[Left ventricular dysfunction in patients following high-dose chemotherapy and autologous hematopoietic stem cell transplantation].

AIM: To evaluate the dynamics of LV global longitudinal strain (GLS) and other EchoCG parameters after high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation (aHSCT). MATERIAL AND METHODS: The risk of LV dysfunction in patients after HDCT followed by aHSCT has not been sufficiently studied. This study included 74 patients with hemoblastosis aged 20 to 65 years who had undergone HDCT followed by aHSCT. All patients had a history of antitumor treatment. EchoCG with assessment of LV GLS and measurements of troponin T and N-terminal pro-brain natriuretic peptide (NT-proBNP) were performed for all patients before and after the treatment. RESULTS: A decrease in GLS by 15 % or more from the baseline was detected in 6 (8.1 %) patients. The decrease in GLS was associated with increased NT-proBNP >125 pg / ml at baseline (odds ratio, 8.667; 95 % confidence interval, 1.419-52.942; p=0.022). CONCLUSION: The decrease in LV GLS in patients after aHSCT was associated with increased NT-proBNP before the intervention.

Preventable Hazards from in Vitro Fertilization - A Case Series of CF Patients from Bulgaria.

Pre-implantation genetic diagnosis (PGD) is not often performed when donor gametes are used, due to its high cost. This is with the presumption that the donors are healthy. We report on five cases of babies with confirmed cystic fibrosis (CF), being the result from in vitro fertilization (IVF) with donor (4 cases) or own gametes (one case). There has been no family history for CF in any of the families affected. The clinical presentation in the children ranged from meconium ileus to recurrent respiratory infections and severe nasal polyposis. The age of diagnosis also varied from birth until 9 years. Since one of the presented cases was discovered in a very renowned private IVF clinic, the clinic changed their own protocol, and currently they test every donor for CF carriership. The percentage of CF carriers in the donor population is roughly the same as the one predicted in the general population of Bulgaria - 1/33. Although PGD is costly, the costs for proper care for a CF patient are currently much higher. The more economical option would to screen every donor for CF carriership. IVF requires a lot of physical and psychological stamina. The couples that go through this procedure also require a great deal of hope. It is essential to be more preconscious for possible congenital diseases. We advocate every IVF center to test the donors for CF carriership or to provide PGD for their clients.

[ASSESSMENT OF PATIENT SATISFACTION WITH THE MEDICAL ORGANIZATION AND ITS SERVICES].

The relevance of the problem under study is due to the fact that the medical organization must be aware of the target patient: to know who he is, how and why he wants to receive a particular medical service. All the information received and its analysis will allow us to develop a real scheme of mutually beneficial communication, convenient for each of the parties-the medical organization and the patient, which will allow us to reveal the weaknesses in the work and respond to them in a timely manner. The purpose of the study: to form an assessment of the patient's satisfaction with the medical organization and its services, taking into account the interest, feelings, purpose, arguments and thoughts that appear in the patient from the moment of the first contact with the clinic, with the display of the point of contact in graphic form, in order to minimize all possible obstacles in his route to receiving quality medical services and increasing the economic efficiency of the clinic.

[Recreational potential of medical tourism of Russia].

Since January 1, 2019, the Russian Federation has entered the global medical tourism market thanks to the approved federal project "Development of the export of medical services". The level of attractiveness of a country as a global destination for medical tourists is determined by a number of factors: the level of medical technology, transport accessibility, proximity to donor countries of foreign patients; the level of realization of export potential, international reputation, medical marketing; the level of healthcare organization, international staff training, etc. Among the factors determining the success of the country as the destination of medical tourism, a special place is held by the recreational complex, spa treatment. The level of development of the recreational complex within the framework of medical tourism performs several tasks at once: it provides a full cycle of medical assistance to foreign medical tourists - from outpatient admissions and in-patient treatment to rehabilitation and recovery; sanatorium-resort treatment and rehabilitation are considered not only as an integral part of the complex of medical services, but also as an independent promising direction for the export of medical services by domestic health resorts. Also, the fight against the consequences of COVID-19, when hundreds of thousands of neighboring states citizens need qualified rehabilitation, can become a driver for the development of the sanatorium-resort complex of Russia. The purpose of the study is to identify bottlenecks in the development strategy of the recreational potential of the regions of the Russian Federation and make suggestions for its improvement. The number of foreign patients who received medical care from January to May 2020 in the federal districts is 729,000. This indicator was achieved during the pandemic, and therefore does not reflect the true potential of rehabilitation as an element of the full cycle of medical care for foreign patients. The target audience for rehabilitation programs is up to 100,000 foreign patients.

