Vol 102, No 6 (2021)

Aim. To study the frequency of polymorphisms in genes associated with lipid metabolism disorders in young people with risk of sudden cardiac death, to identify the relationships between gene polymorphisms and risk factors of sudden cardiac death, and to develop mathematical models to identify the probability of carrying mutations in these genes.

Methods. The study included 436 young people (mean age 19.8±1.6 years). A standard examination and survey by questionnaire specially developed by us were conducted to identify an increased risk of sudden cardiac death. 59 individuals with a risk of sudden cardiac death were selected. The control group was 65 people, which was comparable to the study group. A blood test was performed to determine lipid profile and polymorphisms: Leu28Pro (rs 429358) in gene APOE, C3238G (rs 5128) in gene APOC3, Gln192Arg (rs 662) in gene PON1, Ser447Ter (rs 328) in gene LPL, G250A (rs 1800588) in gene LIPC. Statistical analysis was performed using the statistical package SPSS 17.0 and Statistica 6.0. The parametric Kruskal–Wallis test, the Mann–Whitney U-test, the Pearson’s chi-squared test, the Spearman rank correlation coefficient, and logistic regression analysis were used.

Results. We revealed a high frequency of Gln192Arg (rs 662) polymorphism in the PON1 gene in the group of individuals at risk of sudden cardiac death and its correlation with the deaths in relatives under age 50 years. Mathematical models for predicting the presence of polymorphisms in genes associated with lipid metabolism disorders have been developed. Among the developed mathematical models, the models for identifying carriers of the minor allele of Gln192Arg polymorphism in the PON1 gene, Ser447Ter in the LPL gene, and 250 G>A in the LIPC gene had the highest sensitivity, specificity, and accuracy.

Conclusion. In persons at risk for sudden cardiac death, it is advisable to conduct a screening for mutations in genes associated with lipid metabolism disorders, especially in Gln192Arg polymorphism in gene PON1.

Aim. To study the indicators of the immune status and manifestations of allergic diseases in HIV-infected patients in the Novgorod region.

Methods. We studied the data of HIV-infected patients living in the Novgorod region for the years 2000–2021. A total of 1020 cases of HIV infection were studied, in which 121 (12%) patients were diagnosed with allergic reactions. In patients with allergic manifestations, the human immunodeficiency virus type 1 ribonucleic acid content was measured by the polymerase chain reaction method, and the indicators of the immune status (the content of lymphocytes, eosinophils, basophils, the levels of CD3+, CD3+CD4+, CD3+CD8+ cells, immunoregulatory index) were assessed. For statistical analysis, the Student's test (t) was used to assess the statistical significance of diffe¬rences in immune status indicators, and the Pearson χ2 test to assess the statistical significance of differences in allergic manifestations in patients with HIV.

Results. The subjects of the study were divided into 2 groups based on the levels of HIV viral load. Analysis of these groups using the Pearson χ2 test showed a statistically significant (p <0.012) correlation between high viral load and the development of drug hypersensitivity reaction in HIV-infected patients. The following etiology of allergic reactions was determined among the subjects: drug (59%), food (19%), pollen (5.7%), household (5.7%), che¬mical (1.9%), unspecified (6.7%). The study of the immune status in two groups did not reveal statistically significant differences (p >0.05). The study of the immune status indicators in HIV-infected patients with drug hypersensitivity reactions and different levels of viral load revealed a significantly higher level of CD3+ cells (p <0.003) in patients with drug hypersensitivity reactions and detectable viral load.

Conclusion. The study revealed statistically significant differences in the immune status of HIV-infected patients with drug hypersensitivity reactions living in the Novgorod region compared with HIV-infected patients without drug allergies.

Aim. To assess the relationship between impaired uteroplacental blood flow and different levels of blood pressure in pregnant women with chronic and gestational hypertension at different stages of pregnancy with the determination of the optimal systolic blood pressure.

Methods. We conducted a prospective cohort study between 2018 and 2019. The study enrolled pregnant women aged 18 to 45 years: 55 women with chronic and gestational hypertension each, as well as 80 healthy pregnant women as control. The groups were formed by the continuous method, in which all pregnant women with arterial hypertension were included in the study until the required number of subjects was obtained. Follow-up was conducted at different gestation periods (14–16, 20–22, 28–30, 34–36 weeks) until delivery. Independent groups were compared by using the Student's t-test, the Pearson’s χ2 test, the Mann–Whitney U test, the Kruskal–Wallis H test.

