rss_2.0Journal of Biomedical and Clinical Research FeedSciendo RSS Feed for Journal of Biomedical and Clinical Research of Biomedical and Clinical Research 's Cover Screening for Single-Gene Disorders – A Brief Review<abstract> <title style='display:none'>Summary</title> <p>Carrier screening (CS) is an approach to pre-reproductive identification of couples at risk of having offspring with a single-gene disorder (SGD). The goal of CS is to facilitate reproductive autonomy and informed decision-making of the revealed risk couples. Initially, CS was introduced in the 1970s among the Ashkenazi Jewish population in the USA with a high incidence of Tay-Sachs disease. Until recently, CS had a limited application, mainly among individuals of a particular ethnicity or family history of SGD, and a limited number of conditions are included. Implementing the revolutionary technology of next-generation sequencing revealed a much more comprehensive range of possibilities for CS. The expanded alternative variant introduced a new concept that allows screening for hundreds to thousands of SGDs without pre-selection of individuals based on their ancestry or family history. Furthermore, the number of detected pathogenic variants is much higher compared to the traditional CS. Currently, there is insufficient experience with the application of expanded CS, and the lack of uniform guidelines is a major problem when it comes to massive implementation. Nevertheless, the significant potential of the expanded CS has given rise to a growing interest in it and provoked in-depth discussions about the opportunities of widespread application in practice.</p> </abstract>ARTICLE2022-01-18T00:00:00.000+00:00Single-Dose Cold Modified Bretschneider Solution for Myocardial Protection in the Surgical Treatment of Patients with Aortic Valve Stenosis and Left Ventricular Hypertrophy<abstract> <title style='display:none'>Summary</title> <p>Aortic valve stenosis (AS) is predominantly caused by degenerative calcification in patients over 70 years. It obstructs the left ventricular outflow tract. The result is concentric left ventricular hypertrophy (LVH) wall stress and ischemia-induced myocardial fibrosis. [1] According to the European Association of Cardiothoracic Surgery, all high-grade AS patients are indicated for Aortic valve intervention [2]. One of the most recommendable methods for myocardial protection during surgical aortic valve replacement is antegrade delivery of cold crystalloid cardioplegia. Our retrospective study included 173 operated patients with AS and LVH. We observed the MB fraction of the enzyme creatine phosphokinase (CPK-MB) as a postoperative marker for myocardial hypoprotection in different patients. Our results showed that a single dose of modified Bretschnaider solution provided safe and long enough myocardial protection during conventional and minimally invasive aortic valve replacement in patients with AS and LVH [3].</p> </abstract>ARTICLE2022-01-18T00:00:00.000+00:00Relationship between Elevated Maternal Serum Podocalyxin Concentrations with Blood Pressure Values and Routine Laboratory Parameters in Preeclampsia<abstract> <title style='display:none'>Summary</title> <p>Podocalyxin (PCX) is a glycoprotein member of the CD34 transmembrane sialomucin family and covers the surface of podocytes. It is assumed to be a marker of glomerular endothelial injury. In conditions, podocalyxin excretion in the urine is increased as a result of podocyte injury. Recent studies show that PCX is expressed not only in kidneys but also in the endothelial cells of other organs. Preeclampsia (PE) is characterized by new-onset hypertension, generalized endothelial injury, and glomerular alteration. Having this in mind, in the present study, we aimed to: (1) determine circulating PCX levels in sera of women with preeclampsia and normal pregnancy; (2) explore for an association between PCX and blood pressure and (3) investigate a possible relationship between PCX and routine laboratory markers of cardiac and renal injury/dysfunction. Fifty-five women with preeclampsia were examined. The mean age of patients was 24.9±6 years, and the mean age of the control group of 35 women with normal pregnancies was 24.7±5.4 years. The enzyme-linked immunosorbent assay (ELISA) was used to determine concentrations of PCX. Levels of serum PCX in preeclamptic women were statistically significantly higher than those in women with normal pregnancy: 2.66±0.67 vs. 2.40±0.33 ng/ml (p=0.03). Podocalyxin correlated with SBP (r=0.30; p=0.004), DBP (r=0.35; p=0.0007), uric acid (r=0.32; p=0.002), CPK (r=0.22; 0.03) and its isoenzyme CK-MB (r=0.21; p=0.04). Our results showed significantly higher levels of serum PCX in women with preeclampsia than in healthy pregnancy. Elevated podocalyxin levels are associated with an increase in blood pressure in preeclampsia. We found a relationship between PCX and routine laboratory indicators of cardiac (CPK and CK-MB) and renal injury/dysfunction (uric acid). PCX has the potential as a future preeclampsia diagnostic biomarker.