Vol 94, No 11 (2022)

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Informativeness estimation for the main clinical and laboratory parameters in patients with severe COVID-19

Stanevich O.V., Bakin E.A., Korshunova A.A., Gudkova A.Y., Afanasev A.A., Shlyk I.V., Lioznov D.A., Polushin Y.S., Kulikov A.N.


Aim. To conduct a retrospective assessment of the clinical and laboratory data of patients with severe forms of COVID-19 hospitalized in the intensive care and intensive care unit, in order to assess the contribution of various indicators to the likelihood of death.

Materials and methods. A retrospective assessment of data on 224 patients with severe COVID-19 admitted to the intensive care unit was carried out. The analysis included the data of biochemical, clinical blood tests, coagulograms, indicators of the inflammatory response. When transferring to the intensive care units (ICU), the indicators of the formalized SOFA and APACHE scales were recorded. Anthropometric and demographic data were downloaded separately.

Results. Analysis of obtained data, showed that only one demographic feature (age) and a fairly large number of laboratory parameters can serve as possible markers of an unfavorable prognosis. We identified 12 laboratory features the best in terms of prediction: procalcitonin, lymphocytes (absolute value), sodium (ABS), creatinine, lactate (ABS), D-dimer, oxygenation index, direct bilirubin, urea, hemoglobin, C-reactive protein, age, LDH. The combination of these features allows to provide the quality of the forecast at the level of AUC=0.85, while the known scales provided less efficiency (APACHE: AUC=0.78, SOFA: AUC=0.74).

Conclusion. Forecasting the outcome of the course of COVID-19 in patients in ICU is relevant not only from the position of adequate distribution of treatment measures, but also from the point of view of understanding the pathogenetic mechanisms of the development of the disease.

Terapevticheskii arkhiv. 2022;94(11):1225-1233
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Original articles

Regional Vascular Center in a COVID-19 pandemic: what changed in 2020 compared to 2019 in patients with ST Elevation Myocardial Infarction?

Syrkina A.G., Ryabov V.V.


Aim. To assess the effect of pandemic COVID-19 on the course of STEMI patients of the Regional Vascular Center in 2020, compared with the previous year.

Materials and methods. Patients with acute coronary syndrome and, in particular, STEMI hospitalized at Regional Vascular Center in 2019 and 2020.

Results. In 2019, 981 patients with STEMI were admitted; in 2020 – 728 patients. The baseline clinical and demographic patients characteristics did not differ significantly. In 2020, the number of pneumonia has doubled, the number of mechanical ventilator support has increased by 20%; sepsis was diagnosed 5 times more often. However, patients in 2020 were less likely to develop delirium, minor and major bleeding. There were more patients admitted in the 1st day of the disease, and they were more frequently performed both primary angioplasty and angioplasty in general. Patients with STEMI in 2020 had more frequently registered pulmonary edema, cardiogenic shock and re-infarction. Lethality in the group of patients without angioplasty tended to be higher in 2020 compared with the previous year. None of 30 patients with COVID-19 died in our department, they were timely transferred either to COVID-hospital or to outpatient follow-up care. When analyzing various parameters during the spring and autumn periods, which were the peak periods for pneumonias in 2020, only mortality had a clear upward trend.

Conclusion. The patient portrait of myocardial infarction in 2020 was dominated by pneumonia, sepsis, and re-infarction compared with the previous year. An upward trend in mortality was detected in those without angioplasty and those hospitalized in the spring and autumn wave of COVID-19. We believe that there are hidden mechanisms of pandemic effect on mortality in STEMI.

Terapevticheskii arkhiv. 2022;94(11):1234-1238
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Dynamics of the structure of renal tuberculosis over 20 years

Kulchavenya E.V., Kholtobin D.P.


Background. Tuberculosis is a serious medical and social problem that does not lose its importance, despite all the advances in pharmacology and surgery. Diagnosis of urogenital tuberculosis (UGTB), as a rule, is delayed due to low index of suspicion to tuberculosis and the absence of pathognomonic symptoms.

