Vol 91, No 8 (2019)

Editorial
Current advances in the treatment of gastroesophageal reflux disease: a focus on esophageal protection
Maev I.V., Andreev D.N., Kucheryavyy Y.A., Shaburov R.I.
Abstract
Gastroesophageal reflux disease (GERD) is characterized by high morbidity and a significant decrease in the quality of life of patients, and is a major risk factor for esophageal adenocarcinoma. Nowadays, antisecretory therapy with proton pump inhibitors (PPI) is the "gold standard" of conservative treatment of GERD, but in some cases this therapy is unsuccessful. According to various studies, the prevalence of refractory GERD can reach 30-40%. The latest scientific data in the field of genetics and pathophysiology of GERD demonstrate that a disruption of the barrier function of the esophageal mucosa and an increase of its permeability can be the leading causes of refractoriness. Thus, the optimal therapy for patients with GERD should not only suppress the secretion of hydrochloric acid, but also restore the barrier function of the mucous membrane, providing an esophagoprotective effect. To achieve these goals, Alfasoxx was developed, which consists of a mixture of low molecular weight hyaluronic acid and low molecular weight chondroitin sulfate dissolved in a bioadhesive carrier (poloxamer 407). The clinical efficacy of this product has been confirmed by three prospective, randomized, placebo - controlled trials. Alfasoxx has a healing and restorative effect towards the esophageal epithelium and due to high ability for bioadhesion provides long - term protection of the mucous membrane of the esophagus. Combination therapy for GERD with the use of PPI and an esophagoprotector offers new perspectives for the treatment of patients with GERD.
Terapevticheskii arkhiv. 2019;91(8):4-11
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Analysis of the effectiveness of joint or sequential vaccination with pneumococcal and influenza vaccines in patients with chronic obstructive pulmonary disease
Ignatova G.L., Antonov V.N., Blinova E.V.
Abstract
One of the extremely important problems of managing patients with chronic obstructive pulmonary disease (COPD) is to prevent exacerbations. The article presents data on the clinical and economic efficiency of joint vaccine prevention of conjugate pneumococcal vaccine Prevenar 13 (PCV13) and SOVIGRIPP flu vaccine in patients with COPD. Material and methods. 153 patients were included in the study. They were divided into three groups. The first group (n=53) - consisted of patients who were vaccinated with PCV13. The second group (n=51) included patients who were vaccinated with PCV13 and influenza vaccine simultaneously or with an interval of not more than 2 weeks. The third group (n=49) included not vaccinated patients. The observation period is 1 year. Results and discussion. Combined vaccine prevention of pneumococcal conjugate and influenza vaccines reduces the degree of clinical impairment and stabilizes the main functional parameters of the respiratory system at a significantly lower level compared to monovaccination with only pneumococcal vaccine. Single - stage vaccination with PCV13 and influenza vaccine reduces the risk of adverse events in COPD, reduces the number of exacerbations associated with this hospitalization of patients and the incidence of pneumonia. Conclusion. Combined vaccination with the use of two vaccines minimizes the costs of the health care system. The budget savings can reach an average of 80-83% per year or up to 26 967 - 28 001 rubles per patient with COPD.
Terapevticheskii arkhiv. 2019;91(8):12-17
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Evaluation of the efficiency of combined pharmacotherapy with the use of trimetazidine with prolonged release in patients with stable angina in outpatient practice
Luneva Y.V., Povetkin S.V.
Abstract
Objective. To evaluate the effectiveness of complex pharmacotherapy with the inclusion in the treatment regimen of trimetazidine with a prolonged release in patients with stable angina. Materials and methods. The pilot study included 22 patients aged 45-75 years with combined cardiovascular pathology. In addition to the received therapy, all patients were prescribed the original trimetazidine with a prolonged release at a dose of 80 mg/day (Preductal® OD, Servier, Russia). The observation period was 2 months. The survey included the double implementation of the following methods: the number of strokes per week, the frequency of use of short - acting nitrates per week, blood pressure, heart rate, echocardiography, daily ECG monitoring, assessment of the quality of life (questionnaire SF-36, questionnaire of patients with stable angina SAQ). Results and discussion. When assessing the effect of ongoing pharmacotherapy on clinical and echoCG indicators in patients of the study group, significant positive dynamics was registered in the form of reducing the number of angina attacks and the number of short - acting nitrates used per week, a slight positive dynamics of EF on echoCG, episodes of pain and painless ischemia were eliminated according to the results of Holter monitoring), a significant positive dynamics of quality of life indicators was noted. Conclusion. Combined pharmacotherapy of patients with stable exertional angina with the inclusion of the trimetazidine with a prolonged release at a dose of 80 mg/day (Predductal® OD, Servier, Russia) has a significant positive pharmacodynamic effect in the form of an increase in the antianginal effect, improvement of Holter monitoring indicators and quality of patients life.
