Physicians’ Experience and Willingness to Participate in Non-Interventional Trials in Bulgaria

Summary Non-interventional studies (NIS) are conducted to obtain additional information about a medicinal product prescribed in the usual manner in compliance with the conditions determined in the marketing authorization. They are a valuable source of real-world data for the effectiveness and safety of medicines. This study aims to assess physicians‘ knowledge of non-interventional studies in Bulgaria and identify the primary factors and barriers hindering the NIS at a national level. An individual anonymous questionnaire with 16 items was distributed among physicians in inpatient and outpatient settings. The results showed that 81.3% (n=147) of the respondents have no experience with non-interventional studies. Physicians‘ willingness to participate in NIS in the future is high and independent of their previous experience. The main barriers hindering conducting NIS in Bulgaria are related to organization, the conduct and the design of the trials, and, sometimes, the investigators‘ concerns. There is a need for proper training of the researchers and expanding healthcare resources to grow the NIS sector in Bulgaria in line with the tendencies in Europe.

Dieulafoy Lesion as a Source of Bleeding: A Report of Two Clinical Cases

Summary Dieulafoy’s lesion is a rare source of gastrointestinal bleeding. It can be found anywhere in the gastrointestinal tract, but is most commonly seen in the proximal third of the stomach. It is a submucosal artery, adjacent to the mucosal surface, with no evidence of superficial ulcers. Lesions are routinely diagnosed and treated endoscopically. Their frequency is currently not well known, because as Dieulafoy lesions can be easily missed during endoscopy, and bleeding lesions are sometimes misidentified.In this article, we describe two cases of bleeding from the upper gastrointestinal tract, manifested by hematemesis and melena. Bleeding was successfully managed endoscopically by means of injection of adrenaline solution and application of an endoscopic hemoclip.

Intrahepatic Hematoma and Haemobilia After Percutaneous Liver Biopsy: A Clinical Case Report

Summary Assessing the severity of liver disease and predict the response to treatment in clinical practice requires the determination of the degree of inflammation progression and liver fibrosis. Percutaneous liver biopsy is the gold standard for grading and staging liver diseases. Complications are more common in the presence of vascular liver lesions, dilation of the bile ducts, ascites, or whether examination has been performed by less experienced physicians. Bleeding after liver biopsy is considered the most common cause of severe complications. Bleeding usually presents as a subcapsular or parenchymal hematoma, free intraperitoneal hemorrhage, hemobilia, or, rarely, hemothorax. The rarest of hemorrhagic complications is hemobilia, a term used to describe bleeding in the bile ducts. Hemobilia is usually suspected when there is a drop in hemoglobin after the procedure, pain in the upper right quadrant of the abdomen, hyperbilirubinemia, and unexplained gastrointestinal bleeding. The clinical manifestations range from chronic anemia to rapid, massive bleeding with hematemesis and/or melena.

The Role of Triglyceride to HDL Cholesterol Ratio in Sera as a Clinical Surrogate Marker for Cardiovascular Risk and Insulin Resistance in Patients with Metabolic Syndrome

