Vol 94, No 12 (2022)

Cover Page

Full Issue


Anemia of chronic diseases: current state of the problem and perspectives

Mironova O.I., Panferov A.S.


Anemia of chronic diseases is a condition, that accompanies several chronic conditions, that have inflammation as an underlying cause. The article covers current concepts of pathogenesis, evaluation and treatment of this type of anemia. The new perspectives in the development of investigational methods and treatment are discussed. The new methods of iron deficiency assessment in patients with systemic inflammation are discussed separately.

Terapevticheskii arkhiv. 2022;94(12):1349-1354
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Original articles

Vasoprotective effect of effective lipid-lowering therapy in patients with ST-segment elevation myocardial infarction

Salyamova L.I., Khromova A.A., Kvasova O.G., Avdeeva I.V., Borisova N.A., Korenkova K.N., Polezhaeva K.N., Oleynikov V.E.


Aim. To study the vasoprotective effects of atorvastatin depending on the achievement of the target level of low-density lipoprotein cholesterol (LDL-C) in patients with ST-segment elevation myocardial infarction (STEMI) within 48 weeks of follow-up.

Materials and methods. Included were 112 STEMI patients who received atorvastatin 20–40–80 mg. On days 7–9 from the onset of the disease, after 24 and 48 weeks, ultrasound examination of the carotid arteries with RF technology and applanation tonometry were performed, the lipid profile was determined. The patients were divided into groups: group 1 (n=41) of highly effective therapy (HET) – who achieved the target LDL-C after 24 and 48 weeks; group 2 (n=29) in relatively effective therapy (RET) – achieving target values at 24th or 48th week; group 3 (n=42) insufficiently effective therapy (IET) – did not reach the target LDL-C.

Results. When examining the carotid arteries in the HET group, the intima-media thickness (IMT) decreased by 10.7–13.1%, the b index – by 14.9–26.3% after 24–48 weeks. In the RET group, the IMT regression was 10.4–13.3%; b index – 23.9% by the 48th week. In the IET group, the b index decreased by the 48th week by 14.3%. According to applanation tonometry in the HET group, the central pressure did not change. In the RET group, systolic pressure in the aorta increased by 10–15.7% after 24–48 weeks, pulse pressure – by 33.9% by the end of observation. With IET, the increase was 8.6–6.8 and 19.8–25.9%, respectively. The odds ratio of developing endpoints in the RET group was 4.7 (95% CI 1.2–26.4; p=0.02), in the IET group – 3.9 (95% CI 1.1–24.8; p=0.03) compared with HET.

Conclusion. The most pronounced vasoprotective effect and a decrease in cardiovascular risk are associated with the achievement of the target LDL-C throughout the entire treatment period.

Terapevticheskii arkhiv. 2022;94(12):1355-1360
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Lipid metabolism in non-alcoholic fatty liver disease in patients with different body weights in mid-mountain conditions

Toktogulova N.A., Sultanalieva R.B., Tuhvatshin R.R., Kaliev T.K.


Aim. To study the peculiarities of lipid metabolism disorders in non-alcoholic fatty liver disease in lean and obese patients in medium altitude conditions.

Materials and methods. The study was carried out within the framework of the project “Etiopathogenetic features and rates of development of non-alcoholic fatty liver disease (NAFLD) in the conditions of Kyrgyzstan” (№ of state registration MHN/TZ-2020-3). An open comparative study of patients with two forms of NAFLD: fatty liver and non-alcoholic steatohepatitis (n=236) living in low mountains (Bishkek, altitude above sea level – 750–800 m; n=111) and middle mountains (At-Bashy district , Naryn region, height above sea level – 2046–2300 m; n=125) Kyrgyzstan. The average age of the patients was 55.7±0.95 years. Given that genetic factors may play a role in the development of NAFLD, we analyzed a population represented only by ethnic Kyrgyz. Patients in each group were divided into lean (BMI23) and obese (BMI>23) groups. To determine physical activity, a physical activity questionnaire was used, which was compiled on the basis of the materials of the International Physical Activity Prevalence Study www.ipaq.ki.se. Physical examination included measurement of anthropometric parameters (height, body weight, waist circumference), calculation of body mass index (BMI), skeletal muscle mass index (SMM), percentage of body fat. According to the grades of the WHO, the degree of obesity was assessed by BMI for Asians. Blood samples were taken for research in the morning on an empty stomach after at least 12 hours of fasting. The following indicators were determined: glucose, lipid spectrum (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides), alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels. The BARD scale was used as a predictor for assessing the development of liver fibrosis in patients with NAFLD. The scoring system included three variables: BMI, AST/ALT, and the presence of DM 2. The diagnosis of NAFLD made on the basis of history, laboratory tests, ultrasound examination of the liver, and exclusion of other liver diseases. The results were analyzed using the SPSS 16.0 statistical software package for Windows. A p-value<0.05 was considered statistically significant at the 95% confidence level.