Terapevticheskii arkhiv. 2019;91(8):18-21
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Comparative clinical and economic evaluation of pharmacogenetic testing application for dabigatran in patients with atrial fibrillation
Abdullaev S.P., Mirzaev K.B., Sychev D.A.
Abstract
Aim. To evaluate the clinical and economic feasibility of pharmacogenetic testing (PGT) for dabigataran etexilate administration in the treatment of atrial fibrillation (AF) without valve in comparison with tactics without pharmacogenetic testing. Materials and methods. The pharmacoeconomic model was done using generalized data from published clinical, epidemiological and clinical - economic studies. Results and discussion. Application of PGT on the carrier of allelic variant rs2244613 of CES1 gene for adjustment of dabigatrane etexilate dosage in patients with non - valve AF may be more cost - effective strategy for prevention of thromboembolic complications in patients with non - valve AF. Thus, due to the decrease in the number of undesirable drug reactions in the form of minor and major bleedings, the difference in treatment costs in the group with PGT compared to the group with standard pharmacotherapy tactics per 100 patients was 11 827.65 rubles. The expected cost per patient per year for standard treatment was 36 051.35 rubles, while in the group with PGT it was 35 933.07 rubles. The difference was 1182.76 rubles in favor of the pharmacogenetic approach Conclusion. A PGT approach to correct dabigatrane dosage can reduce the cost of pharmacotherapy by reducing the risk of adverse reactions of minor and major bleeding.
Terapevticheskii arkhiv. 2019;91(8):22-27
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The efficacy and safety of quadruple therapy without bismuth (concomitant therapy) in the treatment of patients with Helicobacter pylori - associated gastric and duodenal peptic ulcer disease
Veliev A.M., Maev I.V., Andreev D.N., Dicheva D.T., Zaborovskii A.V., Lobanova E.G., Bektemirova L.G.
Abstract
Aim. Evaluation of the efficacy and safety of quadrupletherapy without bismuth (concomitant therapy) in patients with Helicobacter pylori - associated gastric ulcer and duodenal ulcer in the framework of a comparative research in the population of patients in Russia. Materials and methods. A prospective randomized trial was conducted, which included 210 patients with H. pylori - associated gastric/duodenal ulcer without complications. During the process of randomization, the patients were divided into three equal groups (n=70) depending on the prescribed 10-day scheme of eradication therapy (ET): the first group received the classic triple scheme (Omeprazole 20 mg 2 times a day, Amoxicillin 1000 mg 2 times a day and Clarithromycin 500 mg 2 times a day); the second group received quadruple therapy with bismuth drugs (Omeprazole 20 mg 2 times a day, Tetracycline 500 mg 4 times a day, Metronidazole 500 mg 3 times a day, Bismuth subcitrate potassium 120 mg 4 times a day); the third group received quadruple therapy without bismuth - concomitant therapy (Omeprazole 20 mg 2 times a day, Amoxicillin 1000 mg 2 times a day, Clarithromycin 500 mg 2 times a day and Metronidazole 500 mg 2 times a day). Diagnostics of H. pylori infection during screening and control of eradication was carried out via the fast urease biopsy sample test and urea breath test system. Control of the effectiveness of ET of the microorganism was carried out not earlier than 4 weeks after the end of the treatment. During the course of therapy, the frequency of development of side effects was assessed using a special questionnaire. Results and discussion. The effectiveness of triple therapy was 72.8% (ITT; 95% CI of 62.17-83.54) and 78,4% (PP; 95% CI 68.19-88.72); quadruple therapy with the preparation of bismuth - 80.0% (ITT; 95% CI 70.39-89.6) and 84,8% (PP; 95% CI, 75.96-93.73); quadruple therapy without bismuth - concomitant therapy - 84.2% (ITT; 95% CI 75.54-93.02) and 92.1% (PP; 95% CI 85.43-98.94). Quadruple therapy without bismuth was reliably more effective than the classical triple therapy in the PP selection (p=0.044883). Statistical analysis showed a tendency to poorer effectiveness of ET in patients who had previously used antibiotic therapy (OR 0.4317; 95% CI 0.1776-1.049), and in individuals with a rapid metabolism genotype - CYP2C19*1/*1 (OR 0.12; 95% CI 0.005848-2.4624). The frequency of development of side effects during the use of triple therapy was 18.5% (95% CI of 9.23-27.91), when using quadruple therapy with bismuth - 20.0% (95% CI 10.39-29.6), and with the use of quadruple therapy without bismuth - concomitant therapy - 24.2% (95% CI 13.98-34.58). Conclusion. This prospective randomized study demonstrated the high efficiency of quadruple therapy without bismuth (concomitant therapy) in the framework of eradication of H. pylori infection in Russia.
