Bulletin of the Russian Military Medical Academy

Scientific-practical edition “Vestnik of Russian military medical Academy” is published quarterly. The journal is included in the list of leading reviewed scientific magazines and editions in which should be published basic scientific results of dissertations on competition of a scientific degree of doctor and candidate of Sciences.

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Vol 24, No 1 (2022)

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Research paper

Innovative technologies in the diagnosis and safe surgical treatment of thyroid diseases
Romashchenko P.N., Maistrenko N.A., Krivolapov D.S., Simonova M.S.
Abstract

This study clarified the results of using innovative technologies in the diagnosis and surgical treatment of patients with thyroid diseases by evaluating the role of modern diagnostic methods and effectiveness of minimally invasive thyroid surgery. The results of a comprehensive examination and treatment of 332 patients with thyroid diseases, who were examined using modern diagnostic methods and underwent conventional and various minimally invasive approaches, were analyzed. The sensitivity, specificity, accuracy, and positive and negative predictive values of multiparametric neck ultrasonography, 99mTc-MIBI thyroid scintigraphy, fine-needle cytology, and molecular testing of thyroid nodules were compared. The minimally invasive procedure was performed in 70.4% of the patients. Postoperative complications were found in 4.9% of the patients who underwent surgery, functional dysphonia in 0.9%, and transitory hypoparathyroidism in 2.4%. The use of the main criteria that determine the choice of a rational minimally invasive surgery, such as the nodule size and thyroid volume, hyperfunctioning thyroid, clinical thyroiditis, substernal extension, extrathyroid extension, and necessity of implementation of central and lateral neck dissection due to lymph node metastases, avoids the conversion of access to the traditional approach, prevents damage to the recurrent laryngeal nerve with the development of transitory or permanent recurrent laryngeal nerve palsy, and minimizes injury to the parathyroid glands with the development of isolated cases of transient hypoparathyroidism. Therefore, results of the multiparametric analysis of the examination and surgical treatment outcomes of patients with thyroid diseases show the feasibility of using innovative technologies in their diagnosis and surgical treatment. Modern examination methods allow us to determine with great accuracy the morphological form of thyroid disease and choose a rational volume and surgical intervention. In this study, minimally invasive procedures are optimal and safe in the surgical treatment of this category of patients.

Bulletin of the Russian Military Medical Academy. 2022;24(1):9-15
pages 9-15 views
Genetic polymorphisms of catalase (rs7943316), glutathione peroxidase-1 (rs1050450), and transferrin (rs8177178) in keratoconus on a limited group of Russian patients
Solovev A.I., Churashov S.V., Kulikov A.N., Buleev A.V., Krutikova A.A., Arukov A.R., Kravtsov V.Y.
Abstract

A pilot study of the association of single nucleotide polymorphisms in catalase (rs7943316), glutathione peroxidase-1 (rs1050450), and transferrin (rs8177178) genes with the risk of keratoconus development was conducted in a sample of Russian patients. Genotyping was performed by analyzing the polymorphism of the lengths of restriction fragments using a polymerase chain reaction. Venous blood samples from 25 patients with keratoconus treated at the Ophthalmology Clinic of the Kirov Military medical Academy in 2019 and 2020 were examined. The control group included 20 patients who had no clinical signs of keratoconus. The effect of the single nucleotide polymorphism rs7943316 of the catalase gene on the risk of keratoconus development has not been established. The T allele of the glutathione peroxidase-1 gene containing the rs1050450 polymorphism slightly increases the risk of keratoconus compared with the C allele (odds ratio = 1.91; 95% confidence interval = 0.75–4.85; p = 0.17). A moderate association of the A allele of the transferrin gene containing rs8177178 polymorphism with the occurrence of keratoconus and an increase in the incidence of the disease associated with the AG genotype was revealed (odds ratio = 5.67; 95% confidence interval = 1.07–30; p = 0.12). Thus, when examining a limited sample of Russian patients with keratoconus, it was not possible to identify a link between the disease and single nucleotide polymorphisms of catalase rs7943316 and glutathione peroxidase-1 rs1050450. The relationship between the polymorphism of the transferrin rs8177178 gene (allele A and genotype AG) and the risk of keratoconus development was weak and not significant. Thus, expanding the study sample and further studying the polymorphisms of the transferrin gene that affect the structure of the enzyme and reduce the effectiveness of antioxidant protection of the cornea were recommended.

Bulletin of the Russian Military Medical Academy. 2022;24(1):17-24
pages 17-24 views
Features and significance of the early bronchodilatation effect of the first dose of a long-acting bronchodilator alone and in fixed combination in the treatment of chronic obstructive pulmonary disease
Sharova N.V., Cherkashin D.V., Grishayev S.L., Efimov S.V., Kharitonov M.A., Turdialieva S.A.
Abstract

The early bronchodilatory effects of the first dose of long-acting anticholinergics (glycopyrronium and tiotropium) were compared with those of a fixed double combination of long-acting bronchodilators of various classes (indacaterol/glycopyrronium) in patients with stable chronic obstructive pulmonary disease. The possibility of using the results of an early bronchodilatory response to predict their effectiveness in the basic therapy of chronic obstructive pulmonary disease is evaluated. A total of 176 patients with chronic obstructive pulmonary disease were examined. The patients were randomized into three groups. The first group (n = 66) took glycopyrronium, the second group (n = 60) received a combination of indacaterol/glycopyrronium, and the third group (n = 50, control) took tiotropium. Broncholytic tests with the listed drugs were evaluated. The early bronchodilatory effect of the first dose of 110/50 mcg indacaterol/glycopyrronium was manifested by significant bronchodilation (p < 0.001) from 30 min, reached its maximum value 60 min after drug intake, and persisted after a 28-day course of treatment. The combination of indacaterol/glycopyrronium provided rapid and prolonged bronchodilation in patients with stable chronic obstructive pulmonary disease, demonstrating advantages over the isolated use of glycopyrronium and tiotropium. Maximization of bronchodilation by the sequential use of glycopyrronium and salbutamol leads to an increase in the volume of forced exhalation in the first second on the 90th min, comparable with the results of indacaterol/glycopyrronium on the 60th min after drug intake, which indicates the clinical feasibility of maximizing bronchodilation with drugs both separately and in combination. Based on a direct positive correlation between the initial value of the forced expiratory volume in the first second and the value on day 28 of indacaterol/glycopyrronium therapy, an equation for predicting the individual effectiveness of the drug during treatment is derived.

