Republican Scientific and Practical Center of Neurology and Neurosurgery

Objective. To study the natural course of squamous intraepithelial lesions (high-grade squamous intraepithelial lesions — HSIL) of the cervix of a high degree during pregnancy and the effect of the method of delivery on the outcomes of this disease. Data about the effects of pregnancy on HSIL changes remain limited and contradictory. Material and methods. The data of 65 pregnant women with HSIL were retrospectively analyzed (median age — 30.7 years, median gestation period — 15 weeks). The diagnosis was confirmed by biopsy, excision procedures were not performed during pregnancy. The monitoring included regular cytological monitoring. Among 65 patients, 44 gave birth naturally, 21 by caesarean section. After delivery, conization (23), cervical amputation (20), hysterectomy (2), cervical ablation (6), or follow-up (14) were performed. Results. Postpartum regression of HSIL was noted in 21.5% of cases (in 14 out of 65), persistence — in 78.5% (in 51 out of 65). Further progression to invasive cancer was recorded in 4.6% (in 3 out of 65). The regression rate after natural childbirth was 27.3% versus 9.5% after cesarean section (p=0.122). Conclusion. The method of delivery has no statistically significant effect on the outcome of HSIL (p=0.122). However, the high frequency of persistence (78.5%) and the risk of progression (4.6%) emphasize the need for mandatory postpartum follow-up and excision procedures if indicated.

Objective . To establish the effect of mode of delivery, aspects of obstetric history (parity, miscarriages), and gestational weight gain on cytokines and immunoglobulins content in cord blood (CB) and breast milk (BM). Materials and methods . 379 pregnant women were included in the study. Study materials: CB; BM expressed in 1 (BM1) and 3 months (BM2) after childbirth. L-4, IL-5, IL-6, IL-10, IL-25, TSLP, IFN-γ, TGFβ1, TGFβ2, CCL17, CCL22, CXCL10 were typed in body fluids by the method of enzyme immunoassay (ELISA). Results . Caesarean deliveries are associated with essential higher concentrations of CCL17 in CB (p=0.0006), IgE in BM1 (p=0.02), IL-5 in BM2 (p=0.048) and lower sIgA level in BM2 (p=0.05), more significant decrease in TGFβ1 concentration in BM within first three months (p=0.004). Significantly higher levels of ССL17 (p=0,04) and IgE (p=0,019) in CB, IL-5 (p=0,037) and IFN-γ (p=0,031) in BM2 were in a group of women having miscarriages in their medical history. Primiparous women had higher levels of CCL22 (p=0.0006) and IL-4 (p=0.032) in CB, as well as IL-4 (p=0.047) and IL-5 (p=0.047) in BM1, and IL-6 in BM2 (p=0.035). Conclusion . Women delivered by caesarean section, primiparous women, and women with miscarriages in obstetric history were associated with higher BM and CB IgE levels and T2-associated cytokine concentration (IL-4, IL-5, CCL17, CCL22), as well IL-6 and IFN-γ, but lower sIgA and TGFβ1 concentrations. Effect of such cytokine patterns during the period of immune tolerance development may lead to infant immune maturing trajectory changing towards T2 predominance.

