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The individual approach in the treatment of heart failure (HF) and personalized medicine have been the main topic in recent years in all scientific forums. The combination of chronic obstructive pulmonary disease (COPD) and sleep apnea (SA) further complicates the clinical presentation in patients with HF. The overlap of all three diseases requires a team of specialists and additional therapeutic approach for better control and to improve the prognosis. A large number of the pathophysiological mechanisms of the three diseases also overlap. The novel therapies for HF have shown good results, both in COPD and CA subgroups. Noninvasive ventilation during hospitalization and at home is an established method in the individual groups. In a combination of the three diseases, definitive data from randomized trials are still lacking.

This study analyses the relationships between economic development, environmental investments, and greenhouse gas emissions in the European Union for the period 2008-2022. Using correlation and regression analysis of data from Eurostat, the study assesses the impact of environmental protection expenditure and gross domestic product on greenhouse gas emissions. The results reveal a stable upward trend in environmental protection expenditure, especially in recent years, reflecting the European Union's growing commitment to sustainable development. At the same time, greenhouse gas emissions show an overall downward trend, with the sharpest decline between 2019 and 2020, likely due to the impact of the coronavirus disease pandemic. The correlation analysis confirms a significant inverse relationship between environmental investments and emissions, demonstrating the positive effect of "green" spending on reducing the carbon footprint. An important observation is that in many years, environmental expenditure grows at a faster rate than the European Union's gross domestic product, emphasizing the increased commitment to environmental issues even in conditions of economic growth. The regression analysis shows a strong relationship between the predictors (gross domestic product and environmental expenditure) and greenhouse gas emissions. Despite the expectation that economic growth would increase emissions, the results show that effective measures and technologies for reducing the carbon footprint in the European Union mitigate this effect. Based on these findings, the study proposes strategies for promoting investments in clean technologies, integrating environmental goals into economic policies, intensifying research and innovation, raising public awareness, and strengthening international cooperation.

Human peripheral blood mononuclear cells (PBMCs) are used to examine biological processes and disease, when basal variability in cellular activation and splicing is described and unexplained. Using isolation systems that maintained buffy coat cells (PBMCs, platelets) in their own plasma, poly-A enriched RNA-sequencing (RNASeq) detected 42,720 Ensembl gene IDs, including >95% of the top 100 Genotype Tissue Expression Project (GTEx)-expressed genes in lung, colon, heart, skeletal muscle and liver, and 10/17 clinically-actionable genes listed by the Pharmacogenomics Knowledgebase. Transcriptome changes were defined after 1h treatment with 32°C hypothermia (hsp70 family member change), 10 μmol/L ferric citrate that had no discernible effect, and 100 μg/mL cycloheximide leading to induction of primary response (immediate early) genes including IL1B and TNF. Same-donor PBMCs prepared conventionally using washes then resuspension in serum-supplemented media demonstrated basal upregulation of stress signalling pathway genes that masked and overlapped differential gene expression profiles after 100 µg/L cycloheximide. Plasma-resuspended PBMCs demonstrated minor transcriptome changes after 40 μmol/L ferric citrate, whereas consistent and greater magnitude changes were observed for washed/media-resuspended PBMCs. We conclude that endogenous plasma-maintained PBMCs provide a more robust platform to interrogate acute cellular perturbations triggering innate immunity, and that varying susceptibility of PBMCs to preparative stresses is an important component of experimental variability.

Betulinic acid (BA) is a natural pentacyclic triterpenoid with significant pharmaceutical potential. We found that converting BA into amino acid ethyl ester salts alters its cytotoxic effect on colorectal adenocarcinoma cells (HT-29). Among these salts, the estimated half-maximal inhibitory concentration (IC50) at 72 h varies by up to fifteenfold. The proline ethyl ester [ProOEt] salt, the most active compound, exhibited an IC50 value of 3.8 µM, which is 4.8 times lower than that of the parent BA. We observed that exposure to BA or [ProOEt][BA] induced apoptosis in HT-29 cells. Additionally, the proline-based salt led to a higher level of IL1B gene expression in PBMCs at a lower stimulation concentration.