Results. Comparison of the groups revealed differences in blood pressure levels at different gestation periods. In chronic hypertension compared with gestational hypertension, there was an increase in the impairment of the uteroplacental blood flow in pregnant women, indicating an unfavorable prognosis. The study of impaired uteroplacental blood flow among pregnant women with various forms of arterial hypertension revealed an increase in pregnant women with chronic arterial hypertension compared with gestational (p=0.04), indicating an unfavorable prognosis. In chronic arterial hypertension, the impairment of uteroplacental blood flow was the least for systolic pressures up to 120 mm Hg (up to 0.9%) at 14–16 and 20–22 weeks of gestation, and for 130–139 mm Hg (from 1.8 to 2.7%) in later pregnancy. In gestational hypertension, the least or no impairment rate of uteroplacental blood flow was determined for blood pressures up to 129 mm Hg at all stages of pregnancy compared with chronic hypertension.

Conclusion. The optimal systolic blood pressure in chronic hypertension reducing the risk of impaired uteroplacental blood flow in pregnant women is <129 mm Hg before 20th week of pregnancy and 130–139 mm Hg in later (20–30 weeks); in gestational hypertension, blood pressure reduction to 129 mm Hg is recommended at all stage of gestation.

Aim. To study changes in the topography of the orifice of the deep femoral artery (DFA), markers of proliferation, and apoptosis in patients after open interventions on the femoropopliteal arterial segment.

Methods. The study included 35 patients with atherosclerotic peripheral arterial disease (PAD), femoral-popliteal occlusion, stage IIB–III of the disease according to the classification of A.V. Pokrovsky–Fontaine, who underwent open surgery. The average age of the patients was 69±4.6 years. These patients included 26 men. Patients were divided into two groups: group A included 18 patients who underwent femoral-popliteal prosthetics (distal End-To-End bypass anastomoses), group B included 17 patients with femoral-popliteal bypass surgery (distal End-To-Side bypass anastomoses). The groups were comparable in terms of age and disease severity (p >0.05). Determination of serum platelet-derived growth factor BB (PDGF BB) and soluble form Fas (sFas) levels was carried out immediately before the intervention, on the 1st, 7th days, and 1 month after the operation. Duplex scanning (DS) was performed on day 7, after 1 and 18 months. Statistica 10.0 software was used for statistical data processing. The significance of differences between unrelated samples was assessed using the Student's t-test. The correlations between variables were analyzed by using Pearson's method.

Results. On 1st day, there was a decrease in soluble Fas in patients of group A compared with group B (0.41 ng/ml vs 0.78 ng/ml, p=0.01). On the 7th day, the levels of serum platelet-derived growth factor BB were increased in patients of group A compared with group B (35.2 ng/ml vs 23.2 ng/ml, p=0.00001). After 1 month, the level of serum platelet-derived growth factor BB in patients of group A remained elevated compared with those in patients of group B (22.8 ng/ml vs 14.4 ng/ml, p=0.0003).

Conclusion. Femoropopliteal prosthetics leads to a change in branching angle of the deep femoral artery up to 70–80%, accompanied by changing dynamics of apoptotic markers and cell proliferation, leading to an increase in the thickness of neointimal hyperplasia and the progression of atherosclerosis.

The review presents up-to-date information on the health effects of ambient fine particulate matter, obtained in large cohort epidemiological studies, as well as in meta-analysis of pooled data. In addition, it summarizes the current data on the potential pathological mechanisms and existing monitoring systems. The literature search used the Scopus, PubMed, Russian Science Citation Index databases for 1990–2020. The results of epidemiological studies carried out in different countries indicate that fine particles in ambient air pose a serious threat to health. Scientific publications assessing the health impact of particulate matter show a wide range of adverse effects — from the increasing incidence of upper and lower respiratory tract diseases, including exacerbations of bronchial asthma, pneumonia, chronic obstructive pulmonary disease, to a high incidence of myocardial infarction, strokes, diabetes mellitus type 2, as well as an increase in overall mortality from natural causes, mainly mortality from respiratory diseases, cardiovascular and cerebrovascular diseases, lung cancer. The effects of short-term exposures are described in more detail, while the effects of long-term exposure to fine particles are not well understood. Potential mechanisms of the harmful effects of fine particulate matter include oxidative stress, inflammatory reactions, disorders of autonomic regulation and heart rhythm, fine particles translocation through the alveolar barrier into the vascular bed with endothelial damage and thrombus formation, and genotoxicity. Ambient fine particulate matter is a manageable risk factor, and reductions in air pollution will have a significant impact on public health outcomes.

