Pencho T. Tonchev

Rs5918ITGB3 Polymorphism, Smoking, and BMI as Risk Factors for Early Onset and Recurrence of DVT in Young Women

Objective: To evaluate the contribution of rs5918ITGB3 on the incidence and recurrence of deep venous thrombosis (DVT) in women and the relationship with body mass index (BMI) and smoking and to compare with data in men. Results: Rs5918(C) polymorphism in ITGB3 gene was assessed in 224 patients diagnosed with DVT and 216 controls. Thrombophilic genetic variant rs5918(C) was significantly pronounced in women (χ2 =7.565, P = .008) and total patients (χ2 = 9.266, P = .002) but not in men. Women patients (<45 years) who were carriers of rs5918ITGB3 polymorphism had an early onset of DVT (34.5 vs 39.4 years, χ2 = 7.027, P = .008) as analyzed by Kaplan-Meier and a higher risk of the recurrent event (χ2 = 3.405, odds ratio = 2.581, P = .044). The period before recurrent venous thromboembolism event was related to smoking status and BMI in young female who were carriers of rs5918 polymorphism but not in the males. Conclusions: Carriage of genetic variant rs5918(C) polymorphism in ITGB3 gene in women contributes to higher risk of single and recurrent DVT events at younger age.

PlA2 Polymorphism in Glycoprotein IIb/IIIa Modulates the Morphology and Nanomechanics of Platelets

Glycoprotein IIb/IIIa (GPIIb/IIIa) is the most abundant platelet surface receptor for fibrinogen and von Willebrand factor. Polymorphism PlA1/A2 in the gene of GPIIb/IIIa is among the risk factors for the development of arterial and venous thrombosis. The aim of this study is to evaluate the effect of the carriage of PlA1/A2 on the size, topographic features, and membrane stiffness of platelets from healthy controls and patients with deep venous thrombosis (DVT). Atomic force microscopy (AFM) imaging and nanoindentation (force–distance curves) were applied to investigate the morphological and nanomechanical properties (Young’s modulus) of platelets immobilized on glass surface. The surface roughness (Ra) and height (h) of platelets from patients with DVT, carriers of mutant allele PlA2 (Ra = 30.2 ± 6 nm; h = 766 ± 182 nm) and noncarriers (Ra = 28.6 ± 6 nm; h = 865 ± 290 nm), were lower than those of healthy carriers of allele PlA2 (Ra = 48.1 ± 12 nm; h = 1072 ± 338 nm) and healthy noncarriers (Ra = 49.7 ± 14 nm; h = 1021 ± 433 nm), respectively. Platelets isolated from patients with DVT, both carriers and noncarriers, exhibit much higher degree of stiffness at the stage of spreading (E = 327 ± 85 kPa and 341 ± 102 kPa, respectively) compared to healthy noncarriers (E = 198 ± 50 kPa). In addition, more pronounced level of platelet activation was found in polymorphism carriers. In conclusion, the carriage of PlA2 allele modulates the activation state, morphology, and membrane elasticity of platelets.

[PP.07.20] CORRELATION OF POLYMORPHISM RS699 (G (-6) A) IN THE PROMOTER OF THE GENE CODING ANGIOTENSINOGEN AND EARLY MANIFESTATION OF HYPERTENSION

Objective: The objective of this study is to find the relationship between polymorphisms rs699 in the promoter angiotensinogen encoding a functional change in the final product, and the early manifestation of hypertension and the existence of the earlier target cardiac damage in young hypertensive patients. Design and method: The prospective study design includes a selection of the target group - young hypertensive patients aged 18–50 years with high blood pressure, defined as cases, and the control group includingsame age patients without hypertension. A questionnaire containing demographic, anthropometric and clinical data on the examined groups was used. Blood for genetic analysis was taken, and echocardiography was performed for studying target organs damage. The methods used for DNA analysis were TaqMan- PCR and PCR-HRM. An appropriate statistical analysis were (Fisher exact test,chi-square test, central tendency and descriptive statistics) done to compare groups. Results: The study showed that in a total of 78 subjects (48 young hypertensives and 30 controls) the frequency of the tested polymorphism was 59.0%. As 70.8% (34 patients) of young hypertensive patients werecarriers of rs699 and only 40% (12 patients) in the control group hadthe same polymorphism. RR(risk ratio) for early hypertension in rs699 carriers is eRR = 1.69 (1.15–2.48), p = 0.01 (Fisher exact test). Analysis of data from surveys and echocardiography showed that 96% of young hypertensive carriers of this polymorphism had hypertension onset of about 30 years had expressed LVH and diastolic dysfunction. Conclusions: Our results showed that the frequency of rs699 polymorphism was significantly higher in young hypertensive patients with essential hypertension compared with none-hypertonic in the same age. Also, the presence of this SNA polymorphism in the genome was associated with an earlier manifestation of hypertension and earlier target heart damage.

Original Article. Open Retropubic and Robot-Assisted Radical Prostatectomy in Prostate Carcinoma: Advantages of Methods

Summary Prostate cancer (PC) is the most common type of cancer in men inanumber of countries. The choice of surgical technique for radical prostatectomy (RP) concerns both patients and urologists. The choice is not easy to make, since data is still limited due to the lack of large multicentric randomized research trials. For three years (2011-2014), 244 patients with limited prostate cancer were operated in the Urology Clinic of the University Hospital in Pleven. Robot-assisted radical prostatectomy (RARP) was performed on 35 patients (14%), open retropubic radical prostatectomy (ORP) - on 199 patients (81%), and laparoscopic RP - on 12 patients (5%). The preoperative and post-op results from the first two groups were compared. For the follow-up period of 12 months, functional results in 82 patients of the ORPgroup were compared to the results in the 35 patients of the RARPgroup. The operative time was significantly longer in the RARPgroup, and blood loss was lower. The catheter stay was shorter in patients with RARP. The percentage of significant postoperative complications was 0%in the patients with RARPand 3%in the patients with an ORP. RARPpatients demonstrated better continence: 91%vs. 87%and erectile function46%vs.40%at 12 months.

Original Article. Urinary Tract Desobstruction in Patients with Malignant Neoplasms of the Uterine Cervix

Summary Cancer of the cervix causes internal, external compression or both of the upper urinary tract in 50-60%of patients in advanced stages. Retrograde stenting is the most widely used technique for desobstruction of the upper urinary tract in urology practice. Diversion of urine flow is an alternative, achieved by nephrostomy of one or both kidneys.We studied retrospectively 33 women with upper urinary tract obstruction caused by carcinoma of the uterine cervix operated on between March 2014 and March 2015 in the urology clinic at the University Hospital in Pleven, Bulgaria. Apercutaneous nephrostomy (PNS) was placed in 17 patients, and 11 patients hadaretrograde catheterization with ureteral stent type JJ. Five patients were treated with both methods. Placement ofa JJstent was the first choice procedure for all patients since it providesabetter quality of life. PNSimproves renal function faster than retrograde JJstenting. Therefore, the first method of choice for patients with an untreated primary cervical, uterine cancer is the placement of PNS. Retrograde JJstenting is the method of choice in patients who undergo surgery and radiation therapy withoutarelapse of the disease.

Case Report. Appendiceal Recurrent Colic Due to Enterobius Vermicularis Infection in a 14-Year-Old Female Patient

Summary Acute appendicitis due to Enterobius vermicularis, usually known as pinworm, is very rare and affects mostly children.According to different authors, it is controversial whether pinworms cause inflammation of the appendix or appendiceal colic only.We presentacase ofa14-year-old female with three subsequent hospitalizations in 1 month due to abdominal pain in the right lower abdomen, with rebound tenderness, normal CTscan and laboratory findings. During the last hospitalization, laparoscopic appendectomy was performed. Intraoperatively multiple pinworms were found in the appendix. These were trapped byastercolith in the appendicular base inanoninflamed and histologically normal appendix. Two oral doses of mebendazole were administered postoperatively. Uneventful postoperative period and postoperative follow-up showed lack of symptoms six months after the operation. Despite the widespread idea that acute appendicitis due to Enterobius vermicularis is very rare, it should always be considered in young female patients with repeated abdominal pain in the right lower abdomen with normal laboratory and radiologic findings.

SND Rs1799889(-) In The Promotor Of The Plasminogen Activator Inhibitor-1 Gene Contributes To The Risk Of DVT In Women

Summary The incidence of deep venous thrombosis (DVT) depends on the specific genotype, inheritance of prothrombotic polymorphisms and the influence of environmental risk factors. Rs1799889(-) polymorphism in the promotor of PAI-1 gene has been described as a risk factor for hypercoagulable state. Objective: To evaluate the contribution of thrombophilic rs1799889 (-) in the promotor of PAI-1 gene on the incidence of DVT in women and men in groups below and above 45 years of age. Тhere was significantly higher rs1799889 (-) polymorphism carriage among female patients with DVT vs controls (Chi squared =5.506, OR=2.170, p=0.021) but not in male patients (Chi squared =0.090 OR=1.147, p=0.825). A significant contribution of rs1799889 (-) polymorphism to early onset of the disease was found in female patients aged 45+ and carriers of the polymorphism (Chi squared =7.476, p=0.006), but not in young women.

Predisposition to Thrombophilia and Hypofibrinolysis in Pulmonary Embolism: Analysis of Inherited Factors

Summary Pulmonary embolism (PE) is a relatively common cardiovascular emergency, though its exact incidence is difficult to assess. Accurate diagnosis is critical because of the high 30-day mortality in patients in whom the diagnosis is missed on admission. Doubt for PE is often raised by the presence of risk factors for venous thromboembolism (VTE), which are categorized into inherited and acquired. Among these, the importance of inherited/genetic thrombophilic factors is increasingly recognized. The most frequent markers of inherited thrombophilia are Factor V Leiden (FVL) and G2021OA prothrombin gene mutation. Among the inherited factors causal to thrombophilia, the C677T variant in methylentetrahydrofolate reductase (MTHFR) gene as well as factors like P1A1/P1A2 polymorphism in platelet glycoprotein Ilb/IIIa (P1A2) and hypofibrinolytic polymorphism 4G/4G in PAI-1 gene are discussed with controversial results. In our study, thrombophilic and hypofibrinolytic genetic variants were identified in 54.2% of 115 patients with PE. The most common significant genetic defects were FVL- 16.5% in patients versus 6.2% in controls (OR=3.102; p=0.05), G20210A PT 5.7% versus 2.1% (OR=2.983; p>0.05). P1A2 was found in 27.3% patients versus 19.9% in controls (OR= 1.523, p>0.05) and PAM 27.8% versus 22.6% (OR =1.501 p>0.05). MTHFR C677T carriage was inverse: 6.7% in patients versus 13.4% in controls. (OR=0.461 p=0.05). Of all the patients studied, 15.65% had a history of recurrent embolic incidents. The risk of recurrence was higher for the carriers of FVL and G20210A prothrombin gene mutation. The association between carriage of thrombophilic genetic factor and the early onset of the first embolic episode was found in the patients with PE. The awareness of risk factors and risk stratification is a critical issue in treatment and prevention policy. Preventive measures should be taken in particular medical conditions.