This study analyses the relationship between economic growth, measured by gross value added in agriculture, and greenhouse gas emissions from the sector in 30 European countries during the period 2012–2021. The aim is to assess whether the increase in agricultural production leads to a corresponding increase in harmful emissions. Regression analysis is applied to establish linear statistical dependencies between variables, cluster analysis to group countries, and analysis of trends in the dynamics of indicators. The results show significant differences between countries, with no universal relationship between economic growth and emissions. A “decoupling” between growth and emissions is observed in some countries, demonstrating the potential for “green growth.” Regional and structural differences, as well as the level of technological development, stand out as key factors determining the relationship between economic growth and emissions, highlighting the need for an individualised approach in formulating policies for the sustainable development of the agricultural sector.

The pathogenesis of many diseases, such as obesity, depression, cancer, cataract, and neurodegenerative diseases, is related to the generation of reactive oxygen species (ROS). Structures possessing radical-scavenging properties act as antioxidants and they could prevent the progression of the aforementioned diseases. Therefore, the current work was focused on the resynthesis and the antioxidant evaluation of 13 hydrazide-hydrazones. Two in vitro tests - DPPH and ABTS, were applied for the determination of the antioxidant capacities. The free-radical scavenging assays displayed that the hydrazide-hydrazone synthesized after condensation with a salicylaldehyde (5b) is the most potent antioxidant. The in vitro evaluation through the ABTS test showed that the former structure has greater antioxidant properties compared with the used standard - Trolox (6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid). In concentrations of 31 µM, the pyrrole-based structure showed 35.77% radical-scavenging effects. A possible binding conformation of the most active hydrazide-hydrazone in the active site of NADPH oxidase was visualised through docking simulations. The active amino acids involved in the stabilisation of the complexes were discussed. DFT studies demonstrated that 5b is a stable structure with good hydrogen and electron donating properties. Overall, the pyrrole-based hydrazide-hydrazone possesses promising antioxidant properties, however further in vitro/in vivo biological evaluations are required.

Abstract Background Around 60% of term labours in the UK are continuously monitored using cardiotocography (CTG) to guide clinical labour management. Interpreting the CTG trace is challenging, leading to some babies suffering adverse outcomes and others unnecessary expedited deliveries. A new data driven computerised tool combining multiple clinical risk factors with CTG data (attentive CTG) was developed to help identify term babies at risk of severe compromise during labour. This paper presents an early health economic model exploring its potential cost-effectiveness. Methods The model compared attentive CTG and usual care with usual care alone and simulated clinical events, healthcare costs, and infant quality-adjusted life years over 18 years. It was populated using data from a cohort of term pregnancies, the literature, and administrative datasets. Attentive CTG effectiveness was projected through improved monitoring sensitivity/specificity and potential reductions in numbers of severely compromised infants. Scenario analyses explored the impact of including litigation costs. Results Nationally, attentive CTG could potentially avoid 10,000 unnecessary alerts in labour and 2400 emergency C-section deliveries through improved specificity. A reduction of 21 intrapartum stillbirths amongst severely compromised infants was also predicted with improved sensitivity. Attentive CTG could potentially lead to cost savings and health gains with a probability of being cost-effective at £25,000 per QALY ranging from 70 to 95%. Potential exists for further cost savings if litigation costs are included. Conclusions Attentive CTG could offer a cost-effective use of healthcare resources. Prospective patient-level studies are needed to formally evaluate its effectiveness and economic impact in routine clinical practice.

The endophytic fungus Biscogniauxia mediterranea, a causal agent of charcoal canker disease, was established for the first time on red oak (Quercus rubra) in Bulgaria. Symptomatic trees were found in 2023-2024 in the field protective forest belts planted in the State Hunting Enterprise Balchik (Sokolovo and Trigortsi villages) and State Forest Enterprise Dobrich (Kozloduytsi Village) in northeastern Bulgaria. Water stress during the last growing seasons seems to reduce red oak trees’ resistance and predispose them to be infected with the pathogen B. mediterranea. The disease has caused dieback of infected trees and increased their vulnerability to attacks by xylophagous insect pests.

