Volume 14 (2021): Issue 2 (December 2021)

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.

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.

Colorectal cancer is the 3^rd 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.

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<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.

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.

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.

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.

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), HOMA-IR (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.

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].

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.

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.

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.

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.