Bulletin of the Russian Military Medical Academy. 2022;24(1):25-34
pages 25-34 views
Features of treatment of ureteral injuries
Shanava G.S., Mosoyan M.S., Protoshchak V.V., Soroka I.V., Nalivaiko A.D., Putrenok D.G., Orlov D.N.
Abstract

Choosing the optimal techniques for the treatment of ureteral injuries is necessary. Damage to the ureter accounts for < 3% of cases of injuries of the genitourinary system. More than 70% of iatrogenic ureteric injuries are not detected during surgery. Approximately 75%–80% of ureterotraumas are due to iatrogenic causes, of which 65%–82% are due to gynecological surgeries. Mechanical injuries of the ureter are much less common than iatrogenic ones. Gunshot and stab wounds of the ureter prevail among mechanical injuries. Thirty-one patients who were treated at the I.I. Janelidze Research Institute of Emergency Medicine with various ureteral injuries from 2003 to 2019 were examined. Patients were divided into three groups according to the time of detection of ureteral injury. Group 1 included patients with ureteral injuries identified during surgery, group 2 included those with ureteral injuries diagnosed within 72 h, and group 3 consisted of patients with ureteral injures detected > 72 h later. The choice of treatment techniques for ureterotrauma relied on the general condition of the patient, severity and level of damage to the ureter, timing of its diagnosis, and nature of the complications. On intraoperative detection of ureterotrauma in patients with a stable condition, reconstructive surgery of the ureter should be performed immediately to ensure the passage of urine from the upper urinary tract. If ureterotrauma is diagnosed before 72 h and there are no inflammatory complications, reconstructive ureteral surgery is also appropriate. If an infectious and inflammatory process develops, a staged operation is necessary to drain the upper urinary tract and relieve the developed posttraumatic complications. When ureterotrauma is diagnosed > 72 h later, a staged operation is performed to eliminate complications and drainage of the upper urinary tract. Reconstructive surgery is performed not earlier than after 2 months.

Bulletin of the Russian Military Medical Academy. 2022;24(1):35-42
pages 35-42 views
Use of a local hemostatic agent based on chitosan and external compression of the abdominal area to control intra-abdominal bleeding
Golovko K.P., Samokhvalov I.M., Grishin M.S., Nosov A.M., Yudin A.B., Kovalevsky A.Y., Bagnenko A.S., Kovalishin I.M.
Abstract

The paper presents the intermediate results of an experimental study of three samples of chitosan-based local hemostatic agent in a model of intense intra-abdominal bleeding in an average-sized experimental animal (a Soviet Chinchilla rabbit) with a standard wound on the parenchymal organ (liver) in combination with external compression of the abdominal area to achieve hemostasis in the acute phase of the experiment. At the first stage, nine experimental groups and one control group, with three biological objects each, were involved (n = 30). The composition and properties of laboratory preparations of hemostatics were different from the concentration of the main component. To select the optimal sample of a local hemostatic agent with the least local irritant effect on the organs and structures of the abdominal cavity, three experimental groups with three animals each were formed at the second stage, without modeling blood loss (n = 9) with follow-up from 24 to 72 h. The studied drugs have high hemostatic activity in the model of intense intra-abdominal bleeding with follow-up periods from several hours to 3 days. Moreover, intraperitoneal administration of hemostatic agent samples does not lead to a pronounced local irritant effect. However, during the first 180 min of the experiment, only one fatal outcome was recorded in a group of animals with 15% chitosan in the studied drug because of a technical error in modeling the source of bleeding. External compression of the abdominal area demonstrated its effectiveness as an auxiliary technique for temporary control of the intra-abdominal source of bleeding in the experimental model. The objectification of the obtained results was achieved through a control sectional study and laboratory screening of peripheral blood indicators of experimental animals at different stages of the experiment. To further evaluate the hemostatic activity of chitosan-based drugs, creating an experimental model using a large experimental animal is necessary.

Bulletin of the Russian Military Medical Academy. 2022;24(1):43-54
pages 43-54 views
Effect of glyprolins on white blood cell parameters and phagocytic activity of neutrophils in conditions of experimental hyperthyroidism
Sergalieva M.U., Tsybizova A.A., Andreeva L.A., Myasoedov N.F., Bashkina O.A., Samotrueva M.A.
Abstract

This study investigated the effects of glyproline neuropeptide compounds (selank and Pro-Gly-Pro) on the white blood cell count and phagocytic activity of neutrophils in 40 nonlinear white male rats aged 6–8 months with experimental hyperthyroidism. Experimental hyperthyroidism was simulated by intragastric administration of L-thyroxine sodium salt pentahydrate at a dose of 150 µg/kg/day for 21 days. All animals were equally divided into four groups: healthy rats (control), rats treated with L-thyroxine sodium pentahydrate (hyperthyroidism), rats treated with selank, and rats treated with Pro-Gly-Pro at doses of 200 µg/kg/day intraperitoneally for 21 days, starting one day after the last administration of L-thyroxine sodium pentahydrate. After the animals were removed from the experiment, the white blood cell count and the percentage of lymphocytes, stick, and segmentonuclear neutrophils were calculated, and the phagocytic activity of neutrophils was evaluated. In the case of experimental hyperthyroidism, neutrophilic leukocytosis with a shift to the right, lymphopenia, and decreased phagocytic activity of neutrophils were observed. Glyproline neuropeptides contributed to the correction of observed changes in white blood cell indices and phagocytic processes, which indicates the immunocorrigating effect of the test compounds. Thus, glyproline neuropeptides demonstrated pronounced immunotropic activity, which manifested in the correction of changes arising from the leukocyte count and phagocytosis processes. However, further detailed study of the pharmacological effects of neuropeptide agents on experimental hyperthyroidism is necessary.

