Medical University of Varna

About: Medical University of Varna is a education organization based out in Varna, Varna, Bulgaria. It is known for research contribution in the topics: Population & Medicine. The organization has 1199 authors who have published 1273 publications receiving 32940 citations. The organization is also known as: MU-Varna & Higher Medical Institute of Varna.

Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial

Abstract: Summary Background Activation of the PI3K/AKT/mTOR pathway occurs frequently in breast cancer that is resistant to endocrine therapy. Approved mTOR inhibitors effectively inhibit cell growth and proliferation but elicit AKT phosphorylation via a feedback activation pathway, potentially leading to resistance to mTOR inhibitors. We evaluated the efficacy and safety of buparlisib plus fulvestrant in patients with advanced breast cancer who were pretreated with endocrine therapy and mTOR inhibitors. Methods BELLE-3 was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Postmenopausal women aged 18 years or older with histologically or cytologically confirmed hormone-receptor-positive, HER2-negative, locally advanced or metastatic breast cancer, who had relapsed on or after endocrine therapy and mTOR inhibitors, were recruited from 200 trial centres in 22 countries. Eligible patients were randomly assigned (2:1) via interactive response technology (block size of six) to receive oral buparlisib (100 mg per day) or matching placebo starting on day 1 of cycle 1, plus intramuscular fulvestrant (500 mg) on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day cycles. Randomisation was stratified by visceral disease status. The primary endpoint was progression-free survival by local investigator assessment as per the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 in the full analysis population (all randomised patients, by intention-to-treat). Safety was analysed in all patients who received at least one dose of treatment and at least one post-baseline safety assessment. This study is registered with ClinicalTrials.gov, number NCT01633060, and is ongoing but no longer enrolling patients. Findings Between Jan 15, 2013, and March 31, 2016, 432 patients were randomly assigned to the buparlisib (n=289) or placebo (n=143) groups. Median progression-free survival was significantly longer in the buparlisib versus placebo group (3·9 months [95% CI 2·8–4·2] vs 1·8 months [1·5–2·8]; hazard ratio [HR] 0·67, 95% CI 0·53–0·84, one-sided p=0·00030). The most frequent grade 3–4 adverse events in the buparlisib versus placebo group were elevated alanine aminotransferase (63 [22%] of 288 patients vs four [3%] of 140), elevated aspartate aminotransferase (51 [18%] vs four [3%]), hyperglycaemia (35 [12%] vs none), hypertension (16 [6%] vs six [4%]), and fatigue (ten [3%] vs two [1%]). Serious adverse events were reported in 64 (22%) of 288 patients in the buparlisib group versus 23 (16%) of 140 in the placebo group; the most frequent serious adverse events (affecting ≥2% of patients) were elevated aspartate aminotransferase (six [2%] vs none), dyspnoea (six [2%] vs one [1%]), and pleural effusion (six [2%] vs none). On-treatment deaths occurred in ten (3%) of 288 patients in the buparlisib group and in six (4%) of 140 in the placebo group; most deaths were due to metastatic breast cancer, and two were considered treatment-related (cardiac failure [n=1] in the buparlisib group and unknown reason [n=1] in the placebo group). Interpretation The safety profile of buparlisib plus fulvestrant does not support its further development in this setting. Nonetheless, the efficacy of buparlisib supports the rationale for the use of PI3K inhibitors plus endocrine therapy in patients with PIK3CA mutations. Funding Novartis Pharmaceuticals Corporation.

Nerve growth factor as a signaling molecule for nerve cells and also for the neuroendocrine-immune systems.

Abstract: Nerve growth factor (NGF) is a signaling molecule, originally discovered for its role on differentiation and survival of peripheral sensory and sympathetic neurons. It has also been associated with functional activities of cells of the immune and endocrine systems. NGF biological activity is mediated by two classes of receptors: (i) p75 neurotrophin receptor (p75(NTR)), a 75 kDa glycoprotein, belonging to a superfamily of cytokine receptors including TNF receptors, and (ii) TrkA, a transmembrane tyrosine kinase of 140 kDa. Both TrkA and p75(NTR) are known to play a marked action in neurodegenerative disorders, immune-related deficits, and neuroendocrine (including adipoendocrine) mechanisms. This review focuses on these cellular events and presents a working model which attempts to explain the close interrelationships of the neuro-endocrine-immune triad via a modulatory action of NGF.

Bulgaria health system review.

Abstract: In the last 20 years, demographic development in Bulgaria has been characterized by population decline, a low crude birth rate, a low fertility rate, a high mortality rate and an ageing population. A stabilizing political situation since the early 2000s and an economic upsurge since the mid-2000s were important factors in the slight increase of the birth and fertility rates and the slight decrease in standardized death rates. In general, Bulgaria lags behind European Union (EU) averages in most mortality and morbidity indicators. Life expectancy at birth reached 73.3 years in 2008 with the main three causes of death being diseases of the circulatory system, malignant neoplasms and diseases of the respiratory system. One of the most important risk factors overall is smoking, and the average standardized death rate for smoking-related causes in 2008 was twice as high as the EU15 average. The Bulgarian health system is characterized by limited statism. The Ministry of Health is responsible for national health policy and the overall organization and functioning of the health system and coordinates with all ministries with relevance to public health. The key players in the insurance system are the insured individuals, the health care providers and the third party payers, comprising the National Health Insurance Fund, the single payer in the social health insurance (SHI) system, and voluntary health insurance companies (VHICs). Health financing consists of a publicprivate mix. Health care is financed from compulsory health insurance contributions, taxes, outofpocket (OOP) payments, voluntary health insurance (VHI) premiums, corporate payments, donations, and external funding. Total health expenditure (THE) as a share of gross domestic product (GDP) increased from 5.3% in 1995 to 7.3% in 2008. At the latter date it consisted of 36.5% OOP payments, 34.8% SHI, 13.6% Ministry of Health expenditure, 9.4% municipality expenditure and 0.3% VHI. Informal payments in the health sector represent a substantial part of total OOP payments (47.1% in 2006). The health system is economically unstable and health care establishments, most notably hospitals, are suffering from underfunding. Planning of outpatient health care is based on a territorial principle. Investment for state and municipal health establishments is financed from the state or municipal share in the establishments capital. In the first quarter of 2009, health workers accounted for 4.9% of the total workforce. Compared to other countries, the relative number of physicians and dentists is particularly high but the relative number of nurses remains well below the EU15, EU12 and EU27 averages. Bulgaria is faced with increased professional mobility, which is becoming particularly challenging. There is an oversupply of acute care beds and an undersupply of longterm care and rehabilitation services. Health care reforms after 1989 focused predominantly on ambulatory care and the restructuring of the hospital sector is still pending on the government agenda. Citizens as well as medical professionals are dissatisfied with the health care system and equity is a challenge not only because of differences in health needs, but also because of socioeconomic disparities and territorial imbalances. The need for further reform is pronounced, particularly in view of the low health status of the population. Structural reforms and increased competitiveness in the system as well as an overall support of reform concepts and measures are prerequisites for successful progress.