Modern professional education of internists is being updated at an intensive pace. This is primarily due to the fact that medicine and its technologies do not stand still, rushing into a high-tech future. In this regard, people have great hopes for highly effective conservative care, including for hematological diseases. Basic research on the mechanisms of blood clotting has greatly improved the knowledge of complex pathophysiology. These advances have led to a more complex decision-making process, which is reflected in the complex effect of hemostasis imbalance on the complement system, immunity and inflammation, and hence on the treatment of hemostasis disorders. Given this rapidly changing context, optimal educational activities are needed to disseminate knowledge among health professionals and develop their competencies in this field. Specialized professional associations can provide support and training offerings that facilitate access to relevant resources and tools to enable high-quality, up-todate basic and clinical research.

The purpose of the study: to assess clinical efficacy, dynamics of liver steatosis, effect on insulin resistance and hypolipidemic, ammonia level, systemic inflammation of the Heptrong in patients with non-alcoholic fatty liver disease (NAFLD) and dyslipidemia with obesity.Materials and methods. The study included 40 patients (23 men), age Me 48 (41–53) years, BMI Me 30.5 (28–34) kg / sqm. Inclusion criterion: presence of fatty hepatosis in ultrasound and the ALT level is more than 1.5 norms. Asthenia (AVS) was detected in 78% of patients, abdominal pain in 65% (hepatomegaly, chronic cholecystitis), flatulence in 26%, dyspepsia in 32%. In 36% of patients there was arterial hypertension, in 54% of cases — insulin resistance, in 72% of cases — dyslipidemia with hypertriglyceridemia. Before therapy, patients had an increase in the level of ALT up to 1.9 norms, AST up to 2.1 norms, GGTP up to 1.8 norms, total bilirubin — 1.4 norms, glycated hemoglobin — 1.2 norms, HOMA index up to 1,3 norms, total cholesterol up to 1.3 norms, triglycerides up to 1.4 norms, CRP up to 1.2 norms and ferritin up to 1.3 norms, combined with an increase in CRP and leukocytes up to 1.2 norms. According to the results of liver FIBROSCAN, hepatic steatosis was detected in all patients, Me CAP 295 (254–343), liver fibrosis was detected in 32% of cases (Me 6.4 (5.4–7.6) kPa). The level of ammonia in the peripheral blood on an empty stomach was Me 72 (42–91) mmol / l (with a norm of up to 54 mmol / l). Heptrong was prescribed in the form of 3 courses of 10 intramuscular injections according to the scheme 3.0 ml-3 ml-6.0 ml-6.0 ml-9.0 ml-9.0 ml-6.0 ml-6.0 ml-3.0 ml-3.0 ml for 3 months.Resaults. After 1 month of Heptrong therapy according to the scheme, there was a significant decrease (p≤0.05 according to the Wilcoxon criterion) in the frequency of AVS, pain and dyspeptic syndrome, the level of bilirubin, ALT, CRP, ferritin, ammonia, GGTP. After 3 courses of therapy, the examined patients showed further regression of clinical syndromes. During examination and communication, a positive trend was noted on the scales of quality of life and level of anxiety. Revealed a decrease in Me ALT by 31% (p <0.05); decrease in AST by 28% (p <0.05); GGTP — by 33% (p <0.05); glycated HB — by 15% (p <0.05); CRP — by 10% (p <0.03) ; ferritin — by 11% (p <0.05), ammonia — by24% (p <0.05); HOMA — index by 15% (p <0.04); total cholesterol — by 12% (p <0.05); triglycerides — by 20% (p <0.05); LDL — by 19% (p <0.05); HDL + 18% (p <0.05); Liver steatosis (dВ / m²) –26% (p <0.05); Liver fibrosis — reduction of 1 stage (Metavir) in 28% of patients. A positive response to therapy correlated (r> 0.3) with the patient’s age, male gender, BMI, Homa index, LDL, CRP, ammonia, ferritin.Conclusions. During the course of treatment with Heptrong, patients with NAFLD experience regression of clinical symptoms, stigma of systemic and local inflammation, correction of metabolic disorders, and improvement in the quality of life.

