Molecular Diagnostics and Treatment Patterns in Metastatic Non-small Cell Lung Cancer Patients: Real World Evidence from Greece: LACHESIS Study.

BACKGROUND/AIM: Lung cancer, primarily non-small cell lung cancer (NSCLC), is the leading cause of cancer deaths globally. In Greece in 2020, 8,960 new cases were reported. NSCLC's 5-year survival rates range from 54% (stage I) to less than 2% (stage IV); however, innovative therapies like immune check points inhibitors (ICIs) and targeted treatments have notably enhanced outcomes. The aim of this study was to assess the 1st and 2nd line treatment patterns with the introduction of new treatment modalities. Additionally, we evaluated biomarker testing approaches in NSCLC. PATIENTS AND METHODS: LACHESIS was a retrospective multinational study, collecting and analyzing data from adult patients from Russia, Bulgaria, and Greece with metastatic NSCLC either newly diagnosed or relapsed from earlier stages, who had the option to undergo biomarker testing (genetic alterations/programmed death-ligand 1 protein expression levels, PD-L1), and who received 1st line treatment for squamous (SQ) or non-squamous (N-SQ) NSCLC. Subsequent lines of therapy were also reported. RESULTS: The Greek site registered retrospective data from 250 NSCLC patients, of whom 206 were newly diagnosed (ND) metastatic NSCLC patients and 44 were patients relapsed from earlier stages. Seventy-two had SQ NSCLC and 169 had N-SQ NSCLC. For these patients, treatment patterns including immunotherapy±chemotherapy combinations were recorded. Biomarker testing patterns, including genetic alterations and PD-L1 expression levels were also documented. CONCLUSION: LACHESIS provides treatment patterns and biomarker testing data. Greek patients were treated according to international guidelines, with immunotherapy as a viable option, particularly for PD-L1 levels over 50%. Biomarker testing, crucial for non-squamous (N-SQ) cases, should yield timely results for driver mutations, prioritizing patient benefits.

Complications after limb salvage surgeries for musculoskeletal malignancies: 10-year experience of the main sarcoma center in Bulgaria.

INTRODUCTION: Limb salvage surgery is currently the most frequently used treatment option in Bulgaria for individuals with musculoskeletal malignancies. Clinical data about complications from these procedures is limited in the country, with only a few studies currently available.

Clinical and virological profile of locally acquired acute hepatitis E in South Bulgaria.

INTRODUCTION: Acute hepatitis E virus (HEV) infection is recognized as a zoonosis in several European countries. We describe the characteristics and outcomes of locally acquired acute HEV hepatitis. METHODOLOGY: A prospective study was conducted among adult patients with acute HEV hepatitis at the University Hospital in Plovdiv, South Bulgaria between January 2020 and May 2022. An acute HEV infection case was a patient with acute hepatitis and laboratory-confirmed anti-HEV IgM antibodies and/or HEV RNA in serum. Demographic data, clinical manifestations, laboratory test results, and outcomes were recorded. RESULTS: A total of 46 patients were selected. Median age of 65 years (interquartile range [IQR] 50.8-74.3). 28 (60.87%) were male. 22 (47.83%) had comorbidities such as diabetes (15), liver cirrhosis (3), hepatitis B virus infection (2), and malignancies (2). Of the 46, 18 (39.13%) patients were viremic and, HEV genotype 3 was detected. The median (IQR) serum alanine aminotransferase, aspartate aminotransferase, bilirubin, platelet, and international normalized ratio levels were 992 (495.8-1714.3) U/L, 715 (262.5-1259.3) U/L, 204 (132.3-235.5) µmol/L, 204 (132.3-235.5) ×109 L, and 1.0 (0.89-1.19), respectively. Six patients with underlying liver diseases had severe hepatitis. A young patient with osteoarthritis progressed to acute liver failure and died. The persistent HEV infection was ruled out in 2 malignant patients who tested HEV RNA negative three months after discharge. CONCLUSIONS: Acute HEV hepatitis is a diagnosis to consider after excluding other causes of acute viral hepatitis. A diagnostic workup should include timely testing for HEV to identify the most vulnerable to severe consequences.