Terapevticheskii arkhiv. 2019;91(8):28-33
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Efficacy of H. pylori eradication depending on genetic polymorphism of CYP2C19, MDR1 and IL-1β
Bakulina N.V., Maev I.V., Savilova I.V., Bakulin I.G., Il'chishina T.A., Zagorodnikova K.A., Murzina A.A., Andreev D.N.
Abstract
Aim. To evaluate an association of genetic polymorphisms CYP2C19, MDR1, and IL-1β on the eradication rate by 10-day modified therapy in patients with H. pylori - associated diseases. Materials and methods. In this study was conducted a prospective, randomized trial, included 89 patients with H. pylori - associated diseases. They were divided into 2 groups depending on therapy: clarithromycin 500 mg, b.i.d., amoxicillin 1000 mg, b.i.d., bismuth subcitrate 240 mg, b.i.d. rabeprazole 20 mg or 40 mg, b.i.d. for 10 days. All subjects underwent pharmacogenetic testing of CYP2C19, MDR1, and IL-1β. Results and discussion. Per - protocol (PP) eradication rates in group with rabeprazole 40 mg were 97.6% (41/42; 95% CI 87.7-99.6), in group with rabeprazole 20 mg were 82.1% (32/39; 95% CI 67.3-91.0). Intention - to - treat analysis in group with rabeprazole 40 mg eradication rates were 89.1% (41/46; 95% CI 77.0-95.3), in group with standard dose rabeprazole - 74.4% (32/43; 95% CI 59.8-85.1). No significant differences in eradication rates between the groups of ultrarapid, rapid, normal and intermediate CYP2C19 metabolizers (PP: 93.5%/90.3%/84.6% respectively; χ2=0.87, p=0.65). Eradication rates in group with IL-1β CC genotype there was no difference among the IL-1β CT and TT genotype groups (PP: 92.9%/85.7%/94.7% respectively; χ2=1.34; p=0.51). The cure rate among MDR1 TT genotype was significantly lower than among subjects in the MDR1 CC/CT genotype groups (PP: 76.2% vs 96.3%: χ2=5.04; p=0.025; OR=8.13). Conclusion. Ten - day modified triple therapy with high dose rabeprazole significantly high eradication rates in patients with H. pylori - associated diseases. Independent factor for treatment failure is MDR1 CC/CT genotype status.
Terapevticheskii arkhiv. 2019;91(8):34-40
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Evaluation of efficacy and comparative frequency of adverse events in patients with ulcerative colitis receiving the original infliximab and its biosimilar. One year of observation
Knyazev O.V., Shkurko T.V., Kagramanova A.V., Lishchinskaya A.A., Zvyaglova M.Y., Korneeva I.A., Babayan A.F., Parfenov A.I.
Abstract
Real - life data on the effectiveness and safety of biosimilar and biologic drugs licensed for treatment of inflammatory bowel diseases (IBD) is lacking. Aim. To investigate efficacy of original Infliximab (IFX) and its biosimilar in treating patients with ulcerative colitis (UC) and determine the frequency of adverse events during 1 year follow - up period. Materials and methods. Our cohort consisted of 98 ulcerative colitis patients, treated with original IFX and its biosimilar since December 2017 till December 2018 years. Original Infliximab was prescribed in 56 UC patients (57.1%) during 5 years and longer; 16 patients (16.3%) were switched to IFX biosimilar; 13 UC bio - naïve patients (13.3%) received original IFX, 29 (29.6%) patients - biosimilar IFX. In 14 patients (14.3%) original infliximab was rotated with biosimilar. We picked out 42 patients to assess efficacy of original IFX and biosimilar. Results and discussion. Twelve patients, received original IFX and 28 patients, treated with its biosimilar, showed significant clinical improvement by decreasing Mayo index from 9.7±0.4 and 10.2±0.2 points to 1.9±0.09 and 2.1±0.1 points, accordingly. Also we noticed positive change in laboratory markers - CRP decrease from 89.6±8.7 mg/l and 77.5±8.0 mg/l to 6.5±0.8 mg/l and 6.9±0.8 mg/l (p>0.05), albumin increase from 30.1±4.7 g/l and 29.6±3.6 g/l to 34.1±6.3 g/l and 32.8±5.9 g/l (p>0.05), increase of serum iron levels from 6.4±0.5 mcg/l and 7.1±0.65 mcg/l to 14.6±4.4 mcg/l and 15.9±5.1 mcg/l (p>0.05), hemoglobin increase from 104.7±9.8 g/l and 102.2±8.8 g/l till 124±11.3 g/l and 121±10.9 g/l (p>0.05), and fecal calprotectin decrease from 1680±134 mcg/g and 1720±126 mcg/g till 245.5±33.4 mcg/g and 230.5±29.8 mcg/g (p>0.05). During 1 year follow - up 12 UC patients, treated with original IFX and its biosimilar, developed adverse events. The majority of adverse events (n=8) were registered in patients, rotating administration of original IFX and its biosimilar. Conclusion. IFX biosimilar is effective as well as original IFX. Frequency of adverse events, occurred in patients, treated with original IFX, was comparable with adverse events frequency in patients, received biosimilar IFX. Frequency of adverse events was significantly higher in UC patients, rotating original IFX and its biosimilar.
