Vol 76, No 5 (2021)

Background. Today we have not really highly informative methods for assessing the state of the uterine scar. This fact does not allow us to formulate clear selection criteria for spontaneous delivery for patients who had cesarean section (CS). The result of the formulated problem is not only an increase in the frequency of repeated abdominal delivery, but also a fivefold increase in the risks of intraoperative and postoperative complications for women of reproductive age. Aims — explore the property, structure and morphological features of the myometrial scar tissue by developing a physical model based on morphological predictors. Materials and methods. The study included 49 women who ahead a second caesarean section in the maternity hospital at the S.S. Yudin state medical center. The patients had scar tissue excised in the lower uterine segment and the resulting biopsies were divided into 2 fragments. The first fragment of biopsies was necessary for performing a morphological study, based on the results of which randomization was carried out into groups. The main group included 24 fragments, where the scar tissue was well-established, and the comparison group included 25 fragments, where according to morphological research, signs of its insolvency were revealed. Further assessment of the scar state was performed using the second fragment of biopsies by creating a physical model of the study, on the basis of which the dependence of elongation on the applied force was estimated. The study was conducted in the laboratory of scientific research on the development of bioprostheses of the CSSC A.N. Bakuleva. Results. Based on a morphological study, it was confirmed that the failure of the scar is based on the disorganization of connective tissue, indicating the possible presence of undifferentiated connective tissue dysplasia for the patient. The physical model of the study demonstrated that the presence of such a difficult-to-diagnose pathology leads to a decrease in the elasticity, and therefore-the strength and elasticity of the scar on the uterus. Conclusions. For this period of time, we need to improve methods for assessing the condition of the uterine scar in order to resolve the issue of the possibility of conducting natural childbirth for patients after undergoing CS surgery. It is possible that the created physical model will be able to evaluate the predictive ability of ultrasonic elastography within the framework of this problem. It is important to remember that scar formation is the final stage of regeneration, therefore, the maximum number of answers to a detailed study of morphological and immunohistochemical features of the myometrium, as it is the primary matrix on which will be the formation of scar tissue.

Aims. To evaluate the relationship of menopause and its features with hyperuricemia in Russian women. Methods. In this study, we used data from the cross-sectional phase of the epidemiological study “Epidemiology of Cardiovascular Diseases in the Regions of the Russian Federation” (ESSE-RF) conducted in 2013–2014, in 13 regions of Russia. The final random sample size was 12 781 women. According to the interviews, the fact of menopause and the features of climacteric were identified. Hyperuricemia was defined as a serum uric acid concentration greater than 360 μmol/L. Age, behavioral risk factors and indicators of health status were assessed as covariates. Logistic regression analysis was used for multivariate assessment of associations. Apart from the assessment of the general sample, the analysis of the groups stratified by obesity, diabetes mellitus and the characteristics of climacteric was carried out. The results of logistic regression analysis are presented as odds ratios (OR) and 95% confidence intervals (CI). Results. In the general sample, after adjusting for covariates, menopause was directly associated with hyperuricemia (OR = 1.17; 95% CI 1.06–1.28), the association of hyperuricemia with age was not statistically significant. Menopause was more consistently associated with hyperuricemia in obese compared to non-obese women. In diabetic women, menopause is directly and significantly associated with hyperuricemia, whereas in non-diabetic women there was not the association between menopause and hyperuricemia. Taking into account the features of climacteric, menopause was directly associated with hyperuricemia only in the 4–10 years after the onset of menopause (OR = 1.13; 95% CI 1.02–1.26), in natural menopausal women (OR = 1.18; 95% CI 1.07–1.30) and who were taking hormone replacement therapy (OR = 1.23; 95% CI 1.06–1.43). Conclusions. The results of the study indicate the direct association of hyperuricemia with menopause, but not with the age of women. The stratified analysis has made it possible to identify some features of the association between hyperuricemia and menopause in women with metabolic disorders, as well as to assess the influence of the features of climacteric.

