Vol 11, No 1 (2020)

10th anniversary of the journal Clinical practice
Baklaushev V.P.

10 years ago, on April 1, 2010, the first issue of the quarterly scientific and medical journal Clinical Practice was published.

Journal of Clinical Practice. 2020;11(1):5-6
Urgent publication
COVID-19. Aetiology, pathogenesis, diagnosis and treatment
Baklaushev V.P., Kulemzin S.V., Gorchakov А.А., Lesnyak V.N., Yusubalieva G.M., Sotnikova A.G.

COVID-19 (Coronavirus disease 2019) is a new epidemic infectious disease characterized by a relatively high contagiousness and a high probability of life-threatening complications such as acute respiratory distress syndrome (ARDS), acute respiratory and multiple organ failure. The causative agent of the disease is the enveloped zoonotic RNA virus known as SARS-CoV-2. Together with the SARS-CoV and MERS-CoV viruses, which cause severe acute respiratory syndrome and the Middle East respiratory syndrome, respectively, it belongs to the Coronaviridae family, the genus Betacoronavirus. The COVID-19 epidemic has spread rapidly around the world and currently hit 213 countries with more than 1.6 million confirmed cases, of which more than 90.000 have died so far. In Russian Federation, SARS-CoV-2 infection is included in the list of diseases that pose a danger to others, along with especially dangerous infections. The virus is transmitted by airborne droplets, airborne dust and contact routes, therefore, to protect medical staff it is necessary to use individual protective suits and accessories, with protection of the respiratory tract and eyes, disinfection of hands and surfaces as when working with the BSL-2 microorganisms. The diagnosis of COVID-19 is confirmed using real-time RT-PCR diagnostics detecting the presence of viral RNA. Clinical manifestations of COVID-19 vary from mild and moderate (pneumonia without signs of hypoxemia and impaired O2 saturation, 80% of all cases), to severe (15% of cases, O2 saturation 89–93%) and extremely severe (5% of cases, ARDS, multiple organ failure, mechanical ventilation and resuscitation are necessary). The typical clinical presentation of COVID19 patients includes the following: severe fever, dry cough, respiratory failure, combined with lymphopenia and thrombocytopenia, normal procalcitonin, elevated levels of ferritin and CRP in the blood with signs of bilateral, polysegmental pneumonia and the “ground glass” opacity on CT. Even in the absence of an unfavorable epidemiological anamnesis, these clinical signs can be recommended to admit the patient to an infectious isolation ward where he or she would wait for the results of PCR diagnostics and the diagnosis of COVID-19 be confirmed/ ruled out. Currently, no SARS-CoV-2-specific therapy is available for COVID-19 patients; the only method that has proven effective in several investigational trials is transfusion of convalescent plasma with high titers of neutralizing antibodies. A number of innovative treatments appear promising and include the use of neutralizing monoclonal antibodies, ACE2-derived agents, as well as MSC- and NK-cell based cell therapies.

Journal of Clinical Practice. 2020;11(1):7-20
Basic Science
Creating a public mutation database oncoBRCA: bioinformatic problems and solutions
Nikitin A.G., Brovkina O.I., Khodyrev D.S., Gusev O.A., Gordiev M.G.

Background. The development of hereditary cancer syndromes is caused by genetic disorders in the DNA repair system, which consists of more than 100 genes. However, at present, in the majority of medical centers in Russia, the diagnosis of hereditary OC and BC is limited to the determination of the most frequent mutations (8 points) in BRCA1 and BRCA2 genes using PCR methods. However, the given mutations are frequent for Slavic population while in other populations of Russia they occur less often or do not occur at all. Aim. To reveal the landscape of hereditary pathogenic variants in the genes of the reparation system and develop methods for a fast analysis of the NGS data.

Methods. A panel of 34 genes of the reparation system was analyzed by next generation sequencing (NGS) in 1644 samples of patients with inherited cancer syndromes.

Results. The NGS analysis revealed 119 pathogenic mutations of BRCA1/BRCA2 genes in 374 patients, with a marked difference in mutation frequencies between different ethnic groups — Slavs, Tatars, Bashkirs and Chuvash. A public database of the frequencies of mutations and polymorphisms of the genes of the DNA reparation system in different ethnoses was created at https://oncobrca.ru. Methods were created for automatic parallel processing of any number of samples from the raw data to the final report.

Conclusions. The NGS method has created a possibility to identify rare mutations characteristic of different ethnic groups, which makes it possible to prescribe optimal chemotherapy and develop diagnostic methods of population screening for carrying gene mutations of the DNA repair system. The modern approaches to the analysis of genome sequencing data allowed reducing the time of obtaining the result to several hours after the analysis.