We conducted a Pubmed/Medline database survey of ethical decision-making models in medical practice and health care.

Algal metabolites have been extensively studied as potential anticancer therapeutics. Among them, polysaccharides have attracted much attention because of their beneficial biological effects and safety. In the present research, the chemical characteristics, antitumor, and proapoptotic activities of extracellular polysaccharides (EPS) isolated from a new Bulgarian strain of the green microalga Coelastrella sp. BGV were investigated. A fast and convenient method of precipitation with cold ethanol was used to isolate EPS from the culture medium. The chemical characteristics of the isolated EPS were examined by colorimetric and spectrophotometric analyses, HPSEC-RID and HPLC-UV chromatography, and FT-IR spectroscopy. The results showed that the isolated EPS sample consists of three carbohydrate fractions with different molecular weights (11.5 × 104 Da, 30.7 × 104 Da, and 72.4 × 104 Da, respectively) and contains 7.14 (w/w%) protein. HPLC-UV analysis revealed the presence of galactose and fucose. The total uronic acid content in the sample was 4.5 (w/w%). The IR-FT spectrum of EPS revealed the presence of various functional groups typical of a polysaccharide (or proteoglycan) composed primarily of neutral sugars. The anticancer potential of the obtained EPS was assessed using cell lines with cancerous and non-cancerous origins as in vitro experimental models. The results of the performed MTT assay showed that EPS reduced the viability of the cervical and mammary carcinoma cell lines HeLa and MCF-7, while the control non-cancer cell lines BALB/3T3 and HaCaT were less affected. The HeLa cell line showed the highest sensitivity to the effects of EPS and was therefore used for further studies of its anticancer potential. The ability of EPS to inhibit cancer cell migration was demonstrated by wound-healing (scratch) assay. The cell cycle FACS analysis indicated that the EPS treatment induced significant increases in the sub G1 cell population and decreases of the percentages of cells in the G1, S, and G2-M phases, compared to the control. The fluorescent microscopy studies performed using three different staining methods in combination with Annexin V-FITC flow cytometric analysis clearly demonstrate the ability of EPS to induce cancer cell death via the apoptosis pathway. Moreover, an altered pattern and intensity of the immunocytochemical staining for the apoptosis- and proliferation-related proteins p53, bcl2, and Ki67 was detected in EPS-treated HeLa cancer cells as compared to the untreated controls. The obtained results characterize the new local strain of green microalgae Coelastrella sp. BGV as a producer of EPS with selective antitumor activity and provide an opportunity for further studies of its pharmacological and biotechnological potential.

Alzheimer’s disease is a brain disorder characterized by a gradual decline in memory, thinking, behavior, and social skills. Galantamine hydrobromide is a reversible competitive cholinesterase inhibitor used for managing Alzheimer’s disease. Its oral administration, however, is accompanied by unwanted side effects, such as gastrointestinal disturbances, nausea, and vomiting. These side effects could be avoided by the incorporation of galantamine into nanoparticles. The present study describes the preparation and characterization of HPMC-based fast-dissolving oral films with galantamine-loaded chitosan nanoparticles. Galantamine-loaded chitosan nanoparticles were prepared using the ionotropic gelation method. High values for loading efficiency were established. DLS was used to evaluate the particle size and the Z-potential. The polymer used in this study for the preparation of the fast-dissolving oral films was HPMC, and PEG 400 was used as a plasticizer. The quality of the prepared films was evaluated based on the following criteria: flexibility, spreading ability, adhesiveness, non-sticky and easily peeled, and appearance. The thickness, folding endurance, and disintegration times of the prepared films were determined. In vitro dissolution studies were conducted in order to establish the drug release rate from the films.