Background. Treatment of drug-resistant tuberculosis is associated with numerous medical and societal problems; therefore, the search continues for measures to improve treatment outcomes through the development of new drugs and chemotherapy regimens. Bedaquiline metabolized by the cytochrome P450 isoenzyme CYP3A4. CYP3A4 and CYP3A5 polymorphisms can lead to variability in bedaquiline plasma concentrations, which in turn affects treatment efficacy and safety. Currently, there are no data on the prevalence of CYP3A4*22 and CYP3A5*3 gene polymorphic variants among Yakuts and Russians with tuberculosis. Objective. To study the carrier frequency of CYP3A4*22 (rs35599367) C>T and CYP3A5*3 (rs776746) A>G gene polymorphisms among Yakuts and Russians with drug-resistant tuberculosis compared to the normal variability of the studied gene allelic variants in East Asian and European populations. Methods. A cross-sectional comprehensive study was conducted on 255 patients of Yakut and Russian ethnicity with drug-resistant pulmonary tuberculosis. CYP3A4*22 ( rs35599367 ) C>T and CYP3A5*3 ( rs776746 ) A>G polymorphisms were determined by real-time polymerase chain reaction. For comparative analysis, data on the carrier frequency of CYP3A4*22 and CYP3A5*3 allelic variants in East Asian and European populations were used. Results. In patients with drug-resistant pulmonary tuberculosis, the frequency of the T allele of the CYP3A4*22 gene was significantly lower in the Siberian group compared to the frequency in the Eurasian group ( p = 0.003). The wild-type genotype ( CC ) CYP3A4*22 was significantly more common in the Siberian group of patients than in the Eurasian group, whereas the heterozygous genotype ( CT ) was less represented in the Siberian population ( p = 0.003). The AA genotype of CYP3A5*3 was less common in the Siberian group relative to its frequency in the Eurasian group ( p = 0.021), the heterozygous AG genotype was much less frequently detected in the Siberian population of patients ( p < 0.001), and the GG genotype predominated in the Siberian group and was less frequently determined in the Eurasian population ( p < 0.001). The frequencies of alleles and genotypes of the CYP3A5*3 gene in patients with drug-resistant pulmonary tuberculosis did not differ between the Yakut and Russian populations. The distribution of CYP3A5*3 alleles and genotypes in the Russian population was the same as in the general European profile ( p > 0.05). Differences were found between Yakuts and East Asians for all analyzed parameters ( p < 0.05). Conclusion. Features of the distribution of CYP3A4*22 and CYP3A5*3 gene allelic variants affect the rate of drug metabolism among patients of Yakut and Russian ethnicity. Differences in allelic variants and genotypes of CYP3A4 and CYP3A5 in Russian and Yakut populations with drug-resistant pulmonary tuberculosis can significantly modify clinical efficacy and the development of adverse reactions during bedaquiline treatment, as the CYP3A isoenzyme of cytochrome P450 plays a primary role in its oxidation.

In 80 patients with atopic bronchial asthma and allergic rhinitis living in the Bukhara region, a predominance of sensitization to house dust mites (>50%) and a high prevalence of polysensitization were identified. Polysensitization was associated with poor disease control. The findings indicate the need for a stratified and personalized therapeutic approach, taking into account regional characteristics of allergen exposure.

Gonarthrosis is one of the most common osteoarthrosis problems affecting large joints. It accounts for 50.6–54.5% of cases among patients with degenerative-dystrophic diseases of the large joints of the lower extremities. In 86% of cases, the disease affects individuals of working age, and in 6.5–14.6% of cases, it leads to disability. The aim of the study is to investe the periprosthetic synovial membrane to identify the cause of instability of the primary knee endoprosthesis. A total of25 cases of periprosthetic synovial tissue obtained from patients with instability of the primary knee joint endoprosthesis during revision endoprosthetics were morphologically studied. The average age of patients was 64.6 ± 2.11 (78-44) years. The cohort included17 women (68%) and 8 men (32%). Histological examination of periprosthetic synovial tissue revealed synovitis of varying severity and activity of pathological signs. Based on histological signs, all periprosthetic synovial tissues were divided into four etiopathological groups: periprosthetic synovitis caused by endoprosthesis wear; periprosthetic synovitis caused by infection; periprosthetic synovitis caused by fibrosis; and periprosthetic synovitis caused by autoimmune activation. Our studies have shown that in revision knee arthroplasty a histological examination of the periprosthetic synovial membrane is necessary. We identified 4 different histological patterns of changes in the synovial membrane in cases of endoprosthesis instability: wear-induced periprosthetic synovitis; infection-induced periprosthetic synovitis; fibrosis-induced (indifferent) periprosthetic synovitis; and immune-induced periprosthetic synovitis.Keywords: revision arthroplasty, knee joint, synovial membrane, pathomorphological studies.