Nationwide analysis of the impact of COVID-19 in patients with a cardiovascular, oncological or chronic pulmonary disease in the context of an Eastern European country with a low vaccination rate, Bulgaria: March 2020-April 2022.

OBJECTIVE: This study focused on Bulgarian patient cohorts harbouring a single documented chronic comorbidity-cardiovascular pathology, an oncological disease or a chronic pulmonary diseases (CPD) comparing the outcomes in fully vaccinated and non-vaccinated populations classified by sex and age groups in ambulatory, hospital and intensive care unit (ICU) settings at the national level. DESIGN: Retrospective analysis SETTINGS, PARTICIPANTS AND OUTCOME MEASURES: In total, 1 126 946 patients with confirmed COVID-19, on a national level, were retrospectively analysed between March 2020 and April 2022, using data from the Ministry of Health's United Information Portal, launched in March 2020. RESULTS: Of all the confirmed 247 441 hospitalised cases of COVID-19, 67 723 (27.3%) had documented cardiovascular disease (CVD), 2140 (0.9%) had confirmed solid malignancy (regardless of stage) and 3243 (1.3%) had established CPD as their only chronic pathology. The number of cumulative deaths in each subgroup was 10 165 (in-hospital=5812 and ICU=4353); 4.0% vaccinated (410/10 165, p<0.001), 344 (in-hospital=196 and ICU=148), 4.9% vaccinated (17/344, p<0.001), 494 (in-hospital=287 and ICU=207) and 5.2% vaccinated (26/494, p<0.001), respectively. Statistical significance (p<0.001) was obtained in favour of reduced ambulatory, hospitalisation and both in-hospital and ICU-related mortality in the vaccinated cohorts, and BNT162b2 was the most effective at preventing mortality in all age groups. CONCLUSIONS: This retrospective analysis shows that patients vaccinated against COVID-19 demonstrated trends of reduced hospitalisations and premature mortality in patients with CVD, solid malignancy or CPD as a single comorbidity.

Endometrial carcinoma in patients under 40 years of age: insights from the Bulgarian Cancer Registry.

OBJECTIVES: We aimed to investigate the overall survival (OS) of young women with endometrial cancer (EC) in Bulgaria and the impact of histological type on survival. MATERIAL AND METHODS: This is a population-wide retrospective study of patients with EC (≤ 40 years at diagnosis) registered at Bulgarian National Cancer Registry (BNCR) between 1993 and 2020. Patients were re-classified according to the 8th edition of the TNM classification. RESULTS: In total, 30 597 patients were registered and histologically confirmed with malignant tumors of the uterine body. From that, 29 065 of them (95%) had ECs, and the rest had sarcomas. Around 1.64% of all malignant tumors of the uterine body are diagnosed in women under the age of 40. Most of them are diagnosed in the early stage. There was no significant difference in median OS for patients diagnosed before or after 2003. In recent years there was a slight improvement in survival and patients from the last cohort of this study had a 5-year survival rate of 92.5%. Patients with favorable pathology (T1, G1/2) had no lymph node involvement at the time of diagnosis and their 10-year survival rate was 94%. CONCLUSIONS: EC in young women is a rare disease. In most cases, patients are diagnosed in early stageT1, G1/2, N0 and their prognosis is excellent. However, the lack of improvement of OS of young patients with EC in the last three decades shows the need for treatment optimization.

Assessment of health status and cardiovascular risk factors in a Roma population sample from South Bulgaria.

