Republican Research Center for Radiation Medicine and Human Ecology

Background. Cervical cancer (CC) has become a common malignancy, significantly contributing to the rising mortality rate among women worldwide. The vaginal microenvironment plays a key role in the development of the human papillomavirus (HPV) infection, thereby contributing to the development of CC. Objective. To characterize the main indicators of vaginal microecology in HPV-associated cervical dysplasia. Material and methods. The study involved 102 women of reproductive age (18-49 years). The study material consisted of posterior vaginal fornix swabs and cervicovaginal secretion samples. Vaginal swabs were cultured. The vaginal microbiome was assessed based on the number of microorganisms grown. All lactobacillus isolates were assessed for their functional activity, including their ability to produce hydrogen peroxide, form biofilm, and exhibit antagonistic activity against test strains of opportunistic microorganisms. Results. In HPV-associated dysplasia, there was a significant increase in the pH of the vaginal discharge (p<0.034) and a significantly higher incidence of vaginal dysbiosis (80%), with severe dysbiosis detected in 73.3% of patients. Antagonistic activity and hydrogen peroxide production in lactobacilli of the compared groups did not differ. Biofilmforming capacity was significantly reduced in lactobacilli isolated in the cervical dysplasia group. Thus, the ability to form the main substance was low in all lactobacilli isolates in this group (p=0.02), and the ability to form biomass was absent in 60% of isolates (p=0.003). The study of the parameters characterizing local vaginal immunity did not reveal significant differences between the groups. However, a trend towards an increase in proinflammatory cytokines, regulatory IL-2 and a decrease in sIgA was noted in the group with cervical dysplasia. Conclusion. We detected significant changes in several vaginal microecological parameters in a group of women with HPV-associated cervical dysplasia. It was found that dysplasia was associated with vaginal dysbiosis, and vaginal pH was elevated. Changes in the properties of the resident vaginal microbiota were also observed, including decreased antagonistic activity and the ability to form a physiological biofilm on the vaginal mucosa, leading to decreased colonization resistance of the vaginal biotope. These parameters may indicate a progressive course of HPV-associated dysplasia and can be used as additional markers in assessing the risk of developing precancerous pathology and cervical cancer.

The WIL-31 study demonstrated efficacy and safety of prophylaxis with the plasma-derived von Willebrand factor/factor VIII concentrate wilate in von Willebrand disease (VWD) of all types and was the only prospective study with an on-demand run-in study as an intra-individual comparator. This subgroup analysis examines the efficacy of wilate prophylaxis in patients with type 3 VWD in WIL-31. Patients received 20-40 IU/kg wilate prophylaxis 2-3 times weekly for 12 months. Twenty-two patients in WIL-31 had type 3 VWD. Mean total annualized bleeding rate (ABRs) during on-demand versus prophylaxis was 37.1 versus 5.2 (86% reduction). During prophylaxis, 115 bleeds occurred, most (95%) of which were minor; the most common bleeding site was the nose (40% of bleeds). Mean overall spontaneous ABRs during on-demand versus prophylaxis were 26.5 versus 2.8 (89% reduction); mean treated spontaneous ABRs were 20.3 versus 1.4, respectively (93% reduction). ABRs were reduced further during the second 6 months of prophylaxis versus the first 6 months. Results were consistent in subgroups by age. No serious adverse events related to study treatment and no thrombotic events were observed. Prophylaxis with wilate was effective and well tolerated in patients with type 3 VWD, in all age groups. NCT04052698; https://clinicaltrials.gov/study/NCT04052698.

This study investigated the enhancement of antioxidant activity of rosemary diterpene polyphenols in the presence of thiols. The antioxidant capacity was assessed by measuring the inhibition of lipid oxidation in an aqueous micellar system as a model for many foods containing water. The antioxidant activity of major diterpene polyphenols [carnosic acid (CA), carnosol (CAR), rosmanol (ROS), and isorosmanol (ISO)] under the conditions in the presence or absence of cysteine thiol (1 or 2 mol equiv) was examined at 0.63 mM for 5–8 days. Only CAR and ISO exhibited a significant enhancement in antioxidant activity in the presence of the thiol, with ISO demonstrating a greater effect. To investigate the mechanism underlying the enhancement by ISO, time-course analysis by high-performance liquid chromatography (HPLC) and structural characterization of a key reaction product were first conducted. Subsequently, HPLC and rapid ultraviolet–visible (UV–vis) spectral scanning were employed to examine the reactions of quinone derivatives from ISO and ROS, confirming the markedly higher reactivity of the ISO quinone with the thiol. These experimental findings were further examined by density functional theory (DFT) calculations, which elucidated a reaction mechanism consistent with the notable enhancement in antioxidant activity observed for ISO.