Aortic valve (AV) bioprostheses can be divided into framed and frameless, as well as those implanted using surgical and endovascular methods. The study of hemodynamic criteria for the functioning of sutured, seamless and transcatheter biological prostheses, including the dynamics of reverse structural and functional remodeling of the heart in the long term, is necessary to select the most correct and effective treatment tactics. The aim of the study: to evaluate, using objective radiation methods of research, hemodynamic parameters and the dynamics of reverse structural and functional remodeling of the heart in the late period after correction of degenerative aortic valve defect using cardiac surgery and endovascular methods. Materials and methods. A comparative, non-randomized, longitudinal study was conducted, including 89 people with severe aortic stenosis, who underwent isolated surgical or endovascular valve replacement. The patients were divided into three groups: a group with AV prosthetics using the method of implantation of a seamless biological prosthesis (n = 23); a group using a sewn-in biological prosthesis (n = 45); a group with a transcatheter aortic valve implantation technique (TAVI) (n = 21). The median age of patients using a sutured biological prosthesis was 71.0 [66.7; 74.0] years, the age of patients with implantation of a seamless biological prosthesis was 73.0 [69.0; 76.8] years (p = 0.055); in the group with a transcatheter technique for implantation of a biological prosthesis, the median age was 75.0 [69.0; 79.0] years (p = 0.013). The female gender was 20 (44.4%), 16 (69.6%), 11 (52.4%) (p = 0.050), respectively. In the dynamics of objective monitoring of the condition and implementation of the study goal, all patients underwent echocardiography (ECHO) according to the generally accepted method. Results. In three groups, a comparison of structural and functional parameters “before” and “after” the intervention was carried out, and an intergroup comparison was performed between two groups (surgical correction using suture and sutureless bioprostheses), since the initial characteristics of the group with endovascular treatment, in particular, age, differed from the other groups. After correction of aortic stenosis using both cardiac surgery and transcatheter methods, reverse structural and functional remodeling of the heart is observed in the long term. In patients using sutured biological prostheses, LVMM decreased by -22.0 [-28.0; -17.0]% (p = 0.0002), seamless biological prostheses – by -20.0 [-27.0; -13.0]% (p = 0.01), with transcatheter aortic valve implantation – by -16.0 [-22.0; -10.0]% (p = 0.0001); left ventricular (LV) hypertrophy concentricity decreased by -21.0 [-29.0; -14.0]% (p < 0.0001), -24.0 [-31.0; -15.0]% (p = 0.0002), -24.2 [-35.6; -1.1]% (p = 0.002), respectively. In groups using cardiac surgical methods, an improvement in longitudinal systolic function was demonstrated: absolute values of global systolic longitudinal deformation of the LV, assessed by the speckle-tracking method, increased in patients with implanted biological prostheses by 19.3 [7.5; 54.0]% (p = 0.032), with seamless biological prostheses – by 18.4 [3.3; 42.8]% (p = 0.027), the S’ lat mv tissue dopplerography indicator increased – by 36.7 [22.1; 51.3]% (p < 0.0001) and 42.8 [17.5; 57.1]% (p = 0.0005), respectively. In individuals with TAVI, the S’ lat mv values increased by 25.0 [14.3; 55.3]% (p = 0.005). Recovery of left ventricular systolic function in the remote period, established on the basis of the results of 2D speckle tracking echocardiography, was diagnosed in 12 (60.0%) patients with sutured and sutureless biological prostheses. Conclusion. Correction of severe AS using cardiac surgical and endovascular methods is associated in the long term with favorable indicators of intracardiac hemodynamics and reverse structural and functional remodeling of the LV.