We present a clinical case of a 20-year-old woman with acute myocardial infarction with persistent ST-segment elevation (STEMI). The coronary angiography performed on the patient showed coronary vasospasm with no evidence of atherosclerotic plaque. The aim of this case report is to draw attention to the different types of myocardial infarction, other possible differential diagnoses (DD), and to the investigations necessary for determining a definitive diagnosis.

Lactobacilli are considered important probiotics for the prevention of some infections. In this study, the antifungal effect of both cells and cell-free supernatants of twenty-three strains of lactobacilli were investigated against Candida albicans by co-aggregation, agar diffusion assay, agar spot assay and co-culture assay. In all cases, a fungistatic effect was recorded. In the agar diffusion assay and agar spot assay, an effect was established primarily for heterofermentative species via the production of lactic acid. The anti-Candida effect was higher with microbial suspension than with cultural supernatants in the co-culture assay. A strain-specific reduction in the yeast growth up to 28.9% in MRS broth and up to 17.1% in BHI broth was observed. Cells of Limosilactobacillus fermentum LLF-01 and Limosilactobacillus reuteri LLR-K67 showed the highest activity in both model systems. For all strains, a lower reduction up to 9.7% was recorded with cultural supernatants. L. fermentum LLF-01 showed the highest ability of co-aggregation (64.8%) with C. albicans, followed by Lactobacillus acidophilus LLA-01, Lactobacillus gasseri LLG-V74, Lactobacillus delbrueckii subsp. bulgaricus LLB-02 and two strains of Lactobacillus delbrueckii subsp. lactis LLL-14 and LLL-F18. The present study showed the potential of several strains of lactobacilli to affect the population of C. albicans in vitro. The combination of cultures with proved anti-Candida and co-aggregation activity in a probiotic formula may have a positive effect for the prevention of yeast overgrowth in the gut and hence for the suppression of candidiasis.

During the period 2019-2020, parasitoids of invasive oak lace bug (Corythucha arcuata) were studied in Bulgaria. Biological material (larvae of C. arcuata) was collected from European oak (Quercus robur) or Austrian oak (Quercus cerris) in five localities of the country. Five eulophid specimens (Hymenoptera: Eulophidae) were reared from the host larvae: Tamarixia pubescens, Elasmus sp., Minotetrastichus sp., Pnigalio sp. and Sympiesis sp. The impact of the parasitoids on the host number was very low (0.1-0.3%). The present records in Bulgaria are the first documented case of adaptation of native parasitoids to the host in the newly occupied areas in Europe and Asia.

In this study, the effects of defoliation caused by fungal pathogens on the tree vitality and growth of a 33-year old Douglas-fir (Pseudotsuga menziesii) provenance plantation in northwestern Bulgaria was presented. The results of the conducted surveys in 2011 and 2020 showed that there were significant differences between the individual provenances of Douglas-fir concerning their susceptibility to the needle cast diseases, caused by the fungal pathogens Rhabdocline pseudotsugae and Phaeucryptopus gaeumannii. The extent of damage, expressed as the amount of Douglas-fir needles cast, varied among provenance groups in individual years. A serious degree of defoliation was assessed among all continental provenances. In 2011, all examined trees from the group of continental provenances had severe symptoms of the needle cast disease. In 71.5% of them, the defoliation of the crowns was over 25% – moderately to severely affected. The average degree of defoliation varied from 18.3% (32 Wаrm Springs) to 89.3% (55 Alamogordo). In 2020, severe defoliation was found among all continental provenances. Both fungal pathogens were found as causes of the defoliation of 64.3% of the trees. The growth indicators: average height, average diameter at breast height, average height- and diameter increment for survived provenances in 2011 (at age 24) and 2020 (at age 33) were evaluated. The loss of needles and the reduced physiological function of the trees affected their vitality in the following years. Relationships between the average current annual height and diameter increment by provenance groups for 2003–2011 and 2011–2020 were calculated. It was found that with an increase in the degree of defoliation, the height and diameter increment of the provenances decreases.