[Evaluation of the export potential of the healthcare system of the Russian Federation on the example of a separate taken region].

The relevance of the research is due to the fact that the development of medical services exports in the Russian Federation is based on the eponymous Federal project «Development of medical services exports¼ of the national project «Healthcare¼. The Federal project is being implemented in the Russian Federation in the period 2019-2024 and is unique for two reasons. Firstly, the project has no analogues in the world: for the first time in one country, 71 regions were involved in a project related to the development of planned medical care for foreign citizens. Secondly, the main role in the project is assigned to medical organizations of state ownership. Due to the fact that the key outstanding issue of the project is to assess the export potential of the health care system of subjects of the Russian Federation, which is a Federal project, the goal of research to assess the export potential of the health care system of the Russian Federation (on the example of Tyumen oblast). A methodology for calculating the economic efficiency of the medical services export program in the region has been developed. As the criteria for evaluating the economic efficiency of testing the concept of developing the export of medical services in the above-mentioned regions, it is proposed to set certain parameters.

[The future of computer-aided diagnostics in chest computed tomography]. / Perspektivy ispol'zovaniia kompleksnoi komp'iuter-assistirovannoi diagnostiki v otsenke struktur grudnoi kletki.

Recently, more and more attention has been paid to the utility of artificial intelligence in medicine. Radiology differs from other medical specialties with its high digitalization, so most software developers operationalize this area of medicine. The primary condition for machine learning is met because medical diagnostic images have high reproducibility. Today, the most common anatomic area for computed tomography is the thorax, particularly with the widespread lung cancer screening programs using low-dose computed tomography. In this regard, the amount of information that needs to be processed by a radiologist is snowballing. Thus, automatic image analysis will allow more studies to be interpreted. This review is aimed at highlighting the possibilities of machine learning in the chest computed tomography.

Th17 cells in Bulgarian children with chronic obstructive lung diseases.

INTRODUCTION AND OBJECTIVES: Th17 lymphocytes are now widely believed to be critical in various chronic pulmonary diseases. However, there is still a small number of investigations regarding children. We aimed to assess the percentage of Th17 lymphocytes and IL-17A in peripheral blood of children with chronic obstructive lung diseases. PATIENTS AND METHODS: We included a total of 42 children: 20 with bronchial asthma (BA), 12 with cystic fibrosis (CF) and 10 healthy children without a history of allergies, aged 4-17 years. Th17 cells (CD3+CD4+CD161+CCR6+) were determined in peripheral blood by flow cytometry. The concentration of serum IL-17A was measured by ELISA. RESULTS: The BA patients had a significantly higher percentage of Th17 (12.40±1.16%) compared to the CF children (7.64±0.87%, p=0.0035) and healthy (7.25±0.45%, p=0.008). Stratifying the BA group, we found higher levels of Th17 in patients with severe BA (p=0.03), whereas patients with moderate BA had Th17 cells close to those in CF and healthy children. We found that patients with better control of BA had Th17 closer to those with CF (p=0.98) than BA children with poor control (p<0.001) (post hoc, Bonferroni correction). CF patients with concomitant P. aeruginosa infection showed slightly higher percentages of Th17 cells than those without infection (8.08±3.09% vs. 6.25±2.42%, p=0.294). CONCLUSIONS: The percentage of Th17 cells was significantly increased in the peripheral blood of children with severe BA compared to the children with moderate BA, which suggests that the former could possibly benefit from future target therapies.

IL4Rα and ADAM33 as genetic markers in asthma exacerbations and type-2 inflammatory endotype.

