CLINICAL MEDICINE
Objective. To evaluate genetic mechanisms of antibiotic resistance and virulence of invasive strains of Klebsiella pneumoniae isolated from inpatients using whole genome sequencing.
Materials and methods. For two carbapenem-resistant multiple-antibiotic-resistant invasive strains of K.pneumoniae, as well as two carbapenem-sensitive invasive strains of K.pneumoniae, sequencing was performed using the MiSeq genomic sequencer (Illumina). Genomic sequences were assembled and annotated. Sequence type determination, search for plasmids and virulence factors, antibiotic resistance genes, and efflux mechanisms were performed.
Results. K.pneumoniae strains belonged to sequence types ST395, ST101, ST111, and ST512 s and had a hypermucoid phenotype. The iutA aerobactin genes were detected in both sensitive and carbapenem-resistant strains. Virulence genes fimH, fyuA, and irp2 were detected in one strain isolated from blood. Carbapenemase genes (blaKPC, blaNDM) were detected in two strains. Aminoglycosides and fluoroquinolones resistance genes were detected in 3 of 4 strains. All strains showed the presence of different systems of active antibiotic elimination from the microbial cell.
Conclusion. The possibility of identifying hypervirulent strains of K.pneumoniae using a complex phenotypic test along with hvKp genotyping is shown. The results of full-genome sequencing reflect significant resistance of hypervirulent K.pneumoniae strains isolated from blood to most antibiotics, including β-lactams, aminoglycosides, fluoroquinolones, phosphomycin, chloramphenicol and polymyxins.
Objective. To determine the possibilities of cytological method of urine cellular sediment examination for diagnosis and differential diagnosis of renal and urinary tract pathology in liver cirrhosis.
Materials and methods. A standard observational study of 50 inpatients with liver cirrhosis was performed. Cytological preparations of urine sediment were prepared by liquid cytology and cytocentrifugation methods and after fixation were
Results. Cytological study of cellular urine sediment in hospitalized patients with cirrhosis revealed dysmorphic (leached) erythrocytes in 31% of cases, statistically significantly more frequently in patients with decompensation of the disease and 30-day mortality (p<0,05). Microflora in the urine was found in 63% of patients, more often of mixed nature (27%). In 46% of patients with decompensated liver cirrhosis, including acute renal injury, cytological preparation of urinary sediment is represented by multicellular elements with the presence of superficial and deep urothelium and renal epithelium.
Conclusions. Cytological method of studying the cellular urine sediment is an accessible, informative and cheap diagnostic method, the possibilities of which are to determine the presence and origin of cellular elements (urothelium of the surface and deep layers, altered erythrocytes), microflora and its source (genital tract, urinary tract), which, in combination with other methods, allows to verify the diagnosis of the patient and to carry out differential diagnosis of acute tubular necrosis and hepatorenal syndrome.
Objective. To study the levels of cytokines (γ-interferon, tumor necrosis factor α (TNF-α)) and hormones (cortisol, prolactin, estradiol, progesterone, testosterone) in blood serum of women of reproductive age with pulmonary tuberculosis (TB).
Materials and methods. We studied the serum levels of γ-interferon, tumor necrosis factor α, cortisol, prolactin, estradiol, progesterone, testosterone in women 18-45 years old with newly diagnosed pulmonary TB (n = 47) compared with the same indices in women without TB and with no previous TB (n = 35).
Results. Women with pulmonary TB had higher levels of cortisol (cutoff point, 196.1 nmol/L, AUC 0.75, Se 85.1 %, Sp 70.6 %) and prolactin (cutoff point, 486, 1 mEU/L, AUC 0.69, Se 59.6%, Sp 73.5%) and lower serum progesterone levels (cutoff point 3.9 nmol/L, AUC 0.71, Se 73.9%, Sp 64.7%) than women without TB. The study of the levels of γ-interferon and TNF-α showed less diagnostic significance of the parameters, and there was a slight increase in the levels of both cytokines in women with pulmonary TB.
Conclusion. Changes in cytokine-hormone status in women with TB can both reflect mechanisms of anti-infective defense and be a consequence of the development of the disease.
