Vol 94, No 7 (2022)

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Full Issue


Chronic thromboembolic pulmonary hypertension: from pathogenesis to the choice of treatment tactics

Valieva Z.S., Martynyuk T.V.


Presents data on the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH), which serve as a rationale for approaches to the choice of treatment. CTEPH usually begins with persistent obstruction of the large and/or medium pulmonary arteries by organized thrombi. Impaired lysis of thrombi may be associated with abnormal fibrinolysis, hematological or autoimmune diseases. The molecular processes underlying the lesions of small vessels are not fully understand. The degree of small-vessel disease has a significant impact on the severity of CTEPH and postoperative outcomes. The CTEPH treatment has evolved with the development of three directions – pulmonary endarterectomy, balloon angioplasty of pulmonary arteries and the use of specific therapy used for pulmonary arterial hypertension. The paper demonstrates the possibilities of a multimodal approach in the treatment of this category of patients.

Terapevticheskii arkhiv. 2022;94(7):791-796
pages 791-796 views

Original articles

Seх differences in treatment of acute coronary syndrome patients. Data from federal registry of acute coronary syndrome 2016–2019

Sagaydak O.V., Oschepkova E.V., Chazova I.E.


Introduction. Management of patients with acute coronary syndrome (ACS) is usually universal, regardless of gender, age, and ethnicity. But often in practice, gender and age influence medical decisions, and patients do not receive proper medical care. Medical care for patients with ACS was analyzed by gender according to the federal register of ACS data.

Aim. To analyze the influence of the patient's gender on the course of the disease and on the provision of medical care to patients with ACS who underwent treatment in 2016–2019.

Materials and methods. The data of 95 586 cases was analyzed. Two groups were identified: men (n=59 442, 62.2%) and women (n=36 144, 57.8%).

Results. Anamnesis analysis has revealed, that women were often more burdened with concomitant diseases and had a higher risk on the GRACE scale at admission. It was demonstrated that men underwent revascularization on average significantly more often than women (51.9% versus 32.5%, respectively, p<0.001). In women, conservative therapy was more. When compared with the appropriate use criteria for coronary revascularization, it was shown that more than 70% of women in whom a conservative treatment strategy was chosen, it was expedient to undergo myocardial revascularization using percutaneous coronary intervention.

Conclusion. Gender differences were revealed in the course of the disease, as well as in the choice of treatment by doctors. Women are characterized by a later manifestation of the disease, more often in the form of ST-ACS. The course of the disease in women is associated with a higher comorbidity, atypical symptoms and later call for help. A conservative approach prevails in the choice of ACS treatment tactics in women.

Terapevticheskii arkhiv. 2022;94(7):797-802
pages 797-802 views

Biochemical markers of thrombotic complications in the acute period of ischemic stroke

Kochetov A.G., Lyang O.V., Zhirova I.A., Ivoylov O.O.


Aim. To study the profile of biochemical markers of the hemostasis system, to clarify their role and relationships in the pathogenesis of the development of thrombotic complications (TC) of ischemic stroke (IS) and the associated assessment of the possibilities of their diagnostic application.

Materials and methods. The study group included 302 patients (164 men, 138 women) who were admitted to the hospital with a diagnosis of IS within 24 hours of the onset of the disease. The diagnosis was confirmed by computed tomography. The average age of patients was 69 (50–88) years. Blood was taken from all patients on the 1st day of the disease to determine the profile of analytes presumably associated with the pathogenesis of TC. Levels of homocysteine, protein C inhibitor, thrombomodulin, plasminogen, tissue plasminogen activator, urokinase, plasminogen activator type 1 inhibitor, t-PA/PAI-1 complex, vitronectin, plasmin-α2-antiplasmin complex, D-dimer, fibronectin were determined in blood serum by ELISA.

Results. TC in the acute period of IS (up to 21 days) were recorded in 32 (10.6%, 95% CI 7.37–14.3) patients, of which pulmonary embolism was observed in 27 (8.94%, 95% CI 5.98–12.4) patients, deep vein thrombosis in 5 (1.66%, 95% CI 0.47–3.47) patients. The results of the study of a panel of specific proteins involved in pathogenetic processes accompanying necrosis of brain tissue in IS demonstrated that of the entire list of markers of the hemostasis system activation selected for the study, the most significant are: the concentration of fibronectin in the prognosis of the absence of TC with a threshold value of more than 61 mkg/ml and OR 4.4 (95% CI 1.5–12.9, p=0.011), and the concentration of the t-PA/PAI-1 complex in the prognosis of the development of TC with a threshold value of more than 14 ng/ml and OR 11.3 (95% CI 1.18–109.3, p=0.03).