Aim. Determining the change in the ratio of clinical forms of renal tuberculosis from 1999 to 2020.

Materials and methods. A retrospective cohort comparative non-interventional study on the spectrum of the incidence of extrapulmonary tuberculosis (EPTB) was carried out. Among all 13852 extrapulmonary tuberculosis patients which were diagnosed from 1999 to 2020, patients with renal tuberculosis were selected, and the spectrum of their clinical forms in three periods was analyzed: 1st period 1999–2004 (1155 patients), second period 2005–2014 (2657 patients), and the third period 2015–2020 (671 patients). The clinical features of nephrotuberculosis in 88 patients was also estimated.

Results. Over the 20 years of the analyzed period, the number of patients with UGTB decreased by 80.6%; for the year of the COVID-19 pandemic, this figure fell by another third. In the first period, destructive complicated forms of nephrotuberculosis prevailed (922 patients – 79.8%), while the so-called "minor forms" were diagnosed in 233 patients (20.2%). In the second period, the situation was statistically significantly more favorable: the proportion of destructive and complicated forms of renal tuberculosis decreased to 43.8% (1124 patients), "small forms" were diagnosed in 1443 patients (56.2%). In the third period, destructive and complicated forms of nephrotuberculosis were diagnosed in 531 patients (77.6%), and the proportion of "small forms" in comparison with the previous period decreased by half, to 22.4%. Analysis of the clinical features of renal tuberculosis, depending on the prevalence of the destruction, showed that an asymptomatic course is possible, and pain, dysuria, intoxication and renal colic are present with different frequencies, and the clinical picture of tuberculosis of the renal parenchyma differs significantly from the clinical picture of tuberculous papillitis, cavernous nephrotuberculosis and symptoms of renal tuberculosis as whole.

Conclusion. Currently, there is no screening on urogenital tuberculosis at all. Patients are diagnosed by referral, with a long history, after receiving multiple courses of antibacterial treatment; mainly through the pathomorphological examination of the operating material. Thus, a sharp decrease in the proportion of UGTB patients does not mean the disappearance of tuberculosis of this localization, but only states the tragic defects in timely diagnosis and low index of suspicion of medical doctors in relation to UGTB.

Terapevticheskii arkhiv. 2022;94(11):1239-1245
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Predictors of severe course of new coronavirus infection (COVID-19): study design

Mishchenko T.A., Ermakova P.A., Ermakova A.A., Tseller L.P., Rogozhkina Y.A., Verteletskaya M.I., Burakevich O.A., Kardashina Z.Z.


Aim. To identify predictors of the severe course of a new coronavirus infection.

Materials and methods. A retrospective analysis of 120 clinical case histories of patients hospitalized in hospitals in Tyumen with a confirmed diagnosis of COVID-19 within one year (01.08.2020–01.08.2021) was carried out. The patients were divided into two groups: 1st – with a favorable outcome (n=96), 2nd – with an unfavorable (fatal) outcome (n=24). For a more complete analysis, scales for assessing the clinical condition of patients (SHOCK-COVID), severity assessment (NEWS2) were used. Information processing was carried out in the IBM.SPSS.Statistics-19 program (USA).

Results. As a result of the study, the median age for the 1st group was significantly lower (58 years) than for patients of the 2nd group (69 years; p=0.029). A certain set of laboratory parameters for group 2 patients deviate significantly from the reference values (C-reactive protein – CRP – 7.6 [4.7; 15.2] mg/dl, D-dimer – 1.89 [1.36; 5.3] mcg/ml, ferritin – 605 [446.7; 792] ng/ml). When analyzed in groups, taking into account the main markers of the severity of the disease, using the V.Yu. Mareev CCAS-COVID (Clinical Condition Assessment Scale) scale, for the 1st group, the sum of the set of parameters was 6 [2; 7] points, which corresponds to the average severity of coronavirus infection, for the 2nd group 13 [9; 16] points – severe course. For patients of the 2nd group, a significant increase in the indicators of an unfavorable prognosis was revealed in comparison with the 1st group.

