Objective. To determine changes in coagulation balance and platelet aggregation in patient during the treatment of COVID-19 infection. Methods. A pilot non-randomized prospective clinical study of coagulation balance and platelet aggregation in patients admitted to the intensive care unit with acute respiratory distress syndrome and the diagnosis of COVID-19 (n=50) was performed. Out of 50 patients, 19 patients died, 31 patients were transferred to the therapeutic department. The study of indicators of coagulation balance and platelet aggregation was carried out once in 1-3 days starting from the patient’s admission to the hospital using coagulation analyzer ACL 10000 (Instrumentation Laboratory, USA) and platelet aggregation analyzer AP 2110 (ZAO “SOLAR”, Republic of Belarus). Results. In 45 (90%) patients with COVID-19, there is a significant increase of von Willebrand factor activity 350 (244.5; 480) %. There were no statistically significant differences in the level of von Willebrand factor activity among the deceased and surviving patients: 450.0 (338.8; 530.5) % in deceased patients and 342.0 (188.8; 480.0) % in survivors. At von Willebrand factor activity level of up to 250%, the mortality rate was 8.3%, at a level of 250-400% - 31.3%, at a level of more than 400% - 59.1%. Significantly above the normal range in most patients were fibrinogen (above normal in 68% of patients, 4.63 (3.49; 5.87) g/L) and D-dimers (above normal in 88% of patients, 0.73 (0,31; 1.4) μg/ml). Antithrombin III was below normal in 56% of patients (82 (67.1; 97.2) %). The degree of platelet aggregation has a strong direct correlation with the von Willebrand factor level: with an ADP inducer 0.3 μg/ml (R=0.71, р=0.003); ADP 0.6 μg/ml (R=0.74, р=0.0001); ADP 1.25 μg/ml (R=0.53, р=0.01). Conclusion. Analysis and evaluation of coagulation balance and platelet aggregation should be an integral part in the treatment of patients with COVID-19 infection. What this paper adds For the first time, the indicators of coagulation balance and platelet aggregation have been assessed in the treatment of COVID-19 infection. It has been found that 90% of patients had the increasedlevels ofvon Willebrand factor(VWF) - 350 (244.5; 480)%. In addition to an increase of von Willebrand factor activity, 56% of patients show a reduction of antithrombin III levels, and 88% and 68% of patients have an increasing D-dimers and fibrinogen, respectively. Analysis and assessment of coagulation balance and platelet aggregation indicators should be integral components of the treatment of patients with COVID-19 infection.

Objective. To establish pathomorphologic peculiarities of palmar aponeurosis in the patients with Dupuytren’s contracture and concomitant virus hepatitis B and C. Methods. The data analysis of histomorphometric studies of the operation samples of 122 patients with Dupuytren’s contracture («Control» group, n=100) and Dupuytren’s contracture with virus hepatitis B and C («Hepatitis» group, n=22) were analyzed. Results. In patients of the «Hepatitis» group, the content of adiposed tissue in the palmar aponeurosis was 40.9% less (p <0.01) than in the «Control» group, and the content of dense connective tissue was 18.9% higher (p <0, 05). In all patients, arteries with the diameter up to 150 µm prevailed in the palmar aponeurosis, but in the «Hepatitis» group their percentage was reduced by 20%, with higher proportions of vessels with the diameter of 150-450 µm and the absence or recalibration of the largest arteries. In the «Control» group, the arteries had diameters from 50 to 660 µm, in the «Hepatitis» group they did not exceed 370 µm. Vessels less than 300 µm in diameter in both groups had comparable values of the Kernogan’s index. Arteries with a diameter of more than 300 microns in the «Hepatitis» group had higher values of the Kernogan’s index, which indicated a low conductance capacity compared to the vessels in the «Control» group. Most of the nerve trunks of the palmar aponeurosis in the patients of «Hepatitis» group showed signs of necrobiotic changes, i.e. fibrotic or swollen perineurium, withinflammatory cell infiltration, sometimes lost lamellar structure, and nerve fibers with signs of Wallerian degeneration. Conclusion. Obtained histomorphometric data of the tissue composition of palmar fascial fibromatosis, less amount of adiposed tissue and higher amount of dense connective one and more pronounced disorder of hemodynamics and innervation of the palmar aponeurosis in the group with concomitant virus hepatitis indicate significant effect of the liver pathology on the progression of the disease. What this paper adds For the first time, the pathomorphological features of the palmar aponeurosis have been studied in 122 patients with Dupuytren’s contracture and concomitant viral hepatitis B and C.It has been found that in patients with Dupuytren’s contracture and hepatitis in the palmar aponeurosis, the amount of adiposed tissue is reduced and the amount of dense connective tissue is increased; hemodynamic and innervation disorders are more pronounced.

