Vol 93, No 12 (2021)

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Full Issue


Low adherence to treatment is a weak link in the problems of ulcerative colitis

Parfenov A.I., Knyazev O.V., Babayan A.F., Kagramanova A.V.


Aim. To determine factors of adherence to treatment in patients with ulcerative colitis (UC).

Materials and methods. The study was performed in the department of treatment of inflammatory bowel diseases in Loginov Moscow Clinical Scientific Center from 2019 till 2021 years by surveying 1089 patients with UC. This analysis revealed patients with high adherence (HAP) and low adherence to treatment (LAP).

Results. In the survey analysis was determined, that there were more low-adherence patients, than high-adherence patients [596 (59.6%) and 404 (40.4%), respectively, (p<0.001)]. In the group of HAP (100%) were 297 women (73.5%) and 107 (26.5%) men (p<0.001). Also in this group prevailed patients with duration of disease more 5 years 305 (75.5%) and extraintestinal manifestations – 261 (64.6%); p<0.001. In the group of LAP (100%) were more patients younger 44 years, with bad habits and who did not follow diet (p<0.001). The rate of UC reccurence more than 1 time per year was higher in LAP group – 430 (72.1%), versus 137 (33.9%) patients in HAP (p<0.001). The frequency of surgical procedures in UC patients was significantly higher in LAP – 12 (2.0%) in comparison with 2 (0.5%) in HAP group (p<0.001).

Conclusion. In our study was determined, that among UC patients, examined in the department of inflammatory bowel diseases, 60% patients had low adherence to treatment. High adherence to the treatment is statistically significantly associated with female gender, family accommodation, non-working patients, extraintestinal manifestations, additional medical maintenance. Low adherence to the treatment is associated with steroids, male gender, age less than 44 year, bad habits (smoking, alcohol consumption), higher education, complicated UC and frequency of reccurences.

Terapevticheskii arkhiv. 2021;93(12):1419-1427
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Original articles

Relationship of visceral obesity and coronary calcinosis in ischemic heart disease

Brel N.K., Gruzdeva O.V., Kokov A.N., Masenko V.L., Dyleva Y.A., Belik E.V., Barbarash O.L.


Aim. To assess the relationship between the prevalence of visceral obesity (VO) and the severity of coronary calcification (CC) in patients with verified coronary artery disease (CAD).

Materials and methods. 125 patients with CAD were examined. Assessment of the morphometric characteristics of visceral adipose tissue (VAT) and CC was perform using multislice computed tomography (MSCT). The calcium index (CI) of the coronary arteries (CA) was determine by the Agatston method. Statistical analysis was perform using Statistica 10.0.

Results. VO was detect in 82 (65.6%) patients with CAD. In the presence of VO, higher CC values were observed in the projection of the envelope (p=0.00014), right coronary (p=0.00002) arteries, total CI (p=0.0003), and the prevalence of massive CC. Correlation analysis showed the relationship between the area of VAT and the CC of all the studied localizations. According to the ROC analysis, VO is a significant predictor of massive CC (area under the ROC curve – AUC 0.72, 95% CI 0.56–0.89), in contrast to body mass index – BMI (AUC 0.56, 95% CI 0.31–0.82).

Conclusion. The index of the ratio of VAT to subcutaneous adipose tissue (VAT/SAT), but not BMI, had a direct correlation with CC. Morphology of VAT may be a significant diagnostic sign of massive CC in patients with CAD, as a factor affecting treatment and prognosis.

Terapevticheskii arkhiv. 2021;93(12):1428-1434
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Histological remission of ulcerative colitis with combined anti-cytokine and cell therapy

Knyazev O.V., Khomeriki S.G., Kagramanova A.V., Lishchinskaya A.A., Smirnova O.A., Noskova K.K., Parfenov A.I.


Aim. To conduct comparative analysis of histological remission in patients with moderate and severe ulcerative colitis (UC), receiving biological therapy vedolizumab, mesenchymal stem cell (MSC) treatment and combined stem cells and vedolizumab therapy.

Materials and methods. We studied biopsies of 75 patients with total or left-sided moderate and severe ulcerative colitis, divided into groups depending on treatment. The first group of UC patients (n=29) received stem cell therapy 2 mln per kg; the second group of UC patients (n=27) received vedolizumab and the third group (n=19) – MSC and vedolizumab. The efficacy of treatment was assessed by C reactive protein (CRP), Mayo score (MS), fecal calprotectin (FC) and Geboes score (GS).