Bulletin of the Russian Military Medical Academy. 2022;24(1):55-60
pages 55-60 views
Reconstruction of the ligamentous-tendinous complex of the knee joint, ensuring its varus stability
Khominets V.V., Kudyashev A.L., Gaivoronskiy I.V., Bazarov I.S., Grankin A.S., Semenov A.A., Konokotin D.A.
Abstract

А new technique for anatomical reconstruction of the ligament–tendon complex of the knee joint, which restores its varus stability, in patients with multiligament injury is substantiated. The technical feasibility, safety, and effectiveness of the proposed technique were evaluated in an anatomical experiment. The study was performed on eight lower extremities of four unfixed corpses. After simulating the varus instability of the knee joint, the plasty of the ligament–tendon complex providing the varus stability of the knee joint was performed according to the proposed technique. The essence of the proposed technique is the simultaneous restoration of the peroneal collateral ligament, popliteal tendon, and popliteal–peroneal ligament using a single autograft of a semitendinosus muscle. After simulating the surgical procedure on anatomical specimens, the varus stability of the knee joint was evaluated based on the results of functional radiography. The safety of the experimental procedure was evaluated based on the results of the applied morphometric study of the distance from the reconstructed elements of the posterolateral corner of the knee joint to the popliteal artery and the common peroneal nerve in the 90-degree flexion position in the knee joint. Accordingly, the formed bone tunnels for a single autograft were located at a safe distance from the elements of the neurovascular bundle of the popliteal fossa. The technical possibility of reconstruction of the collateral peroneal ligament, popliteal tendon, and popliteal–peroneal ligament according to the proposed technique. After simulating the reconstruction of elements of the posterolateral corner of the knee joint, varus stability was objectified by a series of functional X-ray studies of the anatomical specimens. The results indicate the technical feasibility, effectiveness, and relative safety of the proposed method of reconstruction of the ligament–tendon complex of the posterolateral corner of the knee joint providing the varus stability of the knee joint in patients with multiligament injury.

Bulletin of the Russian Military Medical Academy. 2022;24(1):61-68
pages 61-68 views
Features of the military population health in the arctic zone
Dybin A.S., Poteryaev A.E., Kuznetsov S.A., Luchnikov E.A., Mavrenkov E.M., Menshikova L.I.
Abstract

Тhe study aimed to assess the population health of military personnel serving under contract in the Arctic region and to identify its features. On the basis of statistical reports on form 3/med., relative indicators characterizing the health status of military personnel are calculated. Polynomial trends of the second degree and absolute increase/decrease values were calculated for dynamic analysis. The determination factor was used to estimate the significance of the changes. Quantitative data are presented as arithmetic mean with 95% confidence interval. For comparison, Student’s t-test and the Man — Whitney test were used. Indicators of the health status of the military personnel in the Arctic region have specific features. The primary incidence rate among all categories of military personnel was 452.28‰, and the total incidence was 993.28‰. The hospitalization rate coefficient was equal to 154.16‰, the incidence with temporary disability coefficient was 3912.29‰, the dismissal rate was 10.61 ‰, and the mortality rate was 118.4 per 100 thousand people. The health coefficient of the sample population was 43.67 units, with a significant downward trend. Respiratory (50%), musculoskeletal (13%), skin and subcutaneous (7%), digestive (6%), and circulatory (6%) diseases account for the highest rates of primary morbidity, whereas the rates of skin diseases decreased and the proportion of musculoskeletal diseases increased. An assessment of the primary morbidity dynamics revealed a significant increase among respiratory, digestive, musculoskeletal, and connective diseases and a significant trend toward a decrease in the rate of primary morbidity of mental and behavioral disorders and a decrease in the number of injuries, poisoning, and some other consequences of external causes. The health of the military population in the Arctic region has specific features. Climatogeographic and heliophysical factors of the Far North significantly influence the health of military personnel under contract in this region. Thus, targeted preventive measures, including improving the health-promoting behaviors of military personnel under adverse environmental conditions, are necessary.

Bulletin of the Russian Military Medical Academy. 2022;24(1):69-80
pages 69-80 views
Russian pharmacovigilance: ways to improve efficiency
Taube A.A., Evko I.Y., Sinitova S.V., Krasheninnikov A.E., Zhuravleva M.V., Romanov B.K., Alyautdin R.N.
Abstract

The paper presents the results of a survey of pharmacovigilance specialists’ awareness of the regulation of reporting on adverse drug reactions, self-assessment of their competencies and readiness for distance learning, creation of a generalized portrait of a pharmacovigilance specialist to create mechanisms for improving pharmacovigilance activities, and continuing education of pharmacovigilance specialists. The results of the correlation analysis of the knowledge of pharmacovigilance specialists with their self-assessment of their position are reflected. Information-analytical and sociological (survey) methods and descriptive statistics were used. A questionnaire consisting of 31 items was developed for the survey. The first part of the questionnaire consisted of general questions, such as on education, work experience in the pharmaceutical field and pharmacovigilance, and position held. The second part focused on the structure of pharmacovigilance in the organization of holders of the registration certificate. The third part consisted of 17 items aimed at identifying the level of knowledge concerning the immediate daily activities in pharmacovigilance and knowledge of the legislative framework. The final element was a question about the attitude to distance learning. Specialists working in the field of pharmacovigilance at enterprises and persons authorized for pharmacovigilance objectively assessed their practical knowledge and skills in the field of drug safety. Moreover, 42 (72%) respondents believe that they do not need to update their knowledge on pharmacovigilance, whereas 51 (87%) people successfully passed the proposed survey on knowledge of current legislation. Employees of senior positions showed higher knowledge in the field of pharmacovigilance. Specialists and senior pharmacovigilance specialists need to increase their level of professional knowledge, and they are aware of the need for further training.