Background: Aortic stiffening is a well-known cardiovascular risk factor. Computed tomography (CT) has proven to be a valuable tool in the assessment of aortic elastic properties. Drugs that inhibit the renin-angiotensin system (RAS) play a central role in cardioprotective therapy. We aimed to evaluate the relationship between aortic elastic properties and RAS-targeted therapy in hypertensive patients. Methods: This is an observational prospective study of hypertensive patients with nonobstructive coronary artery disease who underwent coronary CT angiography (CCTA). Aortic compliance and distensibility were calculated from the ECG-gated CCTA image. Patients were divided into two groups − those with RAS-targeted therapy − RAS(+) and those with non-RAS-targeted therapy − RAS(−). The elastic properties of the aorta were compared between the two groups. Results: A total of 142 patients were included in the final analysis. 53.5 % of the population were in the RAS(+) group and 46.5 % in the RAS(−) group. Elastic properties of ascending and descending aorta were significantly higher in the RAS(+) group compared to the RAS(−) group: AA compliance 1.42 ± 0.75 mm2/mmHg in the RAS(+) vs 1.03 ± 0.91 mm2/mmHg in the RAS(−), p = 0.024; AA distensibility 2.86 ± 1.11 x10-3mm3 in the RAS(+) vs 1.82 ± 0.97 x10-3mm3 in RAS(−), p

Woody biomass serves as a renewable resource for various industries, including pulp and paper production, construction, biofuels, and electricity generation. However, the molecular mechanisms behind biomass traits are poorly understood, which significantly curtails the speed and efficiency of their improvement. We used activation tagging to discover genes that can positively affect tree biomass-associated traits. We generated and screened under greenhouse conditions a population of 2,700 independent activation tagging lines. A total of 761 lines, which had significantly and positively affected at least one biomass-associated trait, were discovered. The tag was positioned in the genome for forty lines which were affected in multiple traits and activation of proximal genes validated for a subset. For two lines we fully recapitulated the phenotype of the original lines through overexpression. Moreover, the overexpression led to more pronounced and additional improvements, not observed in the original lines. Importantly, the overexpression of a Fasciclin-like gene (PtaFLA10) and a Patatin-like gene (PtaPAT) was found to substantially improve biomass, with a 40% increase in dry-stem weight, and enhance drought tolerance, respectively. Additionally, PtaPAT overexpression increased cellulose content, which is crucial for biofuel production. Our work shows that the activation tagging approach applied even on a non-genome saturation scale in a poplar tree can be successfully used for the discovery of genes positively modify biomass productivity. Such dominant forward genetics approaches can aid in biotechnological manipulation of woody biomass traits and help unravel the functions and mechanisms of individual genes, gene families, and regulatory modules.

Background/Aim. Resuscitation and surgical medical aid are the most important medical procedures in disaster relief operations. The limited time frame available for life-saving activities in such circumstances demands that resuscitation and surgical medical teams be established and trained for timely reaction and disaster medical support prior to disaster occurrence. The aim of the study was to analyze the awareness among the hospital medical staff in the Plovdiv Region of the hospital response plan in case of disaster, which concerns surgical and resuscitation team composition and tasks for disaster medical support. Methods. An anonymous survey, consisting of 55 questions about hospital staff awareness of the medical activities described in the hospital disaster medical support plan, was conducted between July and September 2019 among 295 hospital medical professionals in the Plovdiv Region, Bulgaria. Descriptive statistics and Pearson’s χ2 test were used in the statistical analysis of results. Results. The survey showed that the majority of medical staff demonstrated complete ignorance regarding the presence, number, and tasks of the specialized medical teams planned for hospital disaster response. Employees of multidisciplinary hospitals for active treatment were more familiar with the aforementioned plans than their colleagues from the university multidisciplinary hospitals. Conclusion. Insufficient awareness about human resources foreseen for disaster medical support negatively impacts the hospital surge capacity, leading to inadequate medical assistance in such cases. Hospital tactical disaster preparedness must be ameliorated by conducting a more rigorous training program among medical staff related to the planned hospital activities in case of disastrous events, especially for those working in emergency departments, intensive care units, and surgical departments.