Results. We determined medium correlation between basic FC and MS before treatment (r=0.6605, p<0.05). After 12 weeks of treatment in the first group of UC patients (n=29) CRP was 7.8±2.1 mg/l, FC 409.3±44.85 µg/g, medium GS 1.2±0.1 points. After 12 weeks of treatment in the second group of UC patients (n=27) CRP was 8.4±1.4 mg/l, FC 435.5±47.3 µg/g, medium GS 1.35±0.15 points. After 12 weeks of treatment in the third group of UC patients (n=19) CRP was 6.4±1.1 mg/l, FC 290.6±17.5 µg/g, medium GS 0.9±0.1 points. We proved strong direct relationship between FC and GS after 12 weeks of treatment in UC patients, receiving MSC (r=0.8392, p<0.05). The statistically significant majority of patients, achieved histological remission, have less than 5-year duration of disease.

Conclusion. Our study showed that clinical and endoscopic remission in UC patients does not always correlate with histological remission. Combined anti-cytokine and stem cells therapy contributes to achieve deep remission and decrease mucosa inflammation rather than single MSC or vedolizumab treatment. Deep remission could be achieved by earlier start of biological therapy. FC could be a predictor and marker of mucosa healing and histological remission

Terapevticheskii arkhiv. 2021;93(12):1435-1442
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Myocardial remodeling in patients with chronic heart failure and implanted cardiac contractility modulators

Safiullina A.A., Uskach T.M., Dobrovolskaya S.V., Saidova M.A., Zhirov I.V., Tereshchenko S.N.


Aim. To study the effect of cardiac contractility modulation on reverse remodeling and myocardial function in patients with chronic heart failure (HF) according to echocardiography (EchoCG).

Materials and methods. In a group of 40 patients with a combination of chronic HF and atrial fibrillation (AF), the dynamics of standard EchoCG parameters and the effectiveness of myocardial work of the left ventricle (LV) against the background of 12-month therapy of cardiac contractility modulation (CCM) were analyzed.

Results. The results obtained indicate a statistically significant positive effect of CCM on LV remodeling parameters and the effectiveness of myocardial work according to EchoCG.

Conclusion. Transthoracic echocardiography is the main imaging method and provides great opportunities for evaluating the effectiveness of HF treatment, including non-drug methods such as CCM. Evaluation of LV myocardial function in patients with HF and implanted CCM devices is a promising scientific and practical research method.

Terapevticheskii arkhiv. 2021;93(12):1443-1450
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The importance of matrix metalloproteinases in the development of atrial fibrillation in obesity

Podzolkov V.I., Tarzimanova A.I., Bragina A.E., Gataulin R.G., Oganesyan K.A., Pokrovskaya A.E., Osadchy K.K.


Background. One of the trends in modern cardiology is the study of the matrix metalloproteinase (MMP) system. Currently, an increase in plasma concentrations of some MMPs and their tissue inhibitors is considered as one of the earliest biochemical markers of myocardial fibrosis in various diseases of the cardiovascular system. Discusses the importance of MMP in the development of atrial fibrillation (AF).

Aim. To study the effect of the MMP system on the development of AF in obese patients.

Materials and methods. The study included 105 patients with a body mass index of more than 30 kg/m2. Depending on the presence of AF, the patients were divided into 2 groups. The criterion for inclusion of patients in group 1 was the presence of documented AF paroxysm in 55 obese patients. The comparison group (group 2) consisted of 50 obese patients without heart rhythm disorders. When patients were included in the study, in order to assess the severity of visceral obesity, all patients underwent a general clinical examination, echocardiography. To determine the activity of the MMP system, venous blood was taken from patients.

Results. Significantly higher values of MMP-9 were detected in patients with obesity and paroxysmal AF – 315.7±53.4 ng/ml than in patients with obesity without heart rhythm disorders – 220.9±54.7 ng/ml (p=0.002); the values of tissue inhibitor of metalloproteinase 1 were 185.3±42.2 and 119.2±42.6 ng/ml, respectively (p=0.007). In patients with obesity and paroxysmal AF, a correlation of moderate strength between the level of MMP-9 and the volume of left atrium and a direct dependence of moderate strength between the ratio of waist volume to height and the plasma values of MMP-9 was revealed. The MMP-9 index (AUC 0.92) had a high diagnostic value for determining the probability of having a paroxysmal form of AF in obese patients. With an increase in the level of MMP-9 more than 295 ng/ml, it is possible to predict the presence of paroxysmal AF in obese patients with a sensitivity of 74.5% and a specificity of 94%.