OBJECTIVES: Roma population is one of the major ethnic groups in the Central and Eastern Europe, having high rates of chronic diseases and associated risk factors related to their poor social conditions, unhealthy lifestyle and low educational level. The purpose of our study was to assess the health status of Roma from South Bulgaria by means of blood indicators and determine the prevalence of some cardiovascular (CV) risk factors in the Roma population sample. METHODS: The study group consisted of 60 Roma (23 men and 37 women), mean age 53.7 ± 15.9 years, and the control group consisted of 68 non-Roma from the majority population (29 men and 38 women), mean age 45.8 ± 12.2 years. The data were collected via questionnaire, anthropometric measures, and venous blood samples analyses after an overnight fasting. RESULTS: The Roma population subjects were slightly but significantly older compared to the non-Roma group and both study groups included more women. The fasting glucose, body mass index (BMI), triglycerides (TG), total cholesterol (TC), and LDL-cholesterol (LDL-C) levels were significantly higher, and HDL-cholesterol (HDL-C) levels were significantly lower in Roma compared to the control non-Roma group. The values of cardiovascular risk markers such as TC/HDL-C and TG/HDL-C ratios, atherogenic index of plasma (AIP) and lipoprotein combine index (LCI) were significantly higher in Roma compared to non-Roma subjects. The prevalence of obesity in Roma was 35%, diabetes mellitus was recorded in 16.7% of the entire Roma sample, and hyperglycaemia in non-diabetics was recorded in 32%. Hypercholesterolaemia was found in 90% and hypertriglyceridaemia was found in 88.3%. The prevalence of cardiovascular diseases (CVD) was high and was encountered in 71.7% of the Roma participants and most of the subjects (96.7%) reported family history of CVD. The studied population showed high smoking rates with 33.3% active smokers. CONCLUSIONS: Our study confirmed high prevalence of CV risk factors among Roma population, such as abnormal lipid profile parameters, obesity and heavy smoking and very high cardiovascular morbidity rate. Therefore, adequate measures and healthcare programmes aiming at the early identification, treatment and prevention of CVD risks among Roma are necessary.

Economic Burden of Cervical Cancer in Bulgaria.

Bulgaria is among the European Union (EU) countries with the highest burden of cervical cancers and life expectancy below the EU average. The majority of cervical cancer cases (more than 95%) are caused by the human papillomavirus (HPV). The aim of this retrospective, cost of illness study is to identify direct healthcare costs of cervical cancer in Bulgaria from the payer perspective and to calculate indirect costs and the associated years of life lost. Costs data were sourced from the National Health Insurance Fund from January 2018 to December 2020. Years of life lost were calculated based on the country and gender-specific life expectancy. Indirect costs due to productivity loss were calculated using the human capital approach. The total treatment costs for 3540 patients with cervical cancer are EUR 5,743,657 (2018), EUR 6,377,508 (2019), and EUR 6,751,182 (2020). The costs associated with drug acquisition and administration accounted for the majority (63%) of total healthcare costs followed by hospital management costs (14%). An estimated total of 20,446 years of life were lost due to cervical cancer for the period 2018-2020. The costs of productivity losses are estimated at EUR 7,578,014. Our study showed that the economic burden of cervical cancer in Bulgaria is substantial. Focus on cervical cancer prevention via vaccination against the human papillomavirus, timely screening, early diagnosis, and higher vaccine coverage rates could reduce its economic burden in Bulgaria.

Protective Role of IL7A-197 A/G Heterozygosity in the Development and Severity of Colorectal Cancer in the Bulgarian Population.

Background: Interleukin (IL)-17A and IL-17F, expressed mainly by a novel subset of CD-positive (+) T-helper (Th) cells of the immune system, has been closely related to inflammatory conditions underlying colorectal cancer pathogenesis. Accordingly, we conducted a case-control study to investigate the association of common single nucleotide polymorphisms (SNP) in the IL17A and IL17F genes (rs2275913 and rs763780, respectively) with the susceptibility and severity of CRC patients from the Bulgarian population. Methods and Materials: 136 patients with histologically confirmed CRC diagnosis and 116 healthy individuals were recruited in the present study. Genotypes were determined by the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique. Results: The IL17A heterozygous A/G-genotype was overrepresented among the control group (p = 0.003). Additionally, the carriers of the heterozygous A/G-genotype had a 2.39-fold lower risk for CRC compared to the G/G-genotype (OR = 0.418, p = 0.006). Our results also indicated that in the advanced CRC stages (III + IV) the heterozygous genotype (A/G) appeared to be less frequent (p = 0.024, χ2-test). Among the patients with detected distant metastases, the A/G-carriers were the smallest part (14.3%) compared to the homozygous genotypes A/A (42.9%) and G/G (42.8%), p = 0.006. There was no association of the studied IL17F rs763780 SNP with susceptibility and severity of CRC among the studied subjects, although the heterozygous C/T-carriers had shorter median survival compared to the T/T-carriers (p = 0.129). Conclusions: Our study finds a protective role of heterozygosity for the IL17A-197A/G SNP and negative effects of the A-allele on CRC progression.

