TRANSFORMATION OF MYELODYSPLASTIC SYNDROME INTO ACUTE MYELOBLASTIC LEUKEMIA (CLINICAL CASE).

Despite the availability of modern methods for diagnosing and treating myelodysplastic syndrome (MDS) in the arsenal of a hematologist, even with an adequate treatment strategy, it is not always possible to predict the timing of transformation of the disease into acute myeloid leukemia. The clinical case we presented demonstrates the rapid transformation of MDS into acute myeloid leukemia in a relatively young patient whose prognosis turned out to be poorly predictable despite a change in therapy.

MYELODYSPLASTIC SYNDROME: DIAGNOSIS, TREATMENT AND PROGNOSIS (LITERATURE REVIEW).

Given the difficulties of diagnosis, the absence of a typical clinical picture of myelodysplastic syndrome accompanied by cytopenia, a high risk of transformation into acute myeloid leukemia, discussion of the formation, terminology, pathogenesis, classification, clinical course and principles of management of this group of tumor diseases is very relevant. The review article discusses the issues of terminology, pathogenesis, classification and diagnosis of myelodysplastic syndrome (MDS), as well as the principles of management of this category of patients. Due to the absence of a typical clinical picture of MDS, in order to exclude other diseases accompanied by cytopenia, not only routine hematological examination methods are necessary, but also a mandatory cytogenetic examination of the bone marrow. Treatment of patients with MDS should be individualized, taking into account risk group stratification, age and physical status. To improve the quality of life of patients with MDS, epigenetic therapy with azacitidine has an advantage. Myelodysplastic syndrome is an irreversible tumor process with a clear tendency to transform into acute leukemia. The diagnosis of MDS is always made with caution by excluding other diseases accompanied by cytopenia. To make a diagnosis, not only routine hematological examination methods are necessary, but also a mandatory cytogenetic study of the bone marrow. The management of patients with MDS is still an unresolved problem. The approach to the treatment of MDS should be individualized and based on the patient's risk group, age, and somatic status. Epigenetic therapy has an advantage when choosing management tactics for MDS in terms of improving the quality of life of patients.

CLINICAL AND FUNCTIONAL STATE OF THE THYROID GLAND IN WOMEN OF PERI- AND POSTMENOPAUSAL AGE WITH METABOLIC SYNDROME.

The article deals with the problem of the clinical and functional relationship between the state of the thyroid gland in women of menopausal age and the components of the metabolic syndrome (MS). The purpose of the study: to assess the relationship between thyroid dysfunction and various components of MS in women of peri- and postmenopausal age. 80 menopausal women (mean age 55 years) were examined, of which 40 people with MS constituted the main group, and the comparison group - a similar number of women without MS. The inclusion criterion in the study was the presence of signs of abdominal obesity (AO) according to the WHO criteria (2008). Anthropometric, functional (BP), laboratory (lipidogram, TSH, freeT4, antibodies to TPO, FSH, LH, urinary iodine concentration) and instrumental (ultrasound of the thyroid gland) data, statistical analysis using the program SPSSStatistics version 20 were evaluated. The women were divided into two age groups: group 1 - perimenopausal and group 2 - postmenopausal. There were 40 people in each group (20 women with MS and 20 women without MS). It has been shown that peri- and postmenopausal women with MS have subclinical hypothyroidism. The influence of peripheral blood TSH levels in peri- and postmenopausal women with MS on body weight, carbohydrate and lipid metabolism, and sex hormones was established.

[ERRORS IN THE DIAGNOSTICS AND TREATMENT OF PATIENTS WITH GOUT AND THE ALGORITHM OF THERAPEUTIC TACTICS IN DIFFERENT PERIODS OF THE DISEASE (CLINICAL CASE)].