Conclusion. In patients with obesity and paroxysmal AF, a significant increase in the parameters of the MMP system (MMP-9 and tissue inhibitor of metalloproteinase 1) was revealed when compared with obese patients without heart rhythm disorders (p<0.05). With an increase in MMP-9 of more than 285 ng/ml in obese patients, the appearance of AF with a sensitivity of 74.5% and a specificity of 94% can be predicted.

Terapevticheskii arkhiv. 2021;93(12):1451-1456
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Gastric mucosa condition in patients with coronary artery disease and high risk of gastrointestinal bleeding (register REGATTA-1)

Komarov A.L., Shahmatova O.O., Korobkova V.V., Kurilina E.V., Shuleshova A.G., Panchenko E.P.


The key side effects of antiplatelet therapy are associated with the damage of the upper gastrointestinal tract (GIT) mucous that can lead to erosions or ulcers and specifically complicated by bleeding.

Aim. To assess the upper gastrointestinal mucosal condition by endoscopic and histological methods in patients with stable coronary arteries disease receiving long-term antiplatelet therapy with gastrointestinal bleeding (GIB) history or with high risk of this complication.

Materials and methods.The study included patients from the single-center prospective registry of long-term antithrombotic therapy REGATTA-1.

The gastric mucosa endoscopic examination with biopsy was performed in 20 patients with gastrointestinal bleeding history less than 1 year ago and in 24 patients without GIB, which have concomitant risk factors such as erosions and ulcers history and/or persistent dyspepsia clinical signs. The mucosal condition (erosions and ulcers) was estimated using a modified Lanz scale. The presence of Helicobacter pylori was determined by Histological verification. The inflammatory process characteristics were evaluated according to the modified Sydney classification. All participants received antithrombotic therapy at the time of esophagogastroduodenoscopy; 81.8% of patients received proton pump inhibitors.

Results. Chronic inflammation (93.2%), atrophy (59.1%), multiple erosions (45.5%) or ulcers (18.2%) were the most frequent endoscopic finding. H. pylori infection, found in mucosal samples in 90.9% of patients was one of the most important pathogenesis mechanism, which support the gastrointestinal mucosa damage.

Conclusion. Mucosal damage endoscopic signs remains despite long-term proton pump inhibitors therapy in patients with coronary arteries disease and concomitant GIB risk factors, receiving antithrombotic therapy. H. pylori contamination may be the cause of these changes. Therefore, its active screening and eradication is necessary in such patients.

Terapevticheskii arkhiv. 2021;93(12):1457-1462
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Complex assessment of esophageal acidification and motor function in patients with Barrett's esophagus on antisecretory therapy

Maev I.V., Barkalova E.V., Andreev D.N., Ovsepian M.A., Movtaeva P.R., Zayratyants O.V.


Aim. To determine predictors of insufficient effectiveness of proton pump inhibitors based on the parameters of 24-hours pH-impedance and features of motor function of the esophagus in patients with Barrett's esophagus.

Materials and methods. 17 patients with histologically verified Barrett's esophagus undergoing acid-suppressive therapy were examined. All patients underwent 24-hours pH-impedance and high-resolution esophageal manometry.

Results. According to daily pH-impedance, group 1 consisted of 11 patients with an adequate response to antisecretory therapy, group 2 – 6 patients with insufficient effectiveness of antisecretory therapy, 5 of whom had no clinical manifestations. The total number of reflux averaged 52 and 91, respectively, in groups 1 and 2. The average number of acid reflux in group 1 was 4.36, in group 2 – 40.5. The average number of non-acid reflux prevailed in patients of group 2, averaging 58, compared with group 1, where the average was 47. According to the results of high-resolution esophageal manometry, when assessing the structure and function of the esophageal-gastric junction, violations were detected in 6 out of 17 patients. Disorders of the motor function of the thoracic esophagus were detected in 10 out of 17 patients. The tone of the lower esophageal sphincter in group 1 patients was significantly higher in comparison with patients in group 2.

Conclusion. A number of patients with Barrett's esophagus have insufficient effectiveness of antisecretory therapy, which may not manifest itself clinically and thereby increase the risk of progression. There was a tendency to more frequent motor disorders in the group with insufficient effectiveness of antisecretory therapy, as well as significantly lower tone of the lower esophageal sphincter, which may be a potential predictor of suboptimal effectiveness of antisecretory therapy.