Bulletin of the Russian Military Medical Academy. 2022;24(1):81-90
pages 81-90 views
Strategy for the development of specialized medical care for patients with urolithiasis in the armed forces of the Russian Federation
Sergoventsev A.A., Kryukov E.V., Protoshchak V.V., Paronnikov M.V., Savchenko I.F., Orlov D.N.
Abstract

The development of a system of therapeutic, diagnostic, and organizational measures to improve specialized medical care for members of the Armed Forces of the Russian Federation with urolithiasis is scientifically substantiated. The study was conducted in 3 stages. At the first stage, the principal functions of the system of specialized urological care for patients with urolithiasis were singled out, and possible ways of their realization were determined. At the second stage, planning options for the system were formulated and described. In the third stage, the criteria for analyzing the system, estimation of their superiority, and scientific substantiation of the rational concept were elaborated. Three systems of providing specialized urological care to patients with urolithiasis with the conditional names, including “proposed,” “real,” and “adaptive,” were formulated and put forward. The proposed system was based on the principle of the maximum volume of specialized medical care according to the “urology” profile in the district hospitals of each military district and hospital of the Northern Fleet. The real system has a four-stage structure, which was based on staged treatment of patients with urolithiasis receiving the maximum treatment in organizations of central subordination. In the adaptive system, its conceptual basis is the central military medical organizations, and the volume of care in the remaining hospitals is determined by the chief urologist of the Ministry of Defense of the Russian Federation. Using hierarchy analysis, a pairwise comparison of each concept was performed, and the proposed system has the highest priority index. Generally, to improve the specialized care for members of the Armed Forces of the Russian Federation with urolithiasis, we have developed and scientifically proved the system of the organizational treatment and diagnostic measures that assume the decentralization and standardization of the urological care for patients with urolithiasis, staff reorganization, provision of modern equipment, professional training of the medical staff, improvement of research potential, and interaction with medical institutions of the civilian population.

Bulletin of the Russian Military Medical Academy. 2022;24(1):91-100
pages 91-100 views
Features of microcirculation and metabolism in the skin and soft tissues of the injured area in experimental explosive trauma
Shperling I.A., Rostovtsev S.O., Shulepov A.V., Kourov A.S., Bazhenov M.V.
Abstract

Time, nature, and duration of changes in microcirculation and metabolism, as well as their differences in skin and muscle tissue of the injured area during experimental explosive trauma in rats in different wound process phases, are evaluated. Experimental explosive damage was simulated on 30 Wistar rats. The total condition of rats, their activity, interest in food and water, wound area with characteristic wound healing time calculation, the volume of injured pelvic limb, and changes of microcirculation and metabolism in the skin and skeletal muscles of the paravulnar region were evaluated. The explosive damage has led to a deterioration of microcirculation and metabolism in the skin, and especially, in the muscles of the injured area. Compared to the intact group, the microcirculation deterioration resulted in a decreased constant component of perfusion in the skin and muscles by 57.6% and 40.9% and a decreased vial by 76.9% and 76.5%, respectively (p < 0.05), as well as in reducing the fluorescent oxygen intake in the skin and muscles by 25.7% and 51.8% and a complex indicator of effective oxygen exchange by 81.1% and 91.9%, respectively (p < 0.05). During the experiment, the microcirculation and metabolism were gradually restored, which is more pronounced in the skin, except for the repeated deterioration of the non-vascular regulation of microcirculation in the muscle (a decreased vial by 29.3% of the norm, p < 0.05). Changes in the main indicators of microcirculation and metabolism indicate normal skin defect healing and unsatisfactory muscle defect repair (decreased volume of the injured limb (68% of the norm, p < 0.05)), accompanied by the recurrence of extravascular disorders in the muscle. Developing new and improved existing methods of delivering biologically active drugs and drugs to the area of muscular damage in the early days after the injury, which strengthen the local blood flow and create conditions for damaged muscle regeneration, reduce the wound healing time without forming pathological scars.

Bulletin of the Russian Military Medical Academy. 2022;24(1):101-110
pages 101-110 views

Review

Approaches to isolating and purifying nucleic acids from blood for genotyping human leukocytic antigen
Baranov O.A., Bayran D.A., Markin I.V., Shchelkanova E.S., Zhurbin E.A.
Abstract

Donor–recipient histocompatibility results from the presence on cell membranes of the main protein complex of histocompatibility and is a key condition for successful transplantation of cells, tissues, and organs. To determine histocompatibility, human leukocyte antigen is genotyped, and its accuracy relied significantly on the quality and quantity of nucleic acids obtained from the biomaterial. In laboratory practice, the most pure and intact deoxyribonucleic and ribonucleic acids are extracted from the blood; however, the choice of an accessible, effective, time-efficient, and viable method for their production remains challenging. The methods of isolation and purification of nucleic acids from the blood include organic extraction, salting out, and use of spin columns and magnetic particles (“bidids”), and their advantages and disadvantages, efficiency indicators, practicality, and cost were compared. The selection of the peripheral blood as a source of genetic material for genotyping human leukocyte antigen is justified. Experimental data comparing the price–quality ratio of commercial protocols for the extraction of deoxyribonucleic and ribonucleic acids from blood were analyzed. Prospects of modification of procedures for isolation and purification of nucleic acids from biomaterial for sequencing of genes of human leukocyte antigen classes I and II to increase efficiency of high-tech care are evaluated. Generally, the need for affordable and effective protocols for the extraction of deoxyribonucleic and ribonucleic acids from minimal biomaterial volumes stimulates the optimization and modification of existing protocols and the creation of new methods on new physicochemical principles.

Bulletin of the Russian Military Medical Academy. 2022;24(1):111-124
pages 111-124 views
Lumbosacral dorsopathies: modern aspects of diagnosis and pharmacological treatment
Zhivolupov S.A., Kozhevnikov E.Y., Samartsev I.N., Rashidov N.A.
Abstract

Lumbosacral dorsopathy is the most common diagnosis in patients with lower back pain. Issues of conservative treatment of lumbosacral dorsopathies are considered based on the analysis of scientific materials contained in large databases such as PubMed, Cochrane library, MEDLINE, and eLibrary. From all publications, 40 of the most relevant works were selected and considered in detail, and key figures and short conclusions for each work are displayed in a table. Symptoms of lumbosacral dorsopathies often have an extremely negative effect on the patient’s ability to work and quality of life; therefore, effective and prompt treatment is important. Given the complex and multifactorial pathogenesis and multitudes of options for lumbosacral dorsopathies, conservative treatment should be complex and individualized, and drugs should have a high safety profile, especially those used in the treatment of chronic diseases. These requirements are met by some nonsteroidal anti-inflammatory drugs and co-analgesics, such as chondroprotectors and B vitamins. For the treatment of acute and exacerbated lumbosacral dorsopathies, the local use of hormonal drugs, anticonvulsants, antidepressants, muscle relaxants, etc., is possible, while treatment dosage and duration should be strictly limited. The local use of hormonal drugs and hodroprotectors such as therapeutic and diagnostic blockades is justified in the absence of contraindications and availability of opportunities, which helps reduce the likelihood of systemic adverse reactions and provides greater bioavailability.