Objective. To develop a method for additional and differential diagnosis of acute infectious lung destruction (AILD) based on angiopulmonography with the nitroglycerin test. Methods. Angiopulmonography with the nitroglycerin test was used in 10 patients with suppurative diseasesof thelung and pleura for additional and differential diagnosis of AILD The method was used in such situations when chest computed tomography did not allow to determine unambiguously the presence and / or prevalence of necrosis of the lung parenchyma. Results. In 3 patients with the lung abscess, a clear restriction of the decay cavity was registered with the preservation of the main blood flow and weakening of the parenchymal phase of the blood circulation along the periphery of the destructive area. During the nitroglycerin test performance there was no change in the filling of the microvascular bed with contrast along the periphery of the decay cavity, which made it possible to determine the presence of parietal sequesters. According to the results of the study, the lung gangrene was diagnosed in 6 patients. At the same time, two variants of circulatory disorders were noted: the first - with preservation of the blood flow through the main vessels and with the absence of a parenchymal phase in the lesion focus, the second - with the violation of the main blood flow. In the affected area no change in blood flow was observed after the nitroglycerin test performance. Similar results of the study indicated the development of necrosis of the pulmonary parenchyma, which was subsequently confirmed during the operations performed. In the site of inflammatory infiltration of the pulmonary parenchyma with preserved main blood flow, the depletion of the parenchymal phase of blood circulation was determined, but after the nitroglycerin test, a pronounced enrichment of the vascular architecture to the parenchymal phase in the pneumonia affecting part of the lung was noted. Conclusion. It has been established that AILD is characterized by irreversible changes in the vascular bed of the lung parenchyma in the lesion focus. Angiopulmonography with the nitroglycerin test is considered to be an additional highly informative method improving the early and differential diagnosis of AILD in difficult clinical situations. What this paper adds It has been found out that during angiopulmonography the areas of pulmonary necrosis are characterized by the absence of a vascular pattern with or without disturbance of the blood flow through the segmental arteries. At the same time, in contrast to the foci of pneumonia, the nitroglycerin test is not accompanied by an evaluation of the filling of the pulmonary vascular bed in the affected area, i.e. blood supply disorders are irreversible. Thus, based on an assessment of the nature and reversibility of the blood flow disturbances in the affected lung, it is possible to carry out differential diagnosis of the early stages of acute infectious lung destruction (AILD) and pneumonia.

Objective. To assess the presence of specific markers in patients with thymus-independent and thymus-dependent myasthenia gravis for choosing treatment tactics. Methods. The presence of specific markers was assessed in 138 patients with thymus-independent (M - myasthenia gravis without thymus changes) and thymus-dependent (MH - myasthenia gravis with thymus hyperplasia, MT - myasthenia gravis with thymoma). The method ELISA (the content of antibodies to subunits 1 and 7 nAChR in blood serum, to 7 nAChR subunit in thymocyte mitochondria, a detectablelevel of antinuclear antibody(ANA), immunofluorescence (ANA glow) and flow cytometry (expression of CD14+CD11c+and CD14 + HLA-DR +) has been used. Results. The relationship between the clinical phenotypes of myasthenia gravis and the variants of HLA diplotypes was revealed: in young patients with thymus-independent myasthenia gravis (M), a high heterogeneity of the genotypic markers HLA-DR (DR1, DR2, DR3, DR5, DR7) was detected. Patients with thymus-dependent myasthenia (MT) had only the HLA DR2 and HLA DR7 diplo- and haplotypes. The presence of HLA DR2 and HLA DR7 haplotypes in some young patients with progressive thymus-independent myasthenia gravis (M) led to the development of myasthenia gravis with thymoma (MT) in the elderly people. The pathogenic role also belongs to infection (СMV, EBV, HBV, HCV, HSV-1, HSV-2, HHV-6, mycoplasma) and food intolerance (IgE and IgG4) in the development and progression of myasthenia gravis. A four-fold prevalence of α7 subunit nicotinic acetylcholine receptors on the thymocyte mitochondria as an additional targets of autoimmune aggression in myasthenia gravis was determined. Specific antinuclear antibodies to centromere chromosome proteins were visualized in the elderly people with thymoma. Conclusion. The prognosis of the myasthenia gravis progression and the development of remission can be made using genomic (the presence of certain HLA-DR haplotypes) and molecular (ANA antibodies to centromere chromosome proteins, expression of CD20+, CD14+CD11c+, CD14+HLA-DR+) biomarkers, that can be used for the choice of treatment tactics. What this paper adds The change of complex biomarkers has been firstly studied for prognosis and choice of complex treatment tactics for young patients with progressive thymus-independent myasthenia gravis and for the elderly patients with thymus-dependent myasthenia gravis. In the presence of certain HLA-DR haplotypes, antinuclear antibodies to centromere chromosome proteins, an increasing expression of CD20+, CD14+CD11c+ and CD14+HLADR+ in some young patients with thymus-independent myasthenia gravis, analogically to biomarkers in thymus-dependent myasthenia gravis with thymoma, to perform a thymectomy is of high dangerous. potentialrisksof the procedure.