Terapevticheskii arkhiv. 2021;93(12):1463-1469
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The results of phase III multicenter open randomized controlled study REM-Chol-III-16 in patients with intrahepatic cholestasis syndrome caused by chronic diffuse liver diseases

Stel'makh V.V., Kovalenko A.L., Popova V.B., Uspenskiy Y.P., Morozov V.G., Belikova T.N., Rafalskiy V.V., Antonova E.A.


Aim. To assess the safety and efficacy of Remaxol®, solution for infusion, compared with parenteral form of S-adenosyl-L-methionine, in the treatment of patients with intrahepatic cholestasis syndrome accompanying chronic diffuse liver diseases of various etiology.

Materials and methods. In a multicenter open-label comparative study of the safety and efficacy of Remaxol® (inosine + meglumine + methionine + nicotinamide + succinic acid) 317 patients aged 18 to 65 years were randomized into 2 groups: patients of the experimental group (n=168) received intravenous Remaxol®, solution for infusion, 400 ml, and patients of the control group (n=149) – Heptral® (S-adenosyl-L-methionine) 800 mg. The duration of treatment was 10 days. The primary efficacy endpoint was the proportion of patients who responded to therapy, as demonstrated by dynamics of laboratory parameters of liver functional status: decrease in gamma glutamyl transpeptidase level by ≥40%, and/or alkaline phosphatase level by ≥30%, and/or decrease total bilirubin level by ≥30% from baseline by the end of the treatment course.

Results. The proportion of responders was 51% in the Remaxol® group vs. 44.9% in the Heptral® group (p=0.303); the lower limit of the one-sided 95% confidence interval for the difference in the proportions of responders was -4.01%, which exceeds the non-inferiority margin pre-defined by the study protocol, thus, the non-inferiority hypothesis was proven, i.e. Remaxol at a dose of 400 ml/day demonstrates similar efficacy to Heptral at a dose of 800 mg/day in patients with intrahepatic cholestasis syndrome associated with chronic diffuse liver diseases. Similar positive trends in the levels of transaminases, total bilirubin and the severity of pruritus were revealed in both treatment groups. We did not reveal statistically significant between-group differences in the frequency of adverse events definitely related to the study treatment.

Conclusion. Administration of Remaxol® as a part of the pathogenetic therapy of patients with intrahepatic cholestasis syndrome who need hepatoprotection is justified.

Terapevticheskii arkhiv. 2021;93(12):1470-1476
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Evaluation of therapeutic efficiency of various drugs of ursodeoxycholic acid in the treatment of biliary sludge

Isanbaeva A.R., Sakhautdinova G.M.


Background. Biliary sludge (BS) refers to the pre-stone stage of gallstone disease. Timely treatment of this condition with ursodeoxycholic acid (UDCA) drugs helps prevent the progression of the disease. However, not all drugs used in practice are equally effective in relieving clinical manifestations, resolving sludge according to ultrasound results and tolerance.

Aim. To evaluate the therapeutic efficacy of the drug Ursofalk in comparison with other UDCA drugs used for the treatment of BS.

Materials and methods. We examined 105 people with different types of BS identified during ultrasound examination (US); they were divided into 2 groups depending on the UDCA drug taken. In patients, the dynamics of clinical manifestations was assessed using a questionnaire, as well as the dynamics of the ultrasound picture while taking UDCA.

Results. Statistical analysis showed that Ursofalk significantly better relieves biliary pain (p=0.025) and biliary dyspepsia (p=0.039), pain regression occurs faster (p=0.01) – in 21 days. It also has a better tolerance in 94.34% of cases compared to other drugs – 67.31% (p=0.017). Ursofalk has a greater effect on the regression of BS according to ultrasound results after 3 months (p=0.022) and 6 months (p=0.016).

Conclusion. The drug studied by us demonstrated high efficiency in relation to patients with BS, while there were minimal side effects, which led to a better tolerability of therapy.

Terapevticheskii arkhiv. 2021;93(12):1477-1481
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The prevalence of osteoarthritis and its association with geriatric syndromes in people over 65: data from the Russian epidemiological study EVKALIPT

Naumov A.V., Vorobyeva N.M., Khovasova N.O., Moroz V.I., Meshkov A.D., Manevich T.M., Tkacheva O.N., Kotovskaya Y.V., Selezneva E.V., Ovcharova L.N.


Background. Osteoarthritis (OA) in elderly and senile patients is not only common, but also one of the main diseases affecting the duration of active life, its quality, the appearance of addictions and loss of autonomy. Data on the relationship between OA and geriatric syndromes (GS) in our country are extremely scarce.

