 10 years without ON; group 4 (38 eyes; 11.95%) - RRMS from 1 to 10 years with ON; group 5 (49 eyes; 15.41%) - RRMS >10 years without ON; group 6 (37 eyes; 11.63%) - RRMS >10 years with ON; group 7 (34 eyes; 10.69%) - secondary progressive multiple sclerosis (SPMS) without ON; group 8 (30 eyes; 9.43%) - SPMS with ON. Patients underwent standard ophthalmological examinations, including optical coherence tomography., Results: A decrease in structural parameters was diagnosed, progressing with the duration of the disease and the presence of ON: the minimum values of mGCL+IPL (65.83±9.14 μm) and mSNFL (76.37±14.77 μm) were detected in the group with SPMS with ON. High inverse correlations of EDSS with mGCL+IPL and mRNFL were demonstrated, with maximum in the group with the longest duration of MS without ON (-0.48 and -0.52 ( p =0.01), respectively)., Conclusion: Changes in the thickness of the structural parameters of the retina, measured by OCT, can be considered as a predictor of the course of MS.

Peripheral magnetic stimulation (pMS) has shown its effectiveness in the treatment of lower urinary tract symptoms, such as symptoms of an overactive bladder (OAB). The perineal region (pelvic floor) and the sacral roots area (projection S3 of the root) are used as the locus of stimulation. The published literature presents protocols with different parameters of stimulation, while each of them reliably demonstrates clinical efficacy, however, no comparative studies have been found to select priority stimulation modes when analyzing available sources., Objective: To compare the efficacy and safety of different frequency - 1 and 5 Hz - modes of sacral MS in patients with symptoms of OAB., Material and Methods: A single blind prospective randomized comparative clinical study included 59 patients with OAB symptoms. The patients were divided by simple randomization into the group 1 ( n =30), which received MS 3 times a week for 5 weeks with a frequency of 1 Hz per sacral root area (S2-S4), and the group 2 ( n =29), in which stimulation was performed at a frequency of 5 Hz, while the remaining parameters and duration of therapy were identical to group 1., Results: Sacral pMS with different frequency modes (1 and 5 Hz) is reliably equally effective against the clinical symptoms of OAB, which is confirmed by the absence of significant intergroup differences. In patients receiving MS with a frequency of 5 Hz, there was a more pronounced increase in maximum cystometric capacity, normalization of the maximum and average urine flow velocity and regression of the residual urine volume ( p <0.001, p =0.007, p =0.011 and p =0.012 compared with group 1). The greatest difference in indicators was observed in the increase in the maximum cystometric capacity - +31±25 ml at MS with a frequency of 1 Hz and +109±96 ml at MS with a frequency of 5 Hz ( p <0.001). MS is a safe procedure and is well tolerated by patients., Conclusion: pMS when exposed to the area of S2-S4 roots for 20 minutes 3 times a week with a course for 5 weeks is reliably effective against the clinical symptoms of OAB at different frequency modes (1 and 5 Hz). At the same time, MS with a frequency of 5 Hz may have an advantage over stimulation of 1 Hz in terms of its effect on urodynamic parameters (maximum cystometric capacity, peak and average urine flow velocity and residual urine volume), which may be associated with a large inhibitory effect on detrusor.

Objective: To study the efficacy and safety of the use of annual course therapy of choline alfoscerate (CA) as a drug potentially capable of slowing or preventing the transition of amnesic type mild cognitive impairment (aMCI) into clinically pronounced dementia in a three-year open comparative study, as well as to explore the possibility of predicting the preventive effect of such therapy based on a number of clinical and biological parameters., Material and Methods: The study included 100 patients with aMCI, randomly divided into 2 groups: the therapeutic group consisted of 50 patients who received CA course therapy once a year for 3 years (20 intravenous infusions of 1000 mg (4 ml) in 100 ml of saline solution for 4 weeks) and a comparison group of 50 patients who underwent an annual examination at the center and did not receive therapy. Clinical and psychopathological, psychometric, immunological, follow-up, and statistical methods were used., Results: A comparative three-year prospective study conducted in a group of aMCI patients treated with annual course therapy of CA for 3 years and aMCI patients who did not receive therapy with similar initial demographic, diagnostic, psychometric and immunological characteristics showed a lower progression of cognitive deficits (12.2% and 39.1%, respectively) and a lower conversion rate (8.2% and 26.1%, respectively) to dementia in the therapeutic group compared with the comparison group. The differences between the initial and final (after 1, 2 and 3 years of follow-up) cognitive functioning indicators in the therapeutic group and the comparison group were significant ( p <0.05) on all scales and tests in favor of the therapeutic group throughout the entire follow-up period., Conclusion: The results allow us to consider CA as a possible model of preventive dementia therapy aimed at preventing the progression of cognitive deficits and the development of dementia in people at high risk of developing AD - patients with aMCI.