Socio-Economic Burden of Myasthenia Gravis: A Cost-of-Illness Study in Bulgaria.

Background: Myasthenia gravis (MG) is a chronic autoimmune disorder, which is characterized by fatigable muscle weakness with frequent ocular signs and/or generalized muscle fatigue, and occasionally associated with thymoma. MG patients and their families face a significant socio-economic burden. This population is often experiencing unemployment, unwilling job transfers and decreased income. Objective: This study aimed to estimate the annual costs from a societal perspective in a triple dimension of direct health care costs, direct non-health care costs (formal and informal care) and labor productivity losses in MG patients from Bulgaria, as well as to identify the main clinical and demographical cost drivers. Methods: A bottom-up, cross-sectional, cost-of-illness analysis of 54 adult MG patients was carried out in 2020. To collect data on demographic characteristics, health resource utilization, informal care and productivity losses, questionnaires were administered to and completed by patients. Results and Conclusion: Median annual costs of MG in Bulgaria were 4,047 EUR per patient. Direct costs slightly outweighed indirect costs, with drugs cost item having the biggest monetary impact. Despite the zero-inflated median, hospitalizations also influenced the direct costs by an estimated amount of 1,512 EUR in the 3rd quartile. Social services and professional caregiver costs were found to be almost missing, with the vast majority of patients reporting reliance on informal caregivers. Severe generalized disease, disease crises, and recurrent infections were confirmed as statistically significant cost driving factors. There were no severe generalized MG patients in the bottom quartile of the total costs distribution. It should be noted that in both cases of crises or infections, the overall increase in the total costs was mainly due to higher indirect costs observed. Reliance on family members as informal caregivers is routine among Bulgarian MG patients. This phenomenon is likely due to the lack of access to appropriate social services. Moreover, it is directly related with higher disease burden and significant inequalities. There is a need for further research on MG in Bulgaria in order to design targeted health policies that meet the needs and expectations of these patients.

Impact of Polypharmacy, Drug-Related Problems, and Potentially Inappropriate Medications in Geriatric Patients and Its Implications for Bulgaria-Narrative Review and Meta-Analysis.

Objective: Polypharmacy and inappropriate prescribing are overlooked issues in Bulgaria. We aimed at collecting and analyzing global literature on the most prevalent risk factors and investigating what they could reveal about current practice. Materials and Methods: A systematic narrative review and meta-analysis was conducted on the topic, investigating the prevalence of polypharmacy, odds of potentially inappropriate medications (PIMs) due to polypharmacy, and the likelihood of developing a drug-related problem (DRP) due to PIMs. The results were then related to current demographic statistics to estimate the potential impact on Bulgarian elderly patients. Results: The prevalence of polypharmacy was estimated at 41% in elderly populations. The odds of a potentially inappropriate medication being prescribed were 2.095, with an expected 30.84% of those leading to a DRP. These numbers indicated that the expected Bulgarian elderly with polypharmacy should be 709,676 with 212,903 cases of DRPs. Conclusion: Global polypharmacy rates seem to be on the rise, with an expected increase in DRPs.

Peri-operative and survival outcomes analysis of patients with endometrial cancer managed by three surgical approaches: a long-term Bulgarian experience.

The study aim was to assess the peri-operative, oncologic, and survival outcomes for patients with endometrial cancer (EC) managed by abdominal hysterectomy (AH), laparoscopic hysterectomy (LH), or robotic hysterectomy (RH) approaches at premier centers in Bulgaria. We analyzed histologically diagnosed EC cases operated via any of the three surgical methods during 2008-2019. Data analyses included patients and tumor characteristics, peri-operative outcomes, and disease status. We grouped FIGO stages I and II to represent early-stage EC and to investigate their survival. Kaplan-Meier and Cox regression analyses were performed to determine disease-free survival (DFS) and overall survival (OS). Consecutive 917 patients (AH = 466; LH = 60, RH = 391) formed the basis of study analyses. Most of demographics and tumor characteristics of the patients were comparable across the groups except few minor variations (e.g., LH/RH cases were younger, heavier, more stage IA, endometrioid, G1, low-risk group). LH and RH group cases had significantly lower operative time than AH (p < 0.001), shorter hospital length-of-stay (p < 0.001), higher post-operative Hgb (p < 0.001). RH cases had fewer blood transfusions than AH or LH (p < 0.001). Cox multivariate analyses indicate that OS was not influenced by the type of surgical approach. Despite the fact that the DFS in "early-stage" EC is significantly better in AH group than RH, the type of surgery (i.e., AH, LH, or RH) for "all stages" is insignificant factor for DFS. With our long-term experience, minimally invasive surgical approach resulted in superior peri-operative, oncologic, and survival outcomes. Specifically, RH is not only safe in terms of post-operative results, but also for mortality and oncologic rates.