Objective. Assessment of apoptosis proteins Bcl-2 and Bax indices before and after the open vascular reconstructions and X-ray endovascular interventions in patients with the peripheral atherosclerosis of the arteries of the lower extremities. Methods. The study included patients (n=40) with the peripheral atherosclerosis of the lower extremities arteries (stage III-IV) disease who underwent open surgery - group A, and patients (n=40) who underwent endovascular interventions - group B. Two apoptosis proteins were analyzed in blood serum: Bax and Bcl-2 initially before surgery, on the 1<sup>st</sup> day and after 1 month. The reference values of the studied parameters were determined in 40 healthy volunteers. Results. Initial Bax protein index - 27.1 ng / ml (р<0,001) were elevated in patients of group A and reduced Bax protein - 4.4 ng / ml (p=0.00008) in patients of group B compared with indices of healthy volunteers (16.5 ng / ml, 5.3 ng / ml, respectively). On the 1<sup>st</sup> day after the interventions in the patients of the operative groups there was an increasing tendency for Bax index to 35.6 ng / ml (p<0.001) - group A, to 25.6 ng/ml (p<0.001) - group B. By the end of 1<sup>st</sup> month, Bax was increased to 28 ng/ml (p<0.001) in patients of group A and Bcl-2 was reduced to 3.0 ng / ml (p=0.039) compared to the initial indices; in patients of group B, only protein Bax - 23.9 ng / ml (p<0.001) was increased. Conclusion. Open and endovascular intervention on the arteries of the lower extremities leads to the activation of the pro-apoptotic protein Bax on the 1<sup>st</sup> day after surgery. In the postoperative period the open reconstruction leads to an evaluation of the pro-apoptotic potential in comparison with endovascular intervention in the form of increasing Bax protein and reducing Bcl-2 by the end of the first month. What this paper adds The dynamics of changes markers Bcl-2 and Bax in apoptosis at different periods after surgery has been firstly studied in patients with atherosclerosis of peripheral arteries (stage III-IV) of the lower extremities. It has been found that the open surgery leads to a sufficient evaluation of the proapoptotic potential, i.e. the increasing Bax protein index on the 1<sup>st</sup> day and by the end of 1<sup>st</sup> month with reducing Bcl-2 index by the end of 1<sup>st</sup> month compared with the endovascular intervention.

Objective. To evaluate the effectiveness of application radio-wave surgery device “Surgitron” and high-frequency electrosurgery devices “ERBE ICC 200”, “EFA”, “KLS Martin” for treatment of patients with combined anorectal pathology. Methods. The treatment results of patients (n=635) with a combined anorectal pathology have been analyzed. The use of the «Surgitron» radio-wave surgery apparatus 245 (38.6%) patients were operated on, the «ERBE ICC 200» high-frequency electrosurgery apparatus - 169 (26.6%) patients, the «EFA» high-frequency electrosurgery apparatus - 114 (17.9 %) patients, «KLS Martin» high-frequency electrosurgery apparatus - 107 (16.9%) patients. After those surgical interventions to assess the effectiveness of the abovementioned current technologies, patients were conducted a morphological examinationto determine the depth of the necrosis of tissues. Results. According to the study results it has been established that application of the “Surgitron” radio-wave surgery device, “ERBE ICC 200” high-frequency electrosurgical devices “EFA”, “KLS Martin” reduces duration of the operation up to 15-30 min, the volume of bleeding - up to 10-30 ml, need in narcotic drugs - up to 1-4 ml, period of hospitalization - up to 3-6 days. Using these technologies prevented the formation of anal strictures and scar pararectal deformations due to the insignificant depth of tissue necrosis (the depth 0,036 -l 0,453 mm), ensuring the cosmetic effect of combined operations. Conclusion. Application of the “Surgitron” radio-wave surgery device and “ERBE ICC 200” high-frequency electrosurgical devices, “EFA”, “KLS Martin” for treatment of patients with combined anorectal pathology reduces the operation duration, volume of bleeding and intensity of the postoperative pain. Use of these current technologies promotes the formation of a delicate elastic scar causing faster healing of postoperative wounds and improving the terms of patients’ rehabilitation. What this paper adds A comparative evaluation of the effectiveness of using high-frequency electrosurgery devices “ERBEICC 200”, “EFA”, “KLSMartin” and radio-wave surgery device “Surgitron” for treatment of patients with combined anorectal pathology has been firstly made; also a degree of pathomorphological changes in tissues of anal canal and rectum after using the aforementioned current technologies has been studied to assess the effectiveness of their use for treatment of combined anorectal pathology.