Terapevticheskii arkhiv. 2019;91(8):41-46
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Methanobrevibacter smithii in irritable bowel syndrome: a clinical and molecular study
Vlasova A.V., Isakov V.A., Pilipenko V.I., Sheveleva S.A., Markova Y.M., Polyanina A.S., Maev I.V.
Abstract
Aim. To assess the role of Methanobrevibacter smithii in patients with irritable bowel syndrome associated with small intestinal bowel overgrowth. Materials and methods. Sixty - seven patients with IBS according to Rome IV were enrolled into the study in whom hydrogen breath test was performed. Thirty - two healthy subjects with negative breath test was used as a control. All IBS symptoms assessed daily with 5 grade Lykert scale for 7 days, stool was assessed by Brystol stool scale. M. smithii was confirmed in stool samples by PCR. Results and discussion. In 67 IBS patients CH4 overproduction was found in 32 (47.7%), H2 overproduction in 31 (46.2%) and normal values in 4 (5.9%) by hydrogen breath test. M. smithii was confirmed by stool PCR in all patients with CH4 overproduction. Severity and prevalence of main clinical features of IBS were similar in both SIBO groups but were significantly higher than in control (p<0.01). Positive correlation between overproduction of CH4, abdominal pain and uncomplete bowel emptying (p<0.05). Conclusion. SIBO CH4 was found in nearly half of all patients with IBS associated with SIBO, symptoms profile and severity are similar in patients with SIBO CH4 and SIBO H2, however, the abdominal pain and uncomplete bowel emptying are associated with the level of CH4 overproduction.
Terapevticheskii arkhiv. 2019;91(8):47-51
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Glucocorticosteroids for people with alcoholic hepatitis (Cochrane review)
Pavlov C.S., Varganova D.L., Casazza G., Tsochatzis E., Nikolova D., Gluud C.
Abstract
Alcoholic hepatitis (AH) is a form of alcoholic liver disease. Glucocorticosteroids (GCS) are used as anti - inflammatory drugs for people with alcoholic hepatitis. Aim. To assess the benefits and harms of GCS in people with AH. Material and methods. We identified trials through electronic searches in Cochrane Hepato-Biliary's (CHB) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, and Science Citation Index Expanded. We considered for inclusion randomised clinical trials (RCTs) assessing GCS versus placebo/no intervention in adult participants with AH. We allowed co - interventions in the trial groups if they were similar. We followed Cochrane methodology, CHB Group methodology using Review Manager 5 and Trial Sequential Analysis(TSA) to perform meta - analysis (M-A), assessed bias risk of the trials, certainty of evidence using GRADE. Results and discussion. Sixteen trials fulfilled the inclusion criteria. Fifteen trials provided data for analysis (927 participants received GCS, 934 - placebo/no intervention). The GCS were administered to adult participants at different stages of AH orally or parenterally for a median of 28 days. There was no evidence of effect of GCCs on our primary outcomes all - cause mortality up to 3 months following randomisation (RR 0.90, 95% CI 0.70-1.15; n=1861), on health - related quality of life (MD - 0.04 points; 95% CI -0.11-0.03; n=377; trial = 1) (EQ-5D-3L scale), on the occurrence of serious adverse events during treatment (RR 1.05, 95% CI 0.85-1.29; n=1861). We found no evidence of a difference between the intervention groups. The risk of bias was high in all the trials except one. The certainty of evidence was very low or low. One of the trials seems to be not industry - funded. Conclusion. We found no evidence of a difference between GCS and placebo or no intervention on all - cause mortality, health - related quality of life, and serious adverse events during treatment. We cannot exclude increases in adverse events and cannot rule out significant benefits and harms of GCSs. Future trials ought to report depersonalised individual participant data.
Terapevticheskii arkhiv. 2019;91(8):52-66
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Efficacy and safety of narlaprevir/ritonavir and daclatasvir non interferon combination in population of Russian patients with chronic hepatitis C
Klimova E.A., Burnevich E.Z., Chulanov V.P., Gusev D.A., Znoyko O.O., Batskikh S.N., Kizlo S.N., Mamonova N.A., Tarkhova E.P., Krasavina E.N., Samsonov M.Y., Yushchuk N.D.