Endoparasites of the European brown hare (Lepus europaeus Pallas, 1778 L.) (Lagomorpha: Leporidae) from Bulgaria.

In recent decades in Europe there has been a decline in the population of European brown hare (Lepus europaeus L.). Diseases, including parasitoses, are one of the factors considered to be the cause for the phenomenon. In this connection the aim of the present work was to update the data on the composition and distribution of endoparasites of this small mammal in Bulgaria against the background of the situation in Europe. Thirty sets of abdominal organs and forty seven faecal samples of hares from different regions of the country were investigated for presence of parasites. The faeces were analyzed with the coproscopical methods of Fulleborn, serial sedimentations, and the modified Baermann technique. Helminthological necropsies of the abdominal organs were carried out through the common technique. Parasites of the following taxa were established: Trematoda (Dicrocoelium dendriticum), Cestoda (Cysticercus pisiformis, Mosgovoyia pectinata), Nematoda (Trichuris sylvilagi, Strongylidae, Strongyloides sp., Protostrongylus spp.), Protozoa (Eimeria spp.) and Arthropoda (Pentastomum dentatum). Strongyloides sp. is reported for the first time as a part of the parasite fauna of the European brown hare in Bulgaria. Trichuris sylvilagi was the most prevalent parasite (63.3%), followed by gastrointestinal strongylids (57.43%), Eimeria spp. (55.3%), Protostrongylus spp. and Strongyloides sp. (31.9%), D. dendriticum (14.3%), C. pisiformis (10%), and M. pectinata (6.67%). The studies showed that eimeriid coccidia, gastrointestinal strongylids, and trichurids are the most common endoparasites among the population of the European brown hare both in Bulgaria and the European continent.

Analysis of abdominal vs. robotic radical hysterectomies for patients with cervical cancer: a Bulgarian experience.

To assess and compare the peri-operative, oncologic, and survival outcomes for women with cervical cancer (CC) treated with abdominal radical hysterectomy (ARH) versus robotic radical hysterectomy (RRH) approaches in Bulgaria. We retrospectively analyzed patients with histologically diagnosed CC operated via ARH or RRH methods during January-2008 to April-2019. The data analyzed include patients and tumor characteristics, peri-operative outcomes, and disease status. Kaplan-Meier method and Cox regression analysis were performed to determine disease-free survival (DFS) and overall survival (OS). There were consecutive 1347 patients (ARH = 1006, RRH = 341), which formed the basis of study analyses. Women in the RRH group had significantly shorter median hospital length-of-stay than ARH cases (7 vs. 11 days, p < 0.001), higher post-operative hemoglobin (116 vs. 108 g/L, p < 0.001), and fewer blood transfusions (7.3% vs. 21.5%, p < 0.001), respectively. The overall incidence of post-operative complications was also lower in the RRH vs. ARH group (2.1% vs. 9.4%, p < 0.001). Median follow-up time for ARH vs. RRH groups was 4.32 vs. 5.24 years, respectively (p < 0.001). Kaplan-Meier analysis demonstrated that the RRH cohort had a significantly higher survival rate compared to the ARH group (CC-specific death 8.5% vs. 16.5% respectively). Mean time to recurrence did not differ significantly in either surgical approach (p = 0.495). Cox multivariate regression showed no significant impact of surgical approach on DFS or OS. No significant difference in DFS or OS between ARH vs. RRH for CC was observed. RRH approach does not lead to inferior oncologic outcomes and is associated with better peri-operative outcomes. In regard to "all stages" of CC, we found robotic surgery safer compared to laparotomy, and thus consider RRH a better surgical treatment option for patients with CC.