Aim. To estimate the prevalence of OA and to analyze its associations with HS in persons aged ≥65 years.

Materials and methods. The study included 4308 people (30% of men) aged 65 to 107 years, living in 11 regions of Russia. The patients were divided into 2 groups: with OA (n=2464) and without OA (n=1821). All patients underwent a comprehensive geriatric assessment.

Results. The prevalence of OA was 57.6%. With age, the frequency of OA increased significantly. According to the results of a comprehensive geriatric assessment, patients with OA had lower walking speed, the sum of points on the Bartel, Lawton scales and a short battery of physical functioning tests and higher – the sum of points on the geriatric scale of depression and the age is not a hindrance scale. Patients with OA rated the quality of life and health status lower and higher – the intensity of pain syndrome. Patients with OA were more likely to use any assistive device, with the exception of a wheelchair. In patients with OA, the most common HS were chronic pain syndrome (92%), senile asthenia syndrome (64%), basic (66%) and instrumental (56%) dependence in everyday life, cognitive impairment (62%), probable depression (51%) and urinary incontinence (50%). Univariate regression analysis showed that OA is associated with a 1.2–3.0-fold increase in the risk of a number of GS and a 28% decrease in the risk of malnutrition.

Conclusion. OA is widespread in the elderly population. The presence of OA is associated with a number of GS associated with loss of autonomy.

Terapevticheskii arkhiv. 2021;93(12):1482-1490
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Empagliflozin and heart failure: position paper of the experts on the results of the online meeting and discussion of the EMPEROR-Preserved Trial

Arutyunov G.P., Lopatin Y.M., Ametov A.S., Ageev F.T., Antsiferov M.B., Villevalde S.V., Vinogradova N.G., Galstyan G.R., Galyavich A.S., Gilyarevskiy S.R., Glezer M.G., Zhirov I.V., Ilyin M.V., Lebedeva A.I., Nedogoda S.M., Salukhov V.V., Tarlovskaya E.I., Tereshchenko S.N., Fomin I.V., Khalimov I.S., Khasanov N.R., Cherkashin D.V., Yakushin S.S.


At an international online expert meeting held on September 16, 2021, the results of the empagliflozin research program EMPA-REG Outcome, EMPEROR-Reduced and EMPEROR-Preserved were reviewed. We analyzed cardiovascular and renal outcomes during the treatment with empagliflozin in patients with chronic heart failure, regardless of the presence of type 2 diabetes mellitus. The positive results of the EMPEROR-Preserved study are updated and their significance for clinical practice is discussed. Several proposals have been adopted that will accelerate the introduction of empagliflozin therapy into practice in patients with heart failure and overcome clinical inertia.

Terapevticheskii arkhiv. 2021;93(12):1491-1497
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The place of scales and questionnaires in assessing the disease’s severity and the long-term prophylaxis’s prescribing in patients with hereditary angioedema

Manto I.A., Latysheva E.A., Sorokina L.E., Latysheva T.V.


Hereditary angioedema is a hereditary life-threatening disease characterized by recurrent angioedema of various strength and localization. To date, definite disease’s severity criteria have not been developed. There are many different factors to consider not only the frequency of episodes, but also their duration, strength, influence on the patient's appearance, the severity of the pain syndrome. Disease related quality of life, the number of work disability days, and the patient's satisfaction with the prescribed treatment are important. In addition, there are no criteria for prescribing long-term prophylaxis, and no parameters for choosing a specific drug. The introduction of specific scales and questionnaires developed to assess such characteristics as disease activity, disease control, quality of life in patients with recurrent angioedema into clinical practice seems to be the best solution for both questions. The comprehensive understanding of the disease’s severity in a particular patient can be carried out with the combined use of assessment tools.

Terapevticheskii arkhiv. 2021;93(12):1498-1509
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The assessment of renal function during the therapy of arterial hypertension with azilsartan medoxomil in patients with obesity or overweight and concomitant metabolic disorders

Nevzorova V.A., Petrichko T.A., Chazova I.E., Zhernakova J.V.


Aim. To assess the influence of the therapy of arterial hypertension with azilsartan medoxomil on the renal function in overweight or obese patients with concomitant metabolic disorders.

Materials and methods. An international multicenter observational nonintervention prospective study included 1945 patients, taking azilsartan medoxomil in accordance with approved prescribing information. The observation period reached 6 months.

