Kazan medical journal

Background. Despite the obvious successes of the world community in the fight against the spread of SARS-CoV-2, attempts to create new drugs that are active against the COVID-19 pathogen do not stop. In parallel, a targeted search for new prevention opportunities is being carried out. Vaccination does not protect 100% against possible infection, but significantly reduces the risk of developing severe forms of COVID-19, the need for hospitalization and death.

Aim. Describe the course of COVID-19 in patients previously vaccinated against this infection.

Material and methods. On the basis of the Republican Clinical Infectious Diseases Hospital of Kazan, from January 15 to August 28, 2021, an observational retrospective analytical study, which included the observation of 1260 patients who applied to the emergency room of the hospital and had a history of immunization against COVID-19, was conducted. Statistical data processing was carried out using an on-line calculator. The significance of differences between the compared groups was calculated using the χ2 test and Fisher's exact test. Gam-COVID-Vac as a specific prophylaxis was received by 87.8% (1106/1260), EpiVacCorona by 9.5% (120/1260), CoviVac by 2.6% (33/1260), Sputnik Light by 0.1% (1/1260). The assessment of adverse events after immunization was carried out taking into account the recommendations of the World Health Organization (2012).

Results. Laboratory-confirmed (or clinico-epidemiologically) “new coronavirus infection” was registered in 53.4% (673/1260) of patients. The proportion of cases of COVID-19 in each group vaccinated with a particular vaccine differed: among those vaccinated with Sputnik V it was 51.3% (567 people out of 1106 who applied), with EpiVacCorona — 71.7% (86 out of 120; p <0.001), KoviVak — 62.5% (20 out of 32). Side effects after immunization due to the action of the vaccine (previously such phenomena were called post-vaccination reactions) were registered in 1% (12/1260) of the vaccinated. Breakthrough infection (developing 14 days after the completed vaccination course) was recorded in 26.4% (333 out of 1260). It was characterized by a milder course and minimal manifestations on computed tomograms. The highest epidemiological efficacy among the three domestic vaccines (Gam-COVID-Vac, EpiVacCorona and KoviVac), according to our results, was shown by Gam-COVID-Vac. Those vaccinated with it fell ill with COVID-19 less frequently (33%, 365/1106) than those vaccinated with EpiVacCorona (56.7%, 68/120) and CoviVac (31.3%, 10/32), p <0.001 and p=0.836, respectively.

Conclusion. Breakthrough COVID-19 infection was characterized by a milder course, even among hospitalized ¬patients, exceptionally low mortality rate (0.9%, 3/333) in vaccinated compared to unvaccinated against SARS-CoV-2. Our study has shown that a full course of immunization reduces the incidence of moderate and severe forms of the disease.

Background. Chronic polyposis rhinosinusitis is characterized by an immune-dependent type of polyp formation with a defect in local protective factors. The use of local immunomodulators will improve immune protection in the nasal cavity.

Aim. To study cytokine levels in nasal secretion and blood serum in patients with chronic polyposis rhinosinusitis after therapy with interferon gamma.

Material and methods. To study immunological indices, 32 patients with chronic polyposis rhinosinusitis, who were treated with intranasal interferon gamma, and 30 healthy people (control group) were examined. In the group of patients with the disease, the levels of interleukins-4, -10 and -18, tumor necrosis factor α, and secretory immunoglobulin A were determined in the nasal secretion and blood serum before treatment and 1 month after it. Statistical analysis of the results was performed using the Statistica 12.0 software package. The test for normality of distribution in the sample was carried out using the Shapiro–Wilk test. Most of the parameters did not have a normal distribution; therefore, nonparametric statistical methods were used for further analysis. The description of the results obtained in the study was carried out by calculating the median (Me) and the interquantile range in the form of the 25th and 75th percentiles (Q0.25 and Q0.75). Comparative analysis of quantitative signs in independent groups was performed according to the Mann–Whitney test, in dependent groups — using the Wilcoxon method. Differences were considered significant at p <0.05.