Abstract
Aim. Evaluate efficacy and safety of a combination of direct - acting antivirals narlaprevir/ritonavir with daclatasvir in patients with viral hepatitis C. Materials and methods. The study enrolled adult patients with HCV genotype 1b infection without demonstrated NS5A resistance - associated substitutions Y93C/H/N/S and/or L31F/M/V/I. Patients were treated with narlaprevir 200 mg QD, ritonavir 100 mg QD and daclatasvir 60 mg QD. Treatment duration was 12 weeks. Proportion of patients achieving sustained virological response 12 weeks after treatment (SVR12) was the primary efficacy endpoint. Results and discussion. In total, 105 (75.0%) patients were treatment with the study combination. Patients’ age varied from 21 to 69 years, the mean age being 43.2±10.9 years. There were slightly more women (55.2%), and 69 patients (65.7%) had comorbidities. SVR 12 was 89.5% (95% CI 82.0-94.7%). In 10 of 11 patients with treatment failures NS5A resistance - associated substitutions in residues 31 and/or 93 were found, as well as less clinically relevant substitutions L28M, P58S, R30Q, Q62K. Adverse events (AEs) were found in less than one half of patients (45 patients, or 42.9% in the safety population). Almost all recorded AEs were mild to moderate. Conclusion. Efficacy of treatment with a combination of narlaprevir/ritonavir and daclatasvir in treatment - naïve patients with HCV genotype 1b was close to 90%. This combination was found to be safe and well - tolerated.
Terapevticheskii arkhiv. 2019;91(8):67-74
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Follicular lymphoma: first - line selection criteria of treatment
Nesterova E.S., Kravchenko S.K., Kovrigina A.M., Gemdzhian E.G., Plastinina L.V., Babaeva F.E., Obukhova T.N., Magomedova A.U., Gaponova T.V., Kremenetskaya A.M., Vorobyev A.I.
Abstract
Follicular lymphoma (FL) is a tumor that develops from the B cells of the germinal center; characterized by recurrent and remitting course of the disease, the transformation of a tumor into diffuse large B-cell lymphoma (DLBCL) is possible. In generalized lesions and progression of FL, the most commonly used courses are R-CHOP and R-B. The choice of therapy for different cytological types, clinical and laboratory parameters remains disputable. Aim. To analyze the clinical, laboratory, morphological parameters of patients with FL, who got R-B and R-CHOP therapy; determine the criteria for selecting induction therapy. Materials and methods. The study included 203 patients with FL from 2000 to 2018. R-CHOP treatment was initiated in 126 patients, 14 of whom later received high - dose therapy (HDT) (R-DHAP: rituximab, dexamethasone, cisplatin, cytarabine) without autologous stem cell transplantation (autoSCT), 21 - HDT with autoSCT; treatment of 89 patients was limited to courses of R-CHOP and maintenance therapy with rituximab, two patients (in whom the disease progressed, despite R-CHOP therapy) were assigned the mNHL-BFM-90 program. The efficacy of treatment on various treatment regimens was evaluated primarily by overall survival. Results and discussion. R-B. 77 patients received R-B therapy. Complete remission of the disease was achieved in 47/77 (61%) patients (3 of them later developed a relapse of the disease), partial remission was achieved in 15/77 (19%) patients, in 13/77 (17%) cases progression was recorded tumors. 70 patients had 1-2 cytological type of tumor, 6 patients - 3A cytological type. In cases of progression, 3 of 13 patients (46%) were diagnosed with 3A cytological type FL. Median observation (at the time of analysis) - 34 months. R-CHOP. 89 patients with FL received high - dose therapy with R-CHOP (6-8 courses) and maintenance therapy with rituximab. In 39 (44%) patients, the disease remained in remission, and in 50 (56%), a relapse of the disease developed. 50 patients had 1-2 cytological types, 39 - 3 cytological types. In cases of recurrence of FL, a 3A cytologic type (36%) was diagnosed in 18/50 patients. Median observation - 93 months. R-CHOP + HDT and autoSCT. 21 patients after the R-CHOP courses continued (due to insufficient antitumor response) high - dose chemotherapy (HDT) and auto-SCT were performed. In 18/21 (86%) cases, complete remission of the disease was achieved and maintained, in 3 (14%) cases relapse developed. 16 patients had 1-2 cytological types, 5 - 3 cytological types. Median observation - 81 months. R-CHOP + HDT without autoSCT. 14 patients started therapy under the R-CHOP program as induction therapy, but then (due to insufficient antitumor response), the treatment was continued according to the HDT without autoSCT. 11 (79%) patients are currently in remission of the disease, in 3 (21%) - there was a relapse. 10 patients had 2 cytological types of PL, 4 - 3 cytological types. 11 (79%) patients are currently in remission of the disease, in 3 (21%) - there was a relapse. Median observation - 80 months. 7-year OS of patients with FL on RB therapy was 89% (95% CI 75-99), on R-CHOP therapy - 85% (95% CI 73-90), on R-CHOP + HDT and autoSCT - 87% (95% CI 57-100), on R-CHOP + HDT without autoSCT - 82%. 7-year PFS of FL patients on RB therapy was 70% (95% CI 75-99), on R-CHOP therapy - 44% (95% CI 73-90), on R-CHOP + HDT and autoSCT - 74% (95% CI 57-100), on R-CHOP + HDT without autoSCT - 80%. Conclusion. The R-B is most effective in FL 1 and 2 cytological types. The cytological type does not correspond to the type of tumor growth: at 3A and 3A + 3B cytological types, nodular / nodular - diffuse and diffuse types of growth are found. When choosing an induction course, one should look at the cytological type of FL. A high proliferative activity index (according to Ki67) is a predictor of resistance to R-B therapy. The absence of an interfollicular T-cell reaction in tumor tissue FL is associated with tumor chemoresistance. The presence of the bulky factor is associated (in most patients) with the FLIPI index with values from 3 to 5, and is a predictor of a poor response to therapy. Patients with bulky, high (more than 35%) Ki67 index and FLIPI from 3 to 5 in the debut of the disease as the first line therapy, it is preferable to choose the R-CHOP mode, and in the absence of (after 4-6 courses) to complete or partial remission to continue conducting the HDT.