Conclusion. Thus, in this study, the level of CRP, ferritin, D-dimer, the percentage of lung tissue damage according to computed tomography results, SaO2 were significantly associated with an unfavorable prognosis.

Terapevticheskii arkhiv. 2022;94(11):1246-1251
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Analysis of fatal outcomes of meningococcal infection in adults

Zhdanov K.V., Kovalenko A.N., Chirsky V.S., Gusev D.A., Nalivkina N.A., Zinserling V.A., Grigoriev S.G., Khairutdinova R.A., Isakov A.N., Sharabkhanov V.V.


Clinical characteristics and pathomorphological manifestations in 69 patients aged 18 to 86 years with a fatal outcome of the disease were examined in order to analyze the causes of severe course and high mortality of generalized forms meningococcal infection. It was found that the main clinical form was meningococcemia (90%), in the majority in combination with meningitis (52%). The fulminant course in 77% of patients with meningococcal sepsis manifested itself as a sudden onset, rapid development of typical symptoms. Hemorrhagic exanthema was detected on the first day of meningococcemia. The leading complications and critical conditions were infectious-toxic shock, disseminated intravascular coagulation and acute adrenal insufficiency (Waterhouse–Friederiksen syndrome). The severe course of meningitis (in 10%) led to the development of cerebral coma, the morphological substrate of which was edema – swelling of the brain.

Terapevticheskii arkhiv. 2022;94(11):1252-1256
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Impact of vaccination with pneumococcal vaccines on recurrent pneumonia in patients with chronic obstructive pulmonary disease

Ignatova G.L., Antonov V.N.


Background. Community-acquired pneumonia (САР) and chronic obstructive pulmonary disease (COPD) are among the main causes of mortality worldwide, and, in addition, they also lead to great economic losses for the health system of all countries. Currently, there is an increase in cases of recurrent pneumonia, both in the general population and, in particular, in patients with COPD. One of the most important risk factors for the development of pneumonia is the previous episode of САР. Potential risk factors for recurrent pneumonia are concomitant diseases such as heart failure, COPD, diabetes mellitus, neurological disorders, swallowing dysfunction, immune deficiency.

Aim. To conduct a retrospective analysis of the effect of vaccine prophylaxis with conjugated pneumococcal vaccine (PCV13) and polysaccharide pneumococcal vaccine (PPV23) on the risk of recurrent pneumonia in patients with COPD.

Materials and methods. A total of 302 male patients were included in the retrospective study. When analyzing the data, the fact of the development of pneumonia of any etiology during the 5th observation period was taken into account. For the recurrence of pneumonia, more than two episodes of CAP were taken during the year. 13-valent conjugated pneumococcal vaccine Prevenar-13 and 23-valent polysaccharide vaccine Pneumo23 were used for vaccine prophylaxis. The relative risk of the event was calculated. A 95% confidence interval was used.

Results and conclusion. A retrospective analysis showed that, firstly, CAP is a fairly frequent complication of COPD: initially, the average percentage of cases of САР was 19.3%. Secondly, the risk of developing repeated episodes of pneumonia remains quite high in unvaccinated patients and tends to increase within 5 years: from 17 to 22%. Thirdly, the pneumococcal vaccines used have different effects on the risk of recurrent pneumonia in patients with COPD, a significant decrease in the number of recurrent pneumonia is observed only with the use of conjugated vaccines.

Terapevticheskii arkhiv. 2022;94(11):1257-1261
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The mechanisms of anti-inflammatory action of enisamium iodide

Kareva E.N., Fedotcheva T.A., Semeikin A.V., Kochina N.A., Krasnoshchok E.V., Shimanovskii N.L.


Aim. The role of cyclooxygenases (COX-1 and/or COX-2), transcription nuclear factor NF-κB, anti-inflammatory cytokines – TGF1b, IL-4, IL-10 and pro-inflammatory cytokines IL-1, IL-6 were studied to substantiate the expediency of antiviral agent enisamium iodide (Nobazit) using to regulate key inflammatory components in acute respiratory infections, IL-8, TNF-alpha in the realization of the pharmacological activity of this drug.