Objective. To assess the risk of developing cervical dysplasia depending on the type of human papillomavirus (HPV) and the age of women (on the case of women from Gomel region).Materials and methods. Cytological examination and testing for HPV of Viral Cancer Risk (VCR) were carried out from 2018 to 2023 using the Abbott RealTime hrHPV (USA) kit on the Abbott m2000sp device. This test separately detects HPV 16, HPV 18 and a pool of 12 additional HPV hrHPV types (HPV 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68). Material — scrapes from the cervical canal. 11382 women from Gomel region were examined.Results. According to the results of the molecular genetic study, the infection rate of HPV VCR in women of Gomel region was 8.97% (n=1022). A tendency for the highest infection rate was noted in younger women. Thus, the highest number of HPV-positive samples was detected in the groups of 18-24 years old (n=276), 25-29 years old (n=156), 30-34 years old (n = 154). It was found that the relative risk (RR) of developing high-grade dysplasia in case of infection with HPV VCR was significantly higher in women of the age groups of 25-29 years old (RR — 66.3 (95% confidence interval (CI) 15.58; 281.7)), 35-39 years old (RR 35.4 (95% CI 13.05; 95.79)) and 18-24 years old (RR 18.5 (95% CI 5.31; 64.46)). 711 (6.2%) women with a high probability of developing cervical dysplasia were identified. A high risk of developing dysplasia was noted in cases of infection with type 16 and/or type 18 of the virus, as well as for women aged 18-34 infected with other genotypes of HPV VCR.Conclusion. Information on age and infection ith various genotypes of HPV VCR may be very useful for formation of risk groups of development of cervical dysplasia and effective strategies design for prevention of precancerous processes and cervical cancer associated with HPV.

This study aimed to evaluate the ultrasound findings in skeletal muscle lymphoma and investigate the correlations between ultrasound findings and histopathological characteristics. Ultrasonographic images with skeletal muscle lymphoma obtained between June 2014 and June 2024 were retrospectively reviewed. The ultrasonographic examinations comprised gray-scale (n = 35), color-Doppler (n = 35), contrast-enhanced (n = 5), and elastography imaging (n = 5). Biopsy samples underwent histopathological analysis to identify the histopathologic basis of the typical ultrasound features. Kappa statistics were used to assess the consistency between ultrasound findings and histopathological features. The study comprised 35 patients (mean age, 63 years ±15 [standard deviation], 17 men). In gray-scale sonography, 35 lesions (100%) appeared as hypoechoic areas in the muscle with poorly defined margins. Residual myofiber-like echoes were observed in 25 (71.4%) lesions, and a "cobblestone" appearance was noted in 18 (51.4%). In color-Doppler sonography, 10 (28.6%) patients had intact transverse vessels perpendicular to the long axis of the muscle. In contrast-enhanced sonography, 4 out of 5 (80%) lesions showed synchronous high enhancement. Four out of 5 (80%) lesions exhibited high stiffness on elastography imaging. Myofiber-like echoes (κ: 0.800, P < 0.001) and the "cobblestone" appearance (κ: 0.521, P < .017) are consistent with myofibers in pathology. Skeletal muscle lymphoma demonstrates specific features on multimodal ultrasound.

Analysis of serum CRP levels in 197 patients with polycythemia vera revealed positive correlations with fibrinogen (rs=0,46, p&lt;0,001), interleukin-6 (r=0,38, p&lt;0,001), and erythrocyte sedimentation rate (rs=0,47, p&lt;0,001). A notable association was identified between elevated CRP levels (&gt;5 mg/l) and the frequency of increased D-dimer concentrations (Pearson’s χ2 test p=0,031). Additionally, a weak but detectable correlation was observed with hyperhomocysteinemia and decreased protein S levels, potentially contributing to thrombotic complications. CRP levels correlated significantly with leukocyte count (rs=0,20, p=0,034), particularly neutrophils (rs=0,23, p=0,012) and monocytes count (rs=0,26, p=0,004), as well as with uric acid levels (rs=0,26, p=0,005), gamma-glutamyl transferase activity (rs=0,25, p=0,006), and urea levels (rs=0,20, p=0,036). Elevated CRP values were more prevalent among patients with a history of cancer, diabetes mellitus, or coronary heart disease, although differences did not reach statistical significance.