Results. Clinical efficacy was assessed according to a 4-point scale: excellent treatment result, good result, satisfactory and unsatisfactory. A good effect of the therapy was 78.1% (25 patients). Unsatisfactory effect was registered in 7 (21.9%) patients. After treatment, a decrease in the content of interleukin-4 (p2=0.000034), interleukin-18 (p2=0.000075), an increase in the level of interleukin-10 (p2=0.033), a decrease in the amount of secretory immunoglobulin A in the nasal secretion (p2=0.0001) took place. The levels of tumor necrosis factor α in blood serum were reduced both before treatment compared with the control group (p1=0.005) and after therapy (p2=0.000075).

Conclusion. An increase in the content of interleukin-10 in the nasal secretion and a decrease in the level of proinflammatory cytokines — interleukin-18, tumor necrosis factor α and interleukin-4 — in the blood serum after treatment with interferon gamma in patients with chronic polyposis rhinosinusitis may indicate a decrease in the activity of immune inflammation in the nasal cavity.

Background. COVID-19 is a predominantly respiratory disease caused by the SARS-CoV-2 virus that has spread as a pandemic since 2020; characterized by high mortality and unexplored long-term outcomes.

Aim. To describe the morphological changes in the lungs and other organs in severe forms of COVID-19.

Material and methods. A macro- and microscopic examination of the lungs, kidneys, liver, brain and heart of 45 patients who died from complications of COVID-19 was carried out. Histological preparations were stained with hematoxylin and eosin, by the Picro-Mallory stain, as well as with fluorescent antibodies and dyes to visualize neutrophil extracellular traps.

Results. The leading pathomorphological manifestations of COVID-19 were inflammation and microthrombosis in the lungs. At the same time, diffuse alveolar damage often developed as a manifestation of acute respiratory distress syndrome in an adult. Diffuse leukocyte infiltration of the lungs was combined with the formation of neutrophil extracellular traps in the lumens of the blood vessels. Diffuse microthrombi were found in most lung tissue samples (87%), while macroscopic thrombi were much less common (16%). In single cases, the cause of death was thromboembolism of the branches of the pulmonary artery, originating from deep vein thrombi of the lower extremities or the right atrial appendage. In the tissues of the liver, heart, kidneys and brain, moderate alterative (degenerative and necrobiotic) microscopic changes were observed, as well as morphological signs of concomitant chronic diseases.

Conclusion. COVID-19 is characterized by pathogenically interrelated morphological manifestations of inflammation and primary pulmonary (micro)thrombosis in the form of accumulation of leukocytes both in blood clots and in the alveoli, while regional pulmonary immunothrombosis is associated with diffuse damage to the alveoli; in the heart, brain, liver and kidneys, predominantly dystrophic and necrobiotic changes occur, which are typical of secondary injuries and/or concomitant pathology.

Background. Conducting molecular and genetic studies to investigate susceptibility to multifactorial and polygenic diseases, such as type 2 diabetes melitus and pre-diabetic conditions, is of great importance for the development of personalized prevention programs and the choice of optimal treatment. Taking into account regional and ethnic features, the study of polymorphic markers of candidate genes for fat and carbohydrate metabolism has a great practical value.

Aim. To investigate associations of polymorphisms of the FTO rs9939609, PPARG rs180128, PPARGC1A rs8192678 genes with the risk of developing type 2 diabetes mellitus and pre-diabetic conditions in residents of the Republic of Tatarstan.

Material and methods. An observational single-stage single-center controlled study was conducted in patients with various disorders of carbohydrate metabolism: prediabetes (n=138) and a confirmed diagnosis of type 2 diabetes mellitus (n=134). Molecular genetic analysis of rs9939609 polymorphism of the FTO gene, rs8192678 polymorphism of the PPARGC1A gene and rs1801282 polymorphism of the PPARG gene was performed using real-time polymerase chain reaction. The distribution of patient genotypes and alleles was compared with the Russian population. Statistical data processing included nonparametric correlation analysis using Pearson’s coefficient, calculation of Student's and χ2 tests, odds ratios, arithmetic mean values and their standard deviations using “GraphPad InStat” software.

Results. The A allele of the rs9939609 polymorphism of FTO gene increases the risk of developing type 2 diabetes mellitus and early carbohydrate metabolism disorders (OR=2.73, p=0.00007 and OR=4.17; p=0.00002, respectively). The GG genotype of the rs180128 polymorphism of the PPARG gene is associated with the risk of type 2 diabetes mellitus (OR=2.77, p=0.02).