The creation and implementation of new methods of study and local wound care occur in stages: in vitro, in vivo and clinical trials. The fundamental point of this process is to study the effect of the proposed agent on the experimental wound healing models of laboratory animals taking into consideration the common healing phases of course and similarity of animal wound healing with human one. At the initial stage the main problems faced by the researcher include the selection of the optimal experimental animal, while animal models are suitable for many skindisorders. The lack of strong evidence and relevant guidelines regarding the most appropriate form of local-wound care in literature and the fragmentation of the available information lead to the fact that during the development of the experiment, the scientists spend time, resources and operate on an additional number of animals. This article summarizes the literature data on the applied modeling methods as for the most common and rare types of skin wounds including burns and trophic ulcers in various laboratory animals. Those who prepared the experiment shouldhavepaidcloserattentionto thefeatures of creating such wounds and nuances so as the proven techniques of their creation in various species are shown. Variants of the course and prospects for the development of this area of surgery are presented.

Objective. To study the current Russian and foreign literature dedicated to the problem of application of organometallic compounds immobilized on drugdelivery in the treatment of purulent-inflammatory disease of the skin and soft tissues. Methods. The modern Russian and foreign literature, available in the Pubmed, Medline, Springer, Scopus, e-LIBRARY databases were reviewed according to the problems of purulent-inflammatory diseases, skin and soft tissue infections, the integrated approach to the treatment of purulent-inflammatory diseases, synthesis, immobilized organometallic compounds. Results. The observational study of the specificrecent achievements in the modification of antimicrobial biomaterials is presented. Metal ions havea broad range of antimicrobial activity (especially on proliferation and remodeling), possess by bacteriostatic and bactericidal effect, demonstrate multiple inhibitory effects against bacterial strains and havebeen proveneffectivein improvingwoundhealing in all its phases. Natural products and especially biologically active metals such as silver, copper, zinc and germanium, are believed to be an alternative for the development of perspective biomaterials with antimicrobial properties. In recent years, new approach for the production and application of therapeutic and diagnostic drugs based on the immobilization or grafting of drugsubstances on polymer carriers has been developed. At present, namely the immobilized compounds that have opened the way to the creation of prolonged-action drugs with low toxicity and allergenicity. Conclusion. Template synthesis of new organometallic drug compounds is considered to be a promising direction in the wound infection treatment, which requires further experimental and clinical study.

Objective. To prove the safety and efficacy of distal radial artery (DRA) puncture for endovascular interventions versus the traditional forearm radial artery (RA) puncture site by comparing immediate and long-term results. Methods. In 2017, a multicenter, open, randomized (1:1) study TENDERA (Comparison between Traditional Entry Point and Distal Puncture of Radial Artery) was started. During 2 years, 520 patients were included, mean age 63.4±10.0 years. The observation group (DRA puncture) included 271 patients, the comparison group (RA puncture) - 249 patients. The study included both stable patients and those with NSTEMI: the observation group - 39 (14.4%), the comparison group - 34 (13.7%), p=0.809. The primary endpoint is immediate (hospital) or late radial thrombosis. Secondary endpoints are: 1 - composite point, complications from the access artery; 2 - puncture parameters. Results. The average difference in the diameters of the RA and DRA was 0.3 mm and 0.4 mm, in some patients the DRA diameter corresponded to the RA or even exceeded it. The diameter of RA and DRA in men and women significantly differs, 2.65±0.44 mm and 2.36±0.36 mm (p=0.001), 2.31±0.39 mm and 2.13±0.38 mm (p=0.001). Technical success of DRA access requre the number of attempts. 94.1% - the percentage of successful cardiac catheterization performed through the distal radial artery approach, which is significantly less than via RA - 100% (p<0.001). In the observation group, significantly fewer rebleedings and rehemostasis were occured. In the long-term period, there were registered outstandingly more hematomas in the observation group at the time of discharge and after 1 week. Conclusion. Intermediate analysis of the results of the TENDERA study shows that there is no significant difference in the primary endpoint, but the number of complications in the observation group associated with the puncture markedly - hematoma more than 5 cm to the day of discharge and after 7 days. What this paper adds Intermediate results of the first multicenter open randomized (1:1) study devoted to the comparison of distal puncture of the radial artery versus the traditional entry point of puncture of the radial artery on the forearm during the endovascular interventions have been presented. A significant reduction of the number of local complications has been revealed in the group of distal puncture of the radial artery and the absence of differences according to the primary endpoint: early and late radial artery thrombosis.