Today, the comorbidity of infection caused by the human immunodeficiency virus (HIV) is an important problem due to the complexity of the selection of the optimal antiretroviral therapy and the diagnosing of associated pathological conditions. The study of the comorbidity of HIV-infection and allergy is an important area of research. This article presents a literature review on different types of comorbidity. Special attention is paid to the development of allergic reactions to antiretroviral drugs. The presence of an allergic reaction in a patient can cause low adherence to therapy and subsequent development of HIV resistance to the treatment. The review provides information on the possible causes of the development of hypersensitivity in HIV-infected patients. The data on the development of hypersensitivity reactions in response to treatment with the main classes of antiretroviral drugs (nucleoside and non-nucleoside reverse transcriptase inhibitors, synthesis inhibitors, protease inhibitors, integrase inhibitors, cysteine-cysteine chemokine receptor 5 inhibitors) are presented. The most common allergic reactions to these drug classes are itching and rash, as well as increasing hepatic transaminase levels and cough. The existing scientific data on allergic reactions to drugs prescribed for other concurrent conditions (tuberculosis, fungal diseases) is also considered. The examples of studies reflecting the relevance of using immunogenetic and molecular genetic approaches in the study of comorbidity of HIV-infection and allergy are given. The identification of immunogenetic markers of the development of the hypersensitivity to therapy will optimize the diagnostic and treatment algorithms, especially in complex comorbid conditions.

Low anterior resection, unlike other large bowel resections with anastomosis, is characterized by a high incidence of postoperative complications, repeated surgical interventions, accompanied by high mortality. To reduce these indicators, the creation of a protective stoma and drainage of the pelvis has become widespread. However, the efficiency of pelvic drainage after low anterior resection remains unclear and controversial. This literature review is devoted to the relevance of the problem of efficiency and analysis of studies on this issue. Most randomized trials have not proven the effectiveness of drainage in colorectal surgery, but in these studies, as a rule, little or no attention was paid to draining the small pelvis after total mesorectal excision. This work analyzes the studies of supporters and opponents of pelvic drainage after low anterior resection of the rectum and provides arguments for and against drainage of the pelvic cavity. Although there are randomized trials showing no benefit of pelvic drainage, many clinics use pelvic drain after low anterior resection. The personal experience of the surgeon and the occurrence of intraoperative complications such as bleeding, contamination, technical difficulties in colorectal anastomosis formation has an important role to play in this. A lower rate of repeated operation in the use of pelvic drainage suggests the possibility of conservative treatment.

The invention of an electric pacemaker in the middle of the 20th century led to a revolution in the treatment of cardiac conduction system diseases. The improvement of pacemakers continued. In 1962, the first small series of external pacemakers for percutaneous and direct stimulation was produced in Kaunas. After a while, electric pacemakers became more reliable, smaller and lighter in weight, but the problem of foreign body associated infection and limited service life remained unresolved. Modern high-tech medicine strives to create less invasive electric pacemakers, but nevertheless, biological pacemakers can expand the therapeutic arsenal for the treatment of cardiac patients, being the most physiological for humans. The concept of an artificial biological pacemaker consists of the creation of an organic structure that generates a spontaneous rhythm from the implantation site in the myocardium. Various gene and cellular approaches were used to create biological pacemakers: a functional reorganization approach (use of adenovirus vectors for hyperexpression of genes encoding ion channels in cardiomyocytes); hybrid approach (use of fibroblasts to deliver genes of ion channels that provide heart automation); somatic reprogramming approach (overexpression of the transcription factor TBX18 using adenoviral vectors, which reprograms cardiomyocytes into induced sinoatrial node cells, creating cardiac stimulatory activity); cellular approach (transplantation of stem cells to a specific place in the heart, thereby creating biological stimulation). Modern methods of electrical cardiac stimulation and the developed concepts of the biological pacemaker clearly show the possibility of eliminating current problems associated with the use of an artificial pacemaker by replacing it with a biological one. Each of the approaches (gene, cellular, hybrid-cellular, somatic reprogramming) has its own advantages and disadvantages, which predisposes to further study and improvement in order to introduce a biological pacemaker into clinical practice.