Conclusion. The expected association of the rs9939609 FTO polymorphic marker, which determines the development of insulin resistance, with the development of type 2 diabetes mellitus and the presence of early carbohydrate metabolism disorders was obtained.

Background. The sodium-dependent phosphate transporter NaPi2b is expressed in a number of tumors and serves as a target for monoclonal antibody therapy. The NaPi2b transporter has a large extracellular domain containing 4 cysteines and an MX35 epitope recognized by the corresponding monoclonal antibodies.

Aim. To study the recognition of the MX35 epitope in cysteine mutants C303 and C350 of the sodium-dependent phosphate transporter NaPi2b by monoclonal antibodies in ovarian cancer cells.

Material and methods. Ovarian cancer cells of the OVCAR-8 line were transfected with plasmids encoding mutant forms of the NaPi2b transporter. The recognition of these forms by monoclonal antibodies was studied by Western blot and flow cytometry. Statistical analysis of flow cytometry data was performed using Pearson’s Chi-squared test with Yates’ correction.

Results. Western blot analysis of lysates of OVCAR-8 cells expressing the wild-type NaPi2b transporter demonstrated the presence of a specific signal only in samples without the addition of dithiothreitol, while in all samples with NaPi2b cysteine mutants, even without the addition of dithiothreitol, no specific signal from monoclonal antibodies was detected. The flow cytometry results showed that proportion of OVCAR-8 cells with positive staining of the MX35 epitope with antibodies is less when expressing the NaPi2b mutants compared to the wild type.

Conclusion. Cysteines C303 and C350 are involved in disulfide bonds formation, which is of key importance for the formation of the conformation of the extracellular domain of the sodium-dependent phosphate transporter NaPi2b, which ensures the MX35 epitope recognition by monoclonal antibodies.

The review presents current data on the structure and functional role of cell adhesion molecules belonging to the selectin family (selectins P, L and E), and their involvement in the pathogenesis of cardiovascular diseases. On the one hand, intercellular adhesion molecules of the vascular wall endothelium, platelets and leukocytes are an important link in the processes of vasculogenesis, development and regeneration of the vascular system. On the other hand, these molecules participate in the earliest stages of endothelial dysfunction with the subsequent development of pathology. For this reason, figuring out the mechanisms of activity of this group of molecules is very important for understanding the molecular basis of the cardiovascular diseases pathogenesis. The adhesion of molecules, both between cells and between cells and a component of the extracellular matrix, is the most important stage of physiological and biochemical processes. According to present knowledge, five classes of intercellular adhesion molecules are known: integrins, cadherins, immunoglobulins (including nectins), selectins and addressins. All of them are bonded to a cytoplasmic membrane and provide the interaction of cells with each other. Some of them are transmembrane and associated with the cytoskeleton of the cell. On the cell surface, intercellular adhesion molecules can be located in clusters, forming multipoint binding sites and thereby determining the degree of avidity. One of the most significant functions of selectins is participation in the initial stage of the leukocyte adhesion cascade, which results in their binding to the endothelium, rolling and further extravasation into tissues. The first stage of this process is mediated by specific non-covalent interactions between selectins and their glycan ligands, with the glycans functioning as an interface between leukocytes or cancer cells and the endothelium. Targeting these interactions remains one of the main strategies aimed at developing new methods of treating immune, inflammatory and oncological diseases.

Among the diverse picture of preeclampsia, the hematological component, thrombocytopenia, attracts attention. Platelets are able to form microvesicles by “budding” the plasma membrane from the cell surface during apoptosis, stimulation, and also in a small amount in normal conditions. The membrane of these particles has a negative charge and contains phospholipids and an integral glycoprotein on the outer monolayer, due to which platelet microvesicles are involved in the process of blood coagulation and angiogenesis. Microvesicles are of platelet origin, they were first discovered in the middle of the last century in England when describing the phenomenon of plasma and serum coagulation in the absence of platelets in them. The number of platelet microvesicles dynamically changes during the formation of preeclampsia in pregnant women and in women with risk factors for the development of preeclampsia, which include obesity, arterial hypertension, diabetes mellitus, antiphospholipid syndrome. Exposure to these risk factors for preeclampsia before pregnancy leads to a change in the concentration of cells that produce microvesicles, which in turn can create conditions favorable for the development of preeclampsia during pregnancy. A special risk group are women with a history of preeclampsia. Taking into account the direct role of microvesicles in the processes of angiogenesis and blood coagulation, the study of these particles will allow a more detailed study of the pathophysiological aspects of the preeclampsia development, which will expand the possibilities for early prediction of this pathology and improvement of perinatal outcomes.

The COVID-19 pandemic has greatly affected all spheres of life, including biomedical research. The ethical regulation of clinical trials has a long history in international and domestic practice. An efficient infrastructure of international and national legislation has been created. At the same time, there are features of the organization of ethical review of clinical trials that arise under the restrictions associated with COVID-19. Healthcare of all countries is faced with the need to develop new approaches caused by the speed of the spread of the disease, its severe consequences for the life and health of people, the excessive burden on the medical worker, not only physical, but also psychological, including those associated with ethical problems. The purpose of this research was to study and analyze the experience of ethical review of clinical trials in the context of the COVID-19 epidemic, its regulatory framework in international and domestic practice. For high-quality and lawful conduct of clinical trials in Russia in the context of the COVID-19 epidemic, appropriate conditions were created, namely, a vertical base: the central ethical committee of the Ministry of Health of the Russian Federation — local ethical committees based in clinical institutions and research centers. They are provided with sufficient and high-quality legal support in the form of laws of the Russian Federation, country standards and by-laws. The work of local ethics committees is built in accordance with strict ethical international and domestic standards. Standard operating procedures implemented in local ethics committees provide for all the nuances of situations, including those implemented using modern telecommunication technologies and other end-to-end information technologies. Even if many restrictions are imposed, biomedical research must continue, and accordingly, it must be carried out under the strict control and monitoring of research ethics committees. The article presents an overview of legal sources, an analysis of the main approaches in domestic and foreign literature, taking into account historical retrospective.

Background. In the context of the stabilization of the tuberculosis situation in Russia, including the Tyumen region, work with children at risk (with a latent tuberculosis infection) is of particular importance. In the course of previous studies, a number of problematic issues in the field of organizing phthisiatric care for this contingent were identified.

Aim. To substantiate and develop the structure of the regional register of children with latent tuberculosis infection, as well as the algorithm for collecting and registering information included in it.

Material and methods. The analysis of domestic and foreign publications, the current regulatory framework in the field of creation and use of registers in medicine and healthcare has been carried out. The study used content analysis, legal, historical and descriptive-analytical methods.

Results. The analysis of the literature showed that currently the practice of creating registers in medicine is particularly relevant, but there is no unified definition, classification, tasks and approaches to their management, therefore, the structure of the regional register of children with latent tuberculosis infection, the procedure for collecting and registering information were developed by the authors based on the functions inherent in it. The register is necessary for recording and monitoring of children with latent tuberculosis infection, optimization of medical processes, solving organizational and scientific issues in providing anti-tuberculosis care to this category of patients. The register consists of 8 blocks: identification, follow-up medical care, anamnesis vitae, epidemiological anamnesis, vaccination against tuberculosis, immunodiagnostics, radiation diagnostics, preventive treatment. The functions of filling in the blocks are distributed between the primary health care institutions and the phthisiological service, as well as assigned to certain specialists.

Conclusion. The developed data registration algorithm and the structure of the regional register of children with latent tuberculosis infection contain the data necessary for the implementation of the tasks set, operational and retrospective monitoring of the effectiveness of ongoing activities, as well as management decision-making at all levels of providing phthisiatric care to the children's population of the region.

Background. The ultrasound method of examination is often used to detect liquid formations of a postoperative wound. For this reason, the search for new criteria for assessing the course of the wound process is currently relevant.

Aim. To study the possibility of using the ultrasound method of research to determine the severity of postoperative wound complications according to the Clavien–Dindo classification and further optimal tactics, diagnosis and treatment.

Material and methods. 255 patients after surgery for various urgent diseases of the abdominal organs, as well as patients with elective surgeries were examined. All patients underwent complex clinical, laboratory and instrumental studies. Continuous values that do not have a normal distribution were processed using non-parametric methods — the values were presented in the format Me [Q1; Q3], the difference in unrelated groups was assessed by the Mann–Whitney U test, and in related groups, by the Wilcoxon test.

Results. The postoperative period in 58 (22.7%) of 255 patients was complicated by postoperative wound complications, which had I, II, III severity according to the Clavien–Dindo classification. On the 5th day of ultrasound examination of the surgical site with the III degree of severity of postoperative wound complications, there was a statistically significant increase in the echogenicity width of tissues in the area of the wound defect compared with the I–II severity of complications.

Conclusion. The ultrasound method of research allows to evaluate the effectiveness of reparative processes in damaged tissues and the development of complications, as well as to determine the severity of their course in the postoperative period for planning further surgical tactics.

Background. Despite the improvement of surgical techniques for the treatment of chronic hemorrhoids, the problem of incontinence of the components of the intestinal contents in the postoperative period remains relevant.

Aim. Evaluation of the functional state of the rectal obturator in patients with grade 4 hemorrhoids before and after surgical treatment with an ultrasonic scalpel.

Material and methods. At the National Medical Research Centre for Coloproctology named after A.N. Ryzhikh of the Ministry of Health of Russia, 500 patients with grade 4 hemorrhoids operated on with an ultrasonic scalpel for the period 2015–2017 were examined using anorectal manometry (profilometry). The mean age of the patients was 49.2±12.4 years (from 22 to 65 years). At the same time, initially, 11/500 (2.2%) patients even before the operation had periodic complaints of gas incontinence (grade I anal sphincter insufficiency; 2.5±1.3 points on the Wexner scale). For statistical processing, the Student's t-test or the nonparametric single-sample Wilcoxon criterion were used.

Results. On average, manometric indicators for the group before surgery were within the physiological norms. In 11 patients with complaints of incontinence, the pressure in the anal canal was initially reduced both at rest and during volitional contraction. At the same time, among the rest of the patients without any complaints of incontinence, 55/489 (11.2%) cases of subclinical (without manifestations) form of anal incontinence were identified only by a decrease in the manometric indicators of the sphincter rest tone, which made it possible to refer these patients to the group risk for the development of postoperative anal incontinence. After surgery, clinical complaints of gas incontinence appeared in 14/55 (25.5%) patients with subclinical anal sphincter insufficiency. In total, by the 45th day, anal incontinence according to complaints and the results of an objective study was registered in 25/500 (5.0%) patients.

Conclusion. Clinical and instrumental signs of anal sphincter insufficiency after surgical treatment of stage 4 hemorrhoids with an ultrasonic scalpel were registered in 5.0% of cases, while in 2.2% they were at baseline (in patients with a decrease in intraanal pressure and complaints), and in 2,8% appeared after surgery (in patients with subclinical anal incontinence).

The article was prepared for the 130th anniversary of the head of the Departments of Microbiology and Epidemiology of the Kazan Medical Institute, Professor Alfred Ernestovich Ozol. The article presents the main milestones of the biography of A.E. Ozol, a prominent representative of the Voronezh and Kazan schools of epidemiologists and microbiologists. Materials on the contribution of A.E. Ozol to the elimination of epidemics and outbreaks of infectious diseases: typhus, anthrax, tularemia, brucellosis, smallpox, diphtheria, typhoid fever, dysentery in the Soviet period are presented. The main scientific achievements of A.E. Ozol and his contribution to the development of microbiology and epidemiology, data on his role in the development of the epidemiological direction of the Kazan Research Institute of Epidemiology and Microbiology are described. The article was prepared using primary sources — scientific articles and monographs published during his activity, a personal file from the archive of the personnel department and materials of the Department of Microbiology named after academician V.M. Aristovsky of Kazan State Medical University, as well as the personal archive of the family of A.E. Ozol.

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Bellù R, Romantsik O, Nava C, de Waal KA, Zanini R, Bruschettini M. Opioids for newborn infants recei¬ving mechanical ventilation. Cochrane Database of Systematic Reviews. 2021. Issue 3. Art. No.: CD013732. DOI: 10.1002/14651858.CD013732.pub2.

This publication is a reprint of an article by Prof. E.M. Lepsky “A new way to fight diphtheria”, published in the Kazan Medical Journal in 1923. Reprinting is carried out in preparation for the celebration of the 150th anniversary of the first issue of the Kazan Doctors' Society Diaries, the assignee of which is the Kazan Medical Journal. Original publication: Lepsky E.M. A new way to fight diphtheria. Kazan Medical Journal. 1923;19(6):86–91. DOI: 10.17816/kazmj80106.