Conclusion. The significance of the t-PA/PAI-1 complex and fibronectin as markers of TC in IS may be due to a violation of the activation processes of the fibrinolytic link of hemostasis and the accumulation of non-deposited compounds that damage the vascular wall.

Terapevticheskii arkhiv. 2022;94(7):803-809
pages 803-809 views

Chronic kidney disease in outpatients with arterial hypertension: clinical characteristics and treatment efficacy (according to the national registry)

Oschepkova E.V., Aksenova A.V., Orlovsky A.А., Chazova I.E.


Аim. To investigate the clinical characteristics and quality of treatment (according to the national guidelines) of patients with arterial hypertension (AH) and chronic kidney disease observed in primary health care.

Materials and methods. The study was carried out on the basis of the AH registry data (n=43 133; 2005–2019 years). Glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula; renal structure and albuminuria were not evaluated. The analysis was performed using the SPSS software (version 22; SPSS Inc).

Results. The creatinine level was assessed in 60% of patients, 23.6% of them had decreased eGFR<60 ml/ min/1.73 m2. The incidence of co-morbid CVD and type 2 diabetes in patients with hypertension increased markedly with a decrease in eGFR (1–4 groups): the incidence of coronary artery disease increased 1.8 times (up to 72.5%), myocardial infarction 1.7 times (up to 20.6%), chronic heart failure – 2 times (up to 84.0%), atrial fibrillation – 10 times (up to 18.3%), history of stroke – 3.7 times (up to 15.3%) and type 2 diabetes 2.4 times (up to 32.8%). Achievement of target goals of CV risk factors was not enough: systolic BP – less than 50% of patients, triglycerides – less than 7%, LDL-C in high and very high CVD risk patients – less than 13%.

Conclusion. Conducting timely assessment of renal function, drug therapy and lifestyle changes in patients with AH and decreased renal functional could prevent severe kidney damage, the development of CV complications, chronic renal failure and reduce mortality.

Terapevticheskii arkhiv. 2022;94(7):810-815
pages 810-815 views

Combined use of the GRACE ACS risk score and comorbidity indices to increase the effectiveness of hospital mortality risk assessment in patients with acute coronary syndrome

Zykov M.V., Dyachenko N.V., Velieva R.M., Kashtalap V.V., Barbarash O.L.


Aim. To assess the possibilities of using comorbidity indices together with the GRACE (Global Registry of Acute Coronary Events) scale to assess the risk of hospital mortality in acute coronary syndrome (ACS).

Materials and methods. The registry study included 2,305 patients with ACS. The frequency of coronary angiography was 54.0%, percutaneous coronary intervention (PCI) – 26.9%. Hospital mortality with ACS was 4.8%, with myocardial infarction – 9.4%. All patients underwent a comorbidity assessment according to the CIRS system (Cumulative Illness Rating Scale), according to the CCI (Charlson Comorbidity Index) and the CDS (Chronic Disease Score) scale, according to their own scale, which is based on the summation of 9 diseases (diabetes mellitus, atrial fibrillation, stroke, arterial hypertension, obesity, peripheral atherosclerosis, thrombocytopenia, anemia, chronic kidney disease). All patients underwent a mortality risk assessment using the GRACE ACS Risk scale.

Results. It was found that the CDS and CIRS indices are not associated with the risk of hospital mortality. With CCI≥3, the frequency of death outcomes increased from 4.1 to 6.1% (χ2=4.12, p=0.042). With an increase in the severity of comorbidity from minimal (no more than 1 disease) to severe (4 or more diseases) according to its own scale, hospital mortality increased from 1.2 to 7.4% (χ2=23.8, p<0.0001). In contrast to other scales of comorbidity, our own model more efficiently estimates the hospital prognosis both in the conservative treatment group (χ2=8.0, p=0.018) and in the PCI group (χ2=28.5, p=0.00001). It was in the PCI subgroup that the comorbidity factors included in their own model made it possible to increase the area under the ROC curve of the GRACE scale from 0.80 (0.74–0.87) to 0.90 (0.85–0.95).