Background/Aim. In the event of a disaster, it is necessary for medical personnel to demonstrate the operational component of disaster resilience, which requires certain knowledge and skills regarding disaster medical response algorithms. The aim of this study was to analyze the preparedness of hospital’s healthcare staff for maintaining hospital disaster resilience. Methods. An anonymous survey was conducted from July to September 2019 among 295 medical staff employed in hospitals in the territory of the city of Plovdiv, Bulgaria. Pearson’s Chisquare test, Student’s t-test, and graphical analysis were used in the statistical analysis. Results. Most of the medical staff, i.e., 85.8%, believed that disaster drills are not held regularly in hospitals, 30.8% thought that the training period was shorter than two years, and the majority, i.e., 86.1%, did not participate in exercises. Conclusion. Due to the irregular implementation of exercises and the small number of participants in them, the level of preparedness for responding to disasters is not maintained at a high level in hospitals in the Plovdiv region. Therefore, it is necessary to introduce a specific training program and exercise once a year, which should have a beneficial effect on increasing the preparedness of the medical staff for disasters and improving the operational resilience of the hospital.

During the period 2020-2023, strong damage caused by singing cicadas (Hemiptera: Cicadidae) were registered on ash trees (Fraxinus spp.) in the field protective forest belts (FPFBs) in South Dobrudzha, northeastern Bulgaria. Bioacoustic studies have shown that the sounds are of Cicada orni. Many exuvia of the species were also found on the trunks and branches of ash trees. On the upper shoots and petioles, numerous oviposition holes were observed, which lead to leaf fall and drying of branch tips. In different FPFBs, tree crown damage ranges from a moderate (25-60% defoliation) to a severe (over 60% defoliation) degree. The attacks were stronger on Fraxinus excelsior and F. americana compared to F. angustifolia. The cicadas affect both old trees and young ash saplings. In young plantations, other tree species (Sophora japonica, Gleditsia triacanthos) were also affected. Imaginal activity of Cicada orni was recorded in July and August, and the peak of egg hatching occurred from early August to mid-September. The high number of Cicada orni necessitates the development of measures to control the pest in the FPFBs.

Abstract Introduction Recent data have shown elevated infection rates in several subpopulations at risk of SARS-CoV-2 infection and COVID-19, including immunocompromised (IC) individuals. Previous research suggests that IC persons have reduced risks of hospitalization and medically attended COVID-19 with two doses of mRNA-1273 (SpikeVax; Moderna) compared to two doses of BNT162b2 (Comirnaty; Pfizer/BioNTech). The main objective of this retrospective cohort study was to compare real-world effectiveness of third doses of mRNA-1273 versus BNT162b2 at multiple time points on occurrence of COVID-19 hospitalization and medically attended COVID-19 among IC adults in the United States (US). Methods This retrospective, observational comparative effectiveness study identified patients from the US HealthVerity database from December 11, 2020, through August 31, 2022. Medically attended SARS-CoV-2 infections and hospitalizations were assessed following a three-dose mRNA-1273 versus BNT162b2 regimen. Inverse probability weighting was applied to balance baseline confounders between vaccine groups. Relative risk (RR) and risk difference were calculated for subgroup and sensitivity analyses using a non-parametric method. Results In propensity score-adjusted analyses, receiving mRNA-1273 vs. BNT162b2 as third dose was associated with 32.4% (relative risk 0.676; 95% confidence interval 0.506–0.887), 29.3% (0.707; 0.573–0.858), and 23.4% (0.766; 0.626–0.927) lower risk of COVID-19 hospitalization after 90, 180, and 270 days, respectively. Corresponding reductions in medically attended COVID-19 were 8.4% (0.916; 0.860–0.976), 6.4% (0.936; 0.895–0.978), and 2.4% (0.976; 0.935–1.017), respectively. Conclusions Our findings suggest a third dose of mRNA-1273 is more effective than a third dose of BNT162b2 in preventing COVID-19 hospitalization and breakthrough medically attended COVID-19 among IC adults in the US.