Results. In patients with an initial glomerular filtration rate (GFR)<60 ml/min/1.73 m2 or ≥60 ml/min/1.73 m2 mean change in systolic blood pressure after 6 months of therapy reached -32.5±11.1 and -30.4±13.6 mmHg, correspondingly, while the change in diastolic blood pressure was -13.7±8.8 and -14.2±9.4 mmHg, respectively. No decrease in renal function was observed. Moreover, in patients with an initial GFR<60 ml/min/1.73 m2 GFR increased significantly (p<0.001).

Conclusion. Azilsartan medoxomil, prescribed as monotherapy or in free combinations, provided an effective control of blood pressure in patients with arterial hypertension with both normal or moderately reduced and initially significantly reduced renal function. High efficacy and acceptability of the drug was associated with a beneficial effect on renal function, which allows to consider azilsartan medoxomil as the drug of choice for the treatment of hypertension in patients with concomitant metabolic disorders.

Terapevticheskii arkhiv. 2021;93(12):1510-1515
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The analysis of the availability of fixed-dose combinations in antiretroviral therapy for HIV infection in the Russian Federation

Pyadushkina E.A., Derkach E.V.


Aim. To analyze the features of drugs provision for special groups of treatment-naïve HIV-infected patients initiating antiretroviral treatment with fixed dose combination (FDC) for once-daily single-tablet regimen, in Russian healthcare setting.

Materials and methods. We studied the regulatory legal documents governing the provision of antiretroviral drugs in Russia and analyzed the Russian Program of State Guarantees to determine the inclusion of the investigated FDCs in the lists of regional benefits, as well as regional and federal procurement of these drugs in 2020 and 2021. We compared costs of first line therapy for special groups using FDCs regimens per year in case of regional purchases or centralized purchases.

Results. It was show that doravirin/tenofovir/lamivudine was the least expensive in 2020 and in 2021 among new FDCs form drugs. Worth 325.8 and 323.9 thousand rubles. per patient per year. The most expensive was bictegravir/tenofovir alafenamide/emtricitabine (401.6 and 439.9 thousand rubles, respectively). In case of Ministry of Health centralized purchases, the costs of new FDCs (doravirin/tenofovir/lamivudine and bictegravir/tenofovir alafenamide/emtricitabine), included in Vital and Essential drug list (VEDL) in 2022, will amount to 151,2 and 191.4 thousand rubles respectively, which is 52.9% and 40.4% lower than the cost per course of rilpivirine/tenofovir/emtricitabine.

Conclusion. The inclusion of new effective and economical FDCs “the whole scheme in one tablet once-daily” in VEDL, expands the possibilities of simplify and effective first-line therapy for special groups of HIV-infected patients, as well as reduce the financial burden on the Program of State Guarantees budget and increases treatment coverage. All of this corresponds to the goals of the State Strategy to Combat the Spread of HIV in Russian Federation.

Terapevticheskii arkhiv. 2021;93(12):1516-1521
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Clinical notes

TNFRSF13B gene mutation in adult patient with common variable immunodeficiency. Case report

Sviridov P.S., Bodunova N.A., Danishevich A.M., Litvinova M.M.


Common variable immunodeficiency (CVID) is one form of the primary immunodeficiencies (PIDs). CVID is characterized by variable clinical manifestations. Genetic alteration is a cause of the disease in many cases. In the current paper we described Patient N of 45 years old, who have been suffering from frequent various infections and therefore attended an immunologist and clinical geneticist. Immunoglobulins (Ig) A, M, and G deficiency was found in the patient. As a result of medical genetic counselling primary immunodeficiency has been suggested as a diagnosis. Further molecular genetic testing using clinical exome sequencing (Next Generation Sequencing method) revealed a likely-pathogenic variant c.204dupA (p.Leu69ThrfsX12, rs72553875) of TNFRSF13B gene in the patient. The gene variant was found in homozygous state. According to the international medical literature and genomic databases TNFRSF13B gene mutations lead to the CVID development and in some patients are characterized by isolated IgA deficiency and in the other group of patients can lead to decrease of IgA, IgM, and IgG. The patient had a family history of cancer and autoimmune inflammatory bowel disease (erosive-ulcerative enterocolitis). Moreover, one sibling of the patient died at the age of 3 weeks from complications of toxoplasmosis infection. The other sibling of 51 years old have been also suffering from recurrent infectious diseases. Thus, the genetic cause of the disease was identified in the proband. It has been shown that homozygosity for variant c.204dupA of TNFRSF13B gene is characterized by the deficiency of all three classes of Ig. Medical genetic counselling and modern molecular genetic methods application is an important step in management of people with signs of immunodeficiency. Such approach helps to make a diagnosis to the patient, to find an exact molecular reason of the condition, to use effective treatment, and to perform preventive measures in patient`s family.