Summary The study aimed to investigate the triglycerides to HDL-cholesterol ratio (Tg/HDL) and the interaction of this ratio with insulin resistance (IR) and insulin secretion indices, with the levels of interleukin - 1(IL-1), interleukin-6 (Il-6), and tumour necrotic factor- α (TNF-α) in sera among patients with metabolic syndrome (MS). A prospective, cross-sectional, comparative study was conducted on 45 patients with MS without data for hyperglycemia and 21 metabolically healthy non-obese controls. The levels of fasting and postprandial glucose, immunoreactive insulin (IRI), total cholesterol, triglycerides (Tg), IL-1, IL-6, and TNF-α were measured in all the participants. We calculated the LDL cholesterol levels, Tg/HDL ratio, homeostatic model of insulin resistance (HOMA-IR), and the homeostatic model of β-cell function (HOMA-b). Patients with MS had higher BMI (38.73±1.84 vs. 24.32±2.71 kg/m2; р<0.05) and waist circumference (115.56 ±4.7 vs. 81.1±8.4cm; р<0.05) than non-obese controls. The same patients had higher LDL cholesterol levels (3.42±0.3 vs. 2.63±0.66 mmol/l; р<0.05) and Tg (1.59±0.22 vs. 1.08±0.31mmol/l; р<0.05), as well as lower levels of HDL-cholesterol (1.03±0.09 vs. 1.27 ± 0.24mmol/l; р<0.05) compared to the controls. The Tg/HDL ratio was 2.03±0.87 among the patients with MS and 0.88±0.27 in controls; р<0.05. The plasma levels of basal IRI (19.32±3.22 mIU/l vs. 9.13±0.73mIU/l; р<0.05), HOMAIR (4.02 vs. 1.97; р<0.05) and HOMA-b (258.77±57.76 vs. 183.31±17.52; р<0.05) were significantly higher in the MS group. The same patients with MS had higher concentrations of IL-1 (18.37±4.28pg/ml vs. 7.12±1.74pg/ml; p<0.05), IL-6 (1.01±0.3pg/ml vs. 0.1±0.3pg/ml; р<0.05) and TNF-α (2.13±1.43 pg/ml vs. 1.82±0.94pg/ml; р=0.24) too. Positive correlations between the levels of IL- 1 and Tg/HDL ratio (r= 0.46; p=0.008), IL-1 and HOMA-%В (r=0.47; p=0.005) were found. The Tg/HDL ratio is a potential, cheap and available surrogate marker for screening for cardiovascular risk and insulin resistance in patients with MS in clinical practice.

Health Assessment of Internal Hygiene Control in Sauce Production

Summary Nowadays, usage of sauces as part of a meal has seen a significant increase. In their diversity as raw materials and technology of production, sauces are a potential source of health problems. During their production, primary and secondary contamination with microorganisms and other physical or chemical contaminants is possible. Ineffective internal control is a prerequisite for the emergence of health problems among consumers. The subject of the study is а sauce manufacturer. An algorithm was designed to perform the audit and for the purposes of the. The prerequisite measures were placed in separate Good Hygiene Practices (GHP) and Good Manufacturing Practices (GMP) programs and in the technological documentation for all the sauces produced, with plans, procedures, orders, instructions, lists, registers and other documents, all closely related to the specifics of production. The technological documentation was found to be in agreement with the Food Safety Management System – the HACCP-plan. The technological documentation, which is part of the prerequisite measures, corresponded to its purpose and, with slight adjustments, is a good basis for the effective functioning of the Food Safety Management System. The conclusions contain specific recommendations for revision of the Internal Control System, including correction of elements of health and hygiene importance.

Some of the Immunogenetics Aspects of Aging

Summary The human life span could be influenced by the combined effect of environment, lifestyle, and genetic factors. Twin and family studies suggest that our genes control up to 25% of the lifespan. The aging immune system undergoes age-associated changes at multiple levels, resulting in a gradual loss of its ability to protect the organism against infections, low vaccine responses, and an increased probability of developing autoimmune diseases and malignancies. The highly polymorphic HLA complex is one of the major gene candidates associated with aging due to its crucial role in developing adaptive immunity and protecting the organism. Most of the data available have so far demonstrated a positive association with healthy aging for HLA alleles/haplotypes as protective against malignancies, autoimmune diseases, and conferring better control and response to infections. One of aging’s main manifestations is the chronic, low-grade inflammatory state observed in older people, caused by an imbalance between pro- and anti-inflammatory cytokines. In general, it is has been agreed that longevity is related to anti-inflammatory genotype profiles. With advanced age, changes also occur in the B cell repertoire, which significantly affects the humoral immunity and leads to inadequate responses to infections and vaccines in the elderly. New genetic biomarkers associated with aging are being explored and discovered, contributing to a better understanding of the molecular processes underlying the immune dysfunction related to aging and developing strategies for rejuvenating the immune system based on immune-risk phenotypes.