Materials and methods. Gene expression was determined by real-time RT-PCR, the concentration of interleukins was determined by ELISA, and the viability of peripheral blood mononuclear cells (PBMC) was assessed by the MTT spectrophotometric method. The chemiluminescence method was used to assess PBMC oxidant activity.

Results. Enisamium iodide (10 μM) reduced mRNA levels of COX-1, COX-2, NF-κB, TGF1b, IL-1, IL-6 in stimulated PBMC of healthy donors by an average of 48% (p≤0.05). At 5 times higher concentration, 50 μM, enisamium iodide suppressed the expression of these genes by an average of 43% (p≤0.05). At a concentration of 100 μM, enisamium iodide reduced the expression of COX-2, TGF1b, IL-1, IL-6 by an average of 47% (p≤0.05). At a concentration of 10 μM, enisamium iodide stimulated the secretion of IL-10 by mononuclear cells by 1.2 times, p≤0.05. The tested drug at a concentration of 50 μM did not affected on the concentration of IL-1, IL-4, IL-8 and TNF-alpha, but significantly stimulated the production of IL-10 by 1.5 times, p≤0.05. The chemiluminescence method revealed that enisamium iodide in the entire concentration range (10–100 μM) does not reduce the viability of macrophages, but inhibits their oxidative activity (maximum value of CL intensity) by an average of 55% (p≤0.05).

Conclusion. The anti-inflammatory effect of enisamium iodide at a concentration of 10 μM may be associated with inhibition of the expression of COX-1, 2, NF-κB, IL-1, IL-6, TGF1b and an increase in the expression and production of IL-10. An additional contribution to the anti-inflammatory activity of enisamium iodide is made by its antioxidant and antiradical activity. The absence of the effect of enisamium iodide (10–100 µM) on the viability of PBMC indicates its safety for the cells of the immune system and the expediency of using it to suppress inflammatory reactions in acute respiratory infections, restore the quality of life of patients and the possibility of using Nobazit as an effective agent for treatment of these infections of various etiologies.

Terapevticheskii arkhiv. 2022;94(11):1262-1267
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Non-specific prevention of COVID-19 during vaccination against a new coronavirus infection: results of a multicenter, double-blind, placebo-controlled, randomized clinical trial

Avdeeva M.G., Belousova O.N., Orlova E.A., Khamitov R.F., Shvarts Y.G., Kravchenko I.E.


Background. A multicenter, double-blind, placebo-controlled, randomized clinical trial (RCT) of the phase III efficacy and safety of Ergoferon® for the non-specific prevention of COVID-19 during vaccination against a new coronavirus infection was conducted (permission of the Ministry of Health of the Russian Federation №559 dated 22.09.2021; ClinicalTrials.gov Identifier: NCT05069649).

Aim. To evaluate the efficacy and safety of the use of Ergoferon for the non-specific prevention of COVID-19 during vaccination against a new coronavirus infection.

Materials and methods. From October 2021 to April 2022, 1,057 patients aged 18 to 92 years who received component I of the “Gam-COVID-Vac” vaccine were included. After screening, 1,050 patients were randomized into 2 groups: 526 people received Ergoferon according to the prophylactic scheme – 1 tablet per administration 2 times a day for 3 weeks, the drug is not allowed during the meal and should be kept in the mouth without swallowing, until completely dissolved; 524 patients received a placebo according to the Ergoferon® scheme. The total duration of participation in the study was 5 weeks + 3 days. The primary endpoint is the number of RT-PCR – confirmed cases of SARS-CoV-2 infection, regardless of the presence of symptoms during participation in the study. An additional criterion of effectiveness is the proportion of those hospitalized with COVID-19. The safety assessment included consideration of the presence and nature of adverse events (AEs), their severity, relationship with the drug intake, and outcome. Statistical data processing was carried out using SAS 9.4 with the calculation of the exact Fisher test, χ2 test, Cochrane–Mantel–Hensel test, Wilcoxon test and other parameters.