Terapevticheskii arkhiv. 2021;93(12):1522-1527
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Chronic migraine treatment: multidisciplinary approach. Case report

Golovacheva V.A., Golovacheva A.A., Parfenov V.A.


We described clinical case of chronic migraine and such comorbid disorders as insomnia and panic disorder. The influence of anxiety, insomnia, painkillers overuse on the chronicity of migraine has been shown. Multidisciplinary program was made for treatment of patient with chronic migraine, insomnia and panic disorder. Multidisciplinary program included education, detoxification therapy, cognitive-behavioral therapy and pharmacotherapy. Patient's mistaken ideas about disorders was changed by using of cognitive-behavioral therapy. Also techniques of cognitive-behavioral therapy were needed for education of patient about effective skills to overcome pain, insomnia and anxiety. The transformation of migraine from chronic to episodic, improved sleep, improved emotional state and functional activity were noted after 3 months of treatment. Follow-up of the patient for 12 months showed long lasting positive effect of treatment for chronic migraine, insomnia and panic disorder.

Terapevticheskii arkhiv. 2021;93(12):1528-1532
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Atherosclerosis and cardiovascular risk in patients with inflammatory bowel disease

Mironova O.I., Isaikina M.A., Khasieva S.A.


Inflammatory bowel disease (IBD) can cause early atherosclerosis. There is a correlation between inflammatory activity in IBD and cardiovascular events. Chronic inflammation can lead to endothelial dysfunction. This review discusses the possibilities of the mechanisms underlying the relationship between IBD and atherosclerosis, the role of innate and humoral immunity, intestinal microbiota, biomarkers (C-reactive protein, homocysteine, etc.), as well as the possibility of early instrumental diagnosis of subclinical manifestations of atherosclerosis in patients with IBD by measuring carotid intima–media thickness and aortic pulse wave velocity. The need for active prevention of cardiovascular diseases in this group of patients is emphasized, including through the control of inflammation activity, as well as the inclusion of IBD in one of the risk factors for cardiovascular diseases.

Terapevticheskii arkhiv. 2021;93(12):1533-1538
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Functional dyspepsia: a multifaceted problem in gastroenterology

Osadchuk M.A., Svistunov A.A., Balashov D.V., Osadchuk M.M.


The article presents the views on dyspepsia in world practice, data on the difficulties of diagnosis and the problem of the effectiveness of various therapy regimens. Particular attention is paid to the use of fixed forms of drugs for functional dyspepsia, in particular Omez® DSR.

Terapevticheskii arkhiv. 2021;93(12):1539-1544
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Treatment strategies for patients with atrial fibrillation and chronic heart failure

Tereshchenko S.N., Uskach T.M.


Atrial fibrillation (AF) is associated with significant morbidity and mortality and may lead to the development of chronic heart failure (CHF). Each condition predisposes to the other, requiring a careful choice of the treatment strategy. This article is devoted to the prevalence and prognostic implications of both diseases. The article presents data from meta-analyzes related to the management of this group of patients. The aspects of rhythm control strategy in AF and concomitant CHF are described according to the recent studies and clinical guidelines. The features of anticoagulant therapy in patients with AF and CHF are outlined. Much attention is given to the importance of the safety profile of the anticoagulant therapy in terms of the bleeding risk in patients with concomitant AF and CHF.

Terapevticheskii arkhiv. 2021;93(12):1545-1550
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Chondroitin sulfate in therapy osteoarthritis chronic pain patients according to actual clinical recommendations

Shavlovskaya O.A.