</p> </abstract>ARTICLE2022-01-18T00:00:00.000+00:00A Review of Results from Clinical Trials Based on Co-Variants of the R-CHOP Regimen in Untreated Patients with Diffuse Large B-cell Lymphoma<abstract> <title style='display:none'>Summary</title> <p>Since 2000, new drugs for treating lymphoproliferative diseases have been introduced in haematology, and their initial indications have been gradually expanded. Some of the so-called „target molecules“ have shown good efficacy when treating some malignant non-Hodgkin lymphomas. The possibility of achieving therapeutic disease control in some indolent non-Hodgkin lymphomas using drugs with a different mechanism of action from that of cytostatics has logically raised the question of a change in therapeutic management in other lymphoproliferative diseases. Since 2010, clinical trials have been initiated with untreated patients with aggressive non-Hodgkin‘s lymphoma - diffuse large B-cell lymphoma as the primary target. The key aim of most clinical trials has been to compare the efficacy of the so-called „gold standard“ - rituximab, cyclophosphamide, doxorubicin, oncovin, prednisolone (R- CHOP) versus its derivatives. The review discusses the results of completed clinical trials published on the Internet. These trials covered covariants of the R-CHOP regimen used as first-line treatment of patients with diffuse large B-cell lymphoma. The review also includes drugs registered in Bulgaria for the last ten years but with a different clinical indication at present. The results of five clinical trials in which obinotuzumab, venetoclax, lenalidomide, bortezomib, and ibrutinib were used are presented.</p> </abstract>ARTICLE2022-01-18T00:00:00.000+00:00Study of the Content of Heavy Metals in Foods in Bulgaria<abstract> <title style='display:none'>Summary</title> <p>Food safety is a priority for the European Union (EU). EU food safety policy covers all sectors of the food chain. In recent years, numerous studies have been conducted in Bulgaria on contaminants in plant and animal foods as one of the priority areas of food safety policy. Metals are part of the chemical pollutants in the environment. People are exposed to metals from the environment and food and water contaminated with metals. Researchers have found that the intake of metals with food is different and that food exposure is the primary way of metal exposure.</p> </abstract>ARTICLE2022-01-18T00:00:00.000+00:00Review on Anastomotic Leak Rate after ICG Angiography during Minimally Invasive Colorectal Surgery<abstract> <title style='display:none'>Summary</title> <p>Colorectal cancer is the 3<sup>rd</sup> most common type of cancer worldwide. The most devastating complication after colorectal surgery remains the anastomotic leak (AL). Many techniques have been developed to reduce its rate. One such new method is perfusion angiography using indocyanine green (ICG). A literary search in PUBMED on 1.03.2021 for full-text English articles published between 2014 and 2021 was performed. ICG, colorectal cancer, and angiography were the keywords we used. The review was performed following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The literature search yielded 27 results when searching the database of PUBMED with the above keywords. Twenty-one out of 27 identified articles were included. Six were excluded from the analysis – four case reports, one review on the evolution of treating gastrointestinal cancers, and one containing no information on AL rate with ICG. One included article was RCT, sixteen were cohort studies, and four were meta-analyses or reviews. All articles reported a reduction in the anastomotic leak rate. However, the reduction was significant only in nine of them. Anastomotic leak is a severe complication and a subject of extensive research. Perfusion angiography with ICG is a step towards predicting and preventing AL, although it does not guarantee success in all cases.</p> </abstract>ARTICLE2022-01-18T00:00:00.000+00:00Effect of Aminosteroid U74389G in a Model of Inflammatory Bowel Disease in Rats<abstract> <title style='display:none'>Summary</title> <p>Lazaroid U-74389G is a synthetic 21-aminosteroid with free radical-scavenging and anti-inflammatory effects. This study was designed to evaluate the anti-inflammatory activity of U-74389G on experimental 2,4-dinitrobenzene sulfonic acid hydrate (DNBS)-induced colitis in Wistar rats. Five experimental groups were formed: a sham control group, a control group, treated with 0.25 ml of 50% ethanol intrarectally (n=8), a group treated with DNBS (30 mg in 0.25 ml of 50% ethanol administered intrarectally, (n=8), a group treated with DNBS and U-74389G at a daily dose of 15 mg/kg i.p. (n=8), and a group treated with DNBS and sulfasalazine, orally, at a dose of 300 mg/kg. During the experiment, the bodyweight of the rats, food intake, stool consistency, and presence of blood in the stool were recorded as markers of clinical condition. On