Difficulties and errors in the treatment of patients with the gout arise, mainly, during urate-lowering therapy. The article discusses possible medical errors in acute gouty arthritis and during chronic tophaceous gout in the light of the updated international recommendations of the American College of Rheumatology (ACR) and the European Antirheumatic League (EULAR 2018). As an example of inadequate treatment, the authors describe a case of a patient with chronic tophaceous gout. Errors in the diagnosis and treatment of the patient caused various complications and unjustified surgical intervention - amputation of the right finger and removal of a large tophus in the left forearm. Based on the analysis of mistakes made in the diagnosis and treatment of gout, the authors propose an algorithm for therapeutic tactics in different periods of the disease. So, for the relief of exacerbation in acute gouty arthritis, it is recommended to take the following drugs at starting doses: colchicine at a dose of 1.8 mg/day (1.2 mg immediately followed by 0.6 mg 1 hour later during 7-10 days or until complete relief of the gout attack), non-steroidal anti-inflammatory drugs (nimesulide up to 200 mg/day) or glucocorticosteroids (prednisolone at a dose of 30 mg/day for 3-5 days with subsequent withdrawal). The first-line urate-lowering drugs for chronic tofaceous gout are xanthine oxidase inhibitors - allopurinol and febuxostat. Allopurinol is prescribed no earlier than 2 weeks after the arthritis attack has stopped at a starting dose of no more than 100 mg/day, the dose is gradually increased to the minimum effective. The starting dose of febuxostat is 40 mg/day. Also, together with allopurinol or febuxostat, it is recommended to take uricosuric drugs (probenecid 500 mg/day or benzbromarone 50-200 mg/day). At the same time, the authors draw attention to the inadmissibility of the combination of allopurinol and febuxostat. In case of gout that does not respond to the main methods of therapy, treatment with pegloticase is recommended. When prescribing urate-lowering therapy, dose titration is necessary, to avoid the development of toxic effects.

[INDICATORS OF CARDIOHEMODYNAMICS OF RHYTHM DISTURBANCES IN ELDERLY PEOPLE WITH CHRONIC HEART FAILURE].

The aim of our study was to study and analyze the electrophysiological indicators of rhythm disturbances in heart failure in elderly people who participated in the elimination of the consequences of the Chernobyl accident in the distant period. In order to assess the functional features, 50 elderly patients (65-74 years old) who participated in the liquidation of the consequences of the Chernobyl accident were examined. Patients were divided into 4 groups depending on the length of stay in an environmentally disadvantaged zone: group 1 (April-June 1986) - 8 (16%) people; 2 (June-December 1986) -14 (28%); 3 (1987-1989) -17 (34%) and group 4 (1990-91gg) -11 (22%) people. All patients were on basic therapy. To study cardiogemodynamics in this category of patients, the following electrophysiological research methods were performed: ECG, XM ECG, SMAD, EchoCG. When analyzing electrophysiological studies, the MSExcel and Statistica programs were used. The examined patients showed a high incidence of left ventricular hypertrophy and cardiac arrhythmias. So in the 1st and 2nd groups, atrial fibrillation, sinus tachy and bradycardia, AV blockade of 1-2 degrees were reliably detected. In groups 3 and 4, left ventricular hypertrophy and arrhythmias were detected with a lower frequency. It should be noted that these changes were observed in individuals participating in the LPA from April to December 1986, i.e. in the first year after the accident. According to echocardiography, diastolic dysfunction of the left ventricle was found mainly in individuals of 1-2 groups. High high indices of KDR, BWW and KSO in 1-2 groups are noted. LVMI exceeds its norm in all studied groups. Thus, statistically significant differences of some indicators are revealed with electrophysiological research methods in all groups of elderly patients with heart failure participating in the liquidation of the Chernobyl accident, as well as the high incidence of rhythm disturbances in patients with Chernobyl nuclear power plants.

[CLINICAL, MORPHOLOGICAL AND MOLECULAR GENETIC FEATURES AND PROGNOSTIC FACTORS OF PRIMARY MYELOFIBROSIS. A CASE OF PRIMARY MYELOFIBROSIS TRANSFORMATION INTO ACUTE MYELOID LEUKEMIA].

Primary myelofibrosis is a common disease from the group of Ph-negative myeloproliferative diseases. The article presents modern data on the pathogenesis of Ph-negative myeloproliferative diseases, as well as diagnostic criteria, treatment tactics and prognosis factors for primary myelofibrosis. A clinical case of transformation of primary myelofibrosis into acute myeloid leukemia is described. Purpose of the study - to present up-to-date information on the pathogenesis, diagnostic criteria, principles of treatment and prognostic factors of primary myelofibrosis, as well as to present a clinical case of transformation of primary myelofibrosis into acute myeloblastic leukemia. According to modern concepts, for the early diagnosis of primary myelofibrosis, along with the clinical and morphological methods of examining patients, molecular genetic verification of the disease is extremely important. To improve the survival rate of patients with primary myelofibrosis, molecular genetic verification of the disease and stratification for the choice of treatment tactics are necessary.