Longitudinal Dynamics of Coagulation and Angiogenesis Markers in Cancer Patients During and After Chemotherapy.

Hemostatic parameters have been investigated as molecular determinants of tumor progression. To analyze the dynamics of microparticle-associated tissue factor activity (MPTF), tissue factor antigen (TF-Ag), and angiopоietin-2 (ANG-2) in cancer patients before, during, and after active treatment and to explore their potential as biomarkers for metastatic occurrence and death. Blood for the analysis of MPTF, TF-Ag, ANG-2, and conventional hemostatic tests was sampled in 111 patients with various cancers at 4 consecutive visits: before first chemotherapy cycle, after 3 courses, at the sixth course, and 3 months after chemotherapy cessation. Patients were followed up until metastatic progression/death or the end of the study. MPTF did not change during chemotherapy, but increased significantly after treatment cessation. Total TF-Ag and ANG-2 decreased throughout active treatment. Significant drop of their levels was observed 3 months post therapy cessation. Progressive disease was significantly associated with higher pre-chemotherapy TF-Ag and fibrinogen. Elevated baseline levels of fibrinogen were associated with increased risk of shortened progression free survival. Cessation of chemotherapy is associated with significant change of hemostatic parameters. Pre-chemotherapy levels of TF-Ag and fibrinogen may be informative of disease state and prognosis.

Initial experience in the field of pediatric percutaneous nephrolitholapaxia in Bulgaria.

INTRODUCTION: Pediatric urolithiasis is a very specific and challenging problem in the field of modern urology. Currently, there are three major methods for kidney stone removal: the extracorporeal shock wave lithotripsy (ESWL), the retrograde intrarenal surgery (RIRS), and the percutaneous nephrolithotomy (PCNL), the latter one proving to be an efficient and safe monotherapy of stones even with larger burden. Different sizes of nephroscopes are used (standard, mini, micro), where smaller size is logically correlated with safer profile, especially in pediatric population. AIM: To analyze the initial experience in using PCNL in children for the treatment of kidney concrements - rates of successful stone removal and registered complications. MATERIALS AND METHODS: Twenty-six PCNL procedures of 25 children were performed - both standard and mini. The age ofpatients, size of the stones, operating time, changes in hemoglobin levels, duration of hospital stay, and the postoperative complications were recorded, analyzed and compared to data reported in current relevant literature. RESULTS: The mean age of patients was 9±5.2 years (15 boys and 10 girls). The average size of concrements subjected to nephrolitholapaxia was 16±0.7 mm, most of the cases being single stones. The average operative time was 150±33.4 min, and the average hospital stay was 4.1±1.5 days. The percentage of stone free children postoperatively was 94%. Complications included blood loss requiring transfusion in 1 patient (4%), postoperative urinary tract infection and fever (2 patients), and self-limiting hematuria in 16%. CONCLUSIONS: PCNL is an effective and safe alternative in the management of nephrolithiasis in children. It is a method of choice for the treatment of concretions not suitable to treat with extracorporeal lithotripsy and after a qualitative selection of patients.

Decreased number of p16-positive senescent cells in human endometrium as a marker of miscarriage.

PURPOSE: The aim of this study was to evaluate whether the number of p16-positive cells in the functional layer of the endometrium could be a useful biomarker to identify women with recurrent implantation failure (RIF) undergoing in vitro fertilization (IVF) at risk of miscarriage. METHODS: Immunohistochemical staining was performed in 311 endometrial biopsies taken during mid-luteal phase using antibody against p16INK4A. The percentage of p16-positive cells was determined in luminal, glandular and stromal endometrial cells. After embryo transfer, women were divided into the following groups: unsuccessful embryo implantation (n = 151), miscarriage (n = 66) and live birth (n = 94). The percentage of p16-positive cells in all endometrial compartments was compared among these groups. RESULTS: We found that the percentages of p16-positive glandular and luminal epithelial endometrial cells were significantly higher in patients with live births compared to women with miscarriage (9.3% vs. 2.9%, P < 0.001; and 35.2% vs. 11.7%, P = 0.001, respectively). This tendency was not confirmed in thе stroma. The cut-off values with p16-positive luminal cells lower than 12.5% and p16-positive glandular cells lower than 3.2% could be predictive factors for miscarriage (AUC 0.80 and 0.79; sensitivity 71.3% and 74.5%; specificity 74.2% and 71.2%, respectively). CONCLUSION: A decreased number of senescent p16-positive cells could be involved in the implantation failures and aetiology of recurrent miscarriage. Women with history of RIF with reduced populations of p16-positive cells in the endometrial glandular and luminal epithelium may be at greater risk for unsuccessful implantation and miscarriage. The percentage of p16-positive luminal epithelial cells may be clinically useful as a biomarker of miscarriage.