day 6, colonic tissues were excised and scored for macroscopic and histological damage. Blood samples were taken to measure levels of cytokines by ELISA methods. DNBS decreased significantly body weight (from 237.00±2.52 g to 212.50±6.25 g, p=0.04). The rats treated with U-74389G showed greater food intake and weight gain. U-74389G reduced ulceration index: the U-74389G score was 1.25±0.25, and the DNBS score –3.87±0.61; p&lt;0.05. All other macroscopic parametersassessed were significantly improved in rats treated with U-74389G. The levels of inflammatory cytokines IL-1, IL-6, and TNF-α, were significantly lower than those of the DNBS group, while U-74389G significantly elevated the level of anti-inflammatory IL-10. These findings indicate that U-74389G significantly inhibits colonic inflammatory damages in a rat model of inflammatory bowel disease.</p> </abstract>ARTICLE2022-01-18T00:00:00.000+00:00The Role of Uterine Infection in Pregnancy Outcome: A Case Report<abstract> <title style='display:none'>Summary</title> <p>It was believed in the past that only the lower genital tract is inhabited by microorganisms, and the cervix was considered as a perfect barrier against the ascension of microbes. Nowadays, many studies using new sequencing technologies examining microbiomes with low biomass show that the microorganisms are gradually changing from the lower to the upper genital tract with decreasing bacterial abundance and increasing bacterial diversity. It is well documented that the endometrium is a non-sterile area, and in healthy women, the Lactobacillus spp. is the dominant flora. Lactobacillus - as a dominant endometrial microbiome, has a crucial role in implantation, early pregnancy development. It is also essential for a good pregnancy outcome. Non-Lactobacillus-dominant microbiome is associated with poor reproductive outcomes (recurrent implantation failure, recurrent miscarriages, outgoing pregnancy). This association is evidence of its significance for reproductive health.</p> <p>We present a case of unsuccessful first pregnancy with concurrent bacterial endometrial infection. A definitive antibiotic treatment resulted in a successful full-term second pregnancy. We present the influence of pathogenic microorganisms on uterine function and pregnancy development, current possibilities for diagnosis and treatment.</p> </abstract>ARTICLE2022-01-18T00:00:00.000+00:00A Study on Tumor-Infiltrating Lymphocytes in Different Subtypes of Breast Cancer<abstract> <title style='display:none'>Summary</title> <p>The study aimed to investigate immune cell infiltration in different subtypes of breast cancer (BC). Retrospectively were selected 100 patients with primary BC, grouped into four molecular surrogate subtypes (Luminal A and Luminal B-like, HER2-positive and triple-negative - TN), determined by immunohistochemistry (IHC). In each patient, a percentage of stromal tumor-infiltrating lymphocytes (TILs) was determined by hematoxylin-eosin staining. IHC was performed using primary antibodies CD3, CD4, CD8, CD20, and FOXP3. Immunophenotyped lymphocytes were counted (separately intratumoral and stromal) and semi-quantitatively graded. In the studied tumors, 10% were defined as lymphocyte-predominant BC. A high count of intratumoral and stromal TILs subsets was found mainly in TN and HER2-positive BC. The stroma is the preferred localization for immune cells in all four BC subtypes. CD3+ T predominates over CD20+ B lymphocytes, with CD8+ T cytotoxic and FoxP3+ T regulatory cells dominating T subtypes. HER2 and TN are more immunogenic than Luminal A and Luminal B – like subtypes of BC. The T-cells’ immune response was predominant in the studied cases of BC, with a predominance of CD8+ Tc and Foxp3+ Treg cells located mainly in the stroma.</p> </abstract>ARTICLE2021-07-12T00:00:00.000+00:00Some of the Immunogenetics Aspects of Aging<abstract> <title style='display:none'>Summary</title> <p>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.</p> <p>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.</p> </abstract>ARTICLE2021-07-12T00:00:00.000+00:00Growth Hormone Treatment: First Results of the Partnership Program for the Establishment of a Growth Center at the University Clinic of Pediatrics –Pleven<abstract> <title style='display:none'>Summary</title> <p>In March 2018, in the Clinic of Pediatrics of the University Hospital “G. Stranski ”- Pleven, we have created a Center for diagnosing and treating children with growth disorders, in active collaboration with an established expert center. During the study, 53 children with height &lt;-2 SDS were referred to the newly established Growth Center. The diagnoses of children receiving treatment with growth hormone (GH) were made in clinical settings based on the history, physical status, auxological assessment, imaging studies, basal and stimulated hormone tests, genetic tests. The children‘s mean age was 9.7 ± 4.5 years, with a significant gender difference (p&gt;0.05), living mainly in cities. For 18 months, we treated a total of 11 children (54.5% male) with an average age at the start of GH therapy of 8.1 ± 4.4 years and an average growth velocity of 10.3 ± 7.7 cm/year. Treatment with GH was introduced in Pleven after successfully establishing the Growth Center in the Clinic of Pediatrics. The first results showed a significant increase in the number of diagnosed and treated children whose follow-up we found an acceleration in growth and bone maturation, positive body composition changes, and lack of side effects from the treatment.