[ARTERIAL HYPERTENSION AMONG WORKERS OF A URANIUM PROCESSING ENTERPRISE OF THE REPUBLIC OF KAZAKHSTAN: PREVALENCE, RELATIVE RISKS AND PREDICTORS OF THE DEVELOPMENT].

The aim of this study was to establish the prevalence, relative risks, and predictive factors of the development of arterial hypertension (AH) in workers of a uranium processing enterprise (UPE). An open cross-sectional comparative study of 809 UPE workers was conducted. The compared them to the 696 workers of the bearing plant, located at a distance of 10 km from UPE. Stratification was performed and odds ratios (OR), gross (RR) and standardized relative (SRR) risks of hypertension were calculated. Our results revealed a high prevalence of hypertension among UPE workers (24.8%), as well as greater risk of development of hypertension among workers of UPE in comparison to the personnel of the non-uranium enterprise: RR=2.4 and SRR=2.9. The most significant predictors of hypertension were burdened heredity (OR = 13.6), total radiation dose (OR=1.5), overweight (OR=1.1), high anxiety (OR=0.5) and systematic use of alcohol (OR=0.5). Thus, among workers chronically exposed to radiation toxicity, high prevalence of hypertension, excessive RR and SRR of developing hypertension and the presence of risk factors for hypertension were established.

[Ways of optimization in teaching of internal diseases in a medical institute].

A method of practical clinical games (PCG) performing is represented. For the PCG themes the extreme and urgent situations requiring the doctors of various specialities (especially on the cardiology and hematology cycles) are selected. A model of specific clinical situation, where students play roles, corresponding to the duties of speciality under conditions, maximally approximating to reality, is reproduced.

[Clinicofunctional characteristics of primary mitral prolapse in adolescents]. / Kliniko-funktsional'nye osobennosti pervichnogo prolapsa mitral'nogo klapana u podrostkov.

To investigate clinicofunctional features of primary mitral prolapse (PMP) in adolescents, 60 patients were examined (42 adolescent girls and 18 adolescent boys aged 14 to 20 years). Control group consisted of 15 healthy adolescents of the same age. PMP in adolescents was characterized by marked manifestations of connective tissue dysplasia (CTD) and vegetative dysfunction (VD). As shown by echocardiography, 71.7% patients had bilateral prolapse with mitral regurgitation of degree I and II. 18.7% examinees with pronounced CTD and VD had asymptomatic variant of PMP.

[Morphometric parameters of malignant cells in non-leukemic hemoblastosis with primary lymph node involvement]. / Morfometricheskie parametry zlokachestvennykh kletok pri neleikemicheskikh gemoblastozakh s pervichnym porazheniem limfaticheskikh uzlov.

Morphometric studies were conducted to distinguish reactive and malignant lymphoid processes and to obtain a more objective and reproducible grading system for non-Hodgkin's lymphomas (NHL). Twenty-three untreated patients (3 with reactive lymphadenitis, 2 with diffuse lymphomas, 18 with lymphosarcomas) were studied. The sections of lymph nodes were stained with 50% aqueous silver nitrate solution and then counter-stained with methylene blue. MOP-Videoplan (Reichert, Austria) image analyzer was used for morphometry. The size and shape of nucleus, number and position of nucleoli and the number of silver grains (K1) and relative size (K2) of each grain were investigated. The computer classification of lymphoid cells based on a stepwise linear discriminant analysis resulted in 63% correctly classified cells. Among seven most discriminating parameters, the nucleoli area and the number and size of silver grains demonstrated the highest correlation with malignancy. The data obtained have evidenced that nucleolar parameters can be applied to computer classification of lymphoid neoplastic cells and for objective grading of NHL.

[The characteristics of the clinical course of lymphosarcomas when using combined therapy including splenectomy]. / Osobennosti klinicheskogo techeniia limfosarkom pri ispol'zovanii kompleksnoi terapii, vkliuchaiushchei splenéktomiiu.

The authors relate the results of a clinico-morpho-instrumental analysis of the clinical course of lymphosarcomas in 38 patients with different morphological patterns of the disease with primary injury to the spleen. The patients received multimodality therapy including splenectomy. It has been established that later the short-term effect of splenectomy permits the implementation of different polychemotherapy programs, favouring a better lymphosarcoma prediction.

[Lymphoid cell glycosidases in various forms of lymphoproliferative disorders]. / Glikozidazy limfoidnykh kletok pri raznykh formakh limfoproliferativnykh zabolevanii.