Objective. To evaluate the effectiveness of extremely high frequency (EHF) millimeter range electromagnetic radiation (EMR) of low intensity in patients with malignant neoplasms suffering from chronic pain syndrome (CPS).
Materials and methods. The study included 60 patients with diagnosed malignant neoplasm (MN) who were treated in a palliative care unit. They were divided into 2 groups. The main group consisted of 30 patients who underwent additional EHF-exposure with a course of 10 sessions of 15 minutes simultaneously with the main therapeutic measures. The comparison group consisted of patients who did not undergo electromagnetic exposure 30 people. Questioning was conducted twice: on the 2nd and 14th days of treatment. Treatment efficiency was assessed using standardized questionnaires.
Results. The analgesic effect of additional use of EHF therapy with a fixed frequency of 53.534 ± 0.015 GHz in patients with MN was significantly higher than the analgesic effect of standard treatment. In particular, there was an increase in mobility, as well as a decrease in depression and reactive anxiety.
Conclusion. The additional use of EHF therapy in patients with MN provides the advantage of improving quality of life by reducing CPS, improving psychological well-being and improving the ability to move independently.
Objective. To develop a method for determining the risk of reproductive loss in the 1st trimester of pregnancy.
Materials and methods. Blood serum, whole blood, medical records of an inpatient (form No. 003/-07), and exchange cards (form No. 113/-07) of 94 pregnant women. Interleukin-6 concentration was assessed in the examined patients by immune-enzyme analysis. The level of leukocytes and monocytes was determined in whole blood by general clinical routine methods on a hematology analyzer. Statistica 10.0 software package and “R” programming language, version 4.1, were used for statistical analysis.
Results. The developed logistic regression equation (sensitivity, 87.5%; specificity, 83.33%; classification accuracy, 86.17%) by determining the linear predictor Z makes it possible to assign a pregnant woman to the high risk group for the development of reproductive loss in the 1st trimester (Z > -0.4519).
Conclusion. The proposed new method for determining a high risk of developing reproductive loss in the 1st trimester of pregnancy makes it possible to carry out appropriate therapeutic measures to help preserve women’s reproductive health, improve fertility, and increase the birth rate.
Objective. To study demographic, clinical characteristics and concomitant pathology of patients with extrapulmonary tuberculosis (EPTB) in Gomel city and Gomel region for the period 2017-2021. To evaluate the informative value of different techniques for the detection of Mycobacterium tuberculosis (MBT) in non-respiratory samples in the diagnosis of extrapulmonary tuberculosis.
Materials and methods. A retrospective study of extrapulmonary tuberculosis cases registered from 2017 to 2021 in Gomel and Gomel region (308 patients) was carried out. The results of microscopic, bacteriological and molecular genetic methods of non-respiratory and respiratory samples relevant in the diagnosis of extrapulmonary forms of tuberculosis were analyzed.
Results. Demographic and clinical characteristics of patients with EPTB in Gomel and Gomel region for the period 20172021 were revealed. Concomitant pathology in patients with EPTB was analyzed, the features of EPTB diagnostics were studied. It was determined that EPTB is more susceptible to males aged 31 to 50 years and to women aged over 60 years. EPTB is more frequently diagnosed in patients from urban areas and when patients come to medical institutions with nonspecific complaints, except for intrathoracic lymph node tuberculosis (ITLN).
Conclusion. In the structure of clinical forms of EPTB, lesions of bones and joints (62.7%) and intrathoracic lymph nodes (19.5%) predominate. HIV-positive patients are more common in the ITLN group. MBT is most often detected in the following localizations of extrapulmonary process: intrathoracic and peripheral lymph nodes, pleural tuberculosis. The most highly informative method of examination of biological nonrespiratory material for detection of MBT in extrapulmonary localization is molecular genetic study.
Objective. To study the effect of local photodynamic therapy (PDT) on local immunity in patients with maxillofacial region and neck phlegmonas.
Materials and methods. The study included 62 patients with phlegmon of the maxillofacial region and neck. Two groups of patients were formed. Patients of the 1st group were treated locally according to the traditional methods. Patients of the second group additionally underwent local PDT on the background of the complex of traditional therapeutic measures.