The ongoing growth of artificial intelligence (AI) involves virtually every aspect of oncologic care in medicine. Although AI is in its infancy, it has shown great promise in the diagnosis of oncologic urological conditions. This paper aims to explore the expanding role of artificial intelligence in the histopathological diagnosis in urological oncology. We conducted a focused review of the literature on AI in urological oncology, searching PubMed and Google Scholar for recent advancements in histopathological diagnosis using AI. Various keyword combinations were used to find relevant sources published before April 2nd, 2024. We approached this article by focusing on the impact of AI on common urological malignancies by incorporating the use of different AI algorithms. We targeted the capabilities of AI’s potential in aiding urologists and pathologists in histological cancer diagnosis. Promising results suggest AI can enhance diagnosis and personalized patient care, yet further refinements are needed before widespread hospital adoption. AI is transforming urological oncology by improving histopathological diagnosis and patient care. This review highlights AI’s advancements in diagnosing prostate, renal cell, and bladder cancer. It is anticipated that as AI becomes more integrated into clinical practice, it will have a greater influence on diagnosis and improve patient outcomes.

Bouveret’s syndrome (BS) represents an exceedingly rare clinical entity characterized by gastric outlet obstruction induced by a gallstone passing through a cholecystoduodenal, cholecystogastric or choledochoduodenal fistula and impacting in the duodenum or pylorus. Endoscopy is the preferred first-line therapy. It has a favorable safety profile, but requires high level of expertise to achieve stone clearance. We report here the case of a 75-year-old Caucasian male who presented with vomiting and upper gastrointestinal bleeding and was diagnosed with BS by upper endoscopy. A single session stone extraction utilizing mechanical lithotripsy and laser lithotripsy was executed. Complete clearance of the duodenum and gallbladder was achieved, extracting successfully all fragments larger than 5 mm. The rarity of BS and its non-specific presentation makes it largely overlooked leading commonly to delayed diagnosis, which results in a high mortality rate of 12-30%. Computer tomography is the diagnostic method of choice. Upper endoscopy can establish the presence of obstruction, but fails to visualize a stone in up to 1/3 of the cases. Management is either endoscopic or surgical. Endoscopic treatment has a good safety profile (mortality 1.6% vs. 17.5-25% for surgery) but poor success rate – 43% vs. 94.1%. To achieve higher success rate, more advanced techniques are required such as mechanical or laser lithotripsy. Laser lithotripsy is a feasible option for endoscopic treatment of BS, but the duration of the procedure might be an issue in frail patients.