BACKGROUND: Genetic markers of susceptibility to asthma exacerbations in adults remain unclear. OBJECTIVE: To identify genetic markers of asthma exacerbations, particularly in patients with type-2 inflammatory endotype. METHODS: In this observational study of patients enrolled in the Kinki Hokuriku Airway disease Conference multicenter study, frequency of exacerbations requiring systemic corticosteroids during 2 years after enrolment and associated risk factors was determined. For genetic marker analysis, interleukin-4 receptor α (IL4RA) rs8832 and a disintegrin and metalloprotease 33 (ADAM33) S_2 (rs528557), T_1 (rs2280091), T_2 (rs2280090), and V_4 (rs2787094) variants were included. Elevated serum periostin levels at enrolment (≥95 ng/mL, defined as type-2 inflammatory endotype) were considered in the analysis. RESULTS: Among 217 patients who were successfully followed up for 2 years after enrolment, 60 patients showed at least one asthma exacerbation during the 2 years. Airflow limitation (%FEV1 <80%) and recent exacerbations but not genetic variants were identified as risk markers of exacerbations. A total of 27 patients showed type-2 inflammatory endotype (serum periostin ≥95 ng/mL at enrolment) and subsequent exacerbations; risk factors in these patients were airflow limitation (odds ratio, 6.51; 95% confidence interval (CI): 2.37-18.6; P=.0003), GG genotype of IL4RA rs8832 (odds ratio, 4.01; 95% CI: 1.47-11.0; P=.007), and A allele of ADAM33 T_2 (odds ratio, 2.81; 95% CI: 1.05-7.67; P=.04) by multivariate analysis. In addition, GG genotype of IL4RA rs8832 was associated with type-2 endotype, whereas A allele of ADAM33 T_2 was associated with mixed type of eosinophilic/type-2 and neutrophilic inflammations. CONCLUSIONS AND CLINICAL RELEVANCE: IL4RA and ADAM33 variants may be risk markers of asthma exacerbations in type-2 inflammatory endotype. Precise endotyping may facilitate the identification of genetic risk markers of asthma exacerbations.

THE SENSITIVITY OF CELLS WITH THE VARIOUS LEVEL OF NAD(P)H:QUINONE OXIDOREDUCTASE 1 TO CYTOTOXIC ACTION OF QUINONIMINES AND α-TOCOPHEROL SYNTHETIC DERIVATIVES.

The effects of α-tocopherol with shortened to 6 carbon atoms side chain (α-Toc-C6), α-tocopherol succinate (α-TS) and quinonimine 2,6-dichlorophenolindophenol (DCPIP) on DT-diaphorase activity and viability of rat thymocytes, splenocytes and hepatocytes were investigated. It was shown that the lowest basal activity of the enzyme is inherent in splenocytes. In comparison to splenocytes, DT-diaphorase activity was 1.4 and 5 times higher in thymocytes and hepatocytes, respectively. It was found that the sensitivity of cells to the cytotoxic effect of DCPIP was inversely proportional to the basal level of DT-diaphorase activity and accompanied by its activation with subsequent inhibition at non-toxic and toxic concentrations, respectively. Hepatocytes were least sensitive to the cytotoxic effect of α-Toc-C6. In thymocytes and splenocytes α-Toc-C6 exerts inhibitory effects on DT-diaphorase, whereas in hepatocytes an increased activity of the enzyme was observed, which probably caused their high survival rate. Simultaneous induction of cytochrome P450 enzyme expression by α-Toc-C6 in hepatocytes is also possible. Cytotoxic effect of α-TS does not depend on the basal level of DT-diaphorase activity in cells, is not accompanied by its induction and it is most likely determined by the non-specific esterase activity.

Use of biologics for psoriasis in Central and Eastern European countries.

