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Background Human papillomavirus (HPV) has been shown to adversely affect human reproduction. We aimed to evaluate the prevalence of human papillomavirus (HPV) infection in men and its correlation with semen parameters and reproductive outcomes. Methods Semen samples and penile swabs were collected from potential sperm donors (SD, n = 97) and male partners of infertile couples (IM, n = 328). The presence of HPV DNA in semen samples and penile swabs was analyzed. Associations between hrHPV positive status and fertility outcomes as well as socio-behavioral and health characteristics were evaluated using the R software package. Results High-risk HPV (hrHPV) genotypes were detected in 28.9% of SD and 35.1% of IM (P = 0.312). Penile swabs were more frequently positive for hrHPV genotypes than semen samples in both IM (32.3% vs. 11.9%, P P = 0.006). Men with hrHPV positive semen samples had lower semen volume (median volume 2.5 ml vs. 3 ml, P = 0.009), sperm concentration (median concentration 16 × 106/ml vs. 31 × 106/ml, P = 0.009) and total sperm count (median count 46 × 106 vs. 82 × 106, P = 0.009) than men with hrHPV negative samples. No association was identified between penile hrHPV status and semen parameters. Conclusions Our findings indicate that penile HPV infection is common in both potential sperm donors and men from infertile couples. Although HPV positivity is higher in penile swabs, only HPV infection in semen samples affects sperm parameters. However, there was no association between hrHPV positivity in semen and fertility outcomes including abortion rate.

This prospective population-based study on a group of 132 resected IDH-wildtype (IDH-wt) glioblastoma (GBM) patients assesses the prognostic and predictive value of selected genetic biomarkers and clinical factors for GBM as well as the dependence of these values on the applied therapeutic modalities. The patients were treated in our hospital between June 2006 and June 2015. Clinical data and tumor samples were analyzed to determine the frequencies of TP53, MDM2, EGFR, RB1, BCR, and CCND1 gene aberrations and the duplication/deletion statuses of the 9p21.3, 1p36.3, 19q13.32, and 10p11.1 chromosome regions. Cut-off values distinguishing low (LCN) and high (HCN) copy number status for each marker were defined. Additionally, MGMT promoter methylation and IDH1/2 mutation status were investigated retrospectively. Young age, female gender, Karnofsky scores (KS) above 80, chemoradiotherapy, TP53 HCN, and CCND1 HCN were identified as positive prognostic factors, and smoking was identified as a negative prognostic factor. Cox proportional regression models of the chemoradiotherapy patient group revealed TP53 HCN and CCND1 HCN to be positive prognostic factors for both progression-free survival and overall survival. These results confirmed the influence of key clinical factors (age, KS, adjuvant oncotherapy, and smoking) on survival in GBM IDH-wt patients and demonstrated the prognostic and/or predictive importance of CCND1, MDM2, and 22q12.2 aberrations.

As the predictive role of many risk factors for parasagittal meningioma (PM) recurrence remains unclear, the objective of the meta-analysis was to make a comprehensive assessment of the predictive value of selected risk factors in these lesions. Studies including data on selected risk factors, such as histology, tumor and sinus resection, sinus invasion, tumor localization, and immediate postoperative radiotherapy for PMs recurrence, were searched in the NCBI/NLM PubMed/MEDLINE, EBM Reviews/Cochrane Central, ProQuest, and Scopus databases, and analyