Kazan medical journal

Background. The problem of lymph nodes metastases diagnosing in cervical cancer remains relevant and not fully resolved. The last decade studies results have shown the great potential of molecular markers in lymph nodes metastasis prediction, however, additional studies for their implementation in clinical practice are required.

Aim. Bioinformatic and laboratory screening of molecular markers of cervical tumors regional metastasis for its low invasive diagnosis.

Material and methods. The study was performed on 400 patients with cervical cancer and 40 donors without oncological pathology. To identify potential molecular markers of lymph node metastatic lesions, the Cancer Genome Atlas database was initially analyzed. The identified markers were validated by the Real-Time-polymerase chain reaction in tumor cell samples (extracted using laser microdissection) and extracellular deoxyribonucleic acid (DNA). The Mann–Whitney test was used to assess the differences; the Bonferroni correction was used to account for multiple comparisons.

Results. At the bioinformation stage, the change in the copy number of 5493 genes was analyzed, of which 79 genes were selected that most often change their copy number. During the data validation, it was found that primary tumor cells and tumor cells of metastases from the lymph nodes differ from normal cervix cells in the level of gene copies. The copy number of the CCND1 and PPARGC1A genes has the highest potential for regional lymph nodes metastases diagnosing in patients with cervical cancer; the PIK3CA, SPEN, ERBB3, APC, MUC4, CASP8, HLA-A, IGSF1 and TMTC1 loci have a lower potential. The EP300, TTN, DMD, DST, LAMP3, TORC2, TP53 and FOXO3 genes can be used to diagnose cervical cancer, whether metastatic or not. Additional validation of markers was carried out on extracellular DNA of blood plasma of cervical cancer patients and conditionally healthy donors. The presence of a differential copy number of PIK3CA, SPEN, ERBB3, APC, CCND1, HLA-A, TTN, MUC4, DST, PPARGC1A genes was found in two groups of patients with cervical cancer with and without metastatic lesions of the lymph nodes.

Conclusion. The study made it possible to form a list of potential molecular markers for low invasive diagnostics of cervical cancer in general (EP300, LAMP3, TORC2, FOXO3, TP53) and cervical cancer with metastatic lesions of regional lymph nodes (PIK3CA/DST, APC/PPARGC1A, ERBB3/HLA-A and LAMP3/MUC4).

Background. Recently, the incidence of mycoses in patients with a gastroenterological profile has grown due to an increase in the intensity of the impact on the human body of external factors that cause disturbances in the antimycotic defense system.

Aim. To study the adhesion of Candida albicans on buccal epitheliocytes in children with chronic gastroduodenitis.

Material and methods. 96 children (mean age 12.43±1.24 years) with recurrent respiratory diseases with morphologically proven chronic gastroduodenitis associated with Helicobacter pylori were examined. The adhesion of Candida, contamination of buccal epithelial cells with bacteria were studied. All children underwent paraclinical studies, instrumental methods of research, consultations of specialists were also prescribed. In the study of the adhesive reaction of C. albicans on buccal epitheliocytes, a Candida strain from the collection of the Federal Budgetary Institution of Science “Nizhny Novgorod Research Institute of Hygiene and Occupational Pathology” was used. 100 epitheliocytes were studied, the result was evaluated by the number of Candida in terms of 1 epitheliocyte. Registration of artificial colonization of buccal epithelial cells was carried out according to the method of D. Goldman and E. Goetzl (2003) modified by A.N. Mayansky. The children were divided into 2 groups: the main one — the detected growth of C. albicans over 1000 CFU/g, and the comparative one — the absence of excess growth of C. albicans. Statistical processing included the determination of the correlation coefficient, the arithmetic mean (M) and its standard error (m), differences in indicators according to Student's criteria (the level at p <0.05 was considered statistically significant).

Results. Harmonious proportional development was observed in 55.21% of children, microbiota imbalance was noted: bloating and rumbling along the colon, (p=0.0087), unstable stool (p=0.0241) and constipation (p=0.6092). The spectrum of comorbid pathology revealed the presence of allergic diseases (p=0.0048), up to 10 episodes of acute respiratory viral infection (p=0.1702), more than 10 episodes of acute respiratory viral infection (p=0.0105), adenoid vegetations (p=0.531), chronic pyelonephritis in the stage of clinical and laboratory remission (p=0.0216). Assessment of the intestinal microbial landscape showed a significant decrease in the content of bifidobacteria in the main group (p=0.0482), and lactobacilli were comparable in both groups (p=0.0839). In the comparison group, in 88.63% of cases, the indices of adhesion of C. albicans on buccal epitheliocytes were 6.37±0.46, in the main group — 11.86±0.74 (p=0.0362). A direct relationship between the parameters of artificial colonization of buccal epitheliocytes and the degree of microbiological changes in the intestine was found (r=0.58, p=0.0097).

Conclusion. The study of adhesion of Candida albicans on buccal epitheliocytes in children with chronic gastroduodenitis revealed a unidirectional shift in the quantitative content of the obligate oral and intestinal microbiota, which can be used as a screening for the homeostatic balance of the microbiota.

Background. Ovarian hyperstimulation syndrome is a fatal complication of unknown etiology. In connection with the increase in the frequency of this complication, it is necessary to identify prognostically significant markers to discover the risk of its development.

Aim. To analyze the frequency of ovarian hyperstimulation syndrome and search for the association of genes for differential growth factor 9, luteinizing hormone/horiogonadotropin receptor, and follicle-stimulating hormone receptor with different responses to ovulation stimulation.

Material and methods. A retrospective single-center cohort study of the frequency and clinical parameters of early ovarian hyperstimulation syndrome was carried out in 147 patients, the average age was 36.5 [33–38] years, who underwent an in vitro fertilization program in the period 2006–2021 in the Department of Assisted Reproductive Technologies of the Republican Medical Genetic Center in Ufa. The study of polymorphic loci of the genes for differential growth factor 9, luteinizing hormone/choriogonadotropin receptor, and follicle-stimulating hormone receptor was performed using TaqMan technology and real-time polymerase chain reaction. Deoxyribonucleic acid was isolated from peripheral blood samples. Statistical analysis was performed using the Kruskal–Wallis criteria, median test, Pearson's χ2 test, using the Statistica 12 software package.

Results. 7577 procedures of assisted reproductive technologies were performed. 147 (2.3%) cases of ovarian hyperstimulation syndrome were registered, 53 (0.8%) cases of moderate and severe degree, 84 (1.3%) cases of mild degree. The *CT genotype of the rs254286 polymorphic locus of the differential growth factor 9 gene was associated with a poor ovarian response 15 (0.75); (χ2=4.00; p=0.02; odds ratio 3.4; 95% confidence interval 1.13–10.27). The distribution of allele and genotype frequencies of the other studied genes did not differ statistically significantly in all the studied groups.

Conclusion. The frequency of ovarian hyperstimulation syndrome in the Republic of Bashkortostan was 2.3%; the *CT genotype of the rs254286 polymorphic locus of the differential growth factor 9 gene, as well as the level of anti-Müllerian hormone, can serve as markers of a poor response and ovarian hyperstimulation to ovulation stimulation.

Background. Accurate knowledge of the anatomy of all branches of peripheral nerves is necessary for successful neurotization and muscle plasty.

Aim. Anatomical substantiation of the use of branches of the thoracodorsal nerve in neurotization and muscle plasty.

Material and methods. The study was carried out on 121 preparations of the thoracodorsal nerve and the latissimus dorsi muscle from 105 cadavers of men and women aged 36–100 years. Variants of extra- and intramuscular branching of the thoracodorsal nerve were studied, a classification was developed and the possibilities of using it in reconstructive surgery were shown. A database was formed from the obtained indicators in the MS Excel 2012 program, and their processing was carried out using Statistica for Windows 12. The article presents only those indicators that do not follow the normal distribution according to the single-sample Shapiro–Wilk test. When describing the studied indicators, the median (Me) and quartile values (Q1, Q3) were determined.

Results. Anatomical layering and macro–microscopic dissection revealed 13 variants of extramuscular branching of the thoracodorsal nerve, which were combined into three groups. In the first group, which is 6.6%, the thoracodorsal nerve penetrates the latissimus dorsi muscle in one trunk and is divided into intramuscular branches of the first and second orders. In the second group (40.5%), the thoracodorsal nerve is divided into extramuscular branches of the first order, which penetrate into the latissimus dorsi muscle and branch into intramuscular branches of the first and second orders. In the third group (52.9%), the thoracodorsal nerve branches into extramuscular branches of the first and second orders, which are divided in the latissimus dorsi muscle into intramuscular branches of the first and second orders.

Conclusion. The thoracodorsal nerve is characterized by 13 variants of extramuscular and a wide variety of intramuscular branching, which is a factor that determines the tactics of nerve transposition and muscle plasty.

Background. It was believed that the functioning of the immune organs is photoindependent, but there are a number of works that testify to the effect of the photoperiod shift on the functioning of the immune organs. We hypothesized that the absence of a photoperiod under constant light or constant dark would affect the serotonergic system of the thymus gland, as well as the direction and intensity of melatonin exposure.

Aim. Study of serotonin-containing thymus cells under conditions of experimental desynchronosis and the role of the photoperiod in the realization of the effects of exogenous melatonin.

Material and methods. A comparative study of serotonin-containing thymus cells of 8-week-old Wistar rats, which were divided into 6 groups, was carried out. The first and second groups were kept under conditions of natural photoperiod, the third and fourth — in conditions of constant darkening, the fifth and sixth groups — in conditions of constant illumination within 4 weeks. Melatonin ad libitum at a concentration of 4 mg/l with water was received by animals of the second, fourth and sixth groups for 4 weeks. To determine the level of serotonin in cells, monoclonal antibodies to 5-HT were used. Conclusions about the serotonin content in the cells were made by measuring the optical density of the substance in 100 cells for each animal using the SigmaScan Pro5 program. Descriptive statistical processing was performed using the Statistica 17 program. The data obtained for each group of animals were averaged, the standard error and standard deviation were calculated.

Results. Artificial darkening reduced the serotonin content in 5-HT-immunoreactive cells of the cortical substance by 2.4 times (p=0.001), and constant illumination increased this indicator by 1.9 times (p=0.001). When melatonin was administered to animals kept in dark conditions for 4 weeks, the optical density of serotonin increased by 3.6 times (p <0.0001). Administration of melatonin to animals under constant illumination led to an increase in the optical density of serotonin in the cells of the diffuse endocrine system at the border of the cortex and medulla of the lobules by 1.5 times (p=0.002).

Conclusion. The cells of the diffuse endocrine system of the thymus are sensitive to changes in the photoperiod, and the introduction of melatonin has a multidirectional effect on the amount and optical density of serotonin under different light conditions.

Acute kidney injury is a common complication of acute coronary syndrome that aggravates its prognosis. The article presents the current criteria and stratification of the acute kidney injury severity, its place in the structure of cardiorenal syndromes, renal and cardiorenal continuums. The data on the frequency, severity and clinical variants of complications in acute coronary syndrome, myocardial infarction, unstable angina pectoris are presented. The risk factors for the development of acute kidney injury and its contrast-induced variant are described. The data on the significance of acute renal dysfunction in changing the trajectory of cardiovascular disease, worsening the immediate and long-term prognosis, the development and progression of chronic kidney disease, ischemic complications are presented. The effect of mechanical and pharmacological reperfusion on the incidence of acute kidney injury is described. Promising approaches to the diagnostics of acute kidney injury, including the significance of biomarkers and the problems associated with their use, are outlined. The article presents data on the role of radiopaque agents in the development of acute kidney injury, describes the difference between contrast-induced nephropathy, its contrast-associated, post-contrast and contrast-induced variants. The current approaches to the prevention and treatment of acute kidney injury from the point of view of various professional communities are outlined. Approaches to risk stratification and the possibility of using risk scales are described. The main measures for the prevention and treatment of acute kidney injury, depending on its severity, the place of renal replacement therapy are presented. The paper presents the current hydration regimens and describes the principles of their modification depending on the clinical characteristics of patients, proposed by experts from the Scientific Society of Nephrology of Russia and the consensus of the American College of Radiology, the US National Kidney Foundation.

Background. The assessment of medical technologies based on digital information is prompt and accurate, but it is currently not widely used, and analysis methods for this have not been developed, which became the basis for this study.

Aim. To economically evaluate the technologies of reperfusion therapy and dispensary observation in coronary heart disease using electronic data on medical care.

Material and methods. 586 patients with myocardial infarction treated in 2016 in two vascular centers of the Orenburg region were identified according to the registers-accounts of the compulsory health insurance fund. Among them were 349 patients with reperfusion therapy (main group) and 237 without it (control group). In the groups, the cost-effectiveness indicator, the cost of inpatient treatment of myocardial infarction and treatment in the postinfarction period were determined. Also, according to the registers-accounts for 2016, 17 225 patients with angina pectoris were identified. Among them, 13 208 patients, who applied to polyclinics for dispensary purposes during 2016–2017, and 4017 patients who did not apply, were registered — the main and control groups. Between groups, the total cost of outpatient, emergency, emergency hospital care and the cost-effectiveness ratio were compared. When processing the data, linear statistics methods and parametric comparison methods (Student's t-test and z-test) were used.

Results. The cost-effectiveness indicator in the group with reperfusion therapy was 425 879, without it — 643 069 rubles/unit, 1.5 times more in the control group. In the postinfarction period, the cost of treatment in the main group was lower than in the control group, 1223.66±19.04 and 1321.11±21.15 rubles, respectively, for outpatient care (p=0.001), 35 138.9±1299.85 and 51 189.6±4903.15 rubles for inpatient care (p=0.002), 4093.0±58.98 and 5428.6±52.95 rubles for an ambulance (p=0.001). The cost of angina treatment in the main group was 2.1 times less than in the control group, 6541.3±85.58 and 13 671.4±92.12 rubles (p=0.001). The cost-effectiveness indicator in the main group was 6867, in the control group it was 15 293 rubles/unit, 2.2 times more in the control group.

Conclusion. The use of reperfusion therapy and dispensary observation in coronary heart disease is economically feasible.

Background. The assessment of indirect economic costs associated with psoriasis is relevant due to the poor knowledge of the impact of the disease on key performance indicators, as well as the question of how the expansion of the pool of patients receiving genetically engineered biological drugs affects the indirect costs associated with the disease.

Aim. Evaluation of the indirect economic burden of psoriasis associated with missed work time and reduced performance in the actual presence at the workplace, as well as an assessment of the impact of changing the structure of therapy on indirect costs.

Material and methods. To calculate the indirect economic burden of psoriasis using the human capital method, two approaches were used: through an assessment of the impact on gross domestic product and through the use of the market value of working hours. A Bayesian network meta-analysis was performed to assess the impact of genetically engineered biologics on the indirect economic costs associated with psoriasis. Systematic search and selection of studies for network meta-analysis was performed using several databases (clinicaltrials.gov, Eu Clinical Trials, Pubmed, WHO ICTRP, medRxiv). Studies in patients with moderate to severe psoriasis treated with any genetically engineered biological drug were included.

Results. Indirect economic losses calculated through the assessment of the impact on the gross domestic product amounted to 10.2 billion rubles per year, and through the application of the market value of working time — 17.9 billion rubles per year per 100,000 patients with psoriasis in 2018 in Russian Federation. The genetically engineered biological drugs prescription can lead to a reduction in the annual indirect economic burden by 4.9 billion rubles and 8.6 billion rubles per 100,000 economically active patients with moderate and severe psoriasis, calculated through the assessment of the impact on the gross domestic product and through the application of the market value of working hours, respectively.