A Rare Clinical Case of Lipoma in the Soft Tissues of the Sublingual Space: A Case Report

Summary This report presents clinical case with a histopathologically established lipoma of the sublingual space. Lipomas are benign mesenchymal neoplasms produced by adipocytes. Our search in the literature demonstrated that the development of lipomas in the sublingual space is extremely rare. In the oral cavity, it is seen in less than 5% of patients. In this paper, we describe clinical features, imaging diagnostic and histopathological features. Lipomas are characterized by slow growth and could be asymptomic, therefore diagnosis could be delayed. This report describes and discusses the case of a 64 years-old-man with a formation, located below the left tongue, for a period of 4 years. The patient had repeatedly consulted with Ear-Nose-Throat (ENT) specialists and dentists who recommended surgical treatment. During the last month of the monitoring, the formation had grown significantly and the chewing and speech function had gradually worsened.

Vaginal Bacterial Profile in Pregnant Women

Summary This study aimed to determine the bacterial profile of vaginal samples from pregnant women and the prevalence of identified microorganisms. Materials and methods: A prospective epidemiological study was conducted on 150 pregnant women admitted to the Clinic of Obstetrics and Gynecology at Dr. G. Stranski University Hospital in Pleven. Vaginal secretion samples were collected from all the 150 women. Direct microscopy of native smears prepared by the wet mount method to detect Trichomonas vaginalis and direct microscopy of Gram-stained smears was performed. Aerobic culture studies were conducted to identify pathogenic bacteria and Sabouraud glucose agar (SGA) to detect the presence of Candida spp. Samples were also collected from 107 of the women for PCR tests for mycoplasma detection. Results: The highest relative share in the study was women aged 21 to 35 years 104 (69.33%). Of all the hospitalized and examined pregnant women, 87 (57.99%) had medical problems during the current pregnancy and postpartum complications, and 63 women (42%) gave birth without accompanying complications. In 86 (57.32%) of the women, bacteria were detected by direct microscopy of Gram-stained smears. Of these, 24 (16%) had gram-negative rods, 28 (18.66%) had gram-positive cocci. In 34 (22.66%), we found gram-negative and gram-variable pleomorphic bacteria. The aerobic culture study revealed microbiological growth in 44 (29.33%) of the women investigated. Conclusions: Studies on the profile of the vaginal microbiota in pregnant women and the spread of pathogenic microorganisms are essential for make prognoses for pregnancy outcome, evaluating the risk of developing a maternal-fetal infection, and discussing options for timely treatment.

Glutathione Content and Glutathione Peroxidase Activity of Sperm in Males with Unexplained Infertility

Summary The study aimed to investigate glutathione peroxidase (GPx) activity and glutathione (GSH) levels in the sperm of patients with unexplained infertility. The sperm samples were collected from subjects with normal semen parameters divided into fertile and infertile groups. Sperm analysis was performed according to the 2010 WHO criteria. Measurement of the GPx activity and GSH were performed by enzymatic assay kits. The higher enzymatic activity recorded in spermatozoa and seminal plasma in the infertile group was close to the significant one – p=0.054 for seminal plasma andp= 0.086 for the spermatozoa.GSH levels were higher in the fertile group in the seminal plasma (p=0.045). Defining the causes of unexplained infertility requires the addition of oxidative stress. In patients with unexplained infertility, the level of glutathione is reduced, and the activity of one of the significant enzyme antioxidants GPx is not changed significantly and even shows a tendency to rise.

Granulocytic Expression of CD11b/CD18 and Thrombotic Risk in Patients with Myeloproliferative Neoplasms

Summary Myeloproliferative neoplasms (MPN) are clonal hematological conditions characterized by excessive production of one or more cell lines in the bone marrow. The blood cells produced are often hyperactive in their functions, which could lead to complications in the disorder‘s clinical course. We aimed to define the role of granulocytic CD11b/CD18 expression for the thrombotic risk in MPN patients. We investigated 110 patients with a histologically confirmed diagnosis of a myeloproliferative disease and a control group of 46 healthy volunteers. In the patient group, we found an average expression 4.59 times higher than in the control group. The highest expression was found in a subgroup of patients with polycythemia vera – 71.55% of the patients’ neutrophils. In each subgroup with essential thrombocythemia, myelofibrosis, and chronic myeloid leukemia, the patients with a history of thrombotic complication had a higher expression than the patients without such complications.