Bulletin of the Russian Military Medical Academy. 2022;24(1):125-133
pages 125-133 views
Alphaviruses: a modern view on the problem
Stepanov A.V., Yudnikov I.V., Kvardakov A.V.
Abstract

At present, infectious diseases of alphaviral etiology remain relevant. The study examined the characteristics of alphaviruses, including the present knowledge of the structure and replication of the virion; prevalence of epidemiologically significant species and potential distribution areas of some alphaviruses; pathogenesis and clinical presentation of causative diseases, diagnosis, prevention, and treatment; and their possible use as pathogenic biological agents. Sixteen strains of alphaviruses are hazardous to human health, and some of them can disrupt human activities. Areas with alphaviruses are characterized by specific ecological conditions, presence of vectors, and susceptible hosts. Alphaviruses are predominantly distributed in equatorial and subequatorial belts. Some alphaviruses have been reported in the Russian Federation. The natural foci of alphaviruses are reportedly altered because of the expansion of their existing localizations, including the Russian territory. To predict the occurrence of alphavirus outbreaks, it is necessary to monitor pathogenic populations for mutations that can significantly increase their pathogenicity and virulence. Most alphaviruses, including those registered in Russia, do not have specific products for diagnostics, prevention, and treatment. Meanwhile, alphaviral diseases have great military–epidemiological significance, as they can cause natural focal morbidity in certain regions of the world and injury to the civilian population and service personnel following their use as pathogenic biological agents.

Bulletin of the Russian Military Medical Academy. 2022;24(1):135-142
pages 135-142 views
Modern methods of detection and identification of microbial toxins that inhibit protein synthesis in cells
Miteva O.A., Yudina N.S., Myasnikov V.A., Stepanov A.V., Chepur S.V.
Abstract

Pathogenic microorganisms and products of their metabolism, namely, bacterial protein exotoxins, are considered one of the main sources of biological threat. Microbial toxins are highly active and extremely dangerous to humans. Determining trace amounts of such compounds remains relevant in healthcare and biological protection sector. Timely qualitative- and quantitative-specific indication of biotoxins is a key component in the diagnosis and implementation of therapeutic and preventive measures. Pathogenic microorganisms and products of their metabolism, bacterial protein exotoxins, are considered one of the main sources of biological threat. Microbial toxins are highly active and extremely dangerous to humans. Determining trace amounts of such compounds remains relevant in healthcare and biological protection sector. Timely qualitative- and quantitative-specific indication of biotoxins is a key component in the diagnosis and implementation of therapeutic and preventive measures. The current state and prospects of development in formulating specific indications of microbial toxins that disrupt protein synthesis in cells are analyzed. Modern ideas about the structure and mechanism of action of these toxins are briefly presented. Possibilities were considered, the advantages and disadvantages of classical traditional and modern innovative methods for identifying bacterial toxins that inhibit protein synthesis in cells were compared, and classifications were provided. Examples of the use of various approaches to identify the most significant representatives of this group in both clinical material and in environmental objects, including regulated ones, were given. The review also listed modern domestic and foreign developments in formulating specific indications of microbial toxins inhibiting protein synthesis. The review summarizes the results of studies to determine the current directions in the development of tools and methods for rapid specific indication of microbial toxins. The main trends in the creation of new methods of toxicological screening as part of an effective national system for monitoring biological threats were analyzed. Prospects for the development and introduction to the market of domestic test systems and automatic analysis platforms for the detection of bacterial toxins in environmental objects and biological material were determined.

Bulletin of the Russian Military Medical Academy. 2022;24(1):143-154
pages 143-154 views
Variants of facial nerve neurotization
Gaivoronsky A.I., Skaliitchouk B.V., Vinogradov V.V., Alekseev D.E., Svistov D.V.
Abstract

This study presents facial nerve neurotization, a common method of surgical treatment of facial muscle paralysis. In this surgical procedure, a trunk or some portions of individual fibers are sewn to an intact nerve-neurotizator to the injured facial nerve that can act as sublingual, masseteric, phrenic, accessory, glossopharyngeal nerves, as well as the descending branch of the sublingual nerve and anterior branches of the C2–C3 cervical spinal nerves. Often, neurosurgeons combine various donor nerves and autotransplanting inserts for better results. The main stages of neurotization of the facial nerve includes isolation and transection of the facial nerve, isolation and transection of the trunk or separate fibers of the neurotizer, and nerve suturing in an “end-to-end” or “end-to-side” fashion. Facial cross-plasty, the most innovative method of facial nerve neurotization, should be carefully performed, during which an anastomosis is performed between the damaged and intact facial nerves using autotransplantation inserts from the calf nerve or from a free muscle graft, including a tender muscle and an anterior branch of the locking nerve. Recovery of facial nerve function and regression of characteristic symptoms takes time and specialized recovery treatment. Generally, among the lesions of the cranial nerves, injuries and diseases of the facial nerve rank first and are one of the most common pathologies of the peripheral nervous system. The clinical picture of facial nerve injuries in various origins is quite monotonous and manifested by persistent paralysis or paresis of the facial muscles. Various highly effective techniques are aimed at restoring the function of the facial nerve and facial muscles. Many conservative and operative methods of treating facial nerve neuropathy have been presented in the modern medical literature. However, all methods of facial nerve neurotization have several disadvantages, and the leading ones are the inability to achieve 100% efficiency and development of one degree or another neurological deficit.