Results. It was found that the inhabitants of the middle mountains with NAFLD are represented by a lower BMI relative to the inhabitants of the low mountains. In women, the levels of SMM and the percentage of fat are significantly and statistically significantly correlated (r=-0.971; p<0.001), while in men these two indicators are not related. Men showed a trend towards higher percentages of fat, regardless of body weight and region of residence. For women, this indicator was within acceptable limits and did not exceed 31%. There was found a statistically significant difference in total cholesterol levels between low and middle mountain people in the group of obese patients (p<0.001) suffering from NAFLD. Statistically significant low ALT indices were revealed in the group of obese patients living in mid-mountain conditions.

Conclusion. Taken together, our results suggest that chronic mid-mountain hypoxia may slow down the course of overweight-induced NAFLD.

Terapevticheskii arkhiv. 2022;94(12):1361-1366
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Subclinical markers of liver damage in patients with arterial hypertension and obesity

Sadulaeva I.A., Yushchuk E.N., Khalikova L.F., Krikunova O.V., Trofimenko O.S., Medvedeva E.G.


Aim. To investigate the possibility of preclinical detection of liver damage in patients with hypertension and obesity.

Materials and methods. The study included 168 patients with hypertension aged 30 to 60 years. All patients underwent general clinical and laboratory-instrumental examination, including ultrasound of the abdominal organs with Doppler assessment of blood flow and determination of markers such as ALT, AST, TG, lipid profile indicators at inclusion, after a month, three months and nine months.

Results. Depending on the presence of obesity, all patients with hypertension were divided into two groups. Obese patients had a statistically significant increase in office blood pressure, FSI, the ratio of TG and LDL-C to HDL-C, a more significant higher average levels of glucose, TG and ALT levels, as well as impaired hepatic blood flow according to ultrasound.

Conclusion. Indicators of FSI, ALT/AST ratio, ratio of TG and LDL-С to HDL-C as well as assessment of hepatic blood flow indicators can be used for early diagnosis of nonalcoholic fatty liver disease, as they predict liver steatosis.

Terapevticheskii arkhiv. 2022;94(12):1367-1373
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Resumption of anticoagulant therapy after major bleeding and the risk of negative events in patients with atrial fibrillation (based on REGistry of Long-term AnTithrombotic TherApy-2 – REGATA)

Kropacheva E.S., Zemlyanskaya O.A., Krivosheeva E.N., Panchenko E.P.


Background. It is necessary to strive to resume anticoagulants for patients with atrial fibrillation who have a high risk of thrombosis after the development of large bleeding. Due to the fact that death in these patients is caused not by a recurrence of fatal bleeding, but by the development of stroke in case of refusal of anticoagulant therapy.

Aim. To evaluate the effect of the resumption of anticoagulant therapy on the risk of recurrence of major bleeding, thrombosis and death in patients with atrial fibrillation who have suffered major bleeding.

Materials and methods. To evaluate the frequency of bleeding, thrombosis and death in patients with atrial fibrillation after major bleeding according to prospective follow-up data for one year.

Results. The recurrence rate of major bleeding after the resumption of therapy was 21.7% per year. The frequency of fatal bleeding was 2.2%. In the anticoagulant withdrawal group, the incidence of thrombotic complications (ischemic stroke and myocardial infarction) was significantly higher compared to patients who resumed therapy. The frequency of death from all causes was significantly higher in the group of patients who did not resume anticoagulant therapy. Half of the deaths were due to cardiovascular causes. The presence of more than 5 points of the Charlson Comorbidity Index was a predictor of the development of the sum of all adverse events.

