Vol 72, No 6 (2017)

INFECTIOUS DISEASES: CURRENT ISSUES
THE MECHANISMS OF IMMUNE ESCAPE BY HEPATITIS B VIRUS
Sokolova M.V., Konopleva M.V., Semenenko Т.A., Akimkin V.G., Tutelyan A.V., Suslov A.P.
Abstract
The high prevalence of the hepatitis B virus (HBV) in population occurs mainly due to numerous mechanisms formed in the process of the virus evolution, contributing to its survival under immunological pressure. The review presents the most complete systematization and classification of various HBV protective mechanisms basing on their influence on different parts of congenital and adaptive immune response. The analysis of literature data allows for the conclusion that two basic principles underlie the mechanisms: the strategy of the «stealth virus» (virus’s escape from recognition by the immune system) and strategy of immunosuppression. The stealth virus strategy is performed as follows: special strategy of the HBV replication which prevents the recognition by the receptors of congenital immune system; occurrence of the vaccine escape mutants; isolation of the virus in host cells and tissues providing its inaccessibility to T-cells along with hyperproduction of subviral particles as traps for specific antibodies. The core principle of the immunosuppression implemented in hepatitis B therapy is based on the phenomenon of the viral apoptotic mimicry. The result of this interaction strategy is dysfunction of NK and NKT-cells, inactivation of dendritic cell functions, and suppression of the adaptive immune response. The review demonstrates that interaction between HBV and the immune system of the macro organism is in some kind of «dynamic equilibrium» depending on numerous factors. Specific molecular targets of the viral impact are described. We propose to expand the research on the influence of the host’s genetic factors on the development of congenital and adaptive immune response against HBV, especially during the real infectious process which results in the improvement of approaches to the therapy by developing personalized treatment methods.
Annals of the Russian academy of medical sciences. 2017;72(6):408-419
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CRYPTOSPORIDIA AND MACROORGANISM: FACTORS THAT INFLUENCE ON THE DEVELOPMENT OF CRYPTOSPORIDIOSIS
Starikova E.G., Voronkova O.V., Kovshirina Y.V., Shubina N.I.
Abstract

Cryptosporidiosis is a disease caused by unicellular parasites belonging to the Cryptosporidium genus. The small intestine is the primary site of localization of infection which predicts the main clinical symptom of the disease — diarrhea. The most important factors influencing Cryptosporidium infection and the course of disease are molecular genetic variability of the parasite, its virulence and infectivity, and viability of the mucosa of the digestive tract and local and systemic immunity of the macroorganism. The immune status of the host plays a key role in determining sensitivity to infection and the severity of the disease. Cryptosporidium infection differs in outcomes: asymptomatic in some patients, acute enteritis accompanied by profuse diarrhea, lesions of internal organs, and fatal outcome in others. Current therapeutic approaches to the treatment of cryptosporidiosis are ineffective. Despite the existence of a large number of drugs with antiparasitic effect, there are no medications with a specific effect on cryptosporidia. Understanding the factors that determine both the pathogenicity of Cryptosporidia and the protective properties of host defense systems will allow developing effective prevention measures and therapeutic interventions of this protozoosis.

Annals of the Russian academy of medical sciences. 2017;72(6):420-427
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CARDIOLOGY AND CARDIOVASCULAR SURGERY: CURRENT ISSUES
THE STRUCTURE OF PHARMACOTHERAPY OF ARTERIAL HYPERTENSION AND ADHERENCE IN YOUNG PATIENTS
Tuleutayeva R.Y., Musina A.Y., Cebotarenko N.A., Makhatova A.R.
Abstract

Aim: To determine the indicators of adherence to drug therapy in young patients with arterial hypertension (АН) and the correlation between the indicators and therapy management.

Materials and methods: The study enrolled 514 patients aged 25 to 45 years diagnosed with essential hypertension. We studied the structure of antihypertensive pharmacotherapy and adherence to treatment using the Moriski−Green test and the original questionnaire. The patients were distributed depending on the degree of blood pressure increase, administered treatment, age, economic factor, and drug source.

Results: The adherence level by Moriski−Green test was 36.8%; according to the original questionnaire: high adherence level was 38.3%, incomplete adherence ― 33.7%, and poor adherence ― 28.0%. The monotherapy with ACE inhibitors predominated in the majority of cases; the fixed combinations were more typical for the treatment of the stage II AH, drug combinations ― for stage III AH. The highest therapy adherence was registered in patients with stage III AH receiving treatment with combinations of drugs in a single dosage form. The life quality of respondents and the drug source did not influence the adherence significantly.

Conclusion: In young patients with arterial hypertension, some features of treatment structure determine the therapy adherence.
Annals of the Russian academy of medical sciences. 2017;72(6):428-434
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PSYCHOLOGY AND PSYCHIATRY: CURRENT ISSUES
CHARACTERISTICS OF DEPRESSION IN PATIENTS WITH DIFFERENT CHRONOTYPES
Gerasimchuk M.Y.
Abstract

Background: Approximately 30−40% of depressive patients does not improve or show a partial response. Since biological rhythm involved in the pathogenesis of mood disorders is regarded as a unique characteristic of a person, it opens new opportunities for personalized medicine.