Results. The ITT (Intention-to-treat) and PP [Per Protocol] efficacy analysis included data from 1,050 [970] patients: 526 [489] people – Ergoferon® group and 524 [481] people – Placebo group. The primary endpoint – the number of laboratory-confirmed cases of SARS-CoV-2 infections was 3 times less compared to placebo – 7 (1.43%) vs 22 (4.57%), respectively (p=0.0046; [p=0.0041]). Taking Ergoferon® reduces the risk of SARS-CoV-2 infection by more than 3 times in vaccinated patients during 5 weeks of the vaccination and post-vaccination periods (p=0.0046 [p=0.0041]). Of the COVID-19 patients in the Ergoferon® group (1.33%) nobody was hospitalized. According to the Post hoc analysis, Ergoferon® reduces the risk of COVID-19 disease by 4 times in the period between the components I and II of the “Gam-COVID-Vac” vaccine (p=0.0066 [p=0.006]). The frequency of AEs in both groups did not differ. There were no registered AEs associated with the drug with a reliable degree. There was a high level of patient compliance and good tolerability.

Conclusion. Ergoferon is an effective and safe drug for the prevention of COVID-19 in people vaccinated against a new coronavirus infection.

Terapevticheskii arkhiv. 2022;94(11):1268-1277
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A new approach to etiotropic therapy ARVI in children

Sabitov A.U., Kovtun O.P., Esaulenko E.V., Sorokin P.V.


Aim. Confirmation of the efficacy and safety of the drug riamilovir (Triazavirin®), 100 mg capsules, in children aged 12–17 years with the diagnosis of acute viral respiratory infection (ARVI).

Materials and methods. The multicenter study included 269 patients diagnosed with acute viral respiratory infection (ICD-10 code: J00, J02, J02.9, J04, J04.0, J04.1, J04.2, J06, J06.0, J06.9) in the presence of clinical manifestations and confirmation of the etiology of the disease by laboratory tests (PCR method). Patients were included in the study after one of the patient's parents/adoptive parents and the patient signed an informed consent to participate in the study. The interval between the appearance of the first symptoms of the disease and the inclusion of the patient in the study did not exceed 36 hours.

Results. As a result of a clinical study, the efficacy and safety of treatment with riamilovir (Triazavirin®) in sick children aged 12–17 years with a diagnosis of ARVI was shown. A decrease in the duration of the disease was shown when using the drug riamilovir (Triazavirin®) compared with the control group. No serious adverse events were detected during the study.

Conclusion. As a result of the conducted clinical study, the high efficacy, safety and good tolerability of the drug riamilovir in the treatment of children aged 12–17 years with a diagnosis of ARVI was established. It is recommended to use the drug riamilovir in clinical practice as an etiotropic therapy in children aged 12–17 years with a diagnosis of ARVI due to its high efficacy and safety.

Terapevticheskii arkhiv. 2022;94(11):1278-1284
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Prospects and possibilities for the treatment of patients with long COVID-19 syndrome

Tanashyan M.M., Raskurazhev A.A., Kuznetsova P.I., Bely P.A., Zaslavskaya K.I.


Aim. To study the efficacy and safety of a drug product based on the succinic acid complex with trimethylhydrazine used to treat patients with asthenic syndrome after a new coronavirus infection (COVID-19).

Materials and methods. A prospective, multicenter, comparative, randomized, double-blind, placebo-controlled study of the safety and efficacy of sequential therapy with Brainmax® enrolled 160 patients 12–16 weeks after coronavirus infection (no more than 12 months). The study was conducted at 6 healthcare centers in different regions of the Russian Federation. At the enrollment, clinical and neurological examination and the following tests were performed: complete blood count, urinalysis, blood chemistry, coagulation test, pulse oximetry, electrocardiography, glomerular filtration rate calculation (according to Cockcroft–Gault formula) were performed. Also, the patients were assessed using the following tools: VAS headache rating scale, MFI-20 asthenia scale, PSQI index, FAS-10 fatigue assessment scale, Dizziness Handicap Inventory (DHI), MoCA-test for cognitive impairment assessment, Beck Anxiety Inventory, Kérdö Autonomic Index.