Conclusion. The resumption of anticoagulant therapy after the development of major bleeding in patients with atrial fibrillation reduces the risk of thrombosis and death at a cost, while increasing the risk of recurrence of non-fatal bleeding.

Terapevticheskii arkhiv. 2022;94(12):1374-1380
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Pharmacoepidemiological analysis of antihypertensive therapy in older age groups with senile asthenia syndrome

Davidov E.L., Yaskevich R.A.


Aim. To conduct a pharmacoepidemiological study to determine the characteristics of antihypertensive therapy in older patients with senile asthenia syndrome (SSA) and compliance of this therapy with modern clinical recommendations.

Materials and methods. The study included 146 patients diagnosed with stage I–III hypertension who underwent inpatient treatment in the therapeutic department of the Krasnoyarsk Regional Hospital for War Veterans, the subjects were divided into two groups. The first group included 55 elderly patients (WHO, 2012) with hypertension and SSA. The second group included 35 elderly patients (WHO, 2012) with hypertension and SSA. The comparison group consisted of 56 patients aged 60 to 84 years with hypertension without SSA. Evaluation of the pharmacotherapy was carried out based on extracts from the medical histories of inpatient patients.

Results. The most commonly taken groups of antihypertensive drugs in patients of older age groups with hypertension and SSA according to the study are diuretics and β-blockers. Diuretics were taken by 88.6% of elderly patients and 83.6% of senile patients. The main combinations of antihypertensive drugs in patients with hypertension and SSA were: a two-component scheme of combination of an ACE inhibitor and a diuretic, a three-component scheme of combination of an ACE inhibitor, a β-blocker and a diuretic, four-component schemes of combination of an ACE inhibitor, a β-blocker, a calcium channel blocker and a diuretic, as well as a combination of an angiotensin II receptor blocker, a β-blocker, calcium channel blocker and diuretic with combined medications.

Conclusion. The prescribed antihypertensive therapy in patients of older age groups with hypertension and SSA in most cases is represented by a combination of several drugs. Many patients take three-component antihypertensive therapy regimens. There were no statistically significant differences between patients of older age groups with hypertension and SSA, as well as patients of older age groups with hypertension without SSA. Therefore, it can be concluded that the presence of senile asthenia syndrome does not affect the tactics of treatment of hypertension and regardless of the presence or presence of SSA, patients receive the same hypotensive therapy, which contradicts existing clinical guidelines.

Terapevticheskii arkhiv. 2022;94(12):1381-1386
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Dynamics of NT-proBNP and ST2 levels as markers of heart failure in patients with endogenous Cushing syndrome (hypercortisolism)

Kosharnaia R.S., Belaya Z.E., Zuraeva Z.T., Michurova M.S., Kalashnikov V.Y.


Aim. To evaluate frequency of heart failure syndrome in patients with endogenous hypercortisolism and to establish relationship between effective treatment for hypercortisolism and regression of heart failure with particular emphasis on the observation of NT-proBNP and ST2 levels.

Materials and methods. 56 patients with endogenous hypercortisolism (45 female, mean age 47 years [36; 55] hospitalized with endogenous hypercortisolism to National Medical Research Center for Endocrinology were enrolled in the study. All patients underwent comprehensive clinical investigation including expert echocardiography with speckle tracking and evaluation of NT-proBNP and ST2 cardiac biomarkers at baseline and 6 months after surgical treatment.

Results. According to clinical data and elevated biomarkers of cardiac stress 28 out of 56 patients (50%) at baseline met the criteria for heart failure. 20 patients were included in the final analysis. Follow-up investigation with focus on changes in NT-proBNP and ST2 levels demonstrated that surgical correction of endogenous hypercortisolism resulted in resolution of heart failure syndrome in 11 patients (55%).

Conclusion. These preliminary data suggest that signs and symptoms of heart failure are observed in patients with endogenous hypercortisolism in about half the cases. Surgical correction results in resolution of heart failure in approximately two thirds of the cases. Prospective evaluation NT-proBNP and ST2 levels may provide important diagnostic and prognostic information in patients with endogenous hypercortisolism.