Journal of Clinical Practice. 2020;11(1):21-29
Association of the AGT, ACE, NOS3 polymorphism with subclinical arterial wall changes and cardiovascular diseases risk factors
Akopyan A.A., Kirillova K.I., Strazhesko I.D., Samokhodskaya L.M., Leonov S.L., Gelfand E.M., Sorokina A.G., Orlova I.A.

Background. Renin-Angiotensin-Aldosterone System activation (RAAS) and nitric oxide (NO) reduction lead to the changes in the arterial wall, which, in turn, create a favourable environment for the development of cardiovascular diseases (CVD). There is only limited knowledge of the influence of proteins participating in the RAAS activation and providing NO bioavailability on the parameters of the arterial wall state (pulse wave velocity (PWV), carotid artery intima-media thickness (cIMT), endothelium-dependent vasodilation (EDVD), presence of atherosclerotic plaques) and risk factors of CVD.

Aim. Finding the association between the AGT, ACE, NOS3 polymorphism and PWV, cIMT, EDV, presence of atherosclerotic plaques and risk factors of CVD in healthy subjects.

Methods. Using intergroup analysis and models of multiple logistic regression, we examined the association of AGT с.521С>Т polymorphism, AСE Ins>Del polymorphism, NOS3 с.894G>T polymorphism with arterial wall changes and risk factors of CVD in 160 healthy people of different ages.

Results. The CT genotype of AGT с.521С>Т polymorphism was associated with lower levels of systolic blood pressure (BP) (p=0.013) and central systolic BP (p=0.029), higher level of Insulin-Like Growth Factor (IGF) (p=0.027). The DD genotype of ACE Ins>Del polymorphism was associated with a higher waist/hip ratio (p=0.044), lower level of high density lipoprotein cholesterol (p=0.01), lower index of EDVD (p=0.042), higher incidence ofendothelial dysfunction (ED) (p=0.026). The GG genotype of NOS3 с.894G>T polymorphism was associated with higher levels of central systolic BP (p=0.022) and central mean BP (p=0.033), total cholesterol (p=0.025), low density lipoprotein cholesterol (p=0.014) and IGF (p=0.042), higher incidence of ED (p=0.007), albuminuria (p=0.032) and insulin resistance (p=0.03).

Conclusion. We have found the association of the AСE and NOS3 polymorphism with endothelial dysfunction and the metabolic status.

Journal of Clinical Practice. 2020;11(1):30-41
Sensitivity of antibiotic resistant coagulase-negative staphylococci to antiseptic piсloxydin
Khalatyan A.S., Budzinskaya M.V., Kholina E.G., Strakhovskaya M.G., Kolyshkina N.A., Kovalenko I.B., Zhukhovitsky V.G.

Background. Coagulase-negative staphylococci (CNS), primarily Staphylococcus epidermidis, predominate in the normal microflora of the eye. However, due to irrational antibiotic therapy, resistant strains are widely distributed among CNS.

Aim. To study the sensitivity of the antibiotic resistant CNS isolates to picloxydine, an antiseptic.

Methods. The species, sensitivity to antibiotics and picloxydine were determined for 39 isolates of bacteria obtained from the conjunctival swabs. The cells’ morphology under the antiseptic’s influence was studied by electron microscopy.

Results. 33 isolates of S. epidermidis (17 sensitive or resistant to drugs of no more than 2 classes of antibiotics and 16 MDR), 2 S. haemolyticus (1 resistant to 2 classes of antibiotics and 1 MDR), 3 S. hominis (1 sensitive and 2 MDR), 1 S. caprae (MDR) were characterized. In in vitro tests, picloxydine showed high efficiency in suppressing the growth of staphylococci regardless of their sensitivity to antibiotics, as well as bactericidal activity at concentrations of 15.6–31.2 µg/ml, close to those of chlorhexidine. At these concentrations, the antiseptic had a destructive effect on the surface structures of bacterial cells.

Conclusion. The picloxydine antiseptic is equally effective against antibiotic- sensitive and antibiotic-resistant coagulase-negative staphylococci.

Journal of Clinical Practice. 2020;11(1):42-48
Tumor inflating lymphocytes. Purification, expanding and cytotoxicity analisys on primary tumor cultures
Yusubalieva G.M., Petrichuk S.V., Krivoshapkin A.L., Kedrova A.G., Ivanov Y.V., Vinokurov A.G., Kalinkin A.A., Sandjarov A.E., Kim S.V., Ponomarev A.V., Kuptsova D.G., Ischenko R., Troitskiy A., Baklaushev V.P.

Tumor inflating lymphocytes. Purification, expanding and cytotoxicity analisys on primary tumor cultures

Journal of Clinical Practice. 2020;11(1):49-58
Original Research
Rational antibacterial therapy for toxic osteonecrosis of the jaws
Antakov G.I., Shtraube G.I., Boev I.A.