Of undoubted interest is the search for new drugs comparable in effectiveness to nonsteroidal anti-inflammatory drugs (NSAIDs), but with a safer application profile. NSAIDs are characterized by a good analgesic effect due to the modulation of prostaglandin metabolism by inhibition of cyclooxygenase-2. One of the promising directions of pharmacotherapy of degenerative-dystrophic joint lesions is the use of symptom-modifying drugs of delayed action, which include chondroitin sulfate (CS). CS has antiresorptive activity, anti-inflammatory and anti-inflamaging effects. In addition to the direct effect on pain syndrome severity, he also have a modulating level effect of systemic inflammation of cartilage tissue. According to experts of international and Russian societies, pharmaceutical prescription-quality CS is a basic part of the treatment of osteoarthritis. One of the advantages of CS over NSAIDs is the preservation of the effect for 2–4 months after the treatment. Against the background of the use of CS, it is possible to reduce the dose or completely cancel NSAIDs, which helps to reduce the frequency of adverse events associated with their intake. CS has a favorable safety profile, which is important for elderly patients and those with comorbid diseases (cardioprotective effects). CS drugs can be administered per orally, intramuscularly, intra-articularly and in combination with different administration methods. Several clinical trials of CS (Chondrogard), including randomized, were conducted in Russia. The Russia Health Ministry approved the appointment of parenteral CS in clinical guidelines: “Chronic pain in elderly and senile patients” (2020), “Falls in elderly and senile patients”(2020), "Knee osteoarthritis" (2021), "Hip osteoarthritis" (2021).

Terapevticheskii arkhiv. 2021;93(12):1551-1555
pages 1551-1555 views

The risk of developing cardiovascular disease in bipolar disorder. Clinical and social factors

Mosolov S.N., Fedorova E.Y.


Bipolar disorder (BD) is one of the most common mental disorders in the world with high mortality and a hard economic burden. Although suicide is the leading cause of death in BD, cardiovascular disease (CVD) also contributes significantly to this rate, the risk of which is seriously underestimated in BD. A sample assessment was made of current studies focusing on the link between BD and CVD. The search was carried out in the PubMed and eLIBRARY databases for the following keywords: bipolar disorder, psychopharmacology, cardiovascular disease, metabolic syndrome. The association between BD and vascular disease is large. The analysis of adjusted mortality estimates in patients with bipolar disorder showed a significant contribution of CVD. A detailed study of the mutual influence of bipolar disorder BD and CVD is difficult due to the earlier manifestation of BD in comparison with CVD. Most of the studies have focused on cardiovascular risk factors (CVRFs), which are more common in BD than in the general population. Metabolic syndrome (MS) plays a significant role among CVRFs. The reasons for the development of MS in patients with BD are currently not known for sure, however, the instigated factors are certainly a disturbance of the diet, decreased physical activity, pharmacological therapy, and the lack of early preventive and medical care. Patients with hyperuricemia had a higher risk of developing MS. Lifestyle correction and a reduction of CVFRs, as well as the rational use of certain cardiac drugs can improve the better prognosis of the disease and reduce mortality in patients with BD. The predisposition of patients with BD to CVD is undeniable. It is necessary to consider the high frequency of CVRFs in people with BD, and promptly recommend appropriate treatment and special rehabilitation programs for the prevention of CVD complications, considering the change in affective phases and the applied mood-stabilizing drugs.

Terapevticheskii arkhiv. 2021;93(12):1556-1561
pages 1556-1561 views

Материалы конференций

Antiplatelet drugs and COVID-19: use for prevention of arterial vascular complications in different time periods of the disease


A Council of Experts was held in Moscow with the scientific and organizational support of the National Medical Research Center for Therapy and Preventive Medicine and the Russian Society for the Prevention of Noncommunicable Diseases. Leading experts in various fields of medicine discussed the possibility of using antiplatelet drugs as prevention of arterial vascular complications of COVID-19 in different time periods of the disease. The main outcome of the Council of Experts was a resolution reflecting the general view of the scientific community on the possibility of increasing the use of acetylsalicylic acid in patients with coronavirus infection.

Terapevticheskii arkhiv. 2021;93(12):1562-1563
pages 1562-1563 views

History of medicine

Ulcerative colitis. To the 180th anniversary of the description by Karl Rokytansky

Knyazev O.V., Kagramanova A.V., Parfenov A.I.


The article describes the main historical milestones in the description and study of ulcerative colitis from the time of Hippocrates to the present day. The first description of the morphological picture of non-specific ulcerative colitis (NUC) was presented by the Viennese pathologist Karl Rokitansky in 1842. The term "ulcerative colitis" was coined by S. Wilks in 1859. A detailed description of the disease was presented in 1875 by S. Wilks and W. Maxon. In an independent nosological form, NUC was isolated in 1888 by the English doctor White. Boas in 1903. For the first time, he presented the differential diagnosis of NUC and chronic dysentery. The term "non-specific ulcerative colitis" in Russia was first introduced by A.S. Kazachenko in a report at the XIII Congress of Russian Surgeons in 1913.

Terapevticheskii arkhiv. 2021;93(12):1564-1568
pages 1564-1568 views

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