Conclusion. CCI and its own comorbidity model, but not CDS and CIRS, are associated with the risk of hospital mortality. The model for assessing comorbidity on a 9-point scale, but not CCI, CDS and CIRS, can significantly improve the predictive value of the GRACE scale.

Terapevticheskii arkhiv. 2022;94(7):816-821
pages 816-821 views

Нospital outcomes of coronary artery bypass grafting in patients with coronary heart disease with previous percutaneous coronary intervention

Kremneva L.V., Suplotov S.N., Abaturova O.V., Stognii N.I., Shalaev S.V.


Aim. Evaluation of the frequency hospital cardiovascular events in groups of patients with stable angina who underwent percutaneous coronary interventions (PCI) with stenting of the arteries before coronary bypass surgery, or who did not have previous myocardial revascularization.

Materials and methods. The 120 patients with stable angina who underwent routine coronary artery bypass grafting were examined. Group composition: Men 80.8%, age – 58±7.6, duration of coronary heart disease – 6±5.7 years, history of myocardial infarction (MI) 77.5%. Arterial hypertension was present in 92.5%, diabetes mellitus in 12.5% of patients. Multivessel coronary artery disease in 72.5% of patients. 28 (23.4%) patients had previously undergone PCI with stenting of the coronary arteries. The period from PCI to coronary bypass surgery was 20±32.6 months. Coronary bypass surgery on-pump was performed in 88.3%, coronary bypass surgery on off-pump in 11.7%. The number of distal anastomoses ranged from 1 to 4.

Results. There were no differences in clinical and angiographic indicators, pharmacotherapy, and operation characteristics between the groups of patients who were subjected to or did not have PCI before coronary bypass surgery. There were no differences between the analyzed groups of patients in the frequency of cardiac death (0 and 1.1%, p=0.58), non-fatal MI (3.6% and 9.8%, p=0.29), stroke (0 and 1.1%, p=0.58), acute heart failure (11.7% and 34.8%, p=0.06), the number of patients with paroxysms of atrial fibrillation (28.6% and 17.4%, p=0.94), the proportion of patients with resternotomies (3.6% and 3.3%, p=0.94) and gastrointestinal bleeding (3.6% and 4.3%, p=0.86).

Conclusion. PCI with coronary artery stenting, prior to coronary bypass surgery, does not affect the frequency of post-operative hospital cardiovascular and hemorrhagic complications.

Terapevticheskii arkhiv. 2022;94(7):822-826
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Multiple myeloma: response to treatment and survival of patients according to the interim analysis of the Russian observational, retrospective-prospective, multicenter cohort study (MULTISPECT)

Ptushkin V.V., Kunst M.A., Mitina T.A., Konstantinova T.S., Rachkova N.N., Shelekhova T.V., Elykomov I.V., Kuchma G.B., Farizova K.O., Vinogradova O.Y., Nikitin E.A., Pashanov E.D.


Aim. The primary objective of the interim analysis of the MULTISPECT study was to evaluate the short-term efficacy of the treatment and long-term outcomes in cohorts of primary and pretreated patients with multiple myeloma (MM) receiving treatment in actual clinical practice in various regions of the Russian Federation. Secondary objectives were a description of the main characteristics of patients; analysis of the most commonly used therapy regimens of the 1st and later lines and the sequence of their changes; evaluation of the response to therapy. Additional objectives included evaluation of the effect of the new COVID-19 coronavirus infection on the course of MM in patients.

Materials and methods. The study is an observational retrospective-prospective multicenter cohort study. For its implementation, a structured database of patients with MM was used, provided by hematologists of the centers affiliated for the study.

Results. The study included 1,294 patients (cohort 1 – 806, cohort 2 – 488). In both cohorts, patients aged 60–69 years were in the majority. 3 lines of therapy (L1, L2, L3) were used for cohort 1; in cohort 2, the 4th line of therapy was also used in 2 patients. The therapy regimens were analyzed for 290 (22.41%) of all patients in the study. Responses to therapy were analyzed for 214 patients of cohort 1 and 109 patients of cohort 2. Autologous and allogeneic hematopoietic stem cell transplantations were carried out for a limited proportion of patients in both cohorts. At the end of the study and upon presentation of its results, the status of patients was the following: 96% of patients in cohort 1 and 89% in cohort 2 were alive. The therapy regimens in both cohorts were characterized by variability. The most commonly used regimens in each of the lines of therapy have been identified. The most used therapy regimen in patients with MM of both cohorts was the VCD-regime. Rd-regime in cohort 1 and RD-regime in cohort 2 were the second most frequent used regimens. In patients of both cohorts, the therapy regimens including Bortezomib were most often used.