The object of study was to investigate the clinical and laboratory characteristics, the outcomes of the disease, the susceptibility to antibiotics and to different combinations in the patients with pneumonia caused by K. pneumoniae associated and not associated with COVID-19.We analysed 93 cases of pneumonia with K. pneumoniae detected in biological materials including 65 ones with COVID-19 and 28 ones without COVID-19.In the both groups, the diseases of the circulatory system and metabolic disorders were the most common concomitant conditions. The laboratory data were not statistically different. The lethal outcomes were found reliably more often in the patients with COVID-19 (66 % vs 32 %). K. pneumoniae was detected predominantly after the tenth day of admission to the hospital (nosocomial strains). In the both groups, the majority of detected K. pneumoniae strains had a multiple resistance to antibiotics. The combinations of antibiotics with no colistin demonstrated a low efficacy, including those with carbapenems. A proportion of 40 (61.5 (48.6–73.3) %) K. pneumoniae samples isolated from patients with COVID-19 had carbopenemases detected.The results of the study refer to the preferability of the colistin comprising the schemes of antibiotics for treatment of pneumonia caused by K. pneumoniae associated and not associated with COVID-19.

AIM. To study the prognostic value of the galectin-1 expression by bone marrow (BM) tumor plasma cells (PCs) and the concentration of serum cytokines (interleukins [IL-2, IL-6] and tumor necrosis factor [TNF]) in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (ММ). MATERIALS &amp; METHODS. The trial enrolled 129 patients: 77 patients with newly diagnosed MM (median age 64 years) and 52 patients with MGUS (median age 62.5 years) followed-up at the Republican Scientific and Practical Center for Radiation Medicine and Human Ecology from 2018 to 2023. All patients underwent general clinical examination as well as BM aspirate cytology with myelogram and iliac BM core biopsy with immunohistochemical (IHC) analysis of BM biopsy. RESULTS. In the BM biopsy, the IHC analysis revealed a significant increase of galectin-1 expression (measured by expressing tumor PC count) in MM vs. MGUS patients (p &lt; 0.001). Galectin-1 expression defined as expressing tumor PC count was significantly higher in patients with progressing MGUS compared to progression-free MM patients (p &lt; 0.001). The median galectin-1 expression level was 8.5 % (Q25 0.2 %; Q75 15.7 %) in progression-free MGUS patients and 37.4 % (Q25 24.7 %; Q75 64.0 %) in progressing MGUS patients. Among MM patients, no significant differences were identified either in those with and without tumor progression. The IHC analysis of BM core biopsies in MM patients showed that high galectin-1 expression level is associated with pronounced vasculature but not with fibrotic changes, it also identified an increase in serum concentrations of IL-2 and TNF as well as a direct correlation with β2-microglobulin level. With MGUS progression into ММ, there was a direct correlation between galectin-1 expression level and serum M-protein. An increase of IL-2 concentration was registered only when MGUS progressed into ММ. CONCLUSION. The results of this study indicate the evidence of a high level of galectin-1 expression by tumor PCs in MM. In MGUS, an increase of galectin-1 expression by clonal BM PCs was associated with the disease progression. Galectin-1 expression by clonal BM PCs can well be clinically used as a marker for MGUS progression into MM.

Introduction. Ph-negative myeloproliferative neoplasms (MPN) are chronic clonal disorders characterized by the proliferation of mature cells from one or more myeloid cell lines. These disorders include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The incidence of classical Ph-negative MPN varies significantly throughout the world. These differences may be due to geographical or population features, as well as due to differences in methods of diagnosis and recording. Aim: to determine incidence of Ph-negative MPN in Belarus. Materials and methods. Data on all cases of newly diagnosed Ph-negative MPNs (PV, ET and PMF) for 2014-2018 were collected from central regional medical institutions with a hematology specialization. Population epidemiological analysis of incidence was carried out by determining crude incidence rates per 100 000 population per year with distribution by genderand age groups at diagnosis, age-standardized rates, as well as average annual percent change. Results. The overall annual standardized incidence rate of classical Ph-negative MPN in Belarus was 1.96 (1.86–2.07), PV — 0.93 (0.86–1.01), ET — 0.63 (0.57–0.70) and PMF — 0.40 (0.36–0.45) per 100 000 population per year, respectively. The overall crude incidence rate was 3.26 (3.10–3.43) per 100 000 population. The crude incidence rates increased steadily with the increase in age of patients with a peak value of 12.78 (10.97–14.81) in the age group of 70–74 years. No significant changes were revealed in the overall incidence of the MPN and for each of the studied diseases separately during the study period. Conclusion. For the first time the nationwide features of incidence of the Ph-negative MPN in Belarus were estimated, which made it possible to provide substantial information for public health management. The incidence of MPN in Belarus is generally comparable to the levels determined in the analysis of the populations of other countries.