Aim: to evaluate clinical characteristics and treatment effectiveness in depressive patients with different chronotypes.

Materials and methods: In prospective, hospital-based study MADRS was performed weekly (dMADRS), therapeutic response (R) was defined as a 50% or greater decrease from baseline in the score. Chronotype was evaluated using the Morningness−Eveningness Questionnaire (MEQ). Participants completed a questionnaire package: HDRS-21, PSQI, ТОВ, «individual minute». Statistical analysis was performed using Excel for Windows, Statistica 13.0.

Results: All patients (n=100, mean age 48±16 yrs) were divided into groups based on their circadian type: evening types (ETs) had more severe condition; antidepressants (SSRIs; R=72%) were effective given at morning in ETs, at evening (other; R=100%) ― in morning types (MTs) (p<0.00001) with a greater reduction in depressive symptoms (p<0.05). Prescribing drugs with balanced potency were effective in both groups (F=4.62, p=0.032). Cluster analysis on 25 clinical, biological, and therapeutic variables to establish the role of chronotype as a factor important for identifying patients with similar socio-demographic, clinical, and health characteristics was conducted. Cluster 1 achieved a reduction of depression severity (19% MTs; R=81%; 43.4±17.7 yrs; single episode; dMADRS 16.9±2.7; 23% monotherapy). Cluster 3 (80% ETs; R=50%; 40.4±15.2; early onset dMADRS 15.23±2.29; 7% monotherapy) was the most unfavorable prognostic group.

Conclusions: Depressive patients with morning/evening chronotypes have significant differences in clinical presentation, the course of the illness and efficacy of antidepressants. Evening chronotype was found to be associated with poor prognosis. Circadian typology should be considered when choosing the appropriate therapeutic options.

Annals of the Russian academy of medical sciences. 2017;72(6):435-441
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ONCOLOGY: CURRENT ISSUES
THE ROLE OF DIFFUSION-WEIGHTED MRI IN DIFFERENTIAL DIAGNOSIS AND PREDICTION OF SURVIVAL IN PATIENTS WITH BRAIN METASTASES
Byvaltsev V.A., Stepanov I.A., Kichigin A.I., Kanigin V.V., Stupak V.V.
Abstract

Background: Brain metastases are observed in up to 40% of all intracranial tumors. Some types of metastatic tumors cause difficulties in differential diagnosis, since they have similar signal characteristics with other pathological entities in neuroimaging. Obviously, the additional diagnostic methods to determine the prognosis and tactics of further management of this group of patients should be implemented.

Aim: To study the role of diffusion-weighted magnetic resonance imaging (MRI) in differential diagnostics and predicting the survival rate in patients with brain metastases. Materials and methods: The study included data from MRI and morphological studies of 23 patients with brain metastases. The obtained values of the apparent diffusion coefficient (ADC) of tumors were compared with their histological type, cell density, and the index of proliferative activity Ki-67. In addition, the influence of ADC values on the overall survival rate was assessed.

Results: A reliable inverse correlation of ADC values and the index of proliferative activity for various types of brain metastases (r=-0.74, p=0.014) was established. The dependence of ADC values and overall survival rate of patients with metastases in the brain is presented. The overall survival rate in patients with an ADC value greater than 947.2 mm2/sec was 9.8 months (95% CI: 8.6−11.3), and with ADC value less than 947.2 mm2/sec ― 6.4 months (95% CI: 3.7−9.1).

Conclusion: The technique of diffusion-weighted MRI plays an important role in the differential diagnosis of brain metastases; it can be used as a tool of comprehensive preoperative assessment when planning the surgery and as a prognostic factor of overall survival rate for this group of patients. 

Annals of the Russian academy of medical sciences. 2017;72(6):442-449
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CIRCULATING TUMOR CELLS: CLINICAL SIGNIFICANCE IN BREAST CANCER (REVIEW)
Kaigorodova E.V.
Abstract

Circulating tumor cells (CTCs) constitute a heterogeneous population. Some tumor cells are cancer stem cells (CSCs), while others are in the process of the epithelial-mesenchymal transition (EMT); however, most CTCs are neither stem cells nor participants in the EMT. There is increasing interest in the study of the molecular biological characteristics of CTCs. Many researchers consider circulating tumor cells (CTC) as one of the variants of «liquid biopsy in real time». In this review, we discuss the clinical significance of CTCs in breast cancer and in particular the prognostic and predictive significance both in early stage and metastatic breast cancer, as well as the pathogenetic role of CTCs in venous thromboembolism. Evaluation of various characteristics of CTCs is promising for the study of new biomarkers and targets for targeted therapies. The clinical importance involves the determination of the heterogeneity of the CТC and in particular of the stem subpopulation of these cells, cells with signs of EMТ, with no evidence of stem cells, and with a combination of these features.