BACKGROUND: Despite advances in anesthesiology, postoperative pain following open kidney surgery remains a major clinical challenge. High pain intensity in the early postoperative period often leads to increased opioid consumption and a higher risk of complications. Within the ERAS (Enhanced Recovery After Surgery) concept, increasing attention is given to safe regional analgesic techniques that reduce opioid requirements. One such method is the erector spinae plane block (ESP block), whose effectiveness in open urologic surgery is insufficiently studied. AIM: This study aimed to evaluate the effectiveness of the ESP block as a component of multimodal anesthesia in patients undergoing open kidney surgery during the intraoperative and early postoperative periods. METHODS: A prospective, controlled study included 116 patients divided into two groups: the main group (n = 60, with ESP block) and the control group (n = 56, without block). Patients older than 18 years with ASA physical status I–III and without contraindications to regional anesthesia were included. Primary outcomes were intraoperative fentanyl consumption, postoperative use of trimeperidine, pain intensity assessed by the numerical rating scale, incidence of nausea and vomiting, need for nonsteroidal anti-inflammatory drugs and paracetamol, and length of stay in the intensive care unit. Statistical analysis was performed using SPSS 25.0; significance level p 0.05. RESULTS: ESP block significantly reduced fentanyl consumption: 0.027 ± 0.01 μg/(kg·min) vs. 0.046 ± 0.02 μg/(kg·min) (p 0.01) and the need for trimeperidine within the first 6 hours (5.0% vs. 55.6%; p 0.001). Pain intensity on the numerical rating scale was significantly lower in the main group at all observation points (median 0.0 vs. 3.0–7.0; p 0.001). The incidence of postoperative nausea and vomiting was 10–15 times lower in the main group (p 0.001), as was the need for nonsteroidal anti-inflammatory drugs and paracetamol. Length of stay in the intensive care unit decreased 3.7-fold (2.88 ± 0.17 h vs. 10.89 ± 3.51 h). CONCLUSIONS: ESP block in open renal surgery demonstrates high clinical effectiveness as part of multimodal anesthesia, providing marked analgesia, reducing opioid load, and improving postoperative recovery.

Abstract Background and Aims The kidneys are one of the most vulnerable organs in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Kidney damage can significantly worsen the prognosis and quality of life of patients. Clinical and laboratory manifestations of renal dysfunction vary depending on the subtype of disease and the degree of vascular damage. The aim of this study is to analyze the clinical and laboratory manifestations of renal pathology in patients with various types of ANCA-associated vasculitis. Method The study included 45 patients diagnosed with ANCA-associated vasculitis (60.0% (n = 27) women and 40.0% (n = 18) men), who were observed at the Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology from 2017 to 2024. The average age was 59.1 ± 12.3 years. 57.8% (n = 26) patients had granulomatosis with polyangiitis (GPA), 24.4% (n = 11)—microscopic polyangiitis (MPA), 17.8% (n=8)—eosinophilic granulomatosis with polyangiitis (EGPA). We analyzed blood creatinine levels, estimated glomerular filtration rate (eGFR), hematuria, leukocyturia, cylindruria and daily proteinuria at the time of disease onset to assess the type and severity of renal damage. In addition to clinical and laboratory examination, the diagnosis of ANCA-associated vasculitis and secondary glomerulonephritis was confirmed by the results of immunological tests (ANCA, antibodies to myeloperoxidase and proteinase-3) and nephrobiopsies. Results A higher level of serum creatinine (237 (103; 463) μmol/l) and low eGFR (18.1 (12.3; 76.2) mL/min/1.73 m²) were diagnosed in the group of patients with MPA compared with the GPA and EGPA groups (P < 0.005). Proteinuria was diagnosed in 75.6% (n = 34), most often—in patients with MPA (90.9%). The level of proteinuria ranged from mild to nephrotic. It exceeded 1 g/day in 66.7% (n = 30). Nephrotic syndrome was found in 8.9% (n = 4) patients and was not observed in EGPA group. In 9 cases (20.0%) isolated urinary syndrome was diagnosed, but without significant decrease in renal function and arterial hypertension. In 42.2% (n = 19) cases kidney damage was accompanied by arterial hypertension, its highest frequency was recorded in the MPA group: 7 out of 11 patients (63.6%). eGFR <90 ml/min/1.73 m² was found in 82.2% (n = 37) patients, 20.0% (n = 9) showed the most pronounced decrease (eGFR <15 ml/min/1.73 m²), mainly in MPA group (n = 7), P < 0.05. The clinical picture of rapidly progressive glomerulonephritis developed in 63.6% (n = 11) of patients with MPA, while in the GPA and EGPA groups this figure was 23.1% (n = 6) and 12.5% (n = 1), P < 0.05, respectively. Conclusion Variants of ANCA-associated vasculitis exhibit a wide range of clinical and laboratory manifestations, with the most severe forms of renal damage reported in patients with MPA. Proteinuria is detected in a significant number of patients, especially with MPA. Nephrotic syndrome developed in 8.9% of patients and was absent in the EGPA group. Kidney damage is often accompanied by arterial hypertension, which is most pronounced among patients with MPA. The incidence of rapidly progressive glomerulonephritis supports the fatal role of renal damage in ANCA-associated vasculitis.