Results. Under the influence of local PDT with the preparation «Fotolon» in patients with maxillofacial region phlegmonomas in the postoperative wound we observed activation of phagocytosis, an increase in the population of CD3 + T-lymphocytes, subpopulation CD4 + T-helper, immunoregulatory index (IRI) with a simultaneous decrease in the level of CD8 + T-lymphocytes, The decrease of CD25+ activated Tand B-lymphocytes carrying the receptor for interleukin 2, and CD95+ activated Tand B-lymphocytes carrying the Fas-receptor, the decrease of complement activity, circulating immune complexes (CIC), IgM, IgA levels with an increase of IgG.
Conclusion. Local PDT activates local immunity in patients with maxillofacial and neck phlegmons. Exposure to PDT causes a more balanced immune system response by increasing the innate immune response in patients and a pronounced immunological reactivity in the region of the postoperative wound.
Objective. To analyze the incidence of lymphoid structures of the pharynx among the adult population during the period from January 2021 to August 2022 in three nosological forms: chronic decompensated tonsillitis (CDT), hypertrophy of pharyngeal tonsils (HPT), hypertrophy of lingual tonsillitis (HLT). To determine the relationship of the above pathology between the age and sex of patients at the present stage. To evaluate the role of mycobiota in the structure of pharyngeal morbidity.
Materials and methods. The object of the study was 96 patients with chronic pathology of the lymphoid structures of the pharynx aged from 17 to 70 years, who were on inpatient treatment at the Gomel Regional Clinical Hospital (GRCH) during the period from January 2021 to August 2022. All patients underwent surgical intervention followed by an assessment of the pathohistological conclusions of postoperative samples of pharyngeal lymphatic formations. The patients were divided into 3 nosological study groups: CDT; HPT; HLT. Statistical data processing was performed using software: MS Excel and the programming language for statistical data analysis R (version 4.2.1), packages tidyverse (version 1.3.1), rstatix (version 0.7.0), ggstatsplot (version 0.9.5).
Results. The study revealed the most common nosological groups among patients with pathology of the pharyngeal lymphatic ring of Pirogov-Waldeyer: CDT (44%) and HPT (38%). A significant difference was revealed between the incidence rates of pathology of the Pirogov-Waldeyer pharyngeal lymphatic ring in the study age groups from 17 to 25 years (p=0.0008); from 26 to 35 years (p=0.0021); 56 years and older (p=0.008). The median age of patients in the study group was 35 years (LQ 24.0; UQ 48.5), whereas in some nosological forms: CDT – 30 years (LQ 23.0; UQ 41.0), namely 28 years among women and 36 years among men; HРT – 32.5 years (LQ 24.0; UQ 43.25), namely 34.5 years among women and 31.5 years among men; HLT – 57 years (LQ 49.0; UQ 63.0), and it is 56.5 years among women and 57 years among men. Morphological examination revealed only 2 (2%) cases of mycotic lesions of the removed lymphoid masses.
Conclusion. The relationship between the pathology of lymphoid structures of the pharynx in three nosological forms (CDT, HPT, HLT) and the age of patients was revealed. The role of mycobiota in the overall study group in the structure of pharyngeal morbidity at the present stage was evaluated.
Objective. To study the correlation between the neurological, immunological and neurophysiological signs of paraneoplastic polyneuropathy (PPNP) caused by small cell lung cancer (SCLC), to improve the quality of diagnosis of this pathology.
Materials and methods. Clinical, immunological (anti-Hu) and neurophysiological (electromyography (EMG), electroneuromyography (ENMG), somatosensory evoked potentials (SSEP)) examination of 61 patients with PPNP caused by SCLC are presented.