Summary: Chronic myelogenous leukemia (CML) is a pluripotent hemopoietic stem cell malignancy characterized by the presence of a BCR-ABL1 fusion gene derived from a balanced translocation between the long arms of chromosomes 9 and 22 [t(9;22) (q34; q11)] known as the Philadelphia (Ph) chromosome. CML is an acquired hematopoietic stem cell disease common to myelo- and lymphopoiesis, characterized by uncontrolled proliferation of granulopoiesis (Shuvaev et al. 2015; Yordanov and Varbanova 2019). Relevance and goals: Second-generation tyrosine kinase inhibitors (TKIs) (nilotinib, dasatinib, and bosutinib) have an advantage over imatinib (first-generation) in the frequency and speed of achieving cytogenetic and molecular responses in the treatment of chronic myelogenous leukemia (CML), but they cause severe adverse effects and are much more expensive than imatinib, especially if we compare them to the prices of the registered generic products of Imatinib and Dasatinib. “Novartis Tasigna® trial shows superior results to Glivec® in patients with early-stage chronic myeloid leukemia”, reported on 10/20/2021 by Pierre Perrin-Montlouis. In the first direct comparison of these two oral therapies back in 2009 (Тasigna (nilotinib) 2009), as first-line treatment for CML, the results of Tasigna showed statistically significant improvement over Glivec in every measure of efficacy, including major molecular response (MMR), complete cytogenetic response (CCyR) and prevention of progression to accelerated or blast phase, with responses achieved faster in the Tasigna group than in the Glivec group. Furthermore, in the last ten years, CML patients who have achieved a stable deep molecular response for at least 2 years have been included in clinical trials for the management of treatment-free remission (TFR) (Kim et al. 2013; Saußele et al. 2016). On the other hand, the ever-increasing costs of diagnosis, treatment and monitoring of the response of CML to the various therapeutic strategies require conducting pharmacoeconomic analyses of the cost-effectiveness and cost-utility types in order to evaluate which are the cost-effective strategies with a view to introducing them into therapeutic practice. The present study aims to analyze the pharmacoeconomic efficiency of the TKI inhibitors used by the patients with CML-CP in the first and second lines, treated in the hematology clinic at UMHAT “St. George”, MU- Plovdiv during the period 2018–2022. Methods: An economic analysis of the medicinal use of TKIs for a 5-year period (2018–2022) was performed at the national level according to data from the National Health Insurance Fund and the availability, accessibility, and usability of original and generic TKIs in Bulgaria were evaluated. The direct medical costs for the therapy of all patients were calculated, including the costs of the TKI therapy, laboratory tests, and monitoring of the molecular response for the entire treatment period from the appointment of the TKI therapy until the end of 2022. A comparative analysis was conducted to assess the cost-effectiveness of the different therapeutic strategies with TKIs on the first and second lines of treatment of patients with CML-CP in the hematology clinic at UMHAT “St. George” Medical University, Plovdiv, using the decision analysis method and conducting one-way and probalistic sensitivity analyses. Results: The sensitivity analyzes of all pharmacoeconomic models showed the robustness and reliability of the obtained results. The threshold limits of medical costs and the frequency of achieving a deep molecular response determining the choice of first- and second-generation tyrosine kinase inhibitors as first- and second-line therapy for patients with chronic myeloid leukemia in the chronic phase have been determined. Prescribing doctors prefer the original MPs to generic analogues, which is also assumed by the current regulations, according to which even for expensive MPs dispensing by protocols, the prescription is by trade and not by international non-proprietary names (INN), which is why the use of the much cheaper generic MPs is negligibly low compared to original MPs. A personalized approach to the patient’s therapy and monitoring the patient’s molecular response to it, as well as stopping therapy in 25–30% of patients suitable to stop it safely when in TFR phase with a probability of more than 50% of not having a relapse will save additional costs that, by improving the cost-effectiveness of therapy for patients with CML, will be directed towards the treatment of new patients with this or other diseases. Conclusion: These pharmacoeconomic models can be applied to improve diagnostic and therapeutic standards in clinical practice and for the efficient use of the very limited resources for health care in countries like Bulgaria. The conducted cost-effectiveness analyses confirmed that the hematologists at the University Center in Plovdiv adhere to the recommendations of Leukemia Net and the Bulgarian Medical Society of Hematology and achieve not only good therapeutic but also pharmacoeconomic efficiency in the treatment of CML-СР patients in first- and second- line therapy.

Garment workers are exposed to various factors in the work environment, classified as physical and ergonomic. Occupational injuries of the spine develop as a result of the action of harmful production factors, the most important of which are overstrain, vibrations and an unfavorable production microclimate. The aim of the study is to improve the health and prevention of spine injuries among garment workers. The subject of the study is 75 cases of spine injuries in garment workers. The persons were hospitalized in University Hospital - Pleven during the period 2019-2023. Clinical, laboratory, functional, imaging and statistical research methods were used. Treatment with medication and physical factors was carried out. In 93% of the patients, an improvement in clinical syndromes and the performance of activities of daily living was found. 7% of the examined persons required surgical treatment. Conclusions: Spinal injuries are a current health problem among garment workers. Combined medication and physical therapy is an effective and practically applicable therapeutic approach for the investigated disabilities.