Conclusion. A decrease in the work productivity of patients with psoriasis leads to significant indirect costs, while an increase in the proportion of patients receiving genetically engineered biological drugs leads to a decrease in the indirect economic burden on the state and society as a whole.

Background. By decision of the Commission under the President of the Russian Federation for the Disabled, the Ministry of Labor of Russia was entrusted with monitoring the implementation of federal and regional action plans “road maps” to increase the accessibility of facilities to people with disabilities.

Aim. Monitoring the implementation by state authorities of the constituent entities of the Russian Federation of action plans (“road maps”) to increase the values of accessibility indicators for disabled people in healthcare facilities.

Material and methods. The indicators of accessibility for disabled people of facilities in the healthcare system based on the results of implementation of action plans by executive authorities of 85 constituent entities of the Russian Federation in the field of healthcare, obtained as a result of monitoring the achieved values in the indicators of accessibility for disabled people of facilities in 2019 and 2020, were analyzed. The availability of facilities was calculated on the basis of information from the state authorities of the constituent entities of the Russian Federation, prepared in accordance with the recommendations of the Ministry of Labor of Russia, using the analysis and generalization of the received materials, using the method of comparing absolute and relative indicators.

Results. The accessibility of medical organizations for the disabled is created in two ways — from the standpoint of “universal design” (inclusion of measures to organize the accessibility of facilities and services for the disabled when designing and building new facilities, as well as during reconstruction and major repairs) and using the principle of “reasonable accommodation” for existing facilities (before their overhaul and reconstruction). Ranking the indicators of the e150 domain (design, nature of design, construction and arrangement of buildings for public use) on the basis of a unified assessment scale of the International Classification of the Functioning of Disabilities and Health made it possible to identify regions of the Russian Federation with varying degrees of accessibility of healthcare facilities: absolutely accessible — in 10 (11.8%) regions of the country; with a significant level of accessibility — in 53 (62.4%) regions; with a moderate level of accessibility — in 8 (9.4%) regions; with a low or insignificant level of accessibility — in 9 (10.6%) regions of the Russian Federation; with a very low level of accessibility of healthcare facilities — in 5 (5.8%) regions of the Russian Federation, respectively.

Conclusion. According to the monitoring of the state of accessibility of facilities for the disabled in the healthcare sector in the constituent entities of the Russian Federation, the level of accessibility varied from 100% to 0.5%. The planned indicators of increasing the availability of facilities in the healthcare sector have reached 100% in 52 constituent entities of the Russian Federation.

The formation of posterior continuous capsulorhexis during cataract removal has traditionally been used to prevent visual axis opacification. According to the current literature, closure of the posterior capsulorhexis opening in our patient's case should not have developed in a period of 1 year, but it did in only one of the two eyes, despite the presence of equal conditions — the same surgeon, the same IOL (sharp-edged hydrophilic acrylic with hydrophobic coating), no concomitant eye diseases and somatic pathology. We conducted a literature search to find the cause of the unilateral development of this complication, as well as the optimal treatment method. The difference between two surgeries was in the diameter of the anterior and posterior capsulorhexis — on the right eye they were 0.5–1.0 mm larger than on the left eye, and the left eye has developed opacity, which required surgery. An effective and safe way of treating this problem is the capsulotomy using a 25 gauge-vitreotome. The clinical case shows the need for further research on this topic, as formation of posterior continuous capsulorhexis has a risk of intra- and postoperative complications, and more data should be considered to ensure that there is no such recurrence of opacity.

Background. It is noted that patients with xerostomia after sialometry may notice a decrease in xerostomia.

Aim. To study the effect of stimulated sialometry on the quantitative parameters of salivation, to explain the mechanism and reason for such an effect.