Conclusion. The variety of therapy regimens used to treat MM in actual clinical practice may be due to the factors of availability of new medicines and updated recommendations for the treatment of the disease. Further, in the context of this study, a more detailed analysis of the efficacy of certain therapy regimens in the 1st and later lines on progression free survival and overall survival of MM patients should be carried out.

Terapevticheskii arkhiv. 2022;94(7):827-835
pages 827-835 views

Withdrawal syndrome after tyrosine kinase inhibitors discontinuation in patients with chronic myeloid leukemia

Chelysheva E.Y., Petrova A.N., Shukhov O.A., Bykova A.V., Nemchenko I.S., Gurianova M.A., Tsyba N.N., Turkina A.G.


Background. Withdrawal syndrome (WS) – a musculoskeletal pain after discontinuation of tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukemia (CML) – has been described in the treatment-free remission (TFR) studies. The pathophysiological mechanisms and predisposing factors of WS have not been well established.

Aim. Our aim was to evaluate clinical features and factors associated with WS in the Russian cohort of CML patients who discontinued TKI therapy.

Materials and methods. WS was evaluated in total of 183 CML patients with chronic phase and sustained deep molecular response (DMR). WS was defined as a musculoskeletal pain newly observed after TKI cessation or as a worsening of previously observed symptoms.

Results. DMR loss free survival at 36 months was 49% and 43% in prospective and retrospective groups respectively (p=0.96) with mеdian (Me) time of observation 33 months (range 1–136). WS was observed in 49 (27%) patients: grade 1–2 was in 45 (92%) patients, grade 3 – in 4 (8%) patients. Me time to WS occurrence was 2 months (range 1–7), Ме duration of WS was 5 months (range 1–35). WS was resolved in 14 of 15 patients with molecular relapse after 1–3 months of TKI re-initiation and was decreased in 1 patient. WS was completely resolved in 31 of 34 patients who continued remained in TFR and decreased in 3 patients. WS was resolved spontaneously or with nonsteroidal anti-inflammatory drugs in 14 (45%) and 17 (55%) patients accordingly. Older age (p<0.0001), longer duration of TKI therapy (p<0.0001) and presence of locomotion system diseases (p=0.022) were observed in patients with WS. No WS was observed in pregnant patients (р<0.001). Survival without DMR loss at 12 months after TKI stop was 66 and 42% in patients with and without WS accordingly (р=0.095).

Conclusion. The rate of WS was 27% that is in a good concordance with the data of the other TFR studies. A longer period of TKI exposure, older age and the history of locomotion system diseases were associated with the development of the WS. We found for the first time that WS was not observed in patients with pregnancy. There was no association of WS development and the rate of molecular relapses.

Terapevticheskii arkhiv. 2022;94(7):836-843
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Prevalence and clinical associations of iron deficiency in patients with decompensated heart failure, depending on the diagnostic criteria used for iron deficiency

Kobalava Z.D., Lapshin A.A., Tolkacheva V.V., Galochkin S.A.


Aim. To compare the frequency of iron deficiency (ID) in patients with decompensated heart failure (HF), defined by international guideline criterion – ferritin <100 ng/ml or ferritin from 100 to 299 ng/ml with TSAT<20% (criterion A) and by bone marrow biopsy criterion – TSAT<19.8% and serum iron <13 µmol/l (criterion B); to evaluate the effect of ID, diagnosed on the basis of different ID criteria, on NT pro-BNP, sST2, CRP levels and New York Heart Association (NYHA) functional classes (FC) distribution between groups with ID and without ID.

Materials and methods. The study included 223 patients (median age 73 [65; 82] years, 58% males) who were hospitalized to V.V. Vinogradov Moscow City Clinical Hospital No. 64 with decompensated HF. All patients underwent a standard physiological examination, laboratory and instrumental studies, including determination of NT-proBNP, sST2, CRP, and ferrokinetic parameters (serum iron, transferrin, ferritin). TSAT was calculated as: serum iron / transferrin × 3.98. NYHA FC was determined according to Heart Failure Severity Rating Scale score. All patients underwent echocardiography to assess the ejection fraction of the left ventricle.