Aim. This study is aimed at evaluating the efficacy and safety of Bicyclol administration in patients suffering from non-alcoholic fatty liver disease (NAFLD) («ZIGUN» research) by monitoring laboratory data and non-invasive methods of diagnosis of liver fibrosis and steatosis.Materials and methods. The study included 93 patients with NAFLD with the average age of 44 (38–49) years, having the stage of liver fibrosis and steatosis greater than the 1st according to FibroScan (FibroScan 502 TOUCH with CAP software). Patients were randomized into 2 groups: 1) the main group comprised 67 patients receiving 75 mg/day of Bicyclol for 24 weeks in combination with aerobic exercise and Mediterranean diet; 2) the comparison group (26 patients) prescribed of only aerobic exercise and Mediterranean diet for 24 weeks.Results. During Bicyclol treatment, a decrease in the following indicators was observed: ALT, AST, GGT, CRP by 30 % or more, glycated hemoglobin (–10 %) and HOMA-index (–24 %), cholesterol (–12 %), LDL (–19 %), triglycerides (–31 %), atherogenic coefficient (–22 %). A decrease to the1st stage of fibrosis was observed in 30 patients (44 %), steatosis regression to the 1st stage was noted in 57 patients (85 %). Liver steatosis of the 4th stage was not revealed after treatment with Bicyclol. The number of patients with indolent steatosis (less than 2nd stage) increased 2 times (p < 0.001). No significant changes were found in the group without drug therapy.Conclusions. Bicyclol therapy in NAFLD is accompanied by positive dynamics of inflammation activity markers, insulin resistance and lipid spectrum, which suggests a positive dynamics of the stages of liver fibrosis and steatosis.

В статье на основании данных проспективного наблюдения за больными, получающими терапию варфарином, проанализированы основные факторы, определяющие безопасность подбора поддерживающей дозы препарата. Выявлено, что достижение первого значения МНО ≥2,0 на 3–5-е сут. начала терапии варфарином достоверно связано с развитием чрезмерной гипокоагуляции (МНО ≥4,0). На основании оценки генотипа выявлена зависимость темпов насыщения варфарином от носительства аллельных вариантов CYP2C9 и VKORC1. Показано, что быстрые темпы достижения антикоагулянтного эффекта в подавляющем большинстве случаев связаны с носительством «неблагоприятного генотипа» (аллельных вариантов CYP2C9 *2/*2, или *3/*3, или 2/*3, или аллельного варианта АА VKORC1, или одновременного носительства двух гетерозиготных полиморфизмов CYP2C9 и VKORC1). Учитывая полученные результаты, авторами сделан вывод о высокой практической значимости проведения исследования крови на МНО на 3–5-е сут. от начала терапии. На основании проведенного дискриминантного анализа выявлен клинический предиктор развития чрезмерной гипокоагуляции, обусловленной передозировкой варфарина, — терапия амиодароном. Полученные данные легли в основу модификации существующего алгоритма подбора дозы варфарина.

Aim. To estimate central (aortic) blood pressure (BP) and arterial stiffness and their prognostic value in the development of preeclampsia (PE) in pregnant women with different forms of hypertension.Subjects and methods. The study included 106 patients with chronic hypertension, 21 with the latter concurrent with PE, 63 with gestational hypertension, 10 with PE, and 100 without hypertension. All the women underwent 24-hour BP monitoring by an oscillometric method to estimate central (aortic) BP and arterial stiffness at 16-22 weeks' gestation.Results. The highest average daily central systolic and diastolic BP was in the pregnant women with PE. ROC analysis showed that the average daily aortic systolic BP greater than 115 mm Hg was most significant for the prediction of PE. The highest values of arterial stiffness (augmentation index, stiffness, maximum rate of blood pressure rise) were detected in the pregnant women with PE in the presence of chronic hypertension.Conclusion. 24-four BP monitoring in pregnant women can provide additional characteristics that reflect the stiffness of the aorta and peripheral arteries, which may be used to predict PE.