Results. The primary endpoint was the mean reduction in the MFI-20 asthenia scale score after the therapy (Visit 5, 41st day of therapy) compared to data from Visit 0 (beginning of therapy). A clinically significant advantage of the study drug versus the placebo was demonstrated, with a median absolute change in the MFI-20 score of -19.5 [-27; -11] points in the Brainmax® drug group and -3 [-7; 1] score in the placebo group (p<0.001). A significant sleep quality improvement according to the PSQI index was shown in the study group: by -2.5 [-4; -1] points versus no improvement in the placebo group (0 [-3; 0], p<0,001). Significant differences were also noted for the following secondary endpoints: PSQI sleep quality scale, FAS-10 fatigue assessment scale, DHI, and Beck Anxiety and Depression Inventory. There was also a decrease in patients' complaints of cognitive deterioration according to the CGI scale.

Conclusion. Our study clearly demonstrated the efficacy and high safety profile of Brainmax® in a representative sample of patients with the post-COVID syndrome.

Terapevticheskii arkhiv. 2022;94(11):1285-1293
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The informative value of CD3+CD4+ and CD3+CD8+ T-cell count and cHIS scale as predictors of severe COVID-19 when using interleukin-6 receptor blockers in the in-hospital setting

Kruglova T.S., Fomina D.S.


Background. Clinical and laboratory signs of hyperinflammatory response in COVID-19 may serve as prognostic markers of the disease scenario. In real-world practice, there is an unmet need to determine the optimal timing of identifying predictors of SARS-CoV-2 adverse outcomes in the context of patient stratification to improve the effectiveness of anti-IL-6R therapy. Lymphopenia has a high informative value for the adverse prognosis of the COVID-19 course; however, the informative value of CD3+CD4+, CD3+CD8+ T-cell count remains questionable. In addition to lymphocyte phenotyping, a six-criterion additive scale (cHIS) was used in the study.

Aim. To study the informative value of CD3+CD4+, CD3+CD8+ T-cell phenotyping and cHIS scale as predictors of severe COVID-19 when using IL-6R blockers.

Materials and methods. A single-center, bi-directional study included 179 patients with SARS-CoV-2-induced community-acquired pneumonia with severe acute inflammation and progressing respiratory failure. Data were obtained from electronic patient records. Anti-IL-6R was administered in addition to standard therapy in the cohorts. The following disease outcomes were used to determine the informative value of the studied parameters: mortality and hospital discharge. Inflammatory markers were measured before and after administering anti-IL-6R, followed by monitoring. Statistical analysis was performed using SPSS (version 25.0). The quantitative indices were described using the median and interquartile range. Quantitative indices were compared using nonparametric methods: Mann–Whitney U-test, Kruskal–Wallis test. The groups were compared by qualitative characteristics using Pearson's chi-square test. Correlation analysis of quantitative indicators was performed using Spearman rank correlation. For additional analysis of the cHIS scale, odds ratio and decision tree methods were used. Differences were considered statistically significant at р0,05.

Results. Immunophenotyping of lymphocytes as a predictor of the severe SARS-CoV-2 requires further research. The cHIS scale may be implemented in routine clinical practice due to its high predictive value. A cHIS score of ≥2 on the first day of admission is a critical threshold for intensification and revision of therapy. The prognosis with cHIS is logically relevant in the first three days of hospitalization.

Conclusion. The main result of the study is the definition of target groups of patients with community-acquired SARS-CoV-2 pneumonia for the IL-6R-blockers, considering the timing of their effective use in real clinical practice.

Terapevticheskii arkhiv. 2022;94(11):1294-1302
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Clinical notes

Case of multiple systemic (extrahepatic) manifestations of chronic HCV infection (analysis of the literature and own observations). Case report

Krivosheev A.B., Khvan L.A., Morozov D.V., Krivosheeva I.A., Spitsina S.V., Dobracheva O.A., Eremeeva S.A., Levekina E.E.