High Grade Glioma Surgery - Clinical Aspects and Prognosis.

INTRODUCTION: High grade gliomas (HGG) are a group of tumors with infiltrative nature in general. Surgery is the first step in their treatment. It can be beneficial in two aspects: firstly, in establishing normal intracranial pressure and, secondly, in reducing the tumour volume. The choice of method depends on the location of the lesion, the expected grade of malignancy, and the general condition of the patient. Despite constant development of neuro-oncology and microsurgical techniques, the 5-year survival rate in patients with HGG remains less than 10% and the median survival is still less than 2 years. Aim: At present, there is no final therapeutic "segment" to provide a better outcome than the complex treatment of HGG. Moreover, the treatment's relative efficacy and recurrence of these tumours carry an additional problem. The aim of this study was to estimate the overall survival of patients with HGG operated in our clinic and compare it with literature data. Materials and methods: One hundred twenty-one cranial operations for HGG were reviewed (conducted between 2014 and 2019). Summary characteristics of the various parameters were presented in respect to the radical nature of the operative intervention using Kaplan-Meier analysis and chi square tests. All patients were followed up at regular check-ups. RESULTS: HGGs were 103 or 85.12% of all gliomas operated for the 2014-2019 period. The most common cases were in the 51 to 60 age group. The cases in men were twice as common. The most common localization of the neoplasm is in the temporal region (36.36%) and the rarest was found in the occipital region (3.30%). It was estimated that our operated patients with HGG had 12.23 months over-all survival. Gross total resected patients had a median survival (OS) of 14.53 months, while subtotal resected patients had a median survival (OS) of 10.44 months. It is estimated 7.97 months free tumor survival period (time to relapse - FTS) for our operated patients with HGG. Gross total resected patients had a median FTS of 10.88 months, while subtotal resected patients had median FTS of 5.70 months. We noticed permanent new neurological deficit (NND) in 20 patients (19.45%) operated with GTR, and in 5 patients (4.85%) operated with STR. Conclusions: Median survival - OS, free tumor survival period - FTS and new neurological deficit - NND were statistically significant (p.

Familial Hypercholesterolemia Identification Algorithm in Patients with Acute Cardiovascular Events in A Large Hospital Electronic Database in Bulgaria: A Call for Implementation.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder characterized by a high level of low-density lipoprotein cholesterol (LDL-C) and is an important cause for premature cardiovascular disease. Because of underdiagnoses, an acute event is often the first clinical manifestation of FH. There are limited data on the prevalence and treatment of FH among adults admitted for treatment of acute cardiovascular events in Bulgaria. Our objective was to assess the proportion and management of FH patients from those admitted to hospital for treatment of acute symptomatic acute atherosclerotic cardiovascular events (ASCVD), the achievement of LDL-C targets of European Society of Cardiology/European Atherosclerosis Society guidelines and related public healthcare resources. OBJECTIVE: Digitalized healthcare records for patients admitted for treatment of symptomatic ASCVD acute events between August 2018 and August 2019 were used for the analysis. Five cardiology hospitals provided data for hospitalizations, laboratory tests, and ambulatory follow-ups up to February 2020. Patients' hospital and ambulatory records were linked, and medical histories were extracted via a specifically developed algorithm, and analyzed. Outcomes included the proportion of patients classified as FH as defined by the Dutch Lipid Network Criteria (DLNC), use of lipid-lowering therapy, LDL-C achieved by 1, 3, 6, and 12 months post-index event, and public resources spent on hospital and ambulatory treatment. RESULTS: We reviewed 11,090 hospital records of patients admitted for treatment of acute events in the period August 2018-August 2019 with ICD codes for ASCVD (Supplementary Table S3). FH was identified in 731 (6.6%) patients, with DLNC score ≥ 3, (682 with coronary artery disease, 32 with cerebrovascular disease, and 17 with peripheral artery disease). We did not find the criteria for FH in 5797 patients. The remaining 4562 records were inconclusive due to lack of data in the hospital dossier. Less than half of FH patients (274/731, 37%) were discharged on high-intensity statin therapy prescribed (34/731, 5%) with combination therapy. The vast majority (96.2% with LDL-C ≥ 1.8 mmol/l) had poorly controlled LDL-C during the first year after discharge. Patients with a probable/definite DLNC score ≥ 6 points and those with recurrent events contributed to the higher cost paid both by the healthcare system and the patients themselves. CONCLUSION: These findings reinforce the need for more aggressive lipid-lowering therapy, and underline the efficiency of using an electronic medical records search tool to support physicians in improving early FH diagnosis, aiming to minimize residual and future ASCVD events among FH patients and their family members. Supplementary file1 (MP4 21838 KB).