Aim. To evaluate the influence of target BP achievement on clinical course and outcomes of pregnancy in pregnant women with arterial hypertension (AH).Material and methods. A cohort study with prospective cohort. Totally 300 pregnant women included; of those in to the 1st group 103 included with AH, who had not reached target BP; into the 2nd – 97 women with AH, who had reached target BP; control consisted of 100 women without AH. Women underwent clinical examination and observation, analysis of medical data, standard laboratory and instrumental investigation, genetic investigation by polymerase chain reaction.Results. Women who had not reached target BP pregnancy complicated more often with fetus development retardation and pre-eclampsy, and in pregancy outcomes there were preterm delivery and antenatal fetus death, newborns from this group had lower weight and height; also they had more often mutation of D-allele of ACE gene (I/D) and mutant C-allele of receptor 1 type angiotensine II gene (ATR11166 A/C) comparing to the group with achieved BP and with controls. By the result of logistic regression study the factor independently associated with total worse outcome, were premature deliveries in anamnesis - increase the risk almost 6 times (OR=5,93, 95% CI 1,83-19,2; p=0,003), pre-eclampsy during current preganancy – increases risk 3,7 times (OR=3,68, 95% CI 1,48-9,16; p=0,005), and target BP acievement (less than 140/90 mmHg) decreases the risk of total negative outcome 8 times (OR=0,12, 95% CI 0,05-0,28; p<0,001).Conclusion. Target BP achievement in pregnant women with AH might be an independent factor influencing the prevalence of obstetric complications and negative outcomes of pregnancy. A definite impact on target BP levels achievement make genetic polymorphisms of renin-angiotensin system genes.

Aim of investigation. To estimate outcomes of toxic hepatites (TH) after intake of alcohol surrogates («Mozhzhevelovy» spirit for external use) with development of original prognostic model of patients survival.Material and methods. Retrospective analysis of clinical and laboratory data and survival rates of 80 patients (men 54, women 26, age 32 to 49 years), admitted to the hospital in 2006–2007, with evaluation of outcomes in 2012 was carried out. Statistical analysis of the data was carried out by Statistica-6 and Medcalc (using logistical regression and ROC-curves plotting) software packages. For evaluation of the disease prognosis MELD index and Hy's Law were determined, as well as R ratio (ratio of hepatocellular and-or cholestatic lesions).Results. All patients had clinical signs of severe TH with prominent treatment-resistant cholestatic syndrome. Within the first month of disease 16 (20%) patients died of liver failure, during following period – 13 patients (19%). Calculation of MELD index and Hy's Law showed their low informative value at this group of patients, R index in 78% of cases indicated mixed lesion and did not affect prognosis. Original prognostic model of survival rate of patients was: blood leukocyte count (OR 4,8, 95%-CI 1,12— 20,55; р=0,03) and creatinine (OR 1,1, 95% CI 0,99– 1,22; р=0,09), prognostic value of the model was 93,3%. Level of direct bilirubin (AUROC 0,79; CI 0,58–0,83) and WBC (AUROC 0,93; CI 0,83-0,98) were prognostically significant.Conclusions. According to authors’ model, the most significant predictors of lethal outcome at TH were severity of inflammatory response, hyperbilirubinemia and hepatorenal syndrome.

Aim: to assess of the relationship of clinical and molecular genetic factors in the course and outcome of pregnancy in different forms of hypertension in pregnant women. Patients and methods: a total of 125 pregnant women who were divided into the following groups: with chronic hypertension (n =45), with gestational hypertension (n =20), with pre-eclampsia (n =10), superimposed preeclampsia upon chronic hypertension (n =15) and 35 women without hypertension in control group. Results: in pregnant women with chronic hypertension and superimposed preeclampsia upon chronic hypertension were observed higher incidence of overweight and obesity, smoking before pregnancy and family history of hypertension and thrombosis, the course and outcomes of pregnancy characterized by higher frequency of obstetric complications, higher frequency of polymorphisms of genes identified the renin-angiotensin system, folate cycle and endothelial function. Conclusions: Molecular-genetic factors, combined with the factors of cardiovascular risk may make some contribution to the phenotypic realization of pregnancy complications and adverse pregnancy outcomes in pregnant women with different forms of hypertension.