Bulletin of the Russian Military Medical Academy. 2022;24(1):155-164
pages 155-164 views
Inflammatory response and its correction in forming a host response to exposure to adverse environmental factors
Ponomarev D.B., Stepanov A.V., Ivchenko E.V., Seleznev A.B., Apchel V.Y.
Abstract

This study systematically review knowledge about the mechanisms of formation of an inflammatory reaction under the influence of biological, physical, and chemical factors, their similarities and differences, and possible methods of pharmacological correction of pathological conditions associated with excessive activation. The effect of adverse environmental factors, such as biological, physical, and chemical factors, causes a systemic response, which is aimed at maintaining homeostasis and is caused, among other things, by a coordinated reaction of the immune system. Phlogogenic agents result in the activation and regulation of the inflammatory response, which is formed by cellular and humoral components of innate immunity. The activation of innate immunity is characterized by a rapid host response, which diminishes following the elimination of “foreign” invaders, endogenous killer cells, and neogenesis. Depending on the nature of the active factors (biopathogens, allergens, toxins, ionizing radiation, etc.), the mechanisms of immune response arousal have unique features mainly originating from the differences in the recognition of specific molecular patterns and “danger signals” by different receptors. However, inflammatory mediators and inflammatory response patterns at the systemic level are largely similar even under widely different triggers. Inflammation, having evolved as an adaptive reaction directed at the immune response, can lead to the development of chronic inflammation and autoimmune diseases due to a mismatch in mechanisms of its control. A “failure” in the regulation of the inflammatory process is the excessive activation of the immune system, which leads to the cytokine release syndrome (hypercytokinemia, or “cytokine storm”) and can cause self-damage (destruction) of tissues, multiple-organ failure, sepsis, and even death. Modern advances in the study of the pathogenetic bases of the inflammatory response are suggested, such as pharmacological correction using pattern recognition receptor antagonists, pro-inflammatory cytokine inhibitors, or blocking of key control genes or signaling pathways.

Bulletin of the Russian Military Medical Academy. 2022;24(1):165-177
pages 165-177 views
Prospective directions for innovative development strategies in pharmacy in the military health system of the Russian Federation
Miroshnichenko Y.V., Ivchenko E.V., Kononov V.N., Golubenko R.A., Ovchinnikov D.V., Enikeeva R.A., Shcherba M.P., Merkulov A.V., Mavrenkov E.M.
Abstract

Strengthening the readiness of the medical service system of the Armed Forces of the Russian Federation to fulfill given tasks is possible only with innovative development, which constitutes the scientific and methodological basis for the modernization of military healthcare. In this connection, researchers at the pharmacy department of the Kirov Military medical Academy considered the development of kits and equipment, medical equipment, mobile and special medical equipment, and pharmaceutical technologies as the absolute priority of their scientific development. The requirements for the equipment of different units and military medical organizations both at present conditions and in future wars include high level of mobility, shortened deployment (curtailment) terms, autonomy, increased operational efficiency of units, etc. The realization of these requirements is possible if certain issues are solved, primarily aimed at the digitalization of medical supply system of military forces, improvement of basic equipment, and entering new developments in the field of pharmaceutical technology into the medical service of the Armed Forces of the Russian Federation. The article presents the perspective directions of the innovative development of the medical supply system of the Armed Forces, which is the most important element of military healthcare. Results of the activity such as creation and acceptance for the supply of mobile units for production, accumulation (storage), delivery, distribution of medical gaseous oxygen, registration of medicinal products (“medical oxygen, 93%”), and acceptance of the corresponding pharmacopoeial article are already represented. Still at the development stage, there are innovative sets of service equipment of airborne troops, sterilization, and distillation unit, allowing the use of water from natural surface sources of domestic and drinking water supply, etc.

Bulletin of the Russian Military Medical Academy. 2022;24(1):179-188
pages 179-188 views
The prospects of probiotics and prebiotics in the diet of military personnel in extreme conditions
Subbotina T.I., Smirnova G.A., Kravchenko E.V., Andriyanov A.I., Smetanin A.L.
Abstract

The prospects of using probiotics and prebiotics in the diets of military personnel in extreme conditions have been studied. Domestic and foreign publications were used as the research material using the database of the United States (US) National Library of Medicine, Medline, and PubMed search engine. The nutrition of military personnel in extreme conditions should aim to improve diets by including functional nutrition products in their composition, such as probiotics and prebiotics. Herein, presented the modern concept of targeted probiotics, as well as the advantages of metabolic probiotics (metabiotics). The study results of the combined prebiotic in military personnel under environmental and professional stress, as well as in crew members in a closed hermetic object, are presented. The positive effect of probiotics and prebiotics in persons of dangerous professions against the background of excessive physical exertion or having a reduced nutritional status was revealed. The study of the metabiotic “Bactistatin” confirmed its effectiveness as a means of nutritional and metabolic rehabilitation of military personnel with inadequate body weight. The inclusion in the diets of products that normalize the microbiom is recognized as one of the directions for improving the nutrition of the North Atlantic Treaty Organization military personnel. Probiotics and prebiotics in the US Army diets contributed to intestinal infection prevention and immune system strengthening, thereby increasing endurance, physical, and cognitive performance during combat stress, and thus improving adaptation in extreme conditions. Domestic and foreign experience in the use of probiotics and prebiotics in diets has shown the prospects of their use as a means to improve the health and the military-professional of military personnel in extreme conditions of life.

Bulletin of the Russian Military Medical Academy. 2022;24(1):189-198
pages 189-198 views
Cardiovascular complications in patients after coronavirus DISEASE-2019
Mirzoev N.T., Kutelev G.G., Pugachev M.I., Kireeva E.B.
Abstract

The data of the modern literature describing the long-term consequences of infection of the body with SARS-CoV-2 on the cardiovascular system in the framework of postcovid syndrome are analyzed. To date, postcovid syndrome refers to a condition in which symptoms continue to persist for more than 12 weeks from the moment of diagnosis of COVID-19. Various complaints of patients after undergoing a new coronavirus infection are described, the distinguishing feature of which is their versatility, where cardiovascular manifestations are assigned one of the leading roles. Postural orthostatic tachycardia syndrome, cardiac arrhythmia and conduction disorders are considered. The role of SARS-CoV-2 in the formation of de novo and decompensation of pre-existing cardiovascular diseases has been demonstrated. The possibility of developing heart failure in patients with COVID-19 as an outcome of inflammation of the heart muscle is shown. Particular attention is paid to the analysis of the incidence of myocarditis after 3 months or more from the diagnosis of COVID-19, as well as thrombotic complications, in the genesis of which the main role belongs to the formation of endothelial dysfunction resulting from the interaction of SARS-CoV-2 with vascular endothelial cells. The autoimmune component of the pathogenesis of damage to the cardiovascular system as a result of the formation of endothelial dysfunction in COVID-19 is also considered. The authors present a laboratory-instrumental algorithm for determining cardiovascular complications in people who have undergone COVID-19, including the determination of the N-terminal fragment of the brain natriuretic peptide B-type prohormone, the level of anticardial antibodies, electrocardiography, echocardiography, as well as magnetic resonance imaging of the heart with contrast.