Abstract Background and Aims The incidence of cardiovascular diseases in patients with Stage 5 Chronic Kidney Disease is more than twenty times higher than in the general population. The aim of the study was dynamic assessment of cardiovascular risk factors in patients with chronic kidney disease in the preoperative period and after kidney transplantation. Method The study included 43 patients of the kidney transplant waiting list. At the time of kidney transplantation the average age was 45.3 ± 11.9 years; 53.5% (n = 23) were women, 46.5% (n = 20)—men. Patients were examined in the preoperative period, six months and five years after transplantation. Results The incidence of arterial hypertension was unchanged during the observation period, while episodes of hypotension in the postoperative period were diagnosed less frequently than in the preoperative period—4.7% (n = 2) versus 44.2% (n = 19), P < 0.001. Five years after transplantation, the average body mass index of recipients became higher and the incidence of obesity increased: 26.0 ± 4.8 kg/m2 versus 24.6 ± 4.2 kg/m2 and 25.6% (n = 11) 7.0% (n = 3), P < 0.01, respectively. The blood level of total cholesterol decreased only in the late postoperative period in comparison with the previous stages: 5.20 ± 1.09 mmol/l versus 5.91 ± 1.24 mmol/l and 5.70 ± 1.34 mmol/l, P < 0.05. Blood triglyceride levels decreased progressively: from 2.31 (1.58–3.37) mmol/l to 1.54 (1.16–1.94) mmol/l after six months and to 1.30 (0.90–1.80) mmol/l after five years, P < 0.05. The blood glucose level of recipients was comparable in the preoperative period and six months after transplantation—6.1 (5.5–6.3) mmol/L and 5.8 (4.5–6.3) mmol/L accordingly and decreased five years after transplantation—5.2 (5.0–5.8) mmol/l, P < 0.001, as the frequency of hyperglycemia did: from 44.2% (n = 19) and 32.6% (n = 14) to 11.6% (n = 5), P < 0.05. The average blood concentration of hemoglobin increased in the long-term postoperative period: from 108 ± 17 g/l to 125 ± 18 g/l and 127 ± 18 g/l, P < 0.001, and the frequency of anemia decreased from 79.1% (n = 34) patients in the preoperative period to 48.8% (n = 21) after six months and 34.9% (n = 15) five years after transplantation, P < 0.01. Transplantation also helped reduce the incidence of iatrogenic hypererythropoietinemia: from 27.9% (n = 12) to 4.7% (n = 2), P < 0.05. Dialysis patients had a high level of brain natriuretic peptide (NT-proBNP) in the blood—3300 (1800–3300) pg/ml. In the postoperative period it was significantly lower than in the preoperative period—175 (60–350) pg/ml after six months and 225 (60–500) pg/ml five years after transplantation, P < 0.01. An increased level of NT-proBNP was detected in all recipients in the preoperative period and decreased to normal values in 37.2% (n = 16) in the postoperative period, P < 0.001. Echocardiography showed no changes in ejection fraction and left ventricular myocardial mass index, the incidence of diastolic dysfunction: 64.4 ± 8.1%, 118.79 ± 43.93 g/m2 and 18.6% (n = 8) in the preoperative period versus 66.0 ± 7.5%, 117.32 ± 37.38 g/m2 and 11.6% (n = 5) in the long-term postoperative period, P > 0.05. The absence of negative changes in the structural and functional state of the heart for five years of observation in patients with chronic kidney disease can be considered as a positive stabilizing effect of transplantation. Conclusion Based on the study it was found that in the long-term postoperative period, compared with the preoperative period, kidney transplant recipients have a decrease in the incidence of hypotension, anemia, hypererythropoietinemia, an increase in body mass index and blood hemoglobin concentration, a decrease in the blood levels of total cholesterol, triglycerides, glucose and NT-proBNP, as well as stable the structural and functional characteristics of the heart.