Incidence of Non-melanoma Eyelid Malignancies in Bulgaria (2000-2015).

PURPOSE: Malignant eyelid tumours are the most common malignancies in ophthalmic practice. We report here the incidence of non-melanoma eyelid malignancies in Bulgaria, for the period 2000-2015. METHODS: All cases coded with the International Classification of Diseases (ICD) code C 44.1, received from the Bulgarian National Cancer Registry, were used for estimating crude incidence rates by age and sex. In addition, directly age standardized incidence rates for non-melanoma eyelid malignancies are presented based on the European Standard population (year 2013) for Bulgaria and the region of Varna. RESULTS: Over the 16-year period there were 3,046 cases in total, of which 1,457 (47.8%) were among men. The age standardized rate (ASR) of non-melanoma eyelid malignancies in men was 2.9 per 100,000 (95% CI 2.79-3.11), in women it was 2.4 per 100,000 (95% CI 2.30-2.54), and the mean ASR was 2.6 per 100,000 (95% CI 2.53-2.73) for both sexes during the period. The ASR increased for women and for both sexes combined.The risk of eyelid malignancies was higher for men than for women with RR of 1.21 (95% CI 1.08-1.41) during the whole period. The risk was higher in women up to the age of 55 and over 55 years it was higher in men. CONCLUSION: We report results for the incidence of eyelid non-melanoma malignancies in a south-eastern European country, Bulgaria. They are comparable with earlier reports from other European countries.

Predominance of ON1 and BA9 genotypes of respiratory syncytial virus (RSV) in Bulgaria, 2016-2018.

The objectives of this study were to investigate the prevalence of respiratory syncytial virus (RSV) infections in Bulgaria, to characterize the genetic diversity of the RSV strains, and to perform amino acid sequence analysis of the RSV G protein. Clinical, epidemiological data and nasopharyngeal swabs were prospectively collected from children aged less than 5 years presenting with acute respiratory infections from October 2016 to September 2018. Real-time polymerase chain reaction for 12 respiratory viruses, and sequencing, phylogenetic, and amino acid analyses of the RSV G gene/protein were performed. Of the 875 children examined, 645 (73.7%) were positive for at least one viral respiratory pathogen. RSV was the most commonly detected virus (26.2%), followed by rhinoviruses (15%), influenza A (H3N2) (9.7%), adenoviruses (9%), bocaviruses (7.2%), human metapneumovirus (6.1%), parainfluenza viruses 1/2/3 (5.8%), influenza type B (5.5%), and A(H1N1)pdm09 (3.4%). The detection rate for RSV varied across two winter seasons (36.7% vs 20.3%). RSV-B cases outnumbered those of the RSV-A throughout the study period. RSV was the most common virus detected in patients with bronchiolitis (45.1%) and pneumonia (24%). Phylogenetic analysis indicated that all the sequenced RSV-A strains belonged to the ON1 genotype and the RSV-B strains were classified as BA9 genotype. Amino acid substitutions at 15 and 22 positions of the HVR-2 were identified compared with the ON1 and BA prototype strains, respectively. This study revealed the leading role of RSV as a causative agent of serious respiratory illnesses in early childhood, year-on-year fluctuations in RSV incidence, the dominance of RSV-B, and relatively low genetic diversity in the circulating RSV strains.