Bulletin of the Russian Military Medical Academy. 2022;24(1):199-208
pages 199-208 views
The role of adipokines in the development of adipose tissue dysfunction and other metabolic disorders
Mikhailov A.A., Khalimov Y.S., Gaiduk S.V., Rubtsov Y.E., Kireeva E.B.
Abstract

The role of specific adipokines in the formation of adipose tissue dysfunction is considered. Obesity is a multifactorial disease that is characterized by excessive adipose tissue accumulation in the body and is a risk factor for the development of several other diseases, including type 2 diabetes mellitus, cardiovascular diseases, and non-alcoholic fatty liver disease. Obesity is one of the main causes of chronic diseases and disability in modern society. Adipose tissue takes an active part in cellular reactions and metabolic homeostasis and does not represent inert tissue only for energy storage. In obesity, excessive accumulation of visceral fat causes adipose tissue dysfunction, which greatly contributes to the occurrence of concomitant diseases. Adipose tissue is capable of synthesizing and releasing a large number of hormones, cytokines, extracellular matrix proteins, growth factors, and vasoactive factors, which are collectively called adipokines, affecting various physiological and pathophysiological processes in the body. Perivascular adipose tissue produces cytokines that affect angiogenesis and peripheral vascular resistance. Adiponectin suppresses the production of glucose in the liver and enhances fatty acid oxidation in the skeletal muscles, which together contribute to a favorable metabolic effect in energy homeostasis, protect cells from apoptosis, and reduce inflammation in various cell types through receptor-dependent mechanisms. Leptin modulates vasoconstriction depending on sympathetic activity while resistin is involved in insulin resistance due to inflammation, wherein its high level determines metabolically unhealthy obesity. Additionally, visfatin plays an important role in the pathogenesis of vascular inflammation in obesity and diabetes mellitus while osteopontin regulates the production of inflammatory mediators by immune cells and omentin plays an important anti-inflammatory and insulin-sensitizing role. The production of most inflammatory mediators in adipose tissue dysfunction increases and contributes to the progression of obesity and related metabolic and vascular disorders. Considering adipokines as biological markers of pathological processes is necessary since their study will create prerequisites for preventive measures and will contribute to the positive treatment process.

Bulletin of the Russian Military Medical Academy. 2022;24(1):209-218
pages 209-218 views

History of medicine

Historical and medical-pharmaceutical aspects of the creation of a pharmacopeia
Miroshnichenko Y.V., Perfiliev A.B., Kostenko N.L., Enikeeva R.A.
Abstract

The article presents a historical analysis of the works of ancient authors related to the standardization and use of medicinal products underlying their prescriptions, as well as the “Antidotaria,” “Dispensatoria,” “Ricettaria,” and other publications that became the basis of modern pharmacopoeia. Based on the results of the analysis of literary sources on the history of medicine and pharmacy, issues of the standardization and regulation of prescription of medicinal products have always been given special importance in various societies and cultures. The chronology of the collections of prescriptions of medicinal products and then the establishment of a pharmacopoeia indicates the great need for pharmaceutical information for healthcare, determines the stages of development of pharmaceutical science, production, pharmaceutical and medical practice, and standardization and state regulation of medical and pharmaceutical activities. Particular attention is paid to the history of the creation of the first editions of the Russian pharmacopoeia. From physicians, herbalists, and greenery workers, practical information on the treatment of diseases in Russia was then translated, added to the official editions of the pharmacopoeia, and adopted at the state level. The significant contribution of domestic scientists is reflected, thanks to which the domestic pharmacopoeia not only did not yield to foreign counterparts but in some cases even surpassed them, contributing to the development of the country’s healthcare. The role of the staff of the Imperial Medical–Surgical (Military Medical) Academy, who actively participated in the development of various editions of the national state pharmacopoeia during the XIX–XXI centuries, is emphasized.

Bulletin of the Russian Military Medical Academy. 2022;24(1):219-230
pages 219-230 views
The skeleton of the giant Jacob Lolly is a unique “brand” of the department of normal anatomy
Gaivoronsky I.V., Tvardovskaya M.V., Solovyev K.V., Kirillova M.P., Spirina T.S., Vinogradov S.V., Semenova A.A.
Abstract

The paper presents the history of the appearance of the legendary skeleton of the giant Jacob Lolli in the museum collection of the Department of Normal Anatomy of the Military medical Academy. Research has been conducted on archival documents, including old magazines, newspapers, monographs, and minutes of the Academy Conference meetings stored in the Russian National Library, as well as the catalog and card index of the fundamental museum of the department. Data at the time of making the giant skeleton given in the catalog of the fundamental museum and literary sources of the 19th century were quite different and refer to the period from 1814 to 1818. Probably, the giant’s corpse was taken to the Department of Anatomy and Physiology of the Imperial Medical–Surgical Academy to establish the cause of death. After a while, the skeleton was presented to the Academy Conference as a rare museum exhibit and presented to its president, Jacov Willie, who returned the skeleton to the department. From 1818 to 1824, the skeleton temporarily left the walls of the academy and was examined by I.V. Buyalsky in the home museum. After the scientific work, the skeleton was returned to the department; as a result of the research conducted by I.V. Buyalsky in 1847, the article “Measure of the skeleton and the weight of the bones of the giant Jacob Lolly”, was the only published scientific work on the skeleton of a giant. The measurements were translated into the modern system of units. A brief description of the giant’s skull as a vivid example of typical changes in acromegaly was made a hundred years later by A.P. Bystrov, an employee of the department, in the book, “Past, present, future of man”. Two hundred years after its construction, the giant’s skeleton needed restoration, including delicate cleaning, restoration of destroyed fragments, and replacement of the material to imitate the cartilaginous components of the skeleton. The restorers’ work process is described, and the result of their activity is presented.