This review provides an analysis of a possible relationship between functional diseases of the gastrointestinal tract in children and adults. Some functional disorders previously identified only in the children’s age group, such as abdominal migraine, were increasingly recorded in the adult population. As a rule, the diagnosis of functional gastrointestinal diseases is based primarily on clinical symptoms. However, researchers increasingly note that for some pathologies in children, such as gastroesophageal reflux disease, the main symptoms of reflux, such as heartburn and belching, are not absolutely dominant. All this makes it possible to express an opinion on the formation of a universal functional pathology of the digestive tract with the dominance at certain stages of the pathological process of one or another symptomatology that affects the central nervous system.

Numerous studies in recent years have proven that the oncological process is an independent risk factor for thrombosis. For a long period of time and at the moment, research is continuing on the pathogenesis of a prothrombotic state in cancer patients. It was shown that the degree of risk is influenced by such indicators as the histological type of tumor, the stage of development of the disease, surgery, duration and type of anesthesia, chemotherapy, hormonal therapy, age, the presence of central venous catheters, immobilization, thrombophilia, history of thrombosis, infections. Thrombosis in cancer patients is triggered by thrombogenic factors associated with the tumor, patient-associated factors and environmental factors. The tumor cell affects the balance of hemostasis by releasing procoagulant substances, profibrinolytic, proproteolytic and proaggregant activity, expression of adhesion molecules, secretion of proinflammatory and proangiogenic cytokines; new participants in the process have also been identified. Studies have confirmed the fact that inflammation and thrombosis are inextricably linked with each other and play an important role in the progression of the disease and metastasis. All this opens up new horizons for the development of modern innovative strategies for treating cancer patients and increasing survival.

Background. The technological direction digital Twins is included in the list of the main strategic technological trends of 2019–2021. At the end of 2021, an initiative was announced in the Russian Federation aimed at creating a digital twin in the domestic healthcare system as part of the primary care modernization project. Aims — the purpose of the study is to review possible ways of using digital twins technology in the global healthcare system and in its Russian segment, as well as to build patent and publication landscapes to identify technological and academic leaders of the frontier. Methods. Scientometric and patent analysis. Results. The key stages of the development of the frontier “digital twins in healthcare” are traced. According to the data of the scientometric and patent analyses carried out in the priority direction “digital twins in healthcare and medicine”, the Russian Federation at the end of 2021 ranks 35th in the world in terms of specific weight in the total number of articles in publications indexed in WoS, and 20th in the world in terms of specific weight in the total number of patent applications for an invention, i.e. it is not among the 10 leading countries. The citation of domestic publications in the internationalized segment is significantly lower than the average (normalized) indicator, which does not give grounds to talk about the achievement of research excellence and even world-class domestic competence centers. Conclusion. The creation of the Digital Healthcare Consortium in 2018, the world-class Scientific Center “Digital Biodesign and Personalized Healthcare” in 2020 and the initiative of the regulator (Ministry of Health of Russia) in 2021 should be noted as key events in the development of the frontier in the Russian Federation. At the same time, it is important to note that the main global actors in the transformation of the digital twins frontier into high-tech equipment and services are not research centers, but companies acting simultaneously as qualified customers and beneficiaries of ongoing projects of a full innovation cycle. Having huge R&D budgets and having a clear goal setting, it is these participants in the process that become the main drivers of the technological development of the healthcare sector associated with the introduction of digital twins. In this regard, the absence of the direction of Russian companies on the patent landscape cannot but cause concern, which creates risks of using innovative solutions created in the domestic sector of interdisciplinary research in the interests of foreign corporations identified as technology leaders in this review.

Background. The artificial environment of confined space causes a decrease in the functional reserve of the central nervous system and can affect human health and the success of space missions. In solving this problem, the urgent task is to study adaptation mechanisms that adapt the functioning of the visual sensory system to the conditions of the extreme environment. Purpose — to obtain new objective data on the alterations in the functional activity of the visual system during prolonged stay of a person in extreme environmental conditions. Methods. Before and after a 4-month isolation experiment simulating a flight to the moon, an electrophysiological study was conducted of six practically healthy crew members with registration of a set of electroretinograms (ERG) and pattern-reversal visual evoked cortical potentials (VEP) according to the ISCEV standards. In dynamics, corrected monocular visual acuity (MVA) was assessed on board. Results. After the end of the experiment, on average for the group, there were no statistically significant changes in the MVA and functional activity of the retina and visual cortex compared with the initial data. However, individual changes on the part of the flicker ERG and reduction of VEP to small patterns stimulating the parvocellular channel of the visual system were revealed in three testers. These changes were associated with higher visually intense work and physical activity of these crew members, and with an individual reaction to sleep deprivation of pilots with increased responsibility. Conclusion. Four-month isolation with imitation of a space mission did not cause significant changes in the functional activity of the retina and visual pathways in healthy crew members. Individual differences of VEP-responses of the parvocellular visual system were revealed, which can reflect a high level of psychophysiological adaptation and stress resistance in physically active crew members.