Terapevticheskii arkhiv. 2022;94(12):1387-1393
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Clarithromycin for community-acquired pneumonia in adults: focus on anti-inflammatory properties

Sinopalnikov A.I., Rachina S.A., Vasilyeva I.S., Pigusova N.A., Karpova O.Y.


Aim. To evaluate clinical efficacy, anti-inflammatory and immunomodulatory activity of clarithromycin in adults with severe community-acquired pneumonia (sCAP).

Materials and methods. A prospective observational study recruited adult hospitalized patients with verified sCAP. Clarithromycin was prescribed as a component of combination antibiotic therapy (ABT) with a β-lactam antibiotic (AB). The choice of β-lactam AB was carried out by the attending physician in accordance with national clinical guidelines and routine practice of the medical institution. Along with assessment clinical efficacy, the dynamics of inflammatory markers in blood serum was recorded: C-reactive protein, procalcitonin (PCT), tumor necrosis factor α, interleukins 1-beta (IL-1) and interleukin 6 (IL-6). The total duration of ABT was 7–14 days.

Results. Altogether 20 patients (13 males, 7 females) aged from 18 to 84 years old were enrolled. As a result of the use of combined ABT with β-lactam AB and clarithromycin, a significant decrease in the level of C-reactive protein was noted by the 3–5th day of therapy (from 74.6 to 14.1 mg/l). An increase in serum PCT was observed in half of the patients; during treatment, the level of PCT significantly decreased. Similar dynamics was detected for IL-6 – its content in the blood serum decreased by the time of the end of ABT by 6.8 times compared with the baseline. A decrease in the level of tumor necrosis factor α to the reference value was observed in most patients already in the early stages – by 3–5 days of ABT. The majority of patients showed positive dynamics of clinical signs and symptoms with resolution of respiratory failure and other complications of sCAP. In almost half of the patients, the criteria for clinical stability were achieved in the early stages, which made it possible to switch to oral ABT.

Conclusion. The results of the study are consistent with literature data indicating a rapid decrease in inflammatory markers when clarithromycin is administered to patients with sCAP. Its results can be a starting point for comparative randomized trials assessing both clinical outcomes and immunological parameters when using different classes of antibiotics for the treatment of sCAP.

Terapevticheskii arkhiv. 2022;94(12):1394-1400
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Efficacy and safety of the use of alirocumab in real clinical practice

Korneva V.A., Kuznetsova T.Y., Scopets I.S., Vezikova N.N.


Aim. To evaluate the results of two-year use of alirokumab in Karelia Republic.

Materials and methods. The observation group consisted of 27 patients (17 patients with familial hypercholesterolemia, 10 patients with the history of myocardial infarction), mean age 53.4±4.3 years, 70.3% men, follow-up duration from one year to 2.5 years, 18 (66.6%) patients received therapy for more than 2 years. 19 patients received alirocumab at a dose of 75 mg/ml once every 2 weeks, eight – at a dose of 150 mg/ml once every 2 weeks. Before the start of therapy, the majority received maximally tolerated statin therapy, 10 patients received statin therapy in combination with ezetemibe, 3 patients received ezetemibe monotherapy due to statin intolerance. The target levels of LDL cholesterol were considered for very high risk patients less than 1.4 mmol/L, high risk – less than 1.8 mmol/L, extreme risk – less than 1 mmol/L.

Results. The reduction of LDL on therapy with alirocumab was 58%; target levels of LDL were achieved in 77.8%. The level of decrease in LDL cholesterol less than 50% was noted only in 7.4% of cases. Patients requiring a large dose of the drug were classified as very high risk, had higher cholesterol and LDL-C levels. The level of Lp(a) decrease on 29.7% by 6–12 months. No destabilization of coronary heart disease, new cases of stroke were registered.

Conclusion. The inclusion of alirocumab in the treatment regimen contributed to the stable course of atherosclerosis-associated diseases, the achievement of LDL cholesterol targets in 77.8% of patients, was not accompanied by side effects during 2.5 years therapy.

Terapevticheskii arkhiv. 2022;94(12):1401-1406
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Efficacy of esophagus protection in complex treatment of erosive gastroesophageal reflux disease: a systematic review and meta-analysis of controlled trials

Bordin D.S., Andreev D.N., Maev I.V.