Background. Toxic osteonecrosis of the jaw is a new disease of the XXI century. It develops due to the use of an artificially manufactured narcotic substance — desomorphine.

Aim. To determine the species composition of microflora and to study its sensitivity to antibiotics for toxic osteonecrosis of the jaws, depending on the phase of the inflammatory process to develop the principles of rational antibacterial therapy of this pathology.

Methods. A retrospective study was conducted for 38 patients aged from 21 to 45 years, observed in the PSMU dental clinic from 2012 to 2018, including 25 men and 13 women. They were divided into 2 groups. The first group (19 patients) were admitted for an emergency treatment in the acute phase of the inflammatory process, accompanied by the development of pyo-inflammatory complications in the maxillofacial area. The second group (19 patients) were hospitalized as planned for sequestrectomy. A bacteriological study from the pathological lesion was carried out in all the subjects with the subsequent determination of the sensitivity of the selected microflora to antibiotics.

Results. The analysis of the obtained results revealed the following differences in the composition of the predominant microflora: in the group of patients with osteonecrosis in the acute phase, the prevailing group of bacteria were staphylococci, in the group of patients with osteonecrosis in the chronic phase — streptococci. In addition, the presence of such microorganisms as enterococci and acinetobacter was noted in the first group, and bacilli and fungi were noted in the second group. The isolated microorganisms in the first group were also more susceptible to antibiotics than those in the second group. At the same time, the use of levofloxacin and gentamicin is preferable in both study groups. In addition, antibiotics of the penicillin family, cephalosporins and chloramphenicol may be used in the acute phase.

Conclusion. Our study shows that the composition of microflora in toxic osteonecrosis is diverse and depends on the phase of the inflammatory process. The study results form a basis for the prescription of a rational antibacterial therapy, which contributes to a more successful treatment of this disease, reducing the risk of developing severe purulent complications and the inflammatory process generalization.

Journal of Clinical Practice. 2020;11(1):59-66
Ticagrelor hemorrhagic safety in patients with acute coronary syndrome with ST-segment elevation received thrombolytic therapy in daily clinical practice: 30-day observation results
Bocharov A.V., Sidorov D.V.

Background. Effective antithrombotic therapy is a necessary condition for maintaining the patency of the infarct-dependent coronary artery during a primary percutaneous coronary intervention.

Aim. To compare the safety of ticagrelor use in patients with STEMI after ineffective thrombolytic treatment (TLT) and successfully performed recanalization of infarct-dependent artery (IDA) by PCI, withticagrelor loading dose administered in the time window from TLT to PCI, in comparison with the TREAT study results on the risk of bleeding in the real clinical practice.

Methods. A comparative analysis of the results of a 30-day follow-up of 52 patients with acute coronary syndrome with ST-segment elevation who received a thrombolytic therapy with alteplasa and early ticagrelor administration with the ticagrelor group in the TREAT study on the parameters of hemorrhagic safety.

Results. Arterial hypertension, dyslipidemia, generalized atherosclerosis, chronic obstructive pulmonary disease and a history of myocardial infarction were significantly more common in the study group. The analysis of the results revealed no significant differences between the groups in the frequency and risk of hemorrhagic complications. Conclusion. There are no significant differences in the frequency of major bleeding according to the TIMI and BARC criteria between the groups, which indicates the safety of early (within 24 hours after thrombolysis) ticagrelor use in the pharmacoinvasive approach in the real clinical practice.

Journal of Clinical Practice. 2020;11(1):67-72
The prevalence of cardiovascular risk factors and their structure among healthy women. The main results of the project «Three ages of women»
Voevodina I.V., Maychuk E.Y., Ivanova O.S.

Background. Pathology of the cardiovascular system leads among the causes of mortality.

Aim. To determine the presence and structure of cardiovascular risk factors in healthy women of various age groups for a further in-depth study of their correlation with the initial manifestations of common diseases.

Methods. 408 healthy women took part in the study. The study was conducted among students and employees of MSUMD. All the women were questioned using a questionnaire specially created by the authors of the study. The questionnaire contained questions on identifying the main risk factors for cardiovascular diseases, nutritional characteristics, physical activity, the presence of bad habits and diseases, gynaecological status.