Results. It was established that sensory disorders in the limbs are the first and obligate clinical symptoms of PPNP, which precede the initial diagnosis of SCLC in 56% in 3-12 months, characterized by a predominance of a decrease in surface sensitivity in the form of distal hypoesthesia in 70% of cases. The motor form is characterized by an older age (67 years) than the sensory (60 years) and sensorimotor (58.0 years, p <0,05). Motor disorders in the limbs occur in 46% of cases, manifested by mild symmetrical distal paresis of the legs and subclinical damage to the motor nerves of the upper extremities according to the results of ENMG (p <0,001). Detection of anti-Hu in plasma is highly correlated with a significant increase in latency and a decrease in amplitudes component N22 in the conduct of SSEP, which indicates the defeat of the axons of the sensory nerves of the limbs (p <0,05). Changes in amplitude parameters, with preserved speed indicators of nerves according to the results of ENMG indicate an axonal type of lesion (p <0,05), which, in combination with the detection of anti-Hu in plasma, are pathognomonic signs of the paraneoplastic nature of the process.
Conclusion. As a result of the study, clinical, immunological and neurophysiological features of various forms of PPNP were identified. The obtained correlations make it possible to diagnose the corresponding type of nerve pathology more accurately and in a timely manner and to suspect the development of oncological disease in time. The revealed changes in the indicators of the N22 component of SSEP can serve as a marker of axonal lesion of peripheral nerves, which with high diagnostic efficiency justifies the expediency of inclusion in the protocol of the ENMG study for verification of additional signs characteristic of PPNP.
EXPERIMENTAL MEDICINE AND BIOLOGY
Objectives. To explore data on branching variants of the intrapelvic part of the superior gluteal artery in people of mesomorphic somatotype.
Materials and methods. We used 48 male dead bodies (deceased aged 25 to 82) and 30 female dead bodies (deceased aged 28 to 78) whose deaths were the result of accidental causes unrelated to the pelvic organs pathology. The following methods were used to achieve the goal of the study: vascular injection, dissection, statistical processing.
Results. The pattern of localization of anastomotic branches of the intrapelvic part of the superior gluteal artery (SGA) in humans of both sexes of mesomorphic somatotype was established for the first time. In men, 59.1% of all anastomotic branches of the SGA are located in the proximal third, 36.4% of anastomoses are in the middle third of this artery, and 4.5% of arterial connections are in the distal third of a. glutea superior. In women, arterial anastomoses branch from the proximal third of the intrapelvic portion of the SGA in 66.6% of cases and in the middle third of this artery in 33.3% of cases. The SGA in men of mesomorphic somatotype anastomoses more frequently than in women with the same type of build. It was found that intrathecal branches and anastomoses of the SGA in men and women of mesomorphic somatotype are predominantly localized along the proximal two thirds of this artery length. New data were obtained on the number of branches originating from a. glutea superior in the pelvic cavity, such as the lateral sacral artery (LSA), iliac-lumbar artery (ILA), obturator artery (OA), middle rectus, lower ureteric artery and rami musculares of the SGA. The SGA was found to be the most frequent source of lateral sacral artery formation in the pelvic cavity in men and women of mesomorphic somatotype.
Conclusions. The patterns of branching of the intrathecal part of the SGA are presented. The results obtained are recommended to be used for endovascular occlusion of the SGA to stop bleeding from the damaged distal third of this artery.
Objective. Develop an experimental model of liver cirrhosis and describe pathomorphological changes in organs and tissues of laboratory animals.
Materials and methods. Liver cirrhosis was simulated on 11 sexually mature Wistar male white rats. The control group consisted of 12 healthy laboratory animals. Acute toxic liver injury resulting in cirrhosis was induced by intraperitoneal injection of 50% tetrachloromethane (CCl4) solution on olive oil on the first day of the experiment in the dosage of 0.1 ml CCl4 + 0.4 ml olive oil per 100 g of the animal body weight, on the second day of the experiment 0.3 ml CCl4 + 0.2 ml olive oil per 100 g of the animal body weight. To synergize and potentiate the hepatotoxic effect of CCl4, animals had 10% ethanol solution freely available daily. The duration of the experiment was 65 days. Clinical and laboratory parameters were evaluated, histological evaluation of the preparations was performed. The obtained data were compared with the control group of animals.
Results. Reproducibility of the model was 82% (9 animals). The indicator of lymphocyte blabbing index showed the development of liver cirrhosis in animals of the experimental group. Comprehensive morphological confirmation of the developed liver cirrhosis was obtained.