Terapevticheskii arkhiv. 2019;91(8):75-83
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Treatment of candidemia caused by Candida albicans and Candida non - albicans in patients with hematological malignancies
Klyasova G.A., Malchikova A.O., Tandilova K.S., Blohina E.V., Parovichnikova E.N., Kravchenko S.K., Savchenko V.G.
Abstract
Aim. To study the risk factors, symptoms and outcomes of candidemia caused by C. albicans and C. non - albicans in patients with hematological malignancies. Materials and methods. The study included patients with hematological malignancies and candidemia. The diagnosis of candidemia was established according to the single isolation of Candida spp. from blood culture and the presence of symptoms of infection. Results and discussion. Over 12 years (2006-2017), candidemia was diagnosed in 75 patients aged 17 to 77 years (median 48 years). The causative agents of candidemia were C. albicans in 34.7% of patients, C. non - albicans - in 65.3%. Candidemia caused by C. albicans prevailed in patients of the older age group (median 56.5 years, p=0.04) and in patients with lymphoma (61.5%, p=0.01) with colonization of the gut by the same species of Candida (88.5%, p=0.002). Isolation of C. non - albicans from blood culture was more common in patients with acute leukemia (51%, p=0.01) and in recipients of allogeneic hematopoietic stem cells (22.5%, p=0.01). The ability to form biofilms was observed more frequently among C. non - albicans (59.2%) than C. albicans (19.2%, p=0.001). The clinical symptoms of candidemia were non - specific (fever was in 97%). Septic shock developed in 25 (33%) patients with comparable frequency in both groups. Concomitant infections was also comparable (73% vs. 73.5%). Overall 30-day survival in patients with candidemia caused by C. albicans and C. non - albicans was 61.2% and 61.5%. Treatment with echinocandin was associated with increase of survival compared to other antifungal agents among patients with C. albicans candidaemia (88.9% versus 40%, p=0.02) and among C. non - albicans (77.3% versus 47.8%). Conclusion. C. non - albicans constituted a high proportion among causative agents of candidemia. High mortality rate was observed in both groups. Initial therapy with echinocandin was associated with increase of survival.
Terapevticheskii arkhiv. 2019;91(8):84-92
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Sorafenib - induced thyroiditis in patient with a relapse of acute myelomonocytic leukemia with FLT3-ITD mutation
Balzhanova Y.B., Parovichnikova E.N., Sokolov A.N., Ryzhko V.V., Samtsova M.A., Gribanova E.O.
Abstract
Sorafenib has been used in acute myeloid leukemias with FLT3-ITD mutation improving the outcomes. However the high incidence of treatment - emergent adverse event may be associated with treatment using sorafenib with cytotoxic chemotherapy. We have reported a case of severe thyroiditis in patient with a relapse of acute myelomonocytic leukemia.
Terapevticheskii arkhiv. 2019;91(8):93-97
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New directions of pharmacotherapy of immune - inflammatory rheumatic diseases
Nasonov E.L.
Abstract
Deciphering immunopathogenesis, expanding the scope of diagnostics and developing new methods for treating human autoimmune diseases are among the priority areas of XXI century medicine. Particularly widely autoimmune pathology is presented in immunoinflammatory rheumatic diseases (IIRD), such as rheumatoid arthritis, systemic lupus erythematosus, systemic scleroderma, systemic vasculitis associated with the synthesis of antineutrophilic cytoplasmic antibodies, Sjogren's syndrome, idiopathic inflammatory myopathies and other other types of others. Deciphering the pathogenesis mechanisms of IIRD created the prerequisites for improving pharmacotherapy, which in the future should lead to a dramatic improvement in the prognosis for these diseases. The review discusses new approaches to IIRD pharmacotherapy associated with the inhibition of tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β, IL-17, IL-23, and the prospects for using Janus kinase inhibitors, depending on the prevailing pathogenesis mechanisms - autoimmunity or autoinflammation.