Results. All the participants were divided into 4 groups. The 1st group included 157 volunteers of a young early reproductive age from 17 to 24 years. Women of an early and late reproductive age up to 45 years, depending on the presence of a history of childbirth, were divided into two groups: 113 women having given birth made up the 2nd group and 74 nulliparous peers formed the 3rd group. 64 postmenopausal women aged 45 to 66 years made up the 4th group. Complaints of shortness of breath and discomfort in the heart region without regard to physical activity (73% versus 36% of cases in the 1st group, p=0.001), insufficient physical activity (48%, p=0.001) were noted in women of the fourth group. 18.4% of respondents smoked cigarettes. Among chronic diseases, gastrointestinal diseases prevailed in 41.4% (n=169). The gynaecological status analysis revealed ovarian dysfunction in 26.8% of the respondents, premenstrual syndrome in 52% (group 1 volunteers), premature birth in 14.7% of volunteers, Cesarean section in 11.7% of women, birth complications in 15,4%, miscarriages in 11.4% of cases. In 28% of women of the 4th group with a surgical menopause, an increase in the body mass index, in the blood pressure, hot flashes and insomnia were noted (p=0.001).

Conclusion. The presence of a large percentage of CVD risk factors in practically healthy women — smoking, physical inactivity, obesity, hormonal disorders, pregnancy pathologies — in young age groups requires an in-depth study in the identified risk groups.

Journal of Clinical Practice. 2020;11(1):73-80
Magnetic resonance imaging as a tool of differential diagnostic in the brainstem damage in children
Marchenko N.V., Voitenkov V.B., Skripchenko N.V., Bedova M.A., Kurzanceva O.O.

In this review, magnetic resonance imaging (MRI) is presented as a tool for the differential diagnostics of the brainstem lesions in children. It has been shown that both the isolated brainstem lesions or those related to the supratentorial changes occur within a wide range of pathological conditions — in acute stroke, dismetabolic disorders, inflammatory processes of both the infectious and non-infectious (autoimmune, paraneoplastic) etiology, neurodegenerative diseases, tumors. A small size of the brainstem, as well as a less clear distinction between the gray and white matter and certain limitations of visualization of the infratentorial structures with multiparametric MRI often lead to difficulties in the differential diagnosis. Sometimes the most important in the diagnostics is the topography of lesions and their signal intensity. Nevertheless, the clinical data, the results of epidemiological and laboratory studies are of primary importance for the differential diagnosis of brainstem lesions.


Journal of Clinical Practice. 2020;11(1):81-91
The role of human and microbial metabolites of triptophane in severe diseases and critical ill (review)
Getsina M.L., Chernevskaya E.A., Beloborodova N.V.

The growing interest to metabolites circulating in the blood is associated with the accumulation of factual material on the involvement of low-molecular compounds in the development of a number of serious diseases. This review reveals the effect of a whole class of chemical compounds — tryptophan metabolites — on various pathological processes. The following keywords were used to find the publications in the PubMed database for the last 10 years: names of natural indole compounds, methods for their detection, nosology of diseases and critical illness . The data are presented in sections, with the studies of tryptophan metabolites in a variety of disease groups, such as cancer, cardiovascular disease, kidney disease, bowel, mental disorders, atherosclerosis, etc. A particular attention is paid to the role of indole compounds that enter the systemic circulation as a result of microbial biotransformation of tryptophan, serotonin and other indole metabolites, which can be attributed to the “common metabolites” of humans and microbiota. The most interesting clinical studies are summarized in the tables and figures. A number of indole metabolites are considered as potential biomarkers. The authors of the review substantiate the metabolomic approach to the study of a number of oncological, septic, mental and other intractable diseases, which opens up new possibilities of influence on the pathological process by targeted regulation in the metabolome/microbiome system.

Journal of Clinical Practice. 2020;11(1):92-102
Hereditary breast cancer: present status of problem
Gatueva F.S., Lyubchenko L.N., Malygin S.E.

The incidence of breast cancer is increasing in most countries every year. The purpose of this literature review is to provide up-to-date information about the causes, mechanisms of development, various methods of prevention, early diagnosis and treatment of hereditary breast cancer. The effectiveness of bilateral preventive mastectomy is discussed.

Journal of Clinical Practice. 2020;11(1):103-111
Comboridity of chronic obstructive pulmonary disease and cardiovascular diseases: general factors, pathophysiological mechanisms and clinical significance
Chaulin A.M., Grigoryeva Y.V., Duplyakov D.V.

Currently, the comorbidity (combination) of chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD) is an important problem for the health care. This is due to the high prevalence and continuing growth of these pathologies. CVD and COPD have common risk factors and mechanisms underlying their development and progression: smoking, inflammation, sedentary lifestyle, aging, oxidative stress, air pollution, and hypoxia. In this review, we summarize the current knowledge related to the prevalence and frequency of cardiovascular diseases in people with COPD and the mechanisms that underly their coexistence. The implications for clinical practice, in particular the main problems of diagnosis and treatment of COPD/CVD comorbidity, are also discussed.

Journal of Clinical Practice. 2020;11(1):112-121

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