Annals of the Russian academy of medical sciences. 2017;72(6):450-457
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AB0 BLOOD TYPES AND MALIGNANT COLORECTAL NEOPLASMS OF DIFFERENT LOCATION: A RETROSPECTIVE ANALYSIS OF 1570 CASES
Kerimov R.A., Seksenbayev B.D., Galimov O.V., Nurmashev B.K., Znanteyev M.E.
Abstract

Background: AB0 blood type antigens are unequally expressed in different portions of the colon resulting in so-called proximal-distal gradient. In most research studies considering the link between blood types and colorectal cancer, this gradient has not been taken into account. In the present context the findings of such studies are not convincing, no evidence-based results are reflected in literature. Valid studies of this association require antigenic distribution of the colon and malignant tumor location to be taken into account.

Aim: To assess the possible relation between AB0 blood type antigens and malignant tumors located in different parts of the large intestine.

Materials and methods: We performed a case-control study with retrospective analysis of medical records on patients with the presented disease (cases) and patients who did not suffer from it (controls). Required data was obtained from regional oncological centers of South Kazakhstan, Karaganda, East Kazakhstan, and Mangystau regions. Every third case of colorectal cancer registered in 2011−2016 years was included in the survey. The studied association was estimated by means of a chi-square test. A multinomial logistic regression was used to calculate the odds ratio (OR) with confounding risk factors to be taken into account. Shares of the samples were compared by means of Student’s t-test. A critical level of statistical significance (p-value) was considered to be 0.05.

Results: Each group included 1570 patients. Gender, age, and ethnic distribution did not differ statistically in cases and controls (p>0.4 for all comparisons). When blood type distributions were compared between groups regardless of tumor locations, any significant difference was not revealed (p=0.141). When similar calculations were applied to specific parts of the large intestine, the association between 0 blood type and malignancies of distal portions of the colon was demonstrated (p=0.0002). When we calculate the odds ratio for the disease development in the colon parts (using a multinomial logistic regression), the following results were obtained: 1.518 (p=0.004) for 0, 0.781 (p=0.099) for A, 0.785 (p=0.143) for B, and 0.965 (p=0.884) for AB blood types.

Conclusions: The results of the present study revealed a statistical correlation between the 0 blood type and malignant tumors located in the distal portions of the colon.
Annals of the Russian academy of medical sciences. 2017;72(6):458-465
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SURGERY: CURRENT ISSUES
NAT2 GENE POLYMORPHISM AS A PREDICTOR OF FAILURE FOR SURGICAL TREATMENT OF PELVIC ORGAN PROLAPSE: RESULTS OF A PROSPECTIVE COHORT CLINICAL STUDY
Dubinskaya Е.D., Коlesnikova S.N., Khamoshina М.B., Lebedeva М.G., Sounov М.А., Коstin I.N., Sokhova Z.M.
Abstract

Background: Pelvic organ prolapse (POP) is the most frequent disease component in the structure of gynecological pathology (from 28 to 38.9%) and its incidence is increasing. Most of the research studies were initiated to develop various kinds of operative treatment for common prolapse cases (POP-Q III−IV); however, a large number of surgical interventions associated with a high percentage of complications and a high rate of relapses confirm the difficulty for problem-solving. In this regard, there is a need to expand ideas about the pathogenesis of the disease and develop approaches to the prediction of recurrence surgical treatment, choosing the correct and timely treatment strategy. Currently, great importance is given to the study of genetic control of connective tissue metabolism. The evidence demonstrated that polymorphism of NAT2 gene results in genetically determined disorders of connective tissue catabolism which increases the possibility of disease development approximately in 2 times. Point mutations in NAT2 lead to the so-called slow-acetylation which determines the predominance of the decay rate of collagen over its synthesis.

Aim: Analyze the significance of NAT2 polymorphism as a predictor for failure of surgical treatment of pelvic organ prolapse.

Materials and methods: The prospective cohort clinical trial enrolled 140 women of the reproductive age (from 28 to 42 y.o.) with symptomatic prolapse (POP-Q Stage II−III) who were examined and received treatment in the period from 2008 to 2014. All patients underwent surgical treatment of POP. The treatment included colpoperineorrhaphy with levatorplasty. In 12.9% of patients who had stress urinary incontinence — in combination with a loop urethropexies transobturatory access (Transobturator Vaginal Tape, TVT-O). Long-term results of treatment effectiveness were assessed in 3−5 years. Results: The findings revealed that the incidence rate of point mutations of NAT2 gene was >2-fold higher in patients with POP included in the ineffective treatment group (61.8%) if compared to the rate registered in the effective treatment group (30.6%).

Conclusions: The obtained data indicate that the presence of point mutations in NAT2 gene is a poor prognostic factor for general types of genital prolapse and a predictor for failure of surgical treatment.

Annals of the Russian academy of medical sciences. 2017;72(6):466-472
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