OBJECTIVES: To evaluate the use of biological agents for the treatment of psoriasis and to explore country-specific differences within six Central and Eastern European (CEE) countries, namely Bulgaria, Croatia, the Czech Republic, Hungary, Poland and Romania. METHODS: A literature overview on the epidemiology and disease burden of psoriasis in CEE was conducted. The number of patients treated with biologics was obtained from patient registries, ministries of health, national professional societies and health insurance funds. Biological treatment rates were estimated by two different methods: (i) as a proportion of all psoriasis patients of a country (assuming a common prevalence of psoriasis 2%) and (ii) per 100,000 population. Moreover, we provide a detailed comparison of drug coverage policies and guidelines regulating the treatment with biologics in psoriasis. RESULTS: On average 0.25% of all psoriasis patients, or five psoriasis patients out of 100,000 inhabitants are treated with biologics embedding a 14.6-fold difference between the six countries. Bulgaria, Croatia and Poland lag behind the other three countries in the use of biologics. The significant differences among CEE countries cannot be explained by variations in prices of biologics, cost-effectiveness or budget impact of biologics. It seems that the time since coverage decision, the fewer number of covered biologics, the more restrictive criteria to be eligible for covered treatment in terms of baseline Psoriasis Area and Severity Index and Dermatology Life Quality Index scores, and the maximum duration of treatment allowed are responsible for the majority of the differences. CONCLUSIONS: There exists a disconnect between the European psoriasis treatment guidelines and the various CEE country-specific biologic coverage eligibilities. The cost of biologic therapy for psoriasis is not solely and directly responsible for the different use rates amongst the CEE countries. Psoriasis may not be perceived by all payers as a serious disease that can be successfully treated in a cost-effective manner.

Regional differences in diabetic patients' pharmacotherapy in Bulgaria.

BACKGROUND: The regional analyses play an important role in understanding a state of diabetes mellitus management and to support informed policy options. They need to be explored in more details in order to ensure an equal patients' access to health care services of the same value and quality. AIM: The aim of this study is to analyze regional differences in a cost of diabetes therapy for insulin users in Bulgaria. MATERIALS AND METHODS: It is a combined prospective and retrospective observational study with duration of 6 months. Diabetic patients on insulin therapy were recruited by 35 endocrinologists. Information about the health care resources used was collected within 3-prospective and 3 retrospective months in 2010 and 2011. The regional cost of illness analysis was performed by calculating the average cost attributable to each individual patient despite the fact that some might not use a particular health care resource. Subgroup analysis was performed for hospitalized patients. RESULTS: A detailed analysis revealed cost differences in the regions, especially with more vulnerable population like Burgas and Pleven regions. Another reason for the cost differences is the type of insulin or type of therapy. Our study confirms the fact that the hospitalizations are the major cost driver. Rising diabetes prevalence and associated costs, including hospitalizations and management of diabetes complications, are a growing concern. The last possible reason for regional differences is the patients' characteristics and therapy differences. We add evidence demonstrating that the patients on insulin and OAD consume more resources including hospitalizations and suffer from more complications of diabetes. CONCLUSIONS: Reasons for regional differences might have different origin as there are various population characteristics, type of therapy, socio economic status and others.

EPIDEMIOLOGICAL REGISTRY OF NEUROENDOCRINE TUMORS IN BULGARIA--A PILOT SURVEY.

The National registry of patients with neuroendocrine tumors (NET) in Bulgaria was established in 2013 as a joint initiative of the Bulgarian Surgical Society and the Institute for Rare Diseases. The register aims to explore the epidemiology of NET in Bulgaria, as well as the different diagnostic and treatment approaches for the disease throughout the country. This the first of its kind retrospective study of NET in the country is covering the period January 2012 - January 2013. A total of 127 patients with NET were identified. At the time of the survey the average age of patients with NET was 58.61 ± 15.59 years. The data show almost equal distribution between the genders with a slight predominance of women. The largest relative part of NET is those of NET located in the gastrointestinal tract (54.10 ± 4.51%), followed by those located in the pancreas (12.30 ± 2.97%) and in the lungs (10.66 ± 2.79%). In 72.44 ± 3.96% of the patients a immunohistochemical diagnosis was performed. The study confirmed the leading role of the surgery method of the NET management. In 65.83 ± 4.33% of the patients a radical removal of the tumor was conducted, while the relative part of the undertaken partial resection was 7.50 ± 2.40%. A statistically significant association between the type of surgical treatment and during the follow-up of patients was found. An update of the information in the register will allow a more precise determining of the distribution and management of NET in Bulgaria.