Terapevticheskii arkhiv. 2019;91(8):98-107
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Patient's way from acute pulmonary embolism to chronic thromboembolic pulmonary hypertension: diagnostic and treatment options
Edemskiy A.G., Ivanov S.N., Kliver E.N., Novikova N.V., Galstyan M.G., Sevastyanov A.V., Cherniavsky A.M.
Abstract
Сhronic thromboembolic pulmonary hypertension (CTEPH) is a serious, under - diagnosed but potentially curable complication of pulmonary embolism (PE) due to medicine advancements. Lack of specific symptoms and signs makes its diagnosis challenging, requiring clinicians to be ready to suspect its presence in patients with dyspnea of unknown origin or persistent symptoms after the pulmonary embolism event. The success of the treatment of this disease depends entirely on early diagnosis. The complexity of the differential diagnosis is due to the problematic aspects including the lack of doctors' awareness of both the pathology itself and the possibilities of its modern treatment. Recently, in our country, the problem of the availability of expert centers with sufficient experience in providing highly specialized medical care to this rather difficult category of patients who need specific therapy has become very actual. The aim of this review is to provide contemporary information about epidemiology, pathophysiology, and clinical features of treating patients with CTEPH, and also, to increase awareness of potential PE→CTEPH transformation. In the article a 4-year - period of experience of the Meshalkin National Medical Research Center on management of CTEPH patients has been presented.
Terapevticheskii arkhiv. 2019;91(8):108-114
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Micro-RNA as a new biomarker of activity of the cytochrome system P-450: significance for predicting the antiplatelet action of P2Y12 receptor inhibitors
Rytkin E.I., Mirzaev K.B., Bure I.V., Sychev D.A.
Abstract
MicroRNAs are short non - coding RNAs that correlate with the levels of platelet activation which can be utilized as a biomarker when guiding P2Y12 inhibitors therapy. In this literature review, the perspectives of microRNA as a novel biomarker are discussed when guiding P2Y12 inhibitors therapy among the patients with coronary artery disease.
Terapevticheskii arkhiv. 2019;91(8):115-117
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The relationship between the combined use of various proton pump inhibitors with antiplatelet drugs and the risk of cardiovascular complications
Ostroumova O.D., Kochetkov A.I., Pereverzev A.P., Kravchenko E.V., Kazjulin A.N., Andreev D.N., Pavleeva E.E.
Abstract
In the article the problem of the combined use of clopidogrel and various proton pump inhibitors (PPIs) in terms of cardiovascular complications risk and stent thrombosis is considered. The results of meta - analyses and a systematic reviews affecting this issue are represented in detail. The inter - drug interactions mechanisms of various PPIs with clopidogrel based on the characteristics of the metabolism in the liver cytochromes system are discussed. The authors conducted a search, systematization and analysis of studies regarding the association between cardiovascular risk and combined use of individual medications from PPI class with clopidogrel, and these results are presented in the review. Currently available data do not allow to answer the question about the differences between individual PPIs in their impact on the risk of adverse cardiovascular events due to the small number of such studies, design heterogeneity, differences in the inclusion criteria and end points as well as in the rate of administration of individual PPIs.
Terapevticheskii arkhiv. 2019;91(8):118-126
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The clinical significance of disorders of the motor function of the esophagus, stomach and duodenum
Trukhmanov A.S., Ivashkina N.Y.
Abstract
The purpose of the review is to determine the relationship between the clinical symptoms of diseases and disorders of the motor function of the esophagus, stomach and duodenal bulb, to present modern methods of their diagnosis and pathogenetic principles of treatment of diseases. Depending on the pathogenesis, it is possible to distinguish secondary motility disorders resulting from organic lesions, and primary (functional) changes. The emergence of clinical symptoms is associated with impaired motor - evacuation function of the digestive tract, which can be divided into two large groups: changes in the peristaltic activity of the organ wall and the work of the sphincter apparatus. The basis of the regulation of motility of the esophagus, stomach and duodenum is the interaction of nervous and humoral factors, the central processing of impulses is carried out in the cerebral cortex. In case of violation of the coordinated action of inhibitory and excitatory regulation systems, pathological contractile activity occurs, which manifests itself as hypo - or hyper - motor dyskinesia. X-ray, ultrasound, high resolution manometry of the esophagus, pH-meter, scintigraphy, computed tomography, antroduodenal manometry and a number of others are used to diagnose disorders of the motor function of the digestive tract, which can determine the mechanism of the development of symptoms and prescribe pathogenetic treatment to the patient. Thus, the occurrence of clinical symptoms is associated with changes in the motor - evacuation function of the digestive tract due to a violation of the coordinating action of inhibitory and excitatory factors. The use of modern diagnostic methods for the study of motor function makes it possible to determine the mechanism for the development of clinical symptoms, which allows the patient to prescribe an effective pathogenetic treatment.