Activity of 8 glycosidases (6 acid lysosomal and 2 neutral cytosolic enzymes) was estimated in lymphoid cells of 28 patients with different forms of lymphoproliferative disorders: B- and T-chronic lymphocytic leukemia (CLL), non-Hodgkins lymphoma (NHL), Sezary syndrome, hairy cell leukemia (HCL) and B- and T-acute lymphoblastic leukemia (ALL). Activity of these glycosidases was also studied in mononuclear cells and granulocytes of healthy volunteers and in immature myeloid cells of 16 patients with chronic myeloid leukemia (CML). In lymphoid cells of all the patients studied (except of ALL) the glycosidases activity was decreased as compared with that of normal mononuclear cells and immature myeloid cells. Activity of the majority enzymes studied was higher in T-lymphoid cells of patients with lymphoproliferative disorders as compared with B-cells. The highest glycosidases activity was found in ALL cells and the lowest--in CLL cells of the patients with B-lymphoid cells forms of the disease. Activities of N-acetyl-beta-D-hexosaminidase, alpha-D-mannosidase and beta-D-glucuronidase were distinctly dissimilar in cells of the patients with B-CLL, B-NHL and HCL. Estimation of these glycosidases activity in lymphoid cells may be of importance in differential diagnosis of lymphoproliferative disorders.

[The parameters of tumor cell proliferation as a prognostic factor in lymphosarcomas]. / Parametry proliferatsii opukholevykh kletok kak prognosticheskii faktor pri limfosarkomakh.

Cytophotometry of DNA was used to measure cell fractions in the S + G2 phases of the mitotic cycle in imprints of the involved lymph nodes and/or smears of the cells isolated from archival paraffin blocks of 60 patients with lymphosarcoma. Parallel studies have shown that both cell sources permit obtaining similar results (r = 0.98, p less than 0.001). The mean S + G2 values increased with the increment of the histological degree of malignancy, amounting to 1.6 +/- 0.4, 3.4 +/- 0.5 and 7.4 +/- 2.7% for patients with low, intermediate and high degrees, respectively. However, the statistically significant differences in accordance with Wilcoxon's criterion were revealed but for the second and third groups. To estimate the independent prognostic importance of the S + G2 parameter, all the patients were distributed into 2 groups. The first group included patients, in whom the magnitude of S + G2 did not surpass 3%, whereas the second one was made up of patients with the S + G2 values exceeding 3%. In the second group, the mean survival reached 13.8 +/- 4.0 months. At present 45% (9 out of 20) are still alive. In the first group, the mean survival was 25.2 +/- 3.8 months, with 70% of the patients being alive (28 out of 40). The significance of the differences is very high: p less than 0.001. Thus, the S + G2 parameter turned out to be reversely dependent on the survival of lymphosarcoma patients.

[The characteristics of the clinical course of lymphosarcomas in conformity with the morphological variants of the WHO and Working Formulation classifications]. / Osobennosti klinicheskogo techeniia limfosarkom v sootvetstvii s morfologicheskimi variantami klassifikatsii VOZ i rabochei formulirovki.

Histological and cytological preparations of the lymph nodes, spleen, bone marrow and other tumors from 140 patients with different variants of lymphosarcomas were subjected to a comparative clinicomorphological analysis. The data obtained were correlated to the WHO classification and the working formulation of non-Hodgkin's lymphomas intended for clinical use. It has been found desirable that the working formulation may be used for predicting the disease course and elaboration of the programs of lymphosarcoma treatment.

[Hematological masks of malignant neoplasms of the internal organs]. / Gematologicheskie "maski" zlokachestvennykh novoobrazovanii vnutrennikh organov.

Hematological "masks" of malignant tumors of the internal organs are not infrequent in clinical practice. A total of 45 patients with malignant tumors of the internal organs (stomach-12, colon-9, liver-3, lungs-9, kidneys-6, pancreas-2, thyroid-2, bladder-1, prostate-1) were under observation. Hematological signs of bone marrow metastatic involvement were as follows: anemia (mainly hypochromic), leukemoid neutrophilic reaction, leukemoid reaction of myeloid type, erythrocytosis, thrombocytosis, plasmocyte bone marrow reaction. Early cancer diagnosis, especially in obscure peripheral blood changes, requires a complete all-round investigation of a patient including an analysis of clinico-anamnestic data, the use of radiographic and endoscopic methods, sternal puncture and trephine biopsy.