Conclusion. The proposed methodology of liver cirrhosis formation correlates with pathomorphological changes in lymphocyte cell wall, changes in liver tissue and internal organs in human liver cirrhosis.
Objective. To study the possibility of using ultrasonography to identify mild (early), moderately severe and significantly severe dystrophic changes in the sciatic nerve.
Materials and methods. To achieve this goal, we compared ultrasonographic and histological data from 15 pairs of sciatic nerves taken from 8 men and 7 women aged 58 (52; 68) years who had been treated for different oncological diseases and died in 2022 from the underlying disease.
Results. Parallelism was revealed between the ultrasonographic pattern in mild, moderately severe and significantly severe dystrophic changes of the sciatic nerve, on the one hand, and the histological and immunohistochemical patterns, on the other hand.
Conclusion: Ultrasonography (B-mode) allows identifying mild, moderately severe and significantly severe dystrophic changes of the sciatic nerve.
PUBLIC HEALTH AND HEALTH CARE, HYGIENE
Objective. To develop objective criteria applicable in the practice of medical and social expertise when assessing the employability of patients suffering from breast cancer with absolutely life-threatening clinical and labor prognosis.
Materials and methods. In order to realize our aims we conducted a retrospective study of 37 female patients of employable age with malignant neoplasms of the breast, who at examination (primary or repeated) in medical and rehabilitation expert commissions (MREC) were assigned the first disability group due to absolutely unfavorable clinical and labor prognosis in respect of life in the nearest future. Inclusion criteria were morphologically confirmed breast cancer, absolutely unfavorable clinical and clinical and labor prognosis. Exclusion criteria were synchronous and metachronous cancer, presence of significant concomitant pathology.
Results. The results of the study showed that it is reasonable to use quantitative values of the Karnovsky index and ECOG scale as the simplest and the most universal criteria for evaluation of the general somatic status of a patient when examining patients with breast cancer with absolutely unfavorable prognosis at MREC. During the study, the quantitative values of the given indicators correlating with the degree of severity of disability to labor activity are determined: at the values of the Karnovsky index 60 points and more, the ECOG status 2-3, a reliable correlation (τ = 0,51, p < 0,001) with severely limited ability to work (АС 4) is revealed. As a result of the study, it was demonstrated that disabled individuals of the first group can be recognized as able-bodied with limitations only with higher values of these scales, taking into account harmful and dangerous production factors, as well as class of working conditions.
Conclusion. We found that when assessing the degree of severity of limitations to the ability to work in the disabled people of the first group with absolutely unfavorable clinical and labor prognosis, it is reasonable to be guided by the generally accepted scales of assessment of the general condition of a cancer patient (Karnovsky index, ECOG scale), taking into account the existing harmful and/or dangerous production factors, as well as the working conditions class.
Objective. To characterize the process of development of insurance medicine in Belarus in the first third of the twentieth century.
Materials and methods. Archival, periodical and narrative sources processed using general scientific and special historical research methods.
Results. Insurance medicine in Belarus originated in the early twentieth century in the form of hospital sick funds, which provided medical care to workers in case of illness, but was actually destroyed during the First World War. In Soviet Belarus the development of insurance medicine began during a period of massive reduction in healthcare funding associated with the New Economic Policy. In fact, insurance medicine became only a financial donor to the People’s Commissariat for Healthcare, but it was not distinguished as an independent branch, which was typical for the pre-revolutionary period, so the principle of unity of Soviet medicine was preserved. A characteristic feature of the studied period was the small social coverage of medical insurance, which applied only to workers and employees, who constituted a small part of the population of Soviet Belarus, where the rural population was greatly dominated.
Conclusion. Despite the successful experience of organizing insurance medicine, it was only a temporary measure to maintain the resources of unified Soviet state medicine and in reality covered an extremely small percentage of the population, so after the crisis in health care was overcome it was abolished.
Objective. On the basis of the regularities established earlier, to identify professionally and socially oriented, homogeneous by external exposure dose, groups of residents living in the contaminated with radionuclides territories according to the set of informative factor-signs.