The article presents a description of a patient with chronic HCV infection and multiple extrahepatic manifestations, which manifested in dynamics and were recorded with a different sequence during 15 years of follow-up. In the patient we observed, the most frequently recorded extrahepatic manifestations were verified: porphyria cutanea tarda, mixed cryoglobulenemia, and utoimmune thyroiditis. Chronic HCV infection is often diagnosed in the presence of psoriasis was assessed as a paraneoplastic disease.

Terapevticheskii arkhiv. 2022;94(11):1303-1309
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Description of the case of adverse pasteurellosis in a cirrhosis patient. Case report

Malov V.A., Poluektova V.B., Shakotko A.P., Tishkevich O.A., Maleyev V.V., Volchkova E.V., Paevskaja O.A., Nemilostiva E.A., Maloletneva N.V.


The article describes a clinical case of an unfavorable course of pasteurellosis in a patient with liver cirrhosis. Possible variants of the clinical course, clinical and epidemiological data, on the basis of which pasteurellosis can be suspected, modern recommendations for antibiotic therapy are considered.

Terapevticheskii arkhiv. 2022;94(11):1310-1314
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Clinical cases of complicated diverticulitis against the background of severe course COVID-19. Case report

Pshenichcnaya N.Y., Ponezheva Z.B., Marzhokhova A.R., Kharaeva Z.F., Balagova L.E., Marzhokhova M.Y., Shestakova I.V.


Two clinical cases of perforation of a previously undiagnosed colon diverticulum in patients with coronavirus infection caused by the SARS-CoV-2 virus treated at the Hospital №1 of Nalchik. Both patients were elderly, overweight, had a lot of chronic concomitant diseases. Patients received hormone therapy and were targeted: the first patient twice (tocilizumab on the first day of hospitalization and olokizumab on the 7th day of inpatient treatment). The second patient received levilimab on the 3rd day of his stay in the hospital. A short time after targeting, both patients developed acute diffuse abdominal pain, the patients were transferred to the surgical department and operated on. During the operation, both patients were found to have previously undiagnosed diverticular disease, complicated by diverticular perforation and peritonitis on the background of immunosuppression. Both patients died. Thus, when using targeted therapy for patients with COVID-19, it is necessary to take into account that they may have previously undiagnosed chronic diseases that can cause fatal complications against the background of immunosuppression.

Terapevticheskii arkhiv. 2022;94(11):1315-1319
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Clinical case of mucormycosis in patient COVID-19. Case report

Nurtdinova G.M., Suleymanov A.M., Bayazitov I.I., Khismatullina Z.R., Shamigulov F.B., Gumerov R.M., Agaidarova G.M., Zagidullin S.Z., Shchekin S.V., Shchekin V.S., Absalyamova D.F., Pavlov V.N., Zagidullin N.S.


The COVID-19 epidemic is being revealed from a new angle every month. In particular, with the appearance of the delta strain, mucormycosis began to manifest in some patients, which had previously been extremely rare. Mucormycosis is a rare, aggressive infection caused by filamentous fungi of the Mucorales family and associated with high morbidity and mortality rates. The main risk factors for the mucormycosis in patients with COVID-19 are diabetes mellitus and diabetic ketoacidosis, uncontrolled hyperglycemia and massive use of glucocorticoids, vascular damage, thrombosis, lymphopenia, which often occur against the background of COVID-19 and make a person vulnerable to secondary or opportunistic fungal infection. We present a clinical case of mucormycosis in a 21-year-old female patient with COVID-19-associated severe pneumonia and concomitant type I diabetes mellitus. The patient was hospitalized and received standard therapy during inpatient treatment, including glucocorticosteroids in accordance with the severity of the course of COVID-19. On the 12th day from the hospitalization, the patient's condition deteriorated significantly, and the visible changes in the skin and soft tissues of the face, characteristic of mucormycosis appeared. Despite the drug therapy correction, the patient died because of the acute respiratory failure in combination with septic fungal damage of the brain stem.