Results. According to criterion A ID was detected in 89% (n=199) of patients. There were no significant differences between levels of CRP, NT-proBNP and sST2. According to criterion B ID was detected in 70% (n=156) of patients. In the ID group, higher levels of CRP (15.1 mg/l vs 6.2 mg/l, p<0.001), NT-proBNP (5422 pg/ml vs 2380 pg/ml, p<0.001) and sST2 (59.6 ng/ml vs 42 ng/ml, p=0.02) were detected. Intravenous FCM admission according to current international guidelines (diagnosis of ID according to criterion A) is recommended to 57% of patients included in this study. Both methods formed groups with ID, in which patients had higher NYHA FC compared to groups without ID. According to current clinical guidelines, iron deficiency should be assessed according to method 1. More than half of patients (57, n=127) have indications for intravenous FCM to reduce risk of HF hospitalizations.

Conclusion. The frequency of ID in patients with decompensated heart failure varies from 70 to 89% depending on the criterion used to diagnose ID, but in any case, remains high. Intravenous FCM should be prescribed in 57% (n=127) of patients. Criterion B, validated against the gold standard of diagnostics, unlike criterion A, makes it possible to form groups of patients with ID and without ID, significantly differing in CRP, NT-proBNP, and sST2 levels.

Terapevticheskii arkhiv. 2022;94(7):844-849
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Pharmacoeconomics analysis of using a fixed combination of budesonide/formoterol in patients with asthma in the health care system of the Russian Federation

Zyryanov S.K., Dyakov I.N., Aisanov Z.R.


Aim. To evaluate the budgetary impact of using budesonide + formoterol (Symbicort® Turbuhaler®) as maintenance therapy in real clinical practice compared with standard therapy for asthma of varying severity: for mild asthma with on-demand salbutamol; for moderate and severe asthma – with the drug salmeterol + fluticasone and salbutamol on demand.

Materials and methods. A static mathematical model was built to assess the impact on the budget when introducing the drug budesonide + formoterol (Symbicort® Turbuhaler®) in the treatment of asthma into clinical practice from the point of view of the state. Demographic data was taken from the official data of the Federal State Statistics Service. Direct medical costs included the cost of medicines, the cost of hospitalization of patients associated with the development of asthma exacerbations, and the cost of scheduled outpatient visits. Indirect costs considered the loss of GDP due to hospitalization of patients against the background of asthma exacerbations. A one-way sensitivity analysis was performed to confirm the robustness of the study results.

Results. Assessment of direct costs in the treatment of mild, moderate and severe asthma showed that a gradual increase in the proportion of patients receiving the drug budesonide + formoterol (Symbicort® Turbuhaler®) over the years to 5.5, 7.7 and 9.7% accordingly, led to an increase in the cost of pharmacotherapy over 3 years by 1.7 billion rubles, while direct non-drug costs associated with the treatment of complications that developed during the treatment of asthma decreased by 8.3 billion rubles. Thus, the reduction in total direct costs amounted to RUB 6.7 billion. At the same time, indirect costs decreased by 6.0 billion rubles. The total reduction in all costs (direct and indirect) when switching patients to budesonide + formoterol (Symbicort® Turbuhaler®) amounted to 12.5 billion rubles. In addition, the use of the drug budesonide + formoterol (Symbicort® Turbuhaler®) resulted in a decrease in the number of exacerbations: in the first year by 3137, in the second by 4393 and in the third by 5534 cases. A total of 13 064 asthma exacerbations were prevented over 3 years.

Conclusion. Increasing the proportion of patients with asthma of varying severity receiving therapy with budesonide + formoterol (Symbicort® Turbuhaler®) will reduce the financial burden on both the healthcare system and the budgetary system.

Terapevticheskii arkhiv. 2022;94(7):850-858
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Pregnancy in paroxysmal nocturnal hemoglobinuria: from survival to life

Vinogradova M.A., Kulagin A.D., Shmakov R.G.


Background. Pregnancy in paroxysmal nocturnal hemoglobinuria (PNH) patients has historically been a high-risk situation. The combination of chronic complement-mediated hemolysis caused by the disease and physiological activation of the complement system during pregnancy, significantly worsened the prognosis for the life. For a long time, there were no effective methods for the PNH treatment, and pregnancy in patients seemed to be extremely risky, as it significantly increased the risk of life-threatening complications. The advent of targeted therapy with eculizumab turned the prognosis of this disease upside down: patients began not only to survive, but also to live comparable to healthy people. A comparative analysis of the course and outcomes of pregnancy in patients with PNH treated with eculizumab and in patients without targeted therapy was carried out.

