[Results of a clinical and experimental study of the safety and efficacy of Cytoflavin in combination with reperfusion therapy for ischemic stroke]. / Rezul'taty kliniko-eksperimental'nogo izucheniya bezopasnosti i effektivnosti primeneniya Tsitoflavina v sochetanii s reperfuzionnoi terapiei ishemicheskogo insul'ta.

OBJECTIVE: To study the efficacy and safety of Cytoflavin in combination with thrombolytic therapy. MATERIAL AND METHODS: At the first preclinical stage, the effect of Cytoflavin, solution for intravenous administration, on the fibrinolytic activity of alteplase (Actilyse) was studied in vitro. At the second, clinical stage, the safety and efficacy of Cytoflavin treatment, initiated within in the first 24 hours from the stroke onset and continued for 10 days, was evaluated in patients with acute stroke who received reperfusion therapy. At the clinical stage of the study, 200 patients were examined: 100 subjects of the main group who received reperfusion therapy in combination with Cytoflavin; 100 control subjects who received reperfusion therapy in combination with other drugs from the neuroprotective group as part of routine clinical practice. RESULTS: The preclinical study has demonstrated that alteplase in the studied concentrations debulks the mass of a thrombus by 2131%. There were no statistically significant differences in the reduction of thrombus weight with addition of Cytoflavin at various concentrations combined with alteplase to the incubation medium. The addition of Cytoflavin to the incubation medium with alteplase had no effect on the concentration of D-dimer in the rat's plasma. In the clinical study, there were no statistically significant differences in the frequencies of intracranial hemorrhages of various types between the study groups. In the multivariable analysis, significant predictors of intracranial hemorrhage were baseline NIHSS score, systolic blood pressure, history of diabetes and anticoagulant use, baseline CT ASPECTS score, but not the treatment group. CONCLUSION: The use of Cytoflavin in combination with thrombolytic therapy is safe. Up-to-date treatment of stroke which includes timely reperfusion and neurometabolic support of recovery leads to the rapid manifest regression of the neurological deficit and to the improvement in functioning and activity of patients with cerebral infarction.

Personalized Medicine in Brain Gliomas: Targeted Therapy, Patient-Derived Tumor Models (Review).

Gliomas are the most common type of primary malignant brain tumors. The choice of treatments for these tumors was quite limited for many years, and therapy results generally remain still unsatisfactory. Recently, a significant breakthrough in the treatment of many forms of cancer occurred when personalized targeted therapies were introduced which inhibit tumor growth by affecting a specific molecular target. Another trend gaining popularity in oncology is the creation of patient-derived tumor models which can be used for drug screening to select the optimal therapy regimen. Molecular and genetic mechanisms of brain gliomas growth are considered, consisting of individual components which could potentially be exposed to targeted drugs. The results of the literature review show a higher efficacy of the personalized approach to the treatment of individual patients compared to the use of standard therapies. However, many unresolved issues remain in the area of predicting the effectiveness of a particular drug therapy regimen. The main hopes in solving this issue are set on the use of patient-derived tumor models, which can be used in one-stage testing of a wide range of antitumor drugs.

Evaluation of the potential pathogenicity of microorganisms associated with urinary calculi.

Due to the prevalence of postoperative complications in the treatment of urolithiasis, the study of the contamination of urinary calculi and the potential pathogenicity of isolated bacteria is of great importance in laboratory diagnostic practice. It has been shown that uropathogenic bacteria are found in the composition of urinary stones in 65±7.1% of cases, mainly representatives of the Enterobacteriaceae and Staphylococcaceae families. Bacteria of the generas Escherichia, Enterococcus, Staphylococcus were most frequently detected. The analysis of biofilm activity and antibiotic resistance in 50 uropathogenic strains was carried out. It was shown that all the studied strains were resistant to at least two tested drugs, and the average value of the multiple resistance index was 0.51. When cultured on nutrient agar with Congo red, it was shown that more than half of the tested strains have high biofilm activity and about 80% potential for biofilm formation. The greatest biofilm activity was observed in bacteria of the generas Escherichia, Klebsiella, Enterobacter, Staphylococcus.