Material and methods. Controlled dynamic parotid sialometry was performed in 22 patients with xerostomia. Saliva was taken with a Lashley capsule (n=44) and a catheter (n=44), stimulated with 1% pilocarpine solution. At the 1st stage, the capsule was on the right, the catheter was on the left, a week later (2nd stage) the catheter was on the right, the capsule was on the left. The amount of saliva (ml) obtained with a capsule was taken as a control indicator, with a catheter — as a test indicator, the difference between them determined the rheological state of saliva. The study was approved by the ethical committee. The analysis of indicators in dynamics was carried out separately in the group with a capsule, separately in the group with a catheter. Significance of differences was assessed using Student's t-test. The results were considered significant at p ≤0.05.

Results. By the 2nd stage of the study, the sialometry values (ml) obtained using the capsule increased in 13 (69.1%) cases, did not change (n=2; 9.1%) or decreased (n=7; 31.8%) in 9 (40.9%) cases. By the 2nd stage of the study, sialometry values (ml) obtained using a catheter increased in 16 (72.7%) cases, did not change (n=2; 9.1%) or decreased (n=4; 18.2%) in 6 (27.3%) cases. The number of cases with increased secretion was significantly higher than other cases (t=3.385; p <0.001). The dynamics of the rheological state was as follows. A week later, in 7 (31.8%) cases, the indicators of the rheological state of saliva (the difference between the control and test sialometry values of 0.5 ml or more) returned to normal (the difference between the control and test sialometry values of 0.5 ml or less), in 2 (9.1%) cases, the norm was not achieved (t=1.947; p <0.05). Thus, sialometry in the short term can positively influence the secretory function of the salivary glands. However, parasympathetic stimulation of secretory function depletes the number of secretory granules in glandulocytes, which limits the effect of pilocarpine in reducing xerostomia.

Conclusion. Simultaneous sampling of saliva from the parotid glands with a Lashley capsule (control) and a catheter as a capillary viscometer makes it possible to determine the rheological properties of saliva; the improvement in the rheological properties of saliva after stimulated sialometry is associated with the use of the m-cholinomimetic pilocarpine.

The purpose of the article is to highlight the achievements of Kazan obstetricians and gynecologists in replacing general anesthesia with local infiltration anesthesia during obstetric and gynecological surgeries. In the period before the formation of anesthesiology and resuscitation into a separate branch of medicine with its equipment and medicines, local infiltration anesthesia with a tight creeping infiltrate, according to A.V. Vishnevsky, occupied a dominant position in surgery in the first half of the 20th century. In 1925 in Kazan, a student of Professor V.S. Gruzdev, Professor A.I. Timofeev, began to introduce it into the obstetric clinic and developed the technique of this type of anesthesia for gynecological abdominal surgeries. His work was continued by his colleagues, among whom was Professor P.V. Manenkov. He and the staff of the Department and Clinic of Obstetrics and Gynecology of the Kazan State Medical Institute performed more than 5,000 operations in obstetrics and gynecology, refined the technique of local anesthesia, improved technical equipment, expanded the range of indications for surgery under this type of anesthesia. Many years of clinical and laboratory developments, widely covered in the press, made it possible to perform up to 97% of operations in obstetrics and gynecology clinics in Kazan under local infiltration anesthesia.

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Flumignan RLG, Civile VT, Tinôco JD, Pascoal PIF, Areias LL, Matar CF, Tendal B, Trevisani VFM, Atallah ÁN, Nakano LCU. Anticoagulants for people hospitalized with COVID-19. Cochrane Database of Systematic Reviews. 2022. Issue 3. Art. No.: CD013739. DOI: 10.1002/14651858.CD013739.pub2.

This publication is a reprint of an article by Assoc. Prof. K.M. Yakhontov “A case of situs viscerum inversus”, published in the Kazan Medical Journal in 1915. 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: Yakhontov KM. A case of situs viscerum inversus. Kazan Medical Journal. 1915;15(4–6):208–210. DOI: 10.17816/kazmj48934.