Artificial intelligence technologies in medical practice are a promising direction in the world. Artificial intelligence medical decision support systems, diagnostic and screening programs can help medical personnel in routine and complex tasks and improve the level of medical care provided to patients. At the same time, the development, production and distribution of artificial intelligence systems must be regulated without fail. Registration and subsequent control (post-registration monitoring) of artificial intelligence systems in medicine require the creation, adjustment of the legal framework and technological regulation. The Russian Federation has developed a promising development strategy in this area. Seven national standards have been developed by experts in the field of Artificial intelligence in healthcare. These standards establish the procedures for conducting clinical and technical trials, performance requirements and the concept of life cycle, a quality management system and risk management. A separate standards is devoted to dataset creation for training and testing the developed algorithms, requirements for them and a metadata format. There are plans to bring the developed national standards to the international level, which will allow Russian manufacturers of artificial intelligence systems implemented these national standards to comply with foreign counterparts and become more competitive at the international level. The international community has already supported the development of an ISO standard based on the national standard for clinical trials. The development will be performed based on the technical committee ISO/TC 215 (Health informatics) in conjunction with ISO/IEC JTC 1/SC 42 (Artificial intelligence), this will allow bringing the national requirements for the Artificial intelligence to the international level. The cycle of these standards will summarize recognized methodologies, helping both manufacturers and medical organizations, doctors and patients to produce and use a quality, safe and effective product.

The role of hyaluronic acid in the pathogenesis of acute respiratory distress syndrome, including those associated with severe COVID-19, is known. Pro-inflammatory cytokines (interleukin-1, tumor necrosis factor) are strong inducers of hyaluronic acid synthase (HAS2) in CD31+ endothelial cells, EpCAM+ cells of the alveolar epithelium of the lungs and fibroblasts. Hyaluronic acid can absorb water in quantities significantly exceeding its own molecular weight. Reducing the presence or inhibiting of hyaluronic acid synthesis is of great importance for facilitating the breathing of COVID-19 patients. Hyaluronidase-based preparations can reduce the accumulation of hyaluronic acid and promote pulmonary alveoli cleansing. Respiratory viral infections, including pandemic strains of coronaviruses, especially in severe cases with acute respiratory distress syndrome, can be complicated by the development of pulmonary fibrosis. It has been shown that changes in X-ray Computed Tomography findings characteristic of fibrosis in the first year after COVID-19 can significantly regress. A clinical case from the practice of treating a patient with a severe course of COVID-19, significant cardiovascular comorbidity, grade 2 obesity, which was regarded as significant risk factors for an unfavorable outcome, is presented. The patient with signs of progressive respiratory failure was admitted to the intensive care unit. Pulse therapy with glucocorticosteroids and anticoagulants was started. Deterioration of the condition is regarded as the beginning of acute respiratory distress syndrome, which complicated the cytokine storm induced by the coronavirus. The patient was taken for high-flow oxygenation. An anti-cytokine therapy was prescribed. Reduction of inflammatory markers was obtained, but severe respiratory failure persisted. The bovgialuronidase azoximer was included in the treatment. The patient's condition began to stabilize then she was discharged in stable condition without oxygen support. The available data on the negative role of hyaluronic acid in the pathogenesis of acute respiratory distress syndrome in patients with COVID-19, as well as the need to reduce the likelihood of developing residual fibrous changes in the lungs in patients who have undergone acute respiratory distress syndrome, suggest the need for further studies of domestic azoximer bovgialuronidase properties in the treatment of severe forms of COVID-19.

Aim. Comparative analysis of insufficiency rate of bronchial stump sutures in pneumonectomy for lung cancer, depending on suturing techniques.

Methods. A patented technique for bronchial stump suturing has been introduced into the practice of the GOBUZ clinic “Novgorod Regional Clinical Hospital” based on the Department of thoracic surgery since 2015 for pneumonectomy for lung cancer. Before the introduction of the developed technique, various generally accepted methods of bronchial stump forming were used (mechanical suture, manual suture, their combination, bronchial stump coverage with mediastinal pleura, pericardial flap). A retrospective analysis of 173 case histories and operational protocols of patients with lung cancer who underwent pneumonectomy was carried out for the failure of bronchial stump sutures when using conventional suturing techniques between 2010 and 2014 (the first group of patients). We also performed a retrospective and prospective analysis of 204 case histories and operational protocols of patients in a similar clinical group when using a patented suturing technique between 2015 and 2020 (the second group of patients). Statistical analysis was carried out by using Statistica 10.0 software (StatSoft, Inc. 2011). The qualitative and quantitative indicators were analyzed by using the Pearson’s χ2-test with Yates’s correction.

Results. A retrospective analysis shows that the failure rate in the use of generally accepted bronchial stump suturing techniques for 2010–2014 was 10.4%. After the implementation of the method of preventive esophagobronchomyoplasty, complications as bronchial stump suture failure were not detected in any case between 2015 and 2020.

Conclusion. The study shows high efficiency, a decrease in the incidence of complications as the failure of bronchial stump sutures in the use of the developed method of preventive esophagomyobronchoplasty in pneumonectomy for lung cancer.

Aim. To improve surgical treatment outcomes of patients with spontaneous rupture of the esophagus complicated by purulent mediastinitis.

