Jan Luha

The use of medications with anticholinergic properties and risk factors for their use in hospitalised elderly patients

The aims of the present study were to evaluate the use of drugs with anticholinergic properties in elderly patients and to identify risk factors that increase the patients chance of being given such medications.

Relationship between circulating tumor cells, blood coagulation, and urokinase-plasminogen-activator system in early breast cancer patients.

Cancer is a risk factor for venous thromboembolism (VTE) and plasma d‐dimer (DD) and tissue factor (TF) are established VTE associated markers. Circulating tumor cells (CTCs) are associated with the risk of VTE in metastatic breast cancer. This study aimed to correlate CTCs, blood coagulation and the urokinase plasminogen activator (uPA) system in primary breast cancer (PBC) patients. This prospective study included 116 PBC patients treated by primary surgery. CTCs were detected by quantitative RT‐PCR assay for expression of epithelial (CK19) or epithelial‐mesenchymal transition (EMT) genes (TWIST1, SNAIL1, SLUG, ZEB1, FOXC2). Plasma DD, TF, uPA system proteins were detected by enzyme‐linked immunosorbent assays, while expressions of uPA system in surgical specimens were evaluated by immunohistochemistry. CTCs were detected in 27.6% patients. Patients with CTCs had a significantly higher mean plasma DD (ng/mL) than those of patients without CTCs (632.4 versus 365.4, p = 0.000004). There was no association between plasma TF and CTCs. Epithelial CTCs exhibit higher expression of uPA system genes compared to EMT_CTCs. Patients with CTCs had higher plasma uPA proteins than those of patients without CTCs; there was no correlation between tissue expression of uPA system, CTCs, DD or TF levels. In multivariate analysis CTCs and patients age were independent factors associated with plasma DD. We found association between plasma DD and CTCs indicating a potential role for activation of the coagulation cascade in the early metastatic process. CTCs could be directly involved in coagulation activation or increased CTCs could be marker of aggressive disease and increased VTE risk.

Patient‐related characteristics associated with non‐persistence with statin therapy in elderly patients following an ischemic stroke

This study was aimed at evaluating the extent of non‐persistence with statin therapy in elderly patients after an ischemic stroke and identifying patient‐related characteristics that are risk factors for non‐persistence.

HLA DRB1* and DQB1* alleles are associated with disease severity in patients with pemphigus vulgaris

Pemphigus vulgaris (PV) is a rare autoimmune disease that involves the skin and mucosa. The etiology of PV is multifactorial and includes genetic, environmental, hormonal, and immunological factors.

Frequencies of polymorphisms in CYP2C9 and VKORC1 genes influencing warfarin metabolism in Slovak population: implication for clinical practice.

OBJECTIVES The study was aimed at establishing an effective molecular-genetic method for detecting polymorphisms in genes CYP2C9 and VKORC1, which affect the pharmacogenetics of warfarin, and at determining their prevalence in Slovak population. BACKGROUND Warfarin, derivative of coumarin, belongs to the most commonly prescribed oral anticoagulants with narrow therapeutic index. An insufficient dose of warfarin can result in failure to produce the antithrombotic effect, whereas an overdose increases the risk of bleeding. It was proven that genetic variability in two genes, CYP2C9 a VKORC1, has a significant influence on the individuals response to the dosage of warfarin. METHODS In a control group of 112 randomly selected individuals, we tested the frequency of selected single nucleotide polymorphisms including CYP2C9*2 (430C>T), CYP2C9*3 (1075A>C), VKORC1*2 (1173C>T) by allele-specific Real-Time PCR and VKORC1*2 (-1639G>A) by using PCR-RFLP. RESULTS Due to the combination of frequent alleles CYP2C9*2, CYP2C9*3 and VKORC1*2 in Slovak population we determine that 25% of population need a standard 5-mg daily dose of warfarin, while 44%, 23%, and 8% need 4 mg, 3 mg and 2 mg of warfarin per day. CONCLUSION Slovak population is in Hardy-Weinberg equilibrium and frequencies of SNPs were in accordance with other published results in European populations (Tab. 5. Fig. 3, Ref. 51).