Aim. The study was to evaluate the course and outcomes of pregnancy in patients with PNH, depending on the therapeutic approach.

Materials and methods. We analyzed data from 57 pregnancies in 49 women (31 used eculizumab, 26 with supportive care only) observed at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology or with remote consultation (23 clinics from 19 cities of Russia).

Results. The high probability of pregnancy complications and its adverse outcomes outside of targeted therapy indicates the vital need for its use: all observations were accompanied by complications of varying severity. The course of pregnancy with the eculizumab is generally more favorable: an apparently higher rate of live births and a lower likelihood of complications are registered. Without increasing the incidence of complications, eculizumab significantly improves pregnancy outcomes for both mother and fetus, and does not adversely affect the health of newborns.

Conclusion. Thus, eculizumab allows not only to increase the survival rate of patients with PNH, but also to comprehensively improve their quality of life, including the possibility of safe childbirth.

Terapevticheskii arkhiv. 2022;94(7):859-864
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Data from the Russian Severe Asthma Registry (RSAR)

Belevskiy A.S., Nenasheva N.M., Kravchenko N.Y., Makar'iants N.N., Kuntsev D.A.


Aim. Creation of the "Russian register of patients with severe asthma" and obtaining data on the population characteristics of patients with severe asthma (SA), the prevalence of SA phenotypes, treatment outcomes and the degree of disease control.

Materials and methods. Observational non-interventional study, which consists in the data analysis obtained on the basis of registration cards of the Russian Register of Patients with Severe Bronchial Asthma, data collection in which was carried out on the Oracle XE platform. Statistical data processing was carried out using Power BI, PSPP and Microsoft Excel spreadsheets.

Results. The study included 4376 adult patients (mean age 60.6±13.5 years, 65% women) diagnosed with SA from 57 regions of Russia for the period from June 2018 to December 2021. T2 inflammation was detected in 94.8% of patients when determining blood eosinophils and IgE of blood serum; 69% of patients with SA corresponded to the allergic phenotype. 83.3% of patients had no control of BA and 53% had 1 or more exacerbations of BA per year. 8% of patients received systemic corticosteroids as a permanent therapy, while biologics – 10.6%.

Conclusion. The vast majority of adult patients with SA correspond to the T2 phenotype, have uncontrolled asthma with a high frequency of exacerbations and reduced lung function. A more favorable course of the disease was noted in patients receiving biological therapy, which requires appropriate measures to increase the possibility of access to this type of therapy.

Terapevticheskii arkhiv. 2022;94(7):865-871
pages 865-871 views

New opportunities for preventive anti-inflammatory therapy in the management of patients with moderate and severe COVID-19

Gorelov A.V., Kalyuzhin O.V., Bagaeva M.I.


The specific feature of new coronavirus infection (COVID-19) is high risk of hyperinflammatory response or cytokine storm development, which underly the pathogenesis of several life-threatening conditions and determine the disease outcomes. Pathophysiological features of COVID-19 justify the search of effective drugs capable to control the hyperinflammatory response.

Aim. To evaluate the efficacy and safety of Aterixen® (1-[2-(1-Мethylimidazol-4-yl)-ethyl]perhydroazin-2,6-dion) for achieving clinical improvement in adult patients hospitalized with moderate and severe COVID-19.

Materials and methods. Multicenter, adaptive, randomized, double-blind, placebo-controlled, phase III study to evaluate the efficacy and safety of Aterixen® , tablets, 100 mg, in patients with COVID-19. The study analysis included 116 patients who, by randomization, were divided into 2 groups: 57 patients were included in the Aterixen® drug group and 59 patients were in the placebo group.

Results and conclusion. Obtained results have shown high efficacy and statistically significant superiority of Aterixen® over placebo. Thus, it allows us to consider it as viable medication for COVID-19 pathogenetic therapy.

Terapevticheskii arkhiv. 2022;94(7):872-875
pages 872-875 views

Peculiarities of hemostasis in patients with COVID-19

Kalinskaya A.I., Dukhin O.A., Molodtsov I.A., Anisimova A.S., Sokorev D.A., Elizarova A.K., Sapozhnikova O.A., Glebova K.A., Shakhidzhanov S.S., Spiridonov I.S., Ataullakhanov F.I., Shpektor A.V., Vasilieva E.Y.