The aim of publication. To present the case of severe acute drug-induced hepatitis after halothane anesthesia in relation to significance of allergies history preoperative inquiry and assessment of medical management of patients, using modern prognostic scales.Key points. Biotransformation of volatile anesthetics can result in production of toxic metabolites and metabolic by-products, resulting in damage of the liver and kidneys. Disorders of liver function can be of two types: early – transient elevation of transaminase activity and late – liver necrosis. Mortality rate at the latter reaches 50–80%. In presented clinical case both variants developed in the same patient in different terms are described. Despite of acute drug-induced hepatitis with severe liver failure, complex treatment resulted in favorable outcome, including the remote-terms result.Conclusion. The most important factors determining favorable prognosis at drug-induced liver disease, include adequate doses of glucocorticosteroids, application of MARS-therapy and absence of background liver disease. Application of differential diagnostics algorithms and prognostic scales at drug-induced liver disease helps clinician to choose proper treatment approach at specific stage.

The conditions of vascular thrombocyte, coagulatory and fibrinolytic components of hemostasis were evaluated in trimestral dynamics in 65 healthy pregnant women without thrombotic risk factors and with physiologically progressing pregnancy resulted in timely delivery of term fetus. In the process of gestation, the increase of spontaneous and induced aggregative activity of thrombocytes, the increase of levels of fibrinogen, soluble fibrin monomeric complexes, D-dimer and fibrinolysis delay were established.

Aim. To investigate the prevalence of C-677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and hyperhomocysteinemia (HHC) in pregnant women with chronic arterial hypertension (CAH). Material and methods. This prospective cohort study included two groups: Group I – pregnant women with CAH (n=80), and Group II – pregnant women without AH (n=40). In all participants, homocysteine (HC) levels were assessed using immunoenzymatic method, at 9-12 weeks, 22-24 weeks, and 30-32 weeks. Genotyping of the C-677T polymorphism of MTHFR gene was performed using polymerase chain reaction. Results. In pregnant women with CAH, HC levels were higher than in women without AH, throughout the pregnancy. Group I also demonstrated higher prevalence of T allele and T/C genotype. In pregnant women with HHC, relative risk (RR) of pre-eclampsia was 3,5 (95% CI 2,0-5,6), of chronic placental insufficiency - 1,2 (95% CI 0,9-1,6), and of intrauterine growth restriction syndrome - 6,4 (95% CI 3,1-13,3). Conclusion. HCC, as well as its combination with C-677T polymorphism of MTHRF gene, could be regarded as a biomarker of complicated pregnancy in women with CAH.

The aim of the study was to investigate the possibility of the use of simvastatin at a daily dose of 20 mg in elderly patients with coronary artery disease and preserved left ventricular ejection fraction, complicated by CHF. Material and methods. 195 elderly patients (75 years and older) with CHD and CHF IIA-B phase, 2-3 functional class were involved in this study. The intervention group included 95 patients, the control group -100 patients. Patients in the intervention group was treated by simvastatin 20 mg/day. In the control group, lipid-lowering therapy was not performed. The endpoints of the study were the development of any acute vascular events or death from cardio-vascular diseases. Results. The relative risk of acute cardiovascular events and sudden deaths in the intervention group relative to the control group was 0,53 (CI 0,27-1,03, p= 0.05). Appointment of simvastatin in a daily dose of 20 mg significantly improved the lipid profile. Discussion: The study shows the effectiveness of clinical application of high doses of simvastatin in elderly patients with coronary artery disease complicated by heart failure

The conditions of vascular thrombocyte, coagulator and fibrinolytic components of hemostasis were evaluated in trimestral dynamics in 65 healthy pregnant women without thrombotic risk factors and with physiologically progressing pregnancy resulted in timely delivery of term fetus. In the process of gestation, the increase of spontaneous and induced aggregative activity of thrombocytes, the increase of levels of fibrinogen, soluble fibrin monomeric complexes. D-dimer and fibrinolysis delay were established.