Plasma Cytokines Correlated With Disease Characteristics, Progression-Free Survival, and Overall Survival in Testicular Germ-Cell Tumor Patients

Micro‐Abstract We performed a translational study and found a correlation among overall survival, progression‐free survival, and circulating cytokines in metastatic testicular germ‐cell tumor patients. Association between baseline clinicopathologic features and plasma cytokines was also assessed. Plasma cytokines could be a potential biomarker for identification of high‐risk patients. Background: Cytokines are the communicators of immune system and are involved in all immune responses. The aim of this study was to assess the correlation among plasma cytokines, patient and tumor characteristics, and clinical outcome in chemonaive testicular germ‐cell tumor (TGCT) patients. Patients and Methods: This study included 92 metastatic chemotherapy‐naive TGCT patients treated with platinum‐based chemotherapy from July 2010 to March 2014. Plasma was isolated before first administration of chemotherapy, and the concentration of 51 plasma cytokines were analyzed using multiplex bead arrays. Results: At a median follow‐up of 33.2 months (range, 0.1‐54.8 months), 10.9% of patients experienced disease progression, and 7.6% died. Several cytokines were associated with different baseline clinicopathologic features. Elevated plasma levels of interferon (IFN)‐&agr;2, interleukin (IL)‐2R&agr;, IL‐16, hepatocyte growth factor (HGF), and monocyte chemotactic protein (MCP)‐3 were significantly associated with worse progression‐free survival and overall survival (OS). Moreover, elevated levels of stem‐cell growth factor (SCGF)‐&bgr; were also associated with worse OS. Patients with elevated levels of all 6 cytokines experienced significantly worse outcomes compared to patients who had fewer than 6 cytokines elevated (hazard ratio = 12.06; 95% confidence interval, 7.39‐19.49; P = .002 for progression‐free survival, and hazard ratio = 39.65; 95% confidence interval, 25.03‐62.18; P < .00001 for OS, respectively). Results were independent of International Germ Cell Cancer Collaborative Group criteria. Conclusion: We found a correlation among progression free‐survival, OS, and circulating cytokines in TGCT. This suggests the existence an association between plasma cytokines and baseline clinicopathologic features in TGCT. Plasma cytokines could be used for identification of high‐risk patients who are candidates for new therapeutic approaches.

Expression of ezrin and moesin in primary breast carcinoma and matched lymph node metastases

Ezrin, radixin, moesin (ERM) are important membrane-cytoskeletal crosslinkers and are suggested to play important role in cancer progression and metastasis. Even though ERM proteins were generally considered to be functionally redundant and the most studied was ezrin, recent studies highlight their distinct roles in metastatic process. Little information is available regarding the role of individual ERM proteins and their phosphorylated forms in human breast cancer. Our study is the first to examine expression of ezrin, moesin and their phosphorylated forms in primary breast tumors and matched lymph node metastases (LNMs) and their correlation with clinicopathological variables. A total of 88 primary breast cancer, 91 LNMs, 54 intraductal carcinoma and 26 normal adjacent breast tissue samples from tissue microarrays were studied. Expression was determined by immunohistochemistry, the intensity and number of positive cells was scored. Statistical analysis of protein expression and patients’ age, tumor grade and hormonal status was performed. No statistical significant difference was found in ezrin, moesin, p-ezrinTyr353 and pan-p-ezrinThr567/radixinThr564/moesinThr558 expression between primary tumors and LNMs. Even though it was not significant, moesin expression varied between primary tumors, intraductal carcinoma, normal breast adjacent tissue and LNMs. A significant positive correlation between moesin and tumor grade has been proven. Even though primary tumors and matched LNMs did not show different expression patterns, moesin correlated significantly with higher tumor grade. Its positivity in intraductal carcinoma and normal breast tissue adjacent to cancer might indicate its role in tumor intiation/progression.

Thymic tumours associated with Myasthenia gravis: a long term observation study of operated patients

Primary tumours of thymus, thymoma and thymic carcinoma, are very rare, they represent less than 1 % of all neoplasms. The most common manifestation of thymoma with appearance of 40 to 50 % of the neuromuscular autoimmune disease is myasthenia gravis (MG). The performance of a complete resection is the most predictive indicator for long-term survival of patients with thymic tumour, also important prognostic factors are the histological type of thymic tumour and its invasiveness. The aim of our study is to study the long-term survival of patients after the resection of the tumour, as well as enhanced efficiency of radical thymectomy in the complex treatment of myasthenia gravis. From 1989 to 2010 we operated on 369 patients with MG. Out of 49 patients (13.7 %) 38 cases (76.6 %) were thymomas and 11 cases (23.4 %) thymic carcinomas. Complete removal of tumours (stage I, II, and III) were performed in 45 (92 %) cases. Of the 41 living patients (83.7 %), three (7.3 %) were diagnosed with metastatic thymic carcinoma or thymoma, and treated with adjuvant therapy. In one case, the patient died due to generalization of the thymic carcinoma. Statistical analysis with Kaplan-Meier method showed better overall survival of patients with thymoma than patients with thymic carcinoma. The difference in survival curves was not significant. (Mantel-Cox p = 0.479, Generalized Wilcoxon p = 0.326). In terms of treatment of Myasthenia gravis associated with thymoma, we achieved 70 % successful clinical and pharmacological remission. On the other hand, paraneoplastic MGAT has the worst prognosis of all the other forms of MG. The difference between MGAT to every other form of MG was statistically significant (Tab. 6, Fig. 1,Ref. 28).

Solutions for Secure Collaboration, Selection of Methodology, Implementation and Case Studies for Their Use

Many of us never start thinking about secure information communication and collaboration until it is too late, after a security incident has been identified. The problem is that awareness of the issue remains quite low, coupled with a lack of continuing education in the field. Research on the subject and the level of security awareness was undertaken at Comenius University in Bratislava by the Faculty of Management at the end of 2017 and beginning of 2018, with a wide range of organisations participating. A number of interesting results came out of the analysis, all of which need to be followed up. Our paper discusses the outcome of experiments related to the study’s findings, while pointing out possible solutions in the form of process changes and the use of cloud-based tools and technology in order to eliminate risks and potential threats.

Therapeutic effects of N-acetyl-L-cysteine on liver damage induced by long-term CCl4 administration

N-acetyl-L-cysteine (NAC) is a drug routinely used in several health problems, e.g. liver damage. There is some information emerged on its negative effects in certain situations. The aim of our study was to examine its ability to influence liver damage induced by long-term burden. We induced liver damage by CCl4 (10 weeks) and monitored the impact of parallel NAC administration (daily 150 mg/kg of b.w.) on liver morphology and some biochemical parameters (triacylglycerols, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, bile acids, proteins, albumins and cholinesterase). NAC significantly decreased levels of bile acids and bilirubin in plasma and triacylglycerols in liver, all of them elevated by impairment with CCl4. Reduction of cholesterol induced by CCl4 was completely recovered in the presence of NAC as indicated by its elevation to control levels. NAC administration did not improve the histological parameters. Together with protective effects of NAC, we found also its deleterious properties: parallel administration of CCl4 and NAC increased triacylglycerols, ALT and AST activity and significantly increased plasma cholinesterase activity. We have observed nonsignificantly increased percentage of liver tissue fibrosis. Our results have shown that NAC administered simultaneously with liver damaging agent CCl4, exhibits not only protective, but also deleterious effects as indicated by several biochemical parameters.