Materials and methods. The present study is a continuation of the research of factors influencing external radiation dose formation in individuals living in areas contaminated with radionuclides. The data on external radiation doses for 25503 residents of Gomel region living in 289 settlements obtained by individual dosimetric control and the previously identified factors which statistically justify the external radiation dose formation were included in the study.
Results. Analysis of external exposure doses of Gomel region residents according to the set of informative factor-signs revealed that there is a wide dispersion of doses among different social groups which allowed to form professionally and socially oriented homogeneous groups according to external exposure dose taking into account dose forming factors revealed earlier. The results of the study statistically demonstrate that informative factor-signs: professional employment, age and gender affiliation together influence individual external exposure dose formation.
Conclusion. Professional homogeneous groups of different social groups were formed based on a set of informative factor-signs which determine its formation in individuals living in areas contaminated with radionuclides. This will become the basis for developing the method of reconstruction and prognosis of individualized external exposure dose in the future.
CLINICAL CASES
This article presents a clinical case of dissecting thoracic aortic aneurysm. The first clinical manifestations were typical symptoms of the disease. Timely diagnosis and treatment are particularly important to prevent a fatal outcome. Late diagnosis may be related also to the lack of doctors’ caution with regard to dissecting aortic aneurysm.
The article presents a clinical case of a rare primary immunodeficiency syndrome Hyperimmunoglobulinemia E. Typical clinical symptoms, diagnostic and treatment tactics have been demonstrated.
NEW TECHNOLOGIES
Objective. To study primary resistance of H. pylori to clarithromycin in residents of Gomel region by real-time polymerase chain reaction (PCR RT) using TaqMan® MGB probes.
Materials and methods. The study included 184 patients diagnosed with gastritis and duodenitis, K29, median age 48.5 years (25% and 75% were 37 and 61 years old). According to the patients’ questionnaires, no clarithromycin-based eradication therapy was administered. To determine the resistance of H. pylori to clarithromycin, a PCR RV method using TagMan® MGB probes was used.
Results. All 184 tested DNA samples were positive for the Rnase P gene (ICS) and were considered in further analysis (Ct, HEX 20.20-34.14). DNA from the cagH gene (Ct, FAM 21.26-33.04), indicating infection with the bacterium, was confirmed in 152 samples (82.6%). DNA from the 23SrRNA gene (point mutations A2142G and A2143G) was detected in 16 of 152 DNA samples 10.5 % (Ct, Hex 20.24-31.17). The positive control samples had characteristic curve growth in the corresponding detection channels; no curve growth was observed in the negative samples.
Conclusion. The primary resistance of H. pylori to clarithromycin in the residents of Gomel region was 10.5%, and the use of triple first-line eradication therapy, including PPIs, amoxicillin and clarithromycin, as empirical in this region is consistent with the Maastricht III-VI recommendations and Decree of the Ministry of Health of the Republic of Belarus of 01.06.2017 № 54: clinical protocol “Diagnosis and treatment of patients with digestive diseases.” The use of PCR RT using TaqMan® MGB probes is justified to determine the resistance of H. pylori to clarithromycin, to prescribe individualized treatment and to evaluate the effectiveness of eradication regimens.
Objective. To review the main stages of Klebsiella pneumoniae genome sequencing using the Illumina short-read method and describe the peculiarities of sample library preparation and analysis of the obtained data.
Materials and methods. Deoxyribonucleic acid (DNA) for high-throughput sequencing was isolated from Klebsiella pneumoniae cultures. Sample preparation was performed according to the manufacturer’s instructions for the Nextera XT DNA Library Prep kit. Sequencing was performed on an Illumina MiSeq platform using a 2x151 cartridge. Genome assembly to the contigs was performed using the SPAdes Genome Assembler application on the Illumina BaseSpace Sequence Hub service and a set of programs in a Linux environment. The quality of genome assembly was assessed using the QUAST service.
Results. Genome sequencing of K. pneumoniae culture samples was performed, followed by an evaluation of the quality of the launch, assembly of the genome, and determination of its main parameters.
Conclusion. The main steps of K. pneumoniae genome sequencing have been considered using the short-read method on the Illumina platform. The main parameters for assessing the quality of sample preparation, launch and genome assembly are described.
ISSN 2708-6011 (Online)