Vol 91, No 4 (2019)


Hepatic involvement in sarcoidosis

Fomin V.V., Brovko M.Y., Kalashnikov M.V., Sholomova V.I., Rozina T.P., Akulkina L.A., Pershina A.E., Yanakayeva A.S., Nekrasova T.P.


Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Liver is frequently involved in the pathological process. Wide range of clinical manifestations can be seen: from asymptomatic lesion with normal liver function tests to cirrhosis with portal hypertension. Biopsy plays the key role in diagnosis of the hepatic sarcoidosis. It is essential for morphological diagnosis to exclude other causes of granulomatous liver disease, most often - primary biliary cholangitis. Nowadays there are no standard treatment protocols for patients with hepatic sarcoidosis.
Terapevticheskii arkhiv. 2019;91(4):4-12
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Markers of dysbiosis in patients with ulcerative colitis and Crohn's disease

Danilova N.A., Abdulkhakov S.R., Grigoryeva T.V., Markelova M.I., Vasilyev I.Y., Boulygina E.A., Ardatskaya M.D., Pavlenko A.V., Tyakht A.V., Odintsova A.K., Abdulkhakov R.A.


The results of recent studies indicate a significant role of gut microbiota in the pathogenesis of inflammatory bowel diseases (IBD). The aim of the study was to study the taxonomic and functional composition of the gut microbiota in ulcerative colitis (UC) and Crohn's disease (CD) patients to identify key markers of dysbiosis in IBD. Materials and methods. Fecal samples obtained from 95 IBD patients (78 UC and 17 CD) as well as 96 healthy volunteers were used for whole-genome sequencing carried out on the SOLiD 5500 W platform. Taxonomic profiling was performed by aligning the reeds, not maped on hg19, on MetaPhlAn2 reference database. Reeds were mapped using the HUNAnN2 algorithm to the ChocoPhlAn database to assess the representation of microbial metabolic pathways. Short-chain fatty acids (SCFA) level were measured in fecal samples by gas-liquid chromatographic analysis. Results and discussion. Changes in IBD patients gut microbiota were characterized by an increase in the representation of Proteobacteria and Bacteroidetes phyla bacteria and decrease in the number of Firmicutes phylum bacteria and Euryarchaeota phylum archaea; a decrease in the alpha-diversity index, relative representation of butyrate-producing, hydrogen-utilizing bacteria, and Methanobrevibacter smithii; increase in the relative representation of Ruminococcus gnavus in UC and CD patients and Akkermansia muciniphila in CD patients. Reduction of Butyryl-CoA: acetate CoA transferase gene relative representation in CD patients, decrease of absolute content of SCFA total number as well as particular SCFAs and main SCFAs ratio in IBD patients may indicate inhibition of functional activity and number of anaerobic microflora and/or an change in SCFA utilization by colonocytes. Conclusion: the revealed changes can be considered as typical signs of dysbiosis in IBD patients and can be used as potential targets for IBD patients personalized treatment development.
Terapevticheskii arkhiv. 2019;91(4):13-20
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Biochemical and molecular-genetic indicators of inflammation and apoptosis in liver cirrhosis as an outcome of the progression of non-alcoholic steatohepatitis

Kurbatova I.V., Topchieva L.V., Dudanova O.P., Shipovskaya A.A.


Aim. A comparative analysis of the complex of clinical and laboratory indicators (including the content of cytokines in blood plasma and the level of expression of TNF and IL6 genes in peripheral leukocytes, as well as the level of biochemical and molecular-genetic indicators of apoptosis, such as the content of tissue polypeptide-specific antigen (TPS) in the blood, the activity of caspases 3, 8 and 9 and the expression level of the encoding genes in peripheral blood leukocytes) in patients with non-alcoholic fatty liver disease (NAFLD) with non-alcoholic steatohepatitis (NASH) of different activity, liver cirrhosis (LC) classes A and B and in the donors of control group. Materials and methods. 158 patients with NAFLD were examined: 116 patients with NASH diagnosed for the first time (NASH of weak, moderate and high activity) and 42 patients with the NAFLD at the stage of liver cirrhosis diagnosed for the first time (classes A and B according to the Child-Pugh classification). The control group consisted of 54 healthy donors. The clinical blood biochemistry, cytokine profile, tissue polypeptide-specific antigen content, the level of the TNF, IL6 gene and caspase gene transcription as well as caspase activity in peripheral blood leukocytes (PBL) were evaluated. Results and discussion. In the progression of NASH to LC, together with changes in general clinical parameters, the cytokine profile are changed due to an increase in the level of IL-6 and IL-1β; in peripheral leukocytes, the activity of caspase 9 increases and the activity of caspase 8 decreases compared to NASH, and the level of the TNF gene expression decreases as compared to NASH of high activity. These parameters can be considered as promising minimally invasive markers of progression of NAFLD to LC. Conclusion. In nonalcoholic cirrhosis as an outcome of the progression of non-alcoholic steatohepatitis changes in clinical parameters (indicating the development of hepatocellular deficiency, violation of protein and lipid metabolism, progressive inflammation) are accompanied by specific changes in levels of biochemical and molecular-genetic indicators of apoptosis and inflammation. With the progression of NASH to LC, the cytokine profile changes due to an increase in the level of proinflammatory cytokines, the apoptosis processes triggered by the internal pathway increase and the activity of apoptosis activated via the external pathway decreases in PBL
Terapevticheskii arkhiv. 2019;91(4):21-27
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The value of cardiovascular magnetic resonance in myocarditis with different clinical presentation

Stukalova O.V., Gupalo E.M., Chumachenko P.V., Samko A.N., Butorova E.A., Shakhnovich R.M., Mironova N.A., Narusov O.Y., Safiullina A.A., Golitsyn S.P., Ternovoy S.K., Chazova I.E.


Objective: to assess the diagnostic meaning of cardiac magnetic resonance imaging (CMR) in various clinical forms of myocarditis. Materials and methods. 11 (8 men, mean age 32.8±11.1 years) patients (pts), hospitalized with suspected acute coronary syndrome, while an acute myocardial infarction was excluded during the examination (group I); 48 pts (31 men, 43.1±12.7 years), with clinical and instrumental signs of dilated cardiomyopathy (DCM) - group II; and 20 patients (12 men, 39.5±14 years), with episodes of ventricular tachycardia (group III) underwent cardiac magnetic resonance imaging (CMRI). In 38 patients endomyocardial biopsy (EMB) was performed. Results and discussion. According to EMB, signs of active myocarditis were revealed in 10 (34.5%) group II pts and in 3 (37.5%) group III pts; signs of resolved myocarditis - in 8 (27.6%) patients in group II and in 3 (37.5%); minimal morphological changes - in 11 (37.9%) patients of group II and in 2 (25%) patients of group III. In 9 (81.9%) patients of group I MRI data allowed to establish the diagnosis of acute myocarditis. Signs of active inflammation from MRI data were detected in myocardium 5 (10.4%) in group II pts and 7 (35%) in group III pts. In 22 (45.8%) pts in group II and 10 (50%), CMR data corresponded to the picture of resolved myocarditis. In 21 (43.8%) cases of group II and 3 (15%) of group III, MRI revealed minimal structural changes. In pts with clinical and instrumental signs of DCM and/or ventricular tachycardia MRI allows to identify signs of "active myocarditis" with a sensitivity of 37.5% with a specificity of 83.4%. At the same time, in cases of resolved myocarditis and minimal morphological changes MRI has high sensitivity (70 and 71.5%) and specificity (71.5 and 75%, respectively). Conclusion. CMR has high diagnostic significance in patients with infarct-like course of myocarditis. In patients with clinical syndrome of dilated cardiomyopathy or arrhythmias, the sensitivity of MRI in detecting active myocarditis is low (37.5%) with high specificity (83.4%). In cases of minimal structural changes in the myocardium and resolved inflammation, CMR is a good alternative to EMB.
Terapevticheskii arkhiv. 2019;91(4):28-36
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Role of video capsulе endoscopy in the diagnostic algorithm of small bowel Crohn's disease

Parfenov A.I., Akopova A.O., Shcherbakov P.L., Mikcheeva O.M.


Aim. To evaluate the possibilities of video capsule endoscopy (VCE) for diagnosing small bowel Crohn's disease (SBCD). Materials and methods. The study included 25 patients (12 men, 13 women) diagnosed with Crohn's disease. The mean age of the patients was 31.84±10.5 years. The VCE was performed using the GivenImaging system (Yokneam, Israel), OMOM (China). After the end of each test, the data was analyzed at a rate of 8 to 10 frames per second using Rapid® Reader (version 7.0). Results and discussion. The examination of patients in accordance with the diagnostic algorithm showed that for 11 patients (44%) the clinical assumption of SBCD was confirmed only with the help of VCE (1st group). Consequently, the use of VCE in these patients was crucial in the diagnosis of SBCD, since standard methods of analisys were insufficient to establish this diagnosis. For 14 patients (2nd group), the diagnosis of SBCD was established with the help of colonoscopy and/or diagnostic imaging modalities. The use of VCE allowed to confirm the diagnosis, to clarify the localization and extent of inflammation of the small intestine. Conclusion. VCE can be recommended for the diagnosis of SBCD during the period of early inflammatory manifestations in the small intestine mucosa.
Terapevticheskii arkhiv. 2019;91(4):37-42
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Balloon pulmonary angioplasty for patients with inoperable chronic thromboembolic pulmonary hypertension

Danilov N.M., Matchin Y.G., Chernyavsky A.M., Edemsky A.G., Grankin D.S., Sagaydak O.V., Chazova I.E., Boytsov S.A., Karaskov A.M.


Aim. To evaluate the effectiveness of balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Materials and methods. Forty patients with inoperable CTEPH were enrolled in this study. The indications were determined by multidisciplinary team. The average age of patients was 53.5 [43; 63] years. In 65% of cases patients had functional class III (according to WHO); the distance in the 6-minute walk test (6MWD) was 327 [280; 400] m; catheterization of the right heart revealed systolic pulmonary artery pressure (SPAP) 82 [64; 100] mm Hg, mean pulmonary artery (mPAP) 48.5 [38; 56] mm Hg, pulmonary vascular resistance (PVR) 784 [525; 1257] dyn·s/cm-5. Each patient underwent 6 BPA. Results and discussion. The effectiveness of BPA was assessed 2 months after the last session. According to the data of right heart catheterization SPAP decreased by 27.3%, mPAP by 26%, PVR by 34.5% from baseline. After all series of BPA echocardiography and magnetic resonance imaging demonstrated reverse remodeling of the right heart. Also significant decrease in the level of BNP by 62%, increasing in 6MWD distance by 39% and improvement of the functional class up to I in 60% cases and up to II in 40% cases were noted. Conclusion. The results of the present study demonstrated a high efficacy of BPA allowing to normalize hemodynamic and clinical parameters, increasing the physical activity. Balloon pulmonary angioplasty is a new highly effective, safe method for treating patients with inoperable CTEPH.
Terapevticheskii arkhiv. 2019;91(4):43-47
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The marker of adverse prognosis 1.5-anhydroglucitol in patients with coronary heart disease in the long-term period after planned myocardial revascularization

Ignatova Y.S., Karetnikova V.N., Horlampenko A.A., Gruzdeva O.V., Dyleva Y.A., Barbarash O.L.


Aim. Determination of the prognostic value of 1.5-anhydroglucitol (1.5-AG) for the development of cardiovascular events in patients with coronary heart disease (CHD) within a year after a planned percutaneous coronary intervention (PCI). Materials and methods. A prospective study was conducted in Federal State Budgetary Institution Research Institute for Complex Issues of Cardiovascular Disease among 149 patients admitted to planned PCI in the period from 2016 to 2017. Criteria for inclusion in the study: age up to 70 years, angina I-IV functional classes or post-infarction cardiosclerosis, the presence of indications for planned PCI. Exclusion criteria from the study: previous myocardial revascularization; prosthetic heart valves; decompensation of chronic heart failure, anemia of any degree; acute coronary syndrome in index hospitalization; exacerbation of somatic diseases. The results of the research were processed by Statistica Windows 6.0. Results. During the year after planned PCI, 39 (26.14%) cardiovascular events were registered in patients with CHD, of whom more than half of the cases (51.28%) were associated with the presence of indications for PCI of de novo. Lower levels of 1.5-AG were observed in the group of patients with cardiovascular events (p=0.000). When patients were divided according to median of the studied marker patients with a concentration of 1.5-AG less 20.96 μg/ml (before PCI) were more likely to have PCI after restenosis of the stent, compared with patients whose median concentration of this marker was higher (p=0.028). The logistic regression method revealed a significant direct relationship reflecting the prognostic value of lower concentration of 1.5-AG in relation to the development of cardiovascular events in patients regardless of the presence of carbohydrate metabolism disorders [OR 0.25 (0.10-0.62)]. Conclusion. According to the results of the study, the prognostic value of the concentration of 1.5-AG less 20.96 µg/ml was established in relation to the development of cardiovascular events in patients with CHD during the year after a planned PCI, regardless of the presence of carbohydrate metabolism disorders.
Terapevticheskii arkhiv. 2019;91(4):48-52
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O.V. Knyazev, A.V. Kagramanova, I.A. Korneeva, K.K. Noskova, S.V. Belousov, A.I. Parfenov

Knyazev O.V., Kagramanova A.V., Korneeva I.A., Noskova K.K., Belousov S.V., Parfenov A.I.


Aim. To compare fecal calprotectin (FC) concentration with laboratory and diagnostic methods in patients with inflammatory bowel diseases (IBD). Materials and methods. The level of FC was measured in 110 patients with established IBD. Crohn diseases (CD) was diagnosed in 50 patients, ileocolitis - in 38 and terminal ileitis in 12 individuals. Ulcerative colitis (UC) was diagnosed in 60 patients, total colitis in 35, left-side colitis in 21 and 4 patients have proctitis. Laboratory data include measurement of FC, leukocytes, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), fecal occult blood. All patients underwent colonoileoscopy (CIS) at the start of disease flare and after 12 weeks of treatment. Results and discussion. We found linear correlation between level of FCP and endoscopic activity of CD, analyzing FCP level and endoscopic activity of CD before (during disease flare) and after 12 weeks treatment (r=0.66, p<0.001). Linear correlation between FCP and SES-CD sustained after 12 weeks of treatment (r=0.77, p<0.001). We revealed correlation between FCP concentration. And CRP level (r=0.59, p<0.05). The linear correlation was detected between FCP and endoscopic activity of UC (r=0.88, p<0.001) before the treatment. After 12 weeks of treatment linear correlation was shown between FCP and Meyo scale (r=0.73, p<0.001). IBD patients with FCP more than 200 mcg/g have high risk of disease reccurence in short-term period of time (HR - 8.33; 95% CI 2.05-33.8; χ2 - 11.85; p<0.001) and (HR - 2.7; 95% CI 1.1-6.6; χ2 - 5.3; p<0.05), accordingly. Conclusion. Increased FCP level indicates poor effectiveness of treatment and high risk of reccurence. The level of FCP correlates strongly with recent laboratory and diagnostic indices of activity and enables to determine patients with high risk of reccurence. Thus, thorough monitoring, including additional procedures, contributes to just-in-time treatment modification.
Terapevticheskii arkhiv. 2019;91(4):53-61
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Clinical significance of lipohypertrophy without visual and palpable changes detected by ultrasonography of subcutaneous fat

Volkova N.I., Davidenko I.Y.


Aim. To estimate clinical significance of lipohypertrophy (LH) without visual and palpable changes, detected by ultrasonography of subcutaneous fat. Materials and methods. This study included 140 diabetic patients who received insulin in basal-bolus regimen. Ultrasonography of subcutaneous fat was performed for LH diagnostics in these diabetic patients. Than clinical significance of LH without visual and palpable changes was estimated. HbA1c level, fasting and postprandial glucose, episodes of hypoglycemia, body mass index (BMI) and scheme of insulinotherapy were evaluated at the moment of LH, after 3 and 6 months in all patients. Results and discussion. After changing injection sites, good results were demonstrated by measuring glucose and HbA1c level. Thus fasting glucose decreased from 9.03±1.98 mmol/l to 7.11±0.95 mmol/l (p=0.023). Postprandial glucose reduced from 10.27±2.72 mmol/l to 9.34±1.21 mmol/l (p=0.011). HbA1c level reduced from 9.27±1.75% to 7.43±1.02% (p=0.002). Also BMI decreased from 33.75±3.49 kg/m2 to 30.5±2.96 kg/m2 (p=0.018). Conclusion. LH without visual and palpable changes could worsen compensation of glycemic control and leads to hypoglycemia and chronic Somogyi rebound. So, LH without visual and palpable is as important and clinically significant as classic LH.
Terapevticheskii arkhiv. 2019;91(4):62-66
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Early diagnosis of acute renal injury in patients with acute decompensation of chronic heart failure

Nasonova S.N., Zhirov I.V., Ledyakhova M.V., Sharf T.V., Bosykh E.G., Masenko V.P., Tereshchenko S.N.


Early diagnosis of acute kidney injury (AKI) is an urgent problem of providing medical care to patients with acute decompensation of chronic heart failure (ADHF). Aim. To study the possibilities of previously diagnosing acute renal damage in patients with acute decompensation of chronic heart failure with reduced systolic function using biomarkers of acute renal injury. Materials and methods. The study included 60 patients (62.0±11.1 years) with HADS (BNP >500 pg/ml) and a reduced left ventricular ejection fraction (LV 27.05% [23.25; 32.75], c FC III-IV NYHA). The level of creatinine, urea, uric acid, albumin in serum was determined in all patients, as well as a number of biomarkers: lipocalin associated with neutrophil gelatinase (NGAL) and cystatin C (CysC) in serum; kidney damage molecule-1 (KIM-1) and angiotensinogen (AGT) in the urine. Results and discussion. AKI is determined based on changes in serum creatinine concentration or diuresis value. The results obtained indicate a high specificity and sensitivity of the use of biomarkers for the diagnosis of AKI in patients with ADHF. NGAL AUC - 0.833 (p<0.001), Se - 82.8%, Sp - 4.2%. CysC AUC - 0.823 (p<0.001), Se - 79.3%, Sp - 74.2%. KIM-1 AUC - 0.782 (p<0.001), Se - 75.9%, Sp - 74.2%. AGT AUC - 0.829 (p<0.001), Se - 82.8%, Sp - 77.4%. In a multifactorial regression analysis, it was found that with NGAL greater than 157.35 ng/ml, the risk of AKI increases 13.1 times (95% CI 1.365-126.431), with an increase in KIM-1, the risk of the development of AKI increases 20.6 times (95% CI 1.802-235.524), and with an increase in AGT more than 14.31 leng/ml, the risk of AKI increases 32.8 times (95% CI 2.752-390.110). Conclusion. Acute kidney injury develops in 48.3% of patients hospitalized with acute decompensation of chronic heart failure. Patients with acute decompensation of chronic heart failure and AKI have significantly higher serum NGAL and CysC, KIM-1 and AGT values in the urine compared with patients without impairing renal function. These biomarkers can serve both for the early diagnosis of acute kidney damage and the prediction of AKI in patients with acute decompensation of chronic heart failure.
Terapevticheskii arkhiv. 2019;91(4):67-73
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Various approaches for peforming an outpatient coronary angiography

Danilushkin Y.V., Matchin Y.G., Shamrina N.S., Bubnov D.S., Atanesyan R.V., Mitroshkin M.G., Basinkevich A.B., Ageev F.T.


Aim. To study the safety and clinical efficacy of an outpatient coronary angiography in various groups of patients according to a 6-year experience of the laboratory of endovascular diagnostic and treatment methods in the outpatient setting of the NMRC of Cardiology. Materials and methods. 2166 patients which underwent an outpatient coronary agiography from March 2009 to December 2014 were included. The success criteria was the successful completion of the procedure without the occurrence of major cardiovascular complications (death, transmural myocardial infarction; acute cerebrovascular accident, emergency cardiac surgery). Results and discussion. All 2166 patients included in the study were divided into 2 groups: Group 1 - 1316 patients who were discharged home several hours after the study; Group 2 - 850 patients directed from hospitals without catheterization laboratories with the same-day discharge back to the referring hospital. From a clinical point of view, in the second group there were more severe patients. However, the study was successfully completed in all patients in both groups. There were no major adverse cardiovascular complications during the procedure and within 24 hours. In the 1st group, unplanned hospitalization occurred in 2.1% of cases, the cause of which in 93% of cases was the detection during angiography of a critical lesion ≥70% of the left main coronary artery. Conclusion. In our work, the incidence of complications was extremely low and not significantly different in both groups of patients. This is due to the fact that in patients with a more severe symptoms underwent a preliminary stabilization of their clinical condition. The introduction of outpatient technologies will optimize the invasive diagnostics and reduce the costs associated with hospitalization.
Terapevticheskii arkhiv. 2019;91(4):74-82
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New ECG criteria for differential diagnosis of wide QRS complex tachycardias with right bundle branch block pattern

Shlevkov N.B., Salami H.F., Kiktev V.G., Sokolov S.F.


Aim. To evaluate standard 12-lead ECG indices for the differential diagnosis of wide QRS tachycardias with right bundle branch block (RBBB) pattern. Materials and methods. Study analyses the 244 ECG indices in 111 patients (79 males and 32 females, age 53±17 years) with RBBB tachycardias, who underwent electrophysiological studies. First step includes retrospective analysis of QRS characteristics in 20 patients with ventricular tachycardias (VT), 24 pts with aberrant supraventricular tachycardias (SVT+RBBB) and 14 pts with antidromic SVTs (WPW). ROC- and multifactorial analyses were performed to develop diagnostic ECG algorithms. The prognostic accuracy of the algorithms was subsequently evaluated on a prospective group of patients with RBBB tachycardias (n=53). Results and discussion. ECG criteria of RBBB VTs were: 1) the presence Q-wave in lead II, 2) the duration interval R(peak)-S(end) >100 ms in lead V5. ECG criteria for antidromic SVTs with RBBB were: 1) the duration of the R wave in lead I ≥80 ms, 2) the absence of split (M-sharp) R-waves in lead V2, 3) the absence notch in ascending S wave in lead aVL. The accuracy of the algorhythm for diagnostic of VTs with RBBB was 83% (sensitivity 100%, specificity 73%). The accuracy of the algorhythm for diagnostic of antidromic SVTs with RBBB was 91% (sensitivity 85%, specificity 96%). Conclusion. The proposed algorithms are based on new ECG criteria for the differential diagnosis of wide QRS complexes tachycardias with RBBB pattern, unlike the previous algorithms.
Terapevticheskii arkhiv. 2019;91(4):83-89
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ANICHKOV study: the effect of combined hypotensive and lipid-lowering therapy on cardiovascular complications in patients of high and very high risk

Sergienko I.V., Ansheles A.A., Drapkina O.M., Gornyakova N.B., Zubareva M.Y., Shepel R.N., Kuharchuk V.V., Boytsov S.A.


Reducing the risk of cardiovascular complications include lifestyle changes, drug therapy for achieving target blood pressure levels, normalizing the lipid profile, and correcting other risk factors. Adherence to therapy is of particular role, especially in primary prevention, which determines the need to implement the concept of fixed combinations. Approximately 70% of patients with AH have elevated levels of total cholesterol (TCh) and LDL-C, which determines the feasibility of using a FC containing a statin with two antihypertensive drugs. Aim. The aim of the study was to assess cardiovascular risk in patients with elevated levels of total cholesterol and LDL-C and concomitant AH, a comparative analysis of adherence, efficacy and safety of various forms of combined therapy in outpatient practice, including promising lisinopril/amlodipine/rosuvastatin FC (Ekvamer®). Materials and methods. The ANICHKOV study included 702 patients in Moscow and the Moscow region over 18 years old with a cholesterol level ≥7.5 mmol/l and/or LDL-C ≥4.9 mmol/l from March 2017 to December 2018 based on 2 federal centers. According to the results of visit I, patients were prescribed with one of three therapy schemes. In the absence of AH, patients received scheme I (Mertenil® at initial dosage of 10 mg/day). When history of AH existed or AH detected at visit I, patients were randomized to scheme II (Ekvamer® 5/10/10 mg/day) or III (Mertenil® 10 mg/day + Ekvator® 5/10 mg/day). During the observation, the treatment scheme remained unchanged, however, if the target levels of LDL-C and/or BP were not reached, the doses could be increased. The analysis of the main effects of the prescribed therapy were carried out for 12 months, and the frequency of MACE (CVD, ACS, stroke, or hospitalization to perform PCI) was also evaluated Results and discussion. Following the visit I, scheme I was assigned to 390 patients (55.6%), scheme II - 190 (27.1%), scheme III - 122 (17.4%). In 147 patients (20.9%), TG level was >2.3 mmol/l, which required additional fenofibrate intake in a dose of 145 mg/day. Adherence level was 89.5%, including scheme I - 91.7%, scheme II - 90.5%, scheme III - only 81.8%. In general, among compliant patients (n = 590), the decrease in TCh level was 41.0%, LDL-C - 47.4%. 16.6% of patients reached target levels of LDL-C <2.5 mmol/l, 5.6% - <1.8 mmol/l. In the fenofibrate subgroup, TG level decrease was 34.6%. During the follow-up period, 47 cases of side effects were observed in 27 patients (4.6%), that did not require modification of therapy. Systolic BP reduction in compliant patients of schemes II and III was 20 mm. Hg (13.1%), diastolic BP - 12 mm. Hg (13.6%), target BP levels (<140/90 mm. Hg) reached 83.7% and 80.8% of patients, respectively, target levels of BP and LDL-C <2.5 mmol/l reached 14.5% and 13.1% of patients, respectively, <1.8 mmol/l - 5.8% and 5.1%, respectively. During the observation period no deaths were recorded, other components of MACE were observed in 38 patients (5.8%), including 27 among compliant patients (4.6%) and 11 among non-compliant (15.9%, p<0.01). In 19 out of 38 patients (50%), hospitalization for routine PCI was the end point, ACS - in 12 (31.6%), and stroke - in 7 (18.4%). Conclusion. The results of the study demonstrated a sufficient hypolipidemic effect and high safety of Mertenil® and Ekvamer®. A higher adherence to the combined preparation than to two monodrugs was noted. Achieving target levels of BP and LDL-C is problematic, which dictates the expediency of using fixed combinations of drugs, especially in primary prevention.
Terapevticheskii arkhiv. 2019;91(4):90-98
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Morphologically proved ANCA positive Loeffler’s pancarditis: medical and surgical treatment

Blagova O.V., Aliyeva I.N., Nedostup A.V., Kogan E.A., Komarov R.N., Chernyavsky S.V., Seslavinskaya V.V., Shelukha P.A., Sedov V.P., Gagarina N.V., Mershina E.A., Sinitsyn V.E., Fomin V.V.


Loeffler's endocarditis remains is a very rare disease, develops due to eosinophilic inflammation predominantly of the endocardium with an outcome in fibrosis and massive thrombus formation and. He is generally characterized by an unfavorable prognosis. Clinical case of a 42-year-old patient with Loeffler endocarditis is presented. The development of the disease was preceded by a polyvalent allergy, mild dry eye syndrome and pansinusitis with a single eosinophilia of blood up to 16%. The reason for the hospitalization was the appearance of biventricular heart failure. During the previous year, the level of blood eosinophils remained normal, a threefold increase in the level of eosinophilic cationic protein was observed once. A 20-fold increase in the pANCA level, a 2.5-fold increase in the level of antibodies to DNA, an antibody to the nuclei of cardiomyocytes 1:160 were detected. The diagnosis was made on the basis of electrocardiography data (low QRS voltage, atrial hypertrophy), echocardiography, multispiral computed tomography and magnetic resonance imaging of the heart (thickening and delayed contrasting of the endocardium, massive thrombosis of the left ventricular apex with obliteration of its cavity, encapsulated fluid in the pericardium with compression of the right ventricle). Systolic dysfunction, severe signs of restriction and arrhythmias were absent. Trombectomy, tricuspid valve plasty, pericardial resection, suturing of an open oval window were performed. Signs of active inflammation with single eosinophils, vasculitis, perimuscular sclerosis, endocardial sclerosis were detected in morphological and immunohistochemical studies of endo-, myo-, pericardium. Viral genome was not found. The therapy with methylprednisolone 24 mg/day, azathioprine 75 mg/day was started. Six months after the operation, the symptoms of heart failure are completely absent, the thrombosis did not recur.
Terapevticheskii arkhiv. 2019;91(4):99-106
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Gray-zone lymphoma. Examples of rare clinical manifestation

Misyurina A.E., Kravchenko S.K., Mangasarova Y.K., Magomedova A.U., Kovrigina A.M., Shimanovskaya L.T., Fastova E.A., Misyurin V.A., Model S.V., Chebotarev D.I., Kostina I.E., Savchenko V.G.


Mediastinal gray-zone lymphoma (MGZL, lymphoma with features intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma) was declared as a separate entity in WHO classification of Tumors of Haematopoetic and Lymphoid Tissues in 2008 and 2017 years. Despite of similar pathomorphological characteristics between primary mediastinal B-cell lymphoma and Hodgkin lymphoma, clinical features and optimal therapeutic approach to MGZL are not clearly defined. Usually MGZL manifests with mediastinal lymphadenopathy, although extranodal lesions often occur (grey-zone lymphoma, GZL). Patients with MGZL have unfavorable prognosis, taking into account high rate of relapse. This article describes two cases of MGZL. First case manifested by arrhythmias due to primary heart involvement. In spite of cardiac failure antracycline-containing chemotherapy (6 courses of R-DA-EPOCH) it allowed to achieve a complete remission and resolving of arrhythmias. Second case was represented by metachronous tumors: primary mediastinal B-cell lymphoma at the time of disease onset and classical Hodgkin lymphoma, NS II, diagnosed after disease progression. Thus, we demonstrated two examples of MGZL that differ by clinical manifestation, response to chemotherapy, which emphasizes an importance of pathogenesis studying, and using of new therapeutic approaches.
Terapevticheskii arkhiv. 2019;91(4):107-113
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Unsolved issues of pregnancy in liver cirrhosis

Kotzev A.I., Tanchev L.S., Pavlov C.S., Tanchev S.Y.


Pregnancy in patients with liver cirrhosis and portal hypertension occurs very rare, because of their significantly derailed reproductive functions. Тhe risks for the mother and the fetus are connected with worsening of the portal hypertension, progression of decompensated liver cirrhosis and development of its complications: liver failure, ascites, hepatorenal syndrome, hepatic encephalopathy and variceal hemorrhage, and with increased incidence of spontaneous abortions and abnormal uterine bleeding. The decision for continuation of the pregnancy in cirrhotic patients must be based on individual approach and a multidisciplinary team consisting of obstetricians, hepatologists, anesthesiologists, surgeons and hematologists must participate in the therapy. We are presenting a clinical case with 34 years old pregnant woman with Child-Pugh class C cirrhosis and untreated chronic viral hepatitis C. The patient was admitted in emergency with abortus imminens, vaginal bleeding, anemia, thrombocytopenia and impaired hemostasis. The pregnancy was interrupted in the Department of obstetrics and gynecology due to the high risk for mother’s life. Later the patient developed severe disseminated intravascular coagulation (DIC) syndrome with life-threatening uterine bleeding. The DIC syndrome and the bleeding were resolved after therapy in intensive care unit and the patient was discharged from the hospital with stable vital signs.
Terapevticheskii arkhiv. 2019;91(4):114-117
pages 114-117 views

Diagnostic difficulties of primary hemochromatosis in a patient with posthemorrhagic anemia

Podzolkov V.I., Pokrovskaya A.E., Vargina T.S., Oganesyan K.A.


Hereditary hemochromatosis (HH) is a disease with an autosomal recessive hereditary type, stipulated by the genetic defect that leads to a high intestinal absorption of iron and primary accumulation in the parenchymal cells of the liver and other organs. This is the most common hereditary disease among White population, the frequency is about 1 case per 250 people. The prevalence of HH is inhomogeneous, people from countries in Northern Europe, especially Scandinavian, are more susceptible to this disease. Mutations of the HFE gene account for approximately 90% of HH cases. In HH excess iron deposits mainly in the cytoplasm of parenchymal cells of various organs and tissues: in the liver, pancreas, endocrine glands, skin and joints. The clinical picture of HH is characterized by the classical triad development: cirrhosis of the liver, diabetes mellitus (DM) and hyperpigmentation. HH may also manifest itself as various endocrinopathies (hypofunction of hypophysis, adrenal glands, thyroid gland, arthropathy, cardiomyopathy). Diagnostics of HH is based on the determination of the iron metabolism values: serum iron, transferrin saturation, the amount of ferritin, the genetic tests, liver biopsy data are used to confirm the diagnosis. Despite the fact that HH is a well-studied disease, in some cases it is complicated to diagnose it. Developed posthemorrhagic anemia in a patient is one of such reasons when the iron metabolism test is not informative.
Terapevticheskii arkhiv. 2019;91(4):118-121
pages 118-121 views

Neurological disorders in vitamin B12 deficiency

Pavlov C.S., Damulin I.V., Shulpekova Y.O., Andreev E.A.


The review discusses thesteps of vitamin B12 metabolism and its role in maintaining of neurological functions. The term "vitamin B12 (cobalamin)" refers to several substances (cobalamins) of a very similar structure. Cobalamin enters the body with animal products. On the peripherу cobalamin circulates only in binding with proteins transcobalamin I and II (complex cobalamin-transcobalamin II is designated as “holotranscobalamin”). Holotranscobalamin is absorbed by different cells, whereas transcobalamin I-binded vitamin B12 - only by liver and kidneys. Two forms of cobalamin were identified as coenzymes of cellular reactions which are methylcobalamin (in cytoplasm) and hydroxyadenosylcobalamin (in mitochondria). The main causes of cobalamin deficiency are related to inadequate intake of animal products, autoimmune gastritis, pancreatic insufficiency, terminal ileum disease, syndrome of intestinal bacterial overgrowth. Relative deficiency may be seen in excessive binding of vitamin B12 to transcobalamin I. Cobalamin deficiency most significantly affects functions of blood, nervous system and inflammatory response. Anemia occurs in 13-15% of cases; macrocytosis is an early sign. The average size of neutrophils and monocytes is the most sensitive marker of megaloblastic hematopoiesis. The demands in vitamin B12 are particularly high in nervous tissue. Hypovitaminosis is accompanied by pathological lesions both in white and gray brain matter. Several types of neurological manifestations are described: subacute combined degeneration of spinal cord (funicular myelinosis), sensomotor polyneuropathy, optic nerve neuropathy, cognitive disorders. The whole range of neuropsychiatric disorders with vitamin B12 deficiency has not been studied well enough. Due to certain diagnostic difficulties they are often regarded as "cryptogenic", "reactive", "vascular» origin. Normal or decreased total plasma cobalamin level could not a reliable marker of vitamin deficiency. In difficult cases the content of holotranscobalamin, methylmalonic acid / homocysteine, and folate in the blood serum should be investigated besides carefully analysis of clinical manifestations.
Terapevticheskii arkhiv. 2019;91(4):122-129
pages 122-129 views

The role of perivascular adipose tissue in the development of cardiovascular diseases. The importance of diagnosis for assessing the risk stratification of cardiovascular diseases

Uchasova E.G., Gruzdeva O.V., Dyleva Y.A., Belik E.V.


Obesity is closely associated with metabolic and cardiovascular diseases, including dyslipidemia, coronary artery disease, hypertension, and heart failure. Adipose tissue (AT) is identified as a complex endocrine organ, with a wide range of regulatory functions at the cellular, tissue and systemic levels. Various terms, including paracardiac, epicardial and pericardial, are used to describe the fatty deposits surrounding the heart. Among all the fat depots, perivascular AT (PVAT) is of great biological significance for the cardiovascular system due to its anatomical proximity to the vessels. Recent studies have shown the presence of a complex, bidirectional paracrine and vasocardial signaling system between the vascular wall and PVAT. In the review, we will discuss the biological role of PVAT in both the physiological state and cardiovascular pathology, emphasizing its dual proatherogenic and antiatherogenic role. Let us consider PVAT as a target for various therapeutic agents in cardiovascular diseases. We will also analyze data on the role of non-invasive techniques as a diagnostic tool for assessing coronary artery inflammation.
Terapevticheskii arkhiv. 2019;91(4):130-135
pages 130-135 views

Akademik Valentin Ivanovich Pokrovskiy (k 90-letiyu so dnya rozhdeniya)

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В.И. Покровский - создатель ведущей отечественной школы по изучению инфекционных болезней и проблем эпидемиологии. Редколлегия журнала «Терапевтический архив» сердечно поздравляет юбиляра и желает ему крепкого здоровья, семейного благополучия, долгих лет жизни на благо пациентов и учеников.
Terapevticheskii arkhiv. 2019;91(4):136
pages 136 views

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