Extended depth of focus (EDOF) intraocular lenses (IOLs) are the latest IOL designs. In recent years, several models of EDOF IOLs have become available in Russia, two of which (Tecnis Symfony and Acrysof IQ Vivity) are implanted in our clinic. Comparative studies devoted to the results of implantation of the new EDOF IOLs are rare in the available literature., Purpose: This article compares the outcomes of implantation of two EDOF IOLs in patients with presbyopia and/or cataract., Material and Methods: The prospective study included 60 patients (81 eyes) after implantation of EDOF IOL Tecnis Symfony (32 patients, 45 eyes; group 1) or EDOF IOL AcrySof IQ Vivity (28 patients, 36 eyes; group 2). The mean follow-up period was 3.9±1.3 months., Results: All groups showed a significant ( p <0.05) increase in uncorrected near visual acuity (UCNVA), intermediate visual acuity (UCIVA), and distance visual acuity (UCDVA) at the maximum follow-up time compared to preoperative values. In group 1, the best corrected near visual acuity (BCNVA) increased from 0.61±0.10 to 0.82±0.16 at the maximum follow-up time, and in group 2 - from 0.58±0.08 to 0.67±0.12 ( p >0.05). Both groups showed a significant increase in best corrected intermediate and distance visual acuity (BCIVA and BCDVA) at the maximum follow-up time. The increase in the indicator compared to the preoperative period was not significant in both groups ( p >0.05). The frequency of side optical phenomena was low in both groups. No significant differences were found between the groups ( p >0.05)., Conclusion: This study presents a comparative analysis of the results of implantation of two different EDOF IOLs. Both lenses were comparable in most of the studied parameters, including providing good distance and intermediate vision, functional near vision, as well as a low frequency of side optical phenomena. In all cases the patients were satisfied with the results of the surgical intervention.

Objective: To assess the possibilities of therapy with minimal effective doses (MED) of psychotropic drugs for mental disorders (MD) that manifest during the treatment of hematological malignancies (HM)., Material and Methods: A prospective study was conducted at the National Medical Research Center for Hematology of the Russian Ministry of Health (Moscow), which included 204 (39.4%) men and 314 (60.6%) women (518 patients in total), aged 17 to 83 years (median 45 years), with various HM, in which the manifestation of MD occurred during the treatment of the underlying disease. To minimize the side-effects of psychotropic drugs and given the relatively mild level of MD, psychopharmacotherapy of patients was carried out mainly at MED. The severity of MD, manifested in patients, was assessed by the illness severity scale of the Clinical Global Impression (CGI) scale, and the effectiveness of the treatment was assessed by the improvement scale (CGI-I)., Results: Mainly mild (188, 36%) and moderately pronounced (270, 52%) MD were noted in patients with HM during the treatment of the underlying disease. Severe psychopathological disorders (60, 12%) were observed much less often. Because of psychopharmacotherapy with MED, patients experienced a very significant (97, 19%) and significant improvement (354, 68%) of their mental state, less often the improvement was regarded as minimal (67, 13%). Therefore, almost all patients showed a stable relief of MD; in 87% (95% CI 84-90) of patients, this improvement was significant., Conclusion: The tactics of treatment MD that manifest in patients with HM with MED of psychotropic drugs turned out to be therapeutically effective according to the results of the assessment on CGI scales.

Objective: To analyze complaints about sleep disorders and assess the incidence of various sleep disorders, using relevant scales, in patients with medication-overuse headache (MOH) in comparison with patients without MOH., Material and Methods: The prospective case-control study included 171 patients, aged 18 years and older, with MOH (main group), and173 patients with primary headaches without MOH (control group). A neurologist conducted an initial examination and professional interview before the start of treatment. To diagnose sleep disorders, the International Classification of Sleep Disorders (3rd edition, 2014) was used. Additionally, an assessment was made using the Insomnia Severity Index Scale, the Epworth Sleepiness Scale (ESS) and the Lausanne Obstructive Sleep Apnea Syndrome Scale (NoSAS)., Results: Statistically significant differences were revealed in the prevalence of the following complaints about sleep disorders in patients with MOH: lack of sleep (51.5%), frequent awakenings during sleep (43.3%), discomfort in legs before falling asleep or at rest in the evening (37.4%). Difficulties falling asleep occurred equally often in both patients with MOH (43.9%) and without MOH (37.0%), as well as daytime sleepiness (40.4% vs 36.4%) and the presence of snoring (13% of patients in each group). Patients with MOH were significantly more likely to suffer from chronic insomnia (60.2% and 47.4%, respectively, p =0.02; OR 1.7; 95% CI 1.1-2.6) and restless legs syndrome (37.4% and 22.0%, respectively, p =0.002; OR 2.1; 95% CI 1.3-3.4). The incidence of hypersomnia and obstructive sleep apnea syndrome did not have statistically significant differences., Conclusion: Patients with MOH compared to patients without MOH have a significantly higher incidence of main complaints of sleep disorders, chronic insomnia and restless legs syndrome, which indicates the importance of sleep disorders in the pathogenesis of medication-overuse headaches and requires timely diagnosis and treatment to prevent the progression of both headaches and sleep disorders.

Objective: To study a role of serum neurofilament light chains (sNFL) in assessment of course and progression of multiple sclerosis (MS) in the population of patients with MS in the Tomsk region., Material and Methods: The study involved 93 patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) ( n RRMS =75, n SPMS =18). The study was carried out in a two-stage design: the first stage was a cross-sectional study for the entire sample; the second stage was a prospective observation with two visits for patients with relapse. sNFL concentration was determined by solid-phase ELISA., Results: There was no statistically significant difference between RRMS and SPMS, and relapse and remission groups in terms of sNFL levels. Patients with a MS duration exceeding 14 years had higher rates of sNFL than those with a shorter duration ( p =0.02). The subjects of the second study stage showed a decrease in sNFL from 2.05 (1.86; 2.19) pg/ml to 1.92 (1.87; 2.04) pg/ml ( p =0.005), and slowdown in sNFL reduction correlated with the severity of cognitive impairment (k=0.52; p <0.05)., Conclusion: Dynamic monitoring of sNFL allows the evaluation of the activity of the disease, as well as making an assumption about the compensatory possibilities of subsequent recovery.