[Retrospective analysis of endovascular thrombectomy in anterior cerebral circulation out of 6-hours «therapeutic window¼ in regional vascular centers of Saint-Petersburg]. / Retrospektivnyi analiz rezul'tatov vnutrisosudistoi tromboembolektomii v karotidnom basseine za predelami 6-chasovogo «terapevticheskogo okna¼ v regional'nykh sosudistykh tsentrakh Sankt-Peterburga.

OBJECTIVE: Based on a retrospective analysis, to evaluate technical results and functional outcomes at discharge after endovascular thrombectomy (EVT) in anterior circulation out of 6-hours «therapeutic window¼ in patients with stroke. MATERIAL AND METHODS: The retrospective analysis of EVT in 594 acute stroke patients (303 male, 291 female, median age 69 years) with the anterior circulation large vessel occlusion was performed. EVT was carried out before 6 hrs in 550, later in 44 patients. Time to artery puncture was defined as a cut point. Patients were included in the study if they met the criterion for 0-6 hours «therapeutic window¼. RESULTS: No significant differences in functional outcomes at discharge assessed with the Rankin scale (mRs 0-2 29.8% and 20.5% p<0.19; mRs 3-5 38.7% and 38.6% p<0.99; mRs 6 31.5% and 40.9% p<0.2) and the rates of intracranial haemorrhage, haemorrhagic transformation and symptomatic haemorrhagic transformation (4% and 0% p<0.17; 20.9% and 29.5% p<0.49; 10.1% and 11.4% p<0.78) were observed in patients exposed to EVT before 6 hrs and later. CONCLUSION: EVT in anterior circulation stroke over 6 hrs «therapeutic window¼ based on the criterion for 0-6 hrs provides comparable functional outcomes at discharge without the increase in the frequency of intracranial haemorrhages, haemorrhagic and symptomatic haemorrhagic transformations.

[Outcomes of endovascular thrombectomy for acute stroke in regional vascular centers of a metropolis (St.-Petersburg)]. / Rezul'taty lecheniia ishemicheskogo insul'ta s primeneniem vnutrisosudistoi tromboémboléktomii v usloviiakh regional'nykh sosudistykh tsentrov v megapolise (Sankt-Peterburg).

AIM: To assess technical results and close functional outcomes of acute ischemic stroke (AIS) in patients treated with endovascular thrombecomy (ET) in regional vascular centers (RVC) of St-Petersburg. MATERIAL AND METHODS: Retrospective analysis of 183 patients with AIS, including 143 patients with AIS due to a large intracranial vessel occlusion in anterior (AC) and 25 patients in posterior cerebral (PC) circulation, 15 with isolated extracranial carotid occlusion treated in 6 RVC in 2017 was performed. All patients underwent ET. RESULTS AND CONCLUSION: Effective reperfusion (mTICI 2b-3) was achieved in 71.5% (71.3% AC, 72% PC). On discharge, 35,7% patients had good (mRs 0-2) functional outcome (37.1% AC, 28% PC). The incidence of symptomatic intracranial hemorrhage (according to ECASS II criteria) was 10.7% (9.1% AC, 20% PC), the mortality was 29.2% (22.4% AC, 68% PC).). The results of our study show the possibility of effective and safe application of ET in patients with AIS in the anterior and posterior cerebral circulation in regional vascular centers of St.-Petersburg.

[Clinical diagnosis of proximal occlusion of a major cerebral artery in the very early stage of ischemic stroke]. / Klinicheskaia diagnostika proksimal'noi okkliuzii magistral'noi tserebral'noi arterii v ostreishem periode ishemicheskogo insul'ta.

AIM: To find clinical criteria applied in the first hours of disease for the identification of severe ischemic stroke caused by an occlusion of proximal major arteries. MATERIAL AND METHODS: The authors have analyzed 133 medical histories of patients with the diagnosis of acute cerebral blood circulation disorder admitted in the first 6 h from onset. All patients underwent CT-angiography or digital subtraction angiography. Occlusion of the inner carotid artery, occlusion of M1-segment of the middle cerebral artery and occlusion of a major artery were considered as proximal occlusion of major cerebral arteries. Neurological status was assessed by the signs of proximal arterial occlusion (PAO). RESULTS AND CONCLUSION: Checking of 5 PAO symptoms allows the prediction of occlusion location in approximately 80% of cases. Presence of ≥3 out of 5 symptoms is characterized by 70% sensitivity and 90% specificity with regard to the occlusion of the inner carotid artery, M1-segment of the middle cerebral artery and/or a major artery. Predictive value of this model should be verified in a prospective study.

[EFFICACY OF CYTOFLAVIN IN COMPLEX TREATMENT OF DIABETIC FOOT SYNDROME].

The study involved 97 patients with severe diabetic foot syndrome (DFS) subcompensated type 2 diabetes. All patients were available mediacalcification foot and lower leg arteries of different severity. Depending on the treatment, all patients were divided into 2 groups by stratified randomization. The І group received standard therapy, which is indicated for the DFS. A ІІ group of patients additionally received basic therapy drug Cytoflavin 10 ml 0,9% NaCl 200 ml for 10 days, followed by transfer to tablet form Cytoflavin 2 tablets 2 times per day orally for one month. We noted a positive trend of treatment of patients who, in addition to standard therapy received the drug Cytoflavin. Thus, the use of complex surgical treatment of patients with mixed form of DFS Cytoflavin reduces the severity of distal polyneuropathy, improves oxygenation of tissues and restores the enzyme activity of antioxidant system, that manifested neuroprotective, antioxidant and anti-hypoxic effects of drugs, which substantiates the indications for its use in the this pathology.

[THE CLINICAL LABORATORY MARKERS OF ATHEROSCLEROSIS IN PATIENTS WITH ATHEROTHROMBOTIC STROKE].

The laboratory biomarkers can effect on choice of tactics of treatment in patients with atherosclerotic stenosis ofcarotids and high risk of stroke. However, nowadays there is no established laboratory criteria of significant atherosclerotic affection of internal carotid. The purpose of study was to investigate informativeness of biomarkers of atherosclerosis in clinical molecuIar panel of expertise system of determining risk of stroke in patients with significant stenosis of carotid. The study included patients with 50-90% atherosclerotic stenosis of internal carotid in acute period of atherothrombotic stroke or transitory ischemic attack (group 1), patients with stable 50-90% atherosclerotic stenosis of inner carotid having no vascular events during 30 days before engaging into study (group II) and group of healthy volunteers without atherosclerosis of inner carotid. The examination of patients included anamnesis collection, evaluation of neurological status, analysis of serum level of biomarkers of atherosclerosis (lipoprotein-associatedphospholipase A2 (LP-PL A2), serum protein A associated with pregnancy (PA PP-A), lipoprotein (a) (LP(a)), asymmetric dimethylarginine (ADMA), C-reactive protein detected by highly sensitive technique (hsCRP) and lipid spectrum of blood) using enzyme-linked immunosorbent assay, duplex ultrasound scanning of brachiocephalic arteries. The stroke risk factors of other etiology were chosen as exclusion criteria except atherothrombotic one. The Mann-Whitney and Kruskal-Wallis tests were applied to establish group differences. The Data Mining techniques were applied to establish patterns of analyzing sample. Out of 356 examined patients, 30 patients of group 1, 51 patients of group II and 16 healthy volunteers were included in the study. All patients were comparable by gender and age (50-80 years). The serum level of hsCRP and ADMA in the group of patients of acutest period of ischemic stroke was significantly higher than in groups of patients with stable stenosis and healthy volunteers (p < 0.05). The comparison between three groups established no statistically significant differences in serum concentration of PAPP-A, LP-PL A2 and LP(a). The ADMA, hsCRP and PAPP-A can be recommended for including into clinical molecular panel for personalized diagnostic of causes of stroke along with clinical anamnestic data. The serum level of ADMA and hsCRP significantly increases in acute period of atherothrombotic stroke. The analysis of levels of ADMA, hsCR and PPAPP-A interpreted with regard to clinical anamnestic data can be proposed for enhancing quality of diagnostic of causes of stroke.

[Clinical use of chondroitin sulfate in patients with osteoarthritis in geriatric practice].

The article presents the results of prospective longitudinal study. The aim of the study was to investigate influence of complex therapy with chondroitin sulfate on pain and functional disorders in elderly patients with knee osteoarthritis. The study shows sufficient decreasing of pain, stiffness and functional disorders with complex therapy with chondroitin sulfate in comparison with nonsteroidal anti-inflammatory drugs (NSAID) by the second month of therapy with stable effect the next 2 months. All patients decrease their NSAID intake by the end of the study. Satisfaction of complex therapy was high according to patient's and physician's opinion.

[Carcinosarcomas of the uterus: molecular-genetic and morphological features].

13 cases of uterine carcinosarcomas have been studied by molecular-genetic method. The impairment of some genes (K-RAS gene in the first exon, TP53 in the 5th-9th exons, PTEN in the 5th and 8th exons) has been found out. The loss of heterozygosity of TP53 gene in epithelium and mesenchyme of the uterus has been detected. According to the estimation of impairment the studied tumors was divided into monoclonal and biclonal ones. This stratification could be use as prognostic criteria of uterine carcinosarcomas clinical presentation.

[Carcinosarcoma of the corpus uteri: potential of p53, PTEN and COX-2 expression for survival].

Clinico-morphological and immunohistochemical examinations were carried out in 46 patients with carcinocarcinoma of the corpus uteri to evaluate p53, PTEN and cyclooxygenase-2 (COX-2) expression in mesenchymal and epithelial cells of tumor. p53 expression in the epithelium and that of COX-2 in both compartments appeared to be unfavorable prognosticators of survival while that of PTEN is a lesser one in significance.

Melatonin and metformin inhibit skin carcinogenesis and lipid peroxidation induced by benz(a)pyrene in female mice.

Outbred female SHR mice (n=200) were divided at random into 4 groups, 50 per group. Benz(a)pyrene solution in acetone was applied onto a skin site on the back during 26 weeks. In parallel, the animals received melatonin, metformin, or both. Melatonin, metformin, and their combination promoted significant reduction of the number and size of skin tumors. In mice receiving no therapy, benz(a)pyrene applications increased the concentrations of malonic dialdehyde in the serum and skin tumor tissue in comparison with the concentrations in the sera and skin of intact mice. Melatonin, metformin, and their combination normalized LPO level.

[Some indices of lipids metabolism and antioxidant profile in geriatric patients with arterial hypertension].

Arterial hypertension contributes essentially into development of chronic heart failure and chronic ischemia of the brain, which results in social dependence of geriatric patients. One of the important factors in the development of arterial hypertension is the state of lipids peroxidation. Misbalance among the products of lipids peroxidation and components of antioxidation defense system revealed in cardiovascular diseases (mainly in arterial hypertension and heart failure) promotes progress of these diseases and premature aging of an organism. The therapy aimed at normalization of the oxidative profile of the patients with arterial hypertension should include prolonged beta-blockers, ACE inhibitors, calcium antagonists, statines and polyvitamin complexes with vitamins A and E.

[Investigation of biological features of uterine carcinosarcoma].

Results of clinico-morphological and immunohistochemical studies of 44 cases of carcinosarcoma of the uterus are presented in an attempt to provide pathogenetic rationale for prognosticators of the disease. Immunohistochemical reactions were used to evaluate the expression of genes and mediators p53 and PTEN and cyclooxigenase (COX-2) in cells of mesenchyme and epithelium of tumor to gauge the influence of either component on its biological behavior. All patients were divided into two groups depending on whether they revealed expression of p53, PTEN and cyclooxigenase or not. The end results--overall survival and complete remission duration--were compared in both groups. No dominance of either component of carcinosarcoma was established.

Disappearing hyperdense middle cerebral artery sign in ischaemic stroke patients treated with intravenous thrombolysis: clinical course and prognostic significance.

BACKGROUND AND PURPOSE: Hyperdense middle cerebral artery sign (HMCAS) on CT is a well known indication of thromboembolic arterial occlusion. Its disappearance after thrombolytic therapy is poorly described. Taking the rate of HMCAS disappearance as a surrogate for MCA recanalisation, its prognostic value after intravenous thrombolysis was examined. METHODS: 1905 stroke patients with HMCAS on admission CT scan in the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) were studied. On follow-up CT scans 22-36 h after thrombolysis, HMCAS disappeared in 831 cases, persisted in 788 and was uncertain in 122; follow-up CT was not done in 164 cases. RESULTS: Patients whose HMCAS disappeared were younger (median age 67 years vs 69 years for persistent; p = 0.03), with milder stroke (admission National Institute of Health Stroke Scale (NIHSS) score was 16 vs 17; p<0.005) and were less likely to have early infarct signs on admission CT (26% vs 33%; p<0.005). Patients with disappearing HMCAS were more likely to have early improvement in NIHSS score (median improvement 2 vs 0 at 2 h; 4 vs 1 at 24 h), be independent at 3 months (42% vs 19%), with fewer deaths (15% vs 30%) than those with persistent HMCAS. In multivariate analysis, HMCAS disappearance independently predicted functional independence and survival. Early NIHSS improvement independently predicted HMCAS disappearance. CONCLUSIONS: HMCAS disappeared after intravenous thrombolysis in about half of cases and these patients had twice as good outcomes compared with those with persistent HMCAS. The prognosis in patients with MCA occlusion that persists after intravenous thrombolysis is poor, which may indicate the need for an alternative treatment approach to this subgroup.

[Diagnosis of germinogenic ovarian tumors in girls]. / Diagnostika germinogennykh opukholei iaichnikov u devochek.

The paper covers the problems of diagnosis of germinogenic ovarian tumors in girls, which make up as high as 80% of all malignant ovarian tumors. For timely diagnosis, it is necessary to take into account clinical data, the levels of tumor markers (alpha-fetoprotein, chorionic gonadotropin) and ultrasound findings. This all is rather sufficient to verify the diagnosis of ovarian tumor lesions. Other additional studies are aimed at establishing where the process extends.

[Time course of changes in tuberculosis epidemiological parameters in Iakutia over 12 years (1983-1994)]. / Dinamika osnovnykh épidemiologicheskikh pokazateleí tuberkuleza v Iakutii za 12 let (1983-1994gg).

In the past 12 years, there were 1.3- and 1.9-fold reductions in the total morbidity rates of tuberculosis and its spread, respectively. However, its morbidity among children showed 3-fold increases. The reduction rate of bacterial excretion became much slower in the past 4 years. Tuberculosis mortality rates tended to rise. At the moment of study, the basic tuberculosis epidemiological parameters were 1.3-1.5 times higher than those in the Russian Federation. At the same time there was a decrease in the efficiency of antituberculous work at all levels.

[Resistance to the inhibitory effect of dexamethasone in brain tumor patients]. / Rezistentnost' k ingibiruiushchemu éffektu deksametazona u bol'nykh s opukholiami golovnogo mozga.

Out of 24 patients with brain tumors, 22 proved to be resistant to inhibition by dexamethasone. There were no significant differences in the sensitivity to dexamethasone in three study groups established on the basis of the tumor site-to-diencephalic structures distance. A relatively higher frequency of disturbances in dexamethasone inhibition in patients with brain tumors suggests grave disorders induced in glucocorticoid secretion regulation by chronic stress.