Terapevticheskii arkhiv. 2022;94(11):1320-1325
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Liver disease during the pandemic of COVID-19 infection: prediction of the course and tactics of management: A review

Maev I.V., Osadchuk M.A.


The hepatic consequences of SARS-CoV-2 infection are now recognized as an important component of CoronaVIrus Disease 2019 (COVID-19). This aspect is most clinically relevant in patients with pre-existing chronic liver disease (CKD), who are at extremely high risk of severe COVID-19 and death. Risk factors for severe CKD, especially in people with liver cirrhosis and non-alcoholic fatty liver disease, are the direct and indirect cytotoxic effects of coronavirus against the background of systemic inflammation, blood clotting disorders and immune dysfunction. The severe negative impact of the pandemic in the presence of CKD and the difficulties of patient relationships contribute to the progressive increase in the global burden of liver disease on the health system.

Terapevticheskii arkhiv. 2022;94(11):1326-1332
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Pulmonary fibrosis in patients with COVID-19: A review

Chuchalin A.G.


The viral infectious disease pandemic caused by SARS-CoV-2 has affected over 500 million people and killed over 6 million. This is the official data provided by the WHO as of the end of May 2022. Among people who have recovered from COVID-19, post-COVID syndrome is quite common. Scattered epidemiological studies on post-COVID syndrome, however, indicate its high relevance. One of the manifestations of post-COVID syndrome is the development of pulmonary fibrosis (PF). This article is devoted to the analysis of literature data on epidemiology, immunomorphology, as well as X-ray morphological and functional characteristics of PF in patients with post-COVID syndrome. Attention is drawn to the various phenotypes of the post-COVID syndrome and the incidence of PF, which, as clinical practice shows, is most common in people who have had severe COVID-19. This article discusses in detail the molecular biological and immunological mechanisms of PF development. The fibrotic process of the lung parenchyma is not an early manifestation of the disease; as a rule, radiomorphological signs of this pathological process develop after four weeks from the onset of acute manifestations of a viral infection. The characteristic signs of PF include those that indicate the process of remodulation of the lung tissue: volumetric decrease in the lungs, “cellular” degeneration of the lung parenchyma, bronchiectasis and traction bronchiolectasis. The process of remodulating the lung tissue, in the process of fibrosis, is accompanied by a violation of the lung function; a particularly sensitive test of functional disorders is a decrease in the diffusion capacity of the lung tissue. Therefore, in the process of monitoring patients with post-COVID syndrome, a dynamic study of the ventilation function of the lungs is recommended. The main clinical manifestation of PF is dyspnea that occurs with minimal exertion. Shortness of breath also reflects another important aspect of fibrous remodulation of the lung parenchyma – oxygen dissociation is disturbed, which reflects a violation of the gas exchange function of the lungs. There are no generally accepted treatments for PF in post-COVID syndrome. The literature considers such approaches as the possibility of prescribing antifibrotic therapy, hyaluronidase, and medical gases: thermal helium, nitric oxide, and atomic hydrogen. The article draws attention to the unresolved issues of post-covid PF in people who have had COVID-19.

Terapevticheskii arkhiv. 2022;94(11):1333-1339
pages 1333-1339 views

History of medicine

Clinical case conference in medical practice and education: Origins and current status

Dvoretsky L.I.


A genesis of clinical case conference as a form of case discussion that integrates medical and educational functions is presented. The role of the following top figures of medicine in the development of clinical case conference is described: J.-M. Charcot, S.P. Botkin, G.A. Zakharin, V.N. Vinogradov, A.L. Myasnikov, E.M. Tareev, N.A. Mukhin. The article pays special attention to clinical case conference in Russian medical education. The role of clinical case conferences in shaping medical judgment in a clinician and a student is discussed.

Terapevticheskii arkhiv. 2022;94(11):1340-1344
pages 1340-1344 views

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