Aim. Analysis of the dynamics of different stages of clot formation and its lysis in patients with different COVID-19 severity.

Materials and methods. We prospectively included 58 patients with COVID-19 (39 patients with moderate disease severity and 18 patients with severe disease) and 47 healthy volunteers as a control group. All participants underwent the assessment of flow-mediated dilation (FMD) of brachial artery, impedance aggregometry, rotational thromboelastometry and thrombodynamics. Von Willebrand factor antigen (vWF:Ag) quantification was also performed in patients with COVID-19. Measurements were repeated on the 3rd and 9th day of hospitalization.

Results. Compared to the control group, patients with COVID-19 showed reduced values of platelet aggregation and greater values of the clot growth rate, as well as its size and density. On the first day of hospitalization, we found no differences in the activity of plasma hemostasis and endogenous fibrinolysis between subgroups of patients. With the progression of the disease, the growth rate and size of the clot were higher in the severe subgroup, even despite higher doses of anticoagulants in this subgroup. An increase in platelet aggregation was noted during the progression of the disease, especially in the severe subgroup. There were no differences in the results of the FMD test by subgroups of patients. The vWF:Ag level was significantly higher in the severe subgroup.

Conclusion. Thus, plasma hemostasis followed by secondary platelet activation correlates with the severity of COVID-19. Patients with moderate to severe coronavirus infection have predominantly local rather than generalized endothelial dysfunction.

Terapevticheskii arkhiv. 2022;94(7):876-883
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Clinical notes

Aseptic nasal septal abscess in patients with ulcerative colitis: two case reports. Case report

Polyakova I.N., Miroshnichenko A.P., Aleksandrova M.I., Stryuk R.I.


Ulcerative colitis (UC) may be associated with different extra-intestinal manifestations (EIM), which are often difficult to diagnose and treat, and may complicate the course of the disease. EIM are a multidisciplinary problem encountered by doctors of various specializations. However, many incidences of EIM in patients with UC remain unknown. The coexistence of UC and aseptic nasal abscess (ANA) is uncommon. Here, we describe two cases of ANA in young female patients with UC. ANA run in parallel with intestinal disease activity and led to necrosis of the septal cartilage. Moreover, pyoderma gangrenosum was described in one of them. Aseptic abscess syndrome should be kept in mind when a microbial factor is not identified, the diagnosis is not clear or a patient is not improving on appropriate antibacterial therapy. ANA can present as a rare complication of UC.

Terapevticheskii arkhiv. 2022;94(7):884-890
pages 884-890 views

Pathomorphological and clinical characteristics of blastic plasmocytoid dendritic cell neoplasm. Case report

Sherstnev A.A., Kovrigina A.M., Solovyova T.I., Moiseeva T.N.


The paper reveals the 5 cases date about blastic plasmacytoid dendritic cell neoplasm. The presented information demonstrates morphological, immunohistochemical data and clinical manifestations.

Terapevticheskii arkhiv. 2022;94(7):891-896
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Erdheim–Chester disease with cardiac involvement. Case report

Latyshev V.D., Mershina E.А., Kostina I.E., Sinitsyn V.Е., Lukina E.A.


Erdheim–Chester disease (ECD) is a rare non-Langerhans histiocytosis with multisystem inflammatory infiltrates consistent of monocytes/macrophages, reactive microenvironment and fibrotic fields. Cardiovascular involvement is one of the most frequent manifestations of ECD that can lead to life threating complications. In this article we are reporting a clinical case of ECD with cardiac involvement in a young patient.

Terapevticheskii arkhiv. 2022;94(7):897-902
pages 897-902 views


Rehabilitation in patients with chronic thromboembolic pulmonary hypertension

Sagaydak O.V., Danilov N.M., Chazova I.E.


For patients with pulmonary hypertension (PH) there have been no recommendations for physical rehabilitation for a long time, and in fact physical activity was discouraged. Nowadays, the position regarding exercise in patients with PH has changed – studies have shown the safety and effectiveness of exercise in these patients. Most of the studies published to date on rehabilitation in patients with PH have assessed its effect on exercise tolerance. This review provides an overview of published studies and their conclusions on the effectiveness of rehabilitation in patients with chronic thromboembolic hypertension being as a complex therapy using medical and surgical methods of treatment and rehabilitation. The inclusion of rehabilitation in complex treatment allows to achieve patient’s highest possible tolerance to physical activity, increase in the functional class, quality of life and restore working capacity.