Aim. To review the data about the efficacy of esophagus protective agent based on the fixed combination of hyaluronic acid and chondroitin sulfate dissolved in the bioadhesive carrier (poloxamer 407) in the complex therapy of patients with erosive gastroesophageal reflux disease (GERD).

Materials and methods. A search in MEDLINE/PubMed, EMBASE, Cochrane, and Russian Science Citation Index of Scientific Electronic Library electronic databases was performed. Relevant original controlled studies of a fixed combination of hyaluronic acid and chondroitin sulfate as an esophagus protective agent in a population of patients with erosive GERD were included.

Results. The final analysis included three studies that enrolled 181 patients with erosive GERD. All the studies had a uniform design with the assessment of the primary endpoints (complete epithelialization of esophageal erosions and complete resolution of heartburn) 28 days after the start of therapy. Meta-analysis of the three controlled trials has demonstrated that combination therapy with proton pump inhibitors (PPIs) and esophagus protective agents is significantly more effective than PPI monotherapy for complete epithelialization of esophageal erosions at 28 days of treatment (relative risk 1.267, 95% confidence interval 1.082–1.483, p=0.003; I2=21.19%), but did not differ for complete resolution of heartburn on the day 28 of treatment (relative risk 1.638, 95% confidence interval 0.660–4.067, p=0.287; I2=92.59%).

Conclusion. Combined therapy with PPI and Alfasoxx is significantly more effective than PPI monotherapy for the epithelialization of esophageal erosions in patients with erosive GERD.

Terapevticheskii arkhiv. 2022;94(12):1407-1412
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Treatment of toxic hepatitis in COVID-19 patients

Maev I.V., Shaburov R.I., Pavlov A.I., Molodova A.I., Karakozov A.G., Kazakov S.P., Lebedeva E.G., Ivolgin A.F., Eremin M.N., Levchenko O.B.


Background. The article reflects the clinical significance of the early diagnosis of toxic hepatitis in patients who have undergone a new coronavirus infection with the determination of clinical and laboratory predictors of the response to therapy. A dynamic analysis of the effectiveness of toxic hepatitis therapy in patients of three experimental groups and a control group is presented.

Aim. The aim of the present study is to increase the effectiveness of the treatment of toxic hepatitis in patients who have undergone COVID-19.

Materials and methods. On the basis of the newly created infection centers of the Central Clinical Hospital “RZhD-Medicine” and Vishnevsky 3-rd Central Military Clinical Hospital 996 patients with COVID-19, who had clinical and laboratory signs of toxic liver damage (cytolytic and/or cholestatic syndromes) against the background of COVID-19 therapy.

Results. On the 14th day from the start of therapy in group 3, there was a significant decrease in the clinical manifestations of jaundice in 163 (72.8%) patients, on the 21st day of treatment, this symptom was stopped in all patients. In groups 1 and 2, the decrease in clinical manifestations of jaundice was significantly lower – 122 (55.2%) and 134 (58.8%); p<0.05. At the end of therapy, no manifestations of jaundice were observed in all experimental groups, while in the control group, symptom reduction was achieved only in 47 (14.5%) patients.

Conclusion. The use of drugs with hepatoprotective effect in the form of monotherapy in groups 1 (UDCA) and 2 (ademethionine) showed a low therapeutic effect with positive dynamics of clinical and laboratory indicators of toxic hepatitis activity. The use of combined treatment in group 3 (UDCA and ademethionine) demonstrated the maximum therapeutic effect, pronounced positive dynamics in the form of normalization of clinical and laboratory indicators of toxic hepatitis activity.

Terapevticheskii arkhiv. 2022;94(12):1413-1420
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Ferroptosis-associated lesion as a potential target for cardiovascular disease: A review

Podzolkov V.I., Tarzimanova A.I., Ponomareva L.A., Popova E.N., Ponomarev A.B.