Bulletin of the Russian Military Medical Academy. 2022;24(1):231-237
pages 231-237 views
History and continuity of the first therapeutic departments at the Military Medical Academy
Ovchinnikov D.V.
Abstract

The problem of the lack of a statute on the creation of the medical–Surgical Academy arises every time the authors start discussing the history of the medical–Surgical Academy or its subdivisions. There are also misunderstandings in the issue of internal medicine teaching and creation of therapeutic departments. The contents of several historical and archival documents and earlier publications about the period of formation and development of the first therapeutic departments of the Academy (the last third of the 18th to the first half of the 19th century) were clarified. The article also analyzed the general anniversary editions of the academy, dissertations defended on the history of the departments, historical collections, and documents published in the Complete Collection of Laws of the Russian Empire, stored in the archives (Central State Archive of Ancient Acts, Russian State Archive of the Navy, etc.). The teaching of internal medicine started in October 1767 by F.T. Tikhorsky. From 1786, P. Hoffman continued to teach pathology, therapy, and medical practice at the Chief medical School. G.I. Bazilevich was appointed the second professor of pathology and therapy at the Medico–Surgical School. I.A. Smelovsky became the first professor after the college was renamed into academy. I.P. Frank, who created the second therapeutic department, started a direct historical branch of the therapeutic department until 1931, when the Department of the Private Pathology and Therapy merged with the united therapeutic department, and the Department of Propaedeutics of Internal Diseases emerged from it. From 1848 to 1924, the Department of General Therapy, attached to the first department, existed. In 1806, thanks to I.P. Frank, the second therapeutic department was founded, which existed since 1810 and is now the Department of General Therapy. Initially created as the Department of Hospital Therapy Clinic and renamed in 1965 at the insistence of N.S. Molchanov into the Department of Therapeutic Advancement of Physicians № 1 was actually created by the Decree of January 19th, 1842, simultaneously with the appointment of its first full-time head Prof. O.I. Myanovsky.

Bulletin of the Russian Military Medical Academy. 2022;24(1):239-250
pages 239-250 views

Personalia

Anniversary of the scientist: to the 60th anniversary of Corresponding Member of the Russian Academy of Sciences Andrey Nikolaevich Belskikh
Kryukov E.V., Ivchenko E.V., Ovchinnikov D.V.
Abstract

On March 13, 2022, the prominent Russian scientist, specialist in extracorporeal hemocorrection, intensive therapy, and nephrology, Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Major General of medical service in the reserve, Andrey Nikolayevich Belskikh, turned 60. Andrey Nikolayevich spent almost 40 years at the Military Medical Academy, having worked his way up from the cadet and the adjunct to the head of the Academy. For almost two decades he headed the clinical center of extracorporeal detoxification and started his scientific career, defended his doctoral thesis, and received the academic rank of a professor. His research opened a new page in the study of previously unknown fundamental regularities of hemorheological blood changes in hypoxia of different genesis, fundamental mechanisms of etiology, and pathogenesis of critical states formation in intensive medicine. During his 6 years as the head of the Military Medical Academy in a difficult time, Andrey Nikolayevich has done a lot. He organized the training of specialists with secondary medical education at the new faculty, and trained doctors in the specialties of preventive medicine, dentistry, and pharmacy. A simulation training center, one of the first and the best in the country, has been created. New departments of nephrology and efferent therapy and general dentistry were added to the Academy staff. Large-scale reconstruction and re-equipment of the Academy were started. The concept of a multidisciplinary clinic, which was ceremonially opened by the President of the Russian Federation, V.V. Putin, was developed, as well as the clinic. The work of A.N. Belskikh was marked with the Order of Honor and the honorary title “Honored Physician of the Russian Federation.” After retirement from military service, Andrei Nikolaevich Belskikh headed the department of nephrology and efferent therapy, where he continued his successful research and scientific, pedagogical, and medical staff training.

Bulletin of the Russian Military Medical Academy. 2022;24(1):251-254
pages 251-254 views
Academician of the Russian academy of sciences Yu.L. Shevchenko and his contribution to the development of the Military Medical Academy and health care of the Russian Federation (on his 75th anniversary)
Kryukov E.V., Khubulava G.G.
Abstract

April 7, 2022 marks the 75th anniversary of the outstanding national cardiac surgeon, Academician of the Russian Academy of Sciences Yuri Leonidovich Shevchenko. Yu.L. Shevchenko graduated from the Military Medical Academy in 1974 and after a year of servicing in the military he returned to the Academy, where he worked for a quarter of a century, having done his way up from a senior resident of the clinic of the Hospital Surgery Department to the Head of the Academy. During his leadership of the Academy (1992–2000) he did a lot not only for its preservation but also for its development and re-equipment. Great attention was paid to the international scientific cooperation, increasing the public prestige of the Academy and preserving its historical heritage: the academician B.V. Petrovsky medal "For outstanding surgeon in the world" was established; the monument "Military medics who died in wars" was opened; the Institute of honorary doctors and academicians of the Military Medical Academy was restored; the Academy was included in the State List of especially valuable objects of cultural heritage of Russian Federation. Internship and certification of graduates were introduced in the educational and scientific activities, and the Academy scientific schools were preserved and strengthened. As the Minister of Health of Russian Federation Yu.L. Shevchenko participated in the development of a number of federal target programs: justified and implemented in practice the territorial system of health care, also he was one of the initiators of creation and formation of health insurance system. Yu.L. Shevchenko contributed greatly to the development of Russian and world cardiosurgery. His works were a milestone in solving the problems of surgical treatment of infectious endocarditis. For the first time, the "sanitizing effect" of artificial circulation was theoretically substantiated and proved in practice, the optimal values of perfusion during surgical treatment of generalized forms of infection were developed, and the integral approach to sanitation of the heart chambers was substantiated. Since 2002 Yu.L. Shevchenko has been the head of Pirogov National Medical-Surgical Center. For his great contribution to the development of medical science academician Yu.L. Shevchenko was awarded the State Prize and honorary titles of Honoured Scientist and Honoured Physician of Russia, he was awarded the Order of Merit for the Motherland of 4th Class and the Order of Honour.

Bulletin of the Russian Military Medical Academy. 2022;24(1):255-258
pages 255-258 views

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