Terapevticheskii arkhiv. 2022;94(7):903-907
pages 903-907 views

Stress-induced arterial hypertension

Ambatiello L.G.


Stress is considered as one of the factors associated with the development of many diseases, including the cardiovascular system. The history of studying stress as a risk factor for hypertension began in the first half of the 20th century and continued after the introduction of 24-hour blood pressure monitoring (ABPM) into clinical practice. Then it turned out that there is normotension, stable hypertension and latent hypertension: masked (when clinical BP is within the normal range, and arterial hypertension is recorded according to ABPM and/or self-monitoring of BP) and “white coat” hypertension (increased BP during a visit to the doctor when normal values of blood pressure according to ABPM or self-monitoring of BP). Currently, both variants of latent hypertension are classified as stress-induced arterial hypertension. Several models have been proposed for the study of stress, but two of them are more common in clinical studies: the Karasek model (based on an imbalance between job demands and job decision latitude) and the Siegrist model (based on an imbalance of effort and reward). There are only few studies in where attempts have been made to link the increase in BP with the parameters of stress response (for example, with hormonal levels) or genetic predisposition. The review discusses the most significant studies of stress-induced arterial hypertension published to date.

Terapevticheskii arkhiv. 2022;94(7):908-913
pages 908-913 views

Problems associated with effective pharmacotherapy of the elderly patients (geriatrics): A review

Korol L.A., Egorova S.N., Kudlay D.A., Krasnyuk I.I., Sologova S.S., Korol V.A., Smolyarchuk E.A., Mandrik M.A.


The world’s older population is growing dramatically. At the same time, ensuring an appropriate high standard of living for the elderly by reducing of morbidity and disability of geriatric patients is one of the main objectives of the modern healthcare system. However, changes associated with body aging necessitate application of novel approaches to the correction of pharmacotherapy and usage of specialized dosage forms. Such medicinal products provide both an appropriate therapeutic effect and facilitate their use. Presented review considers several features of pharmacotherapy of geriatric patients.

Terapevticheskii arkhiv. 2022;94(7):914-919
pages 914-919 views

Features of the intestine conditions at patients with a new coronavirus infection

Topchiy T.В., Ardatskaya M.D., Butorova L.I., Маslovskii L.V., Мinushkin О.N.


COVID-19 infection may present with gastrointestinal lesions in up to 25% of patients. One of the target organs of the SARS-CoV-2 virus is the intestine. The pathogenesis of intestinal damage in a new coronavirus infection remains unclear and requires further in-depth study. Possible mechanisms include a direct cytotoxic effect of the virus, a persistent reduction in butyrate-producing bacteria, side effects of drugs, Clostridioides difficile infection, microvascular thrombosis, and the immune-mediated inflammatory reactions in the intestine. The most common symptom of intestinal damage during coronavirus infection, both in the acute phase and in the post-COVID period, is diarrhea. The impact of many aggressive factors on the intestines can form both long-term functional disorders and be the cause of the onset of organic diseases. Treatment should be aimed at possible causes of intestinal damage (Clostridioides difficile), as well as reducing inflammation, restoring intestinal permeability, cytoprotection of mucosal cells, replenishing butyric acid deficiency. When choosing a therapy for intestinal disorders, preference should be given to drugs with a pleiotropic effect in order to influence various possible pathogenetic mechanisms.

Terapevticheskii arkhiv. 2022;94(7):920-926
pages 920-926 views

History of medicine

On the formation of cardiology in the USSR: who should be called its founders?

Borodulin V.I., Banzelyuk E.N., Topolyanskiy A.V.


During the XX century, specialized clinical areas gradually emerged from the general body of internal medicine, among which cardiology became one of the first. The literature has not yet explicitly considered the question of who should be considered the founders of Russian cardiology. Our data suggest that D.D. Pletnev, G.F. Lang, N.D. Strazhesco, V.F. Zelenin, A.L. Myasnikov and E.I. Chazov exhaust the nominal composition of the founders of cardiology in the USSR.

Terapevticheskii arkhiv. 2022;94(7):927-930
pages 927-930 views

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