Methods. Over the past 30 years, we have experience in the surgical treatment of 31 patients with spontaneous rupture of the esophagus complicated by purulent mediastinitis. Depending on the tactics and techniques of surgical treatment, we identified two groups of patients. The first group (n=8) consisted of patients operated with conventional techniques: thoracotomy, transpleural mediastinotomy according to Dobromyslov, suturing of the esophagus with drainage of the mediastinum and pleural cavities, “blind” mediastinal drainage. The second group (n=23) consisted of patients treated with “programmed re-thoracotomy”. Re-thoracotomy was performed along with the postoperative thoracotomy wounds. The delimited foci of purulent mediastinitis were opened and sanitized (necrotic tissues were excised and removed). Preventive hemostatic methods were used in the area of pressure ulcers from drainage tubes. Replacing and changing the position of the drainage tubes in the mediastinum was a strictly compulsory technique. Pus and necrotic soft tissue that appeared in the thoracotomy wound were subsequently eliminated by a device consisting of two titanium brackets connected by a lock embodied in the form of an oval ring during the wound suturing at the stage of programmed re-thoracotomy. The groups were comparable in age and comorbidities. The average diagnosis of spontaneous esophageal rupture took 3.5 days; the maximum time is 10 days. The statistical significance of differences in immune status indicators was assessed by using the Student's t-test and Pearson's χ2 test.

Results. A systematic approach using the tactical and technical surgical techniques developed by us (such as suturing esophageal wall defects regardless of the rupture time, multifunctional nasoesophagogastric tube installation; the imposition of a purse string suture to prevent reflux from the stomach into the esophagus; programmed re-thoracotomy using the method of temporary fixation of the ribs) allowed to reduce the number of complications, such as haemorrhage from the mediastinal vessels, by 3 times, sepsis — 1.5 times, mortality — almost 2 times.

Conclusion. The introduction of patented techniques allowed to reduce the number of life-threatening complications and mortality in patients with spontaneous rupture of the esophagus complicated by purulent mediastinitis.

Irina Vitalevna Zaikonnikova is a well-known Soviet pharmacologist, headed the Department of Pharmacology of the Kazan State Medical Institute between 1968 and 1989. The topic of I.V. Zaikonnikova’s Ph.D. thesis was “The influence of dikain on blood vessels and its relationship with adrenaline”. In her dissertation, Irina Vitalievna found that dicaine dilates blood vessels in low concentrations and causes their constriction in high concentrations. The thesis was successfully defended in 1947. In the 50s of the last century in Kazan, for the first time in the Soviet Union, the study of the biological activity of organophosphorus compounds was begun. A large experimental material concerning the correlation between the biological activity and chemical structure of compounds was summarized in his doctoral dissertation “Pharmacological characteristics of a number of dialkylphosphinic acid esters”, which I.V. Zaikonnikova defended in 1968. At the Department of Pharmacology, which she headed since 1968, a close-knit team was formed, united by a common interest — the search and development of new potential drugs. This major work resulted in the creation of cidiphos, glycifon, phosphabenzide, and dimephosphon — organophosphorus compounds of a new type, which mechanism of action is not associated with inhibition of the activity of acetylcholinesterase. In addition, drugs that did not belong to organophosphates were created — the daytime tranquilizer mebikar, a regeneration stimulator with the immunomodulatory effect of xymedon. At present, the Department of Pharmacology of Kazan State Medical University continues the scientific traditions of our outstanding predecessors.

Dr. Charles H.V. Hoyle was a world-renowned neurophysiologist, neuropharmacologist, neuroanatomist. He received his bachelor’s degree from Queen Elizabeth College in London in 1982, and already in 1986 he defended his PhD thesis at King's College London (University College London) under the supervision of Professor Geoffrey Burnstock — the founder of the theory and a re­cognised leader in purine research.

Общение с медицинскими работниками может сыграть важную роль в принятии пожилыми людьми решения о вакцинации. Чтобы помочь принять обоснованное решение о вакцинации, медицинские работники должны уметь определить пробелы в знаниях, потребности и проблемы пожилого человека. Они также должны иметь возможность поделиться и обсудить информацию о риске заболевания человека и тяжести заболевания, об эффективности и безопасности вакцины, а также практическую информацию о том, как человек может получить доступ к вакцинам. Поэтому медицинским работникам необходимы хорошие навыки общения (коммуникаций), и они должны активно держаться в курсе последних доказательств. Понимание их восприятия и опыта общения по вопросам вакцинации может помочь нам в обучении и поддержке медицинских работников и разработке хороших стратегий общения (коммуникаций).