Cell death is an important feature of the development of multicellular organisms, a critical factor in the occurrence of cardiovascular diseases. Understanding the mechanisms that control cell death is crucial to determine its role in the development of the pathological process. However, the most well-known types of cell death cannot fully explain the pathophysiology of heart disease. Understanding how cardiomyocytes die and why their regeneration is limited is an important area of research. Ferroptosis is an iron-dependent cell death that differs from apoptosis, necrosis, autophagy, and other forms of cell death in terms of morphology, metabolism, and protein expression. Ferroptotic cell death is characterized by the accumulation of reactive oxygen species resulting from lipid peroxidation and subsequent oxidative stress, which can be prevented by iron chelates (eg, deferoxamine) and small lipophilic antioxidants (eg, ferrostatin, liproхstatin). In recent years, many studies have been carried out on ferroptosis in the context of the development of atherosclerosis, myocardial infarction, heart failure, and other diseases. In addition to cardiovascular diseases, the review also presents data on the role of ferroptosis in the development of other socially significant diseases, such as COVID-19, chronic obstructive pulmonary disease. With the study of ferroptosis, it turned out that ferroptosis participates in the development of bacterial infection associated with the persistence in the host body of Pseudomonas aeruginosa. The review summarizes the recent advances in the study of ferroptosis, characterizing this type of cell death as a novel therapeutic target.

Terapevticheskii arkhiv. 2022;94(12):1421-1425
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Hyperuricemia and kidney damage in patients with cardiovascular disease: A review

Mironova O.I.


Many studies have been conducted confirming the effect of uric acid (UA) on kidney function. It is obvious that there is a relationship between the effect of UA not only on kidney function, but also on the cardiovascular system, increasing cardiovascular risk. The review article provides basic information about the pathogenesis, principles and features of prescribing therapy to patients with chronic kidney disease (CKD) and cardiovascular disease. A lot of data currently indicates that hyperuricemia, both with and without crystal deposition, is associated with high cardiovascular risk and decreased kidney function. A number of studies and meta-analyses indicate that urate-reducing therapy prevents and slows down the decline in kidney function in patients with CKD, many of whom suffer from cardiovascular diseases or at least have several risk factors. Despite the fact that currently the guidelines for the treatment of CKD do not include a recommendation for the start of urate-lowering therapy, a large amount of data has been accumulated on the potential benefits of such treatment even in the absence of a diagnosis of gout. The preferred group of drugs for this group of patients are xanthine oxidase inhibitors, and for patients with eGFR below 30 ml/min/1.73 m2, it seems that allopurinol currently has larger evidence base for the efficacy and safety of prescribing.

Terapevticheskii arkhiv. 2022;94(12):1426-1430
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Pharmacokinetics and pharmacodynamics of rebamipide. New possibilities of therapy: A review

Bakulina N.V., Tikhonov S.V., Okovityi S.V., Lutaenko E.A., Bolshakov A.O., Prikhodko V.A., Nekrasova A.S.


The MedLine database contains 570 publications, including 71 randomized clinical trials and 6 meta-analyses on the rebamipide molecule in 2022. Indications for the use of rebamipide are gastric ulcer, chronic gastritis with hyperacidityin the acute stage, erosive gastritis, prevention of damage to the gastrointestinal mucosa while taking non-steroidal anti-inflammatory drugs, eradication of Helicobacter pylori. Currently trials are studying the efficacy and safety of the drug in gouty and rheumatoid arthritis, osteoarthritis, Sjögren's syndrome, bronchial asthma, vitiligo, atherosclerosis, diseases of the kidneys and liver; using in traumatology to accelerate bone regeneration; in ophthalmology to improve the regeneration of corneal epithelium; in oncology to reduce inflammatory changes in the oral mucosa after chemoradiotherapy. The review article is about the main pharmacokinetic and pharmacodynamic characteristics of rebamipide. A detailed understanding of pharmacodynamics and pharmacokinetics allows for individual selection of therapy based on the characteristics of the patient's body – gender, age, comorbidities; choose the optimal route of administration and dosing regimen; predict adverse effects and drug interactions; be determined with new clinical indications.

Terapevticheskii arkhiv. 2022;94(12):1431-1437
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History of medicine

Gout: from Hippocrates till the modern time

Guliaev S.V., Chebotareva N.V., Moiseev S.V.


Gout (podagra) is one of the most ancient articular diseases. Its accurate mechanisms and causes were delineated only during the last century. Major historical investigatory steps are described in relation to causality and pathogenesis of the disease from Hippocrates ages till the modern time. The newest genetic and epidemiologic aspects of the disease are presented in this article.

Terapevticheskii arkhiv. 2022;94(12):1438-1441
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