</p> </abstract>ARTICLE2021-07-12T00:00:00.000+00:00Application of Enhanced Recovery after Surgery Protocols in Colorectal Cancer, Complicated by Malignant Bowel Obstruction: a Review of the Literature<abstract> <title style='display:none'>Summary</title> <p>Enhanced recovery after surgery (ERAS) protocols are standard in elective colorectal surgery. They lead to decreasing postoperative complications and shorten the hospital stay and the recovery period. Following these protocols is associated with better short-term results and better and disease-free survival in cases of respectable colorectal carcinomas. There is clear evidence of the beneficial effect of the protocols in reducing the rate of postoperative complications and shortening the hospital stay after elective colorectal surgery. There remains the question of whether these protocols are applicable effective in patients after emergency colorectal surgery. Over the last years, safe and effective ERAS protocols have been reported in patients with life-threatening conditions such as colorectal obstruction and intraabdominal infection.</p> </abstract>ARTICLE2021-07-12T00:00:00.000+00:00A Rare Clinical Case of Lipoma in the Soft Tissues of the Sublingual Space: A Case Report<abstract> <title style='display:none'>Summary</title> <p>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.</p> <p>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.</p> </abstract>ARTICLE2021-07-12T00:00:00.000+00:00Glutathione Content and Glutathione Peroxidase Activity of Sperm in Males with Unexplained Infertility<abstract> <title style='display:none'>Summary</title> <p>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.</p> </abstract>ARTICLE2021-07-12T00:00:00.000+00:00Health Assessment of Internal Hygiene Control in Sauce Production<abstract> <title style='display:none'>Summary</title> <p>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.</p> </abstract>ARTICLE2021-07-12T00:00:00.000+00:00Granulocytic Expression of CD11b/CD18 and Thrombotic Risk in Patients with Myeloproliferative Neoplasms<abstract> <title style='display:none'>Summary</title> <p>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.</p> </abstract>ARTICLE2021-07-12T00:00:00.000+00:00Predictors for Long-Term Prognosis after Acute Coronary Syndrome<abstract> <title style='display:none'>Summary</title> <p>Cardiovascular diseases (CVD) are the leading cause of invalidity and death in developed countries. Among them, the main cause of death is coronary artery disease. In this retrospective study, 172 patients with acute coronary syndrome (STEMI, NSTEMI, UA) are included. They had been hospitalized on an emergency basis in the Cardiology Department, Invasive Sector of Prof. Dr. St. Kirkovich Hospital in Stara Zagora, and the Cardiology Hospital -Yambol between January 2009 and February 2010. We found a significant difference in the age at acute coronary syndrome (ACS) occurrence by sex: earlier manifestation was observed in men (p=0.018). The univariant regression analysis showed that elderly age (p=0.005, OR 1.024), glomerular filtration &lt;90 ml/h (p=0.006, OR 0.964), GRACE-score &gt; 140 pt (p&lt;0.001, OR 1.045), HF (Killip class ≥ II) (p=0.002, OR 15.6) and EF&lt;40% (p=0.003, OR 1) were factors for adverse prognosis in the first, fifth and ninth year. Only GRACE-score was an independent predictor of death obtained by multivariate regression analysis in the study (p=0.002, OR 1.052). The factors influencing long-term survival adversely after ACS are age, smoking, chronic kidney disease, previously experienced myocardial infarction, diabetes mellitus, three-vessel coronary disease, and decreased systolic function of the left ventricle, and GRACE &gt; 140 p.</p> </abstract>ARTICLE2021-07-12T00:00:00.000+00:00Vaginal Bacterial Profile in Pregnant Women<abstract> <title style='display:none'>Summary</title> <p>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.</p> </abstract>ARTICLE2021-07-12T00:00:00.000+00:00Dieulafoy Lesion as a Source of Bleeding: A Report of Two Clinical Cases<abstract> <title style='display:none'>Summary</title> <p>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.</p> </abstract>ARTICLE2022-01-18T00:00:00.000+00:00Physicians’ Experience and Willingness to Participate in Non-Interventional Trials in Bulgaria<abstract> <title style='display:none'>Summary</title> <p>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.</p> </abstract>ARTICLE2022-01-18T00:00:00.000+00:00en-us-1