Background. Meropenem, a broad spectrum carbapenem antibiotic, is often used for newborns despite of limited data available on neonatal pharmacokinetics. Due to pharmacokinetic and pharmacodynamic differences as well as to significant changes in the human body related to growth and maturation of organs and systems, direct scaling and dosing extrapolation from adults or older children with adjustment on patient’s weight can result in increased risk of toxicity or treatment failures. Aims — to evaluate the pharmacokinetics of meropenem in premature neonates based on therapeutic drug monitoring data in real clinical settings. Materials. Of 53 pre-term neonates included in the pharmacokinetic/pharmacodynamic analysis, in 39 (73.6%) patients, gestational age ranged from 23 to 30 weeks. Population and individual pharmacokinetic parameter values were estimated by the NPAG program from the Pmetrics package based on peak-trough therapeutic drug monitoring. Samples were assayed by high-performance liquid chromatography. One-compartment pharmacokinetic model with zero-order input and first-order elimination was used to fit concentration data and to predict pharmacokinetic parameter (%T > MIC of free drug) for virtual “patients” with simulated fast, moderate and slow meropenem elimination “received” different dosage by minimum inhibitory concentration (MIC) level. Univariate and multivariate regression analysis was used to evaluate the influence of patient’s covariates (gestational age, postnatal age, postconceptual age, body weight, creatinine clearance calculated by Schwartz formula, etc) on estimated meropenem pharmacokinetic parameters. Results. The identified population pharmacokinetic parameters of meropenem in pre-term newborns (elimination half-lives T1/2 = 1.93 ± 0.341 h; clearance CL = 0.26 ± 0.085 L/h/ kg; volume of distribution V = 0.71 ± 0.22 L/h) were in good agreement with those published in the literature for adults, neonates and older children. Pharmacokinetic/pharmacodynamic modeling demonstrated that a meropenem dosage regimen of 90 mg/kg/day administered using prolonged 3-hour infusion every 8 hours should be considered as potentially effective therapy if nosocomial infections with resistant organisms (MIC ≥ 8 mg/L) are treated. Conclusions. Neonates and especially pre-term neonates have a great pharmacokinetic variability. Meropenem dosing in premature newborns derived from population pharmacokinetic/pharmacodynamic model can partly overcome the variability, but not all pharmacokinetic variability can be explained by covariates in a model. Further personalizing based on Bayesian forecasting approach and a patient’s therapeutic drug monitoring data can help to achieve desired pharmacodynamic target.

Parathyroid hormone (PTH) is a key hormone responsible for regulation of calcium homeostasis in the body. Since the main body calcium depot is bone tissue, PTH has a decisive effect on its homeostasis. In this case, the hormone can activate both bone formation and resorption. Thus, PTH can ensure the conjugation of anabolic and catabolic processes, which is necessary for the renewal of bone tissue, which is had to function under constant mechanical stress. At the same time, the use of PTH in medical practice is rather small, despite its high potential as a basis for the treatment of various pathologies associated with impaired bone homeostasis. Presented review, describes the intracellular signaling cascades and molecular mechanisms that underlie the action of PTH on bone tissue cells, and intracellular signaling cascades are described. A separate section examines the cellular mechanisms of the action of PTH on bone homeostasis, discusses how the effect of the hormone on different types of cells provides an interface between the processes of synthesis and resorption. In addition, the review examines diseases associated with impaired bone homeostasis, as well as the role of PTH and impaired signaling in their etiology.

August 3, 2021 marks the 70th anniversary of the birth of Corresponding Member of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences Vladislav Remirovich Kuchma, a recognized leader in the field of hygiene of children and adolescents.