Terapevticheskii arkhiv. 2019;91(8):127-134
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Gastroesophageal reflux disease and esophagitis associated with the use of drugs: the modern state of the problem
Osadchuk A.M., Davydkin I.L., Gricenko T.A., Osadchuk M.A.
Abstract
From the standpoint of evidence - based medicine, the ability of various drugs to induce the development of gastroesophageal reflux disease and esophagitis is considered. Thus, all known drugs can be divided into 3 groups: drugs that have the ability to reduce pressure in the lower esophageal sphincter, for example, β-adrenoreceptor agonists, α-adrenoreceptor antagonists, anticholinergics, calcium channel blockers, nitrates, benzodiazepines (diazepam), estrogen, progesterone, aminophylline (theophylline), tricyclic antidepressants, selective serotonin reuptake inhibitors, glucocorticosteroids; means providing a direct damaging effect on the esophageal mucosa, as well as lowering its resistance reflyuktatu, e.g., bisphosphonates, acetylsalicylic acid / non - steroidal anti - inflammatory agents, anticoagulants, antiplatelet drugs, iron preparations, ascorbic acid, potassium chloride, quinidine, phenytoin, calcium dobesilate, 131I sodium iodide, antibiotics (tetracycline, doxycycline, clindamycin, ciprofloxacin, ornidazole, clindamycin, rifampicin), antitumor agents; drugs that impede gastric emptying: calcium channel blockers, anticholinergics. These data can be used in practice in the choice of treatment tactics, especially in individuals with a diagnosis of gastroesophageal reflux disease or heartburn.
Terapevticheskii arkhiv. 2019;91(8):135-140
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Underwater rocks of anti - helicobacter therapy
Livzan M.A.
Abstract
The publication was prepared to systematize the data of the literature and our own research on the practice of effective eradication therapy of patients with HP-associated diseases. The most significant factors influencing the effective implementation of modern anti-Helicobacter therapy regimens should be adherence of physicians to the use of clinical guidelines, patient adherence to prescriptions and recommendations of specialists, as well as adherence to eradication treatment protocols.
Terapevticheskii arkhiv. 2019;91(8):141-147
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Some practical issues in the management of patients with decompensated liver cirrhosis
Fedosina E.A., Byeverov A.O., Bogomolov P.O., Staroverova N.P.
Abstract
The natural course of cirrhosis is characterized by a shift from a compensated stage without clinical manifestations to a subsequent decompensated stage, which is characterized by the development of obvious clinical symptoms, the most frequent of which are ascites, bleeding from varicose veins, bacterial infections, encephalopathy. The articles and reviews of recent years emphasize the importance of etiotropic treatment of liver cirrhosis at any stage, including the final one. In addition, pathogenetic and symptomatic therapy aimed at treating complications of cirrhosis of the liver: ascites, dilution hyponatremia, gastrointestinal bleeding, bacterial infections, and kidney damage comes to the forefront at the stage of decompensation, which allows the patient to be on the waiting list for liver transplantation. This category of patients, as a rule, is difficult to treat and has features and subtleties of reference.
Terapevticheskii arkhiv. 2019;91(8):148-154
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Diagnosis and treatment of acute low back pain
Parfenov V.A., Golovacheva V.A.
Abstract
Low back pain (LBP) is frequent cause for visit to the doctor and common cause of disability. Modern experts’ recommendations for diagnostics and treatment of acute LBP are presented. Common mistakes, difficulties in diagnostics and treatment of acute LBP are discussed. Diagnosis of non - specific acute LBP is based on clinical examination and exclusion of specific causes of back pain. Instrumental studies are not needed in most cases of acute LBP. Key steps in the treatment of patients with acute non - specific LBP are to inform of patients about good prognosis of pain, to recommend daily activity and avoidance of bed rest, to prescribe nonsteroidal anti - inflammatory drug for pain reducing. Effectiveness of vitamins B in acute LBP is discussed.
Terapevticheskii arkhiv. 2019;91(8):155-159
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Hypervitaminosis B12 - a new marker and predictor of prognostically unfavorable diseases
Podzolkov V.I., Dragomiretskaya N.A., Dambaeva O.T., Auvinen S.T., Medvedev I.D.
Abstract
A high serum vitamin B12 level (hypercobalaminemia) is a underestimated anomaly. Clinically, it can be paradoxically accompanied by signs of deficiency, which are related to defects in tissue uptake of vitamin B12. The increase in the level of serum cobalamin occurs mainly in serious diseases that require early diagnosis: hemoblastosis, liver and kidney diseases, etc. This review presents data on the metabolism of vitamin B12 and the potential significance of increasing its level as a marker for the early diagnosis of these diseases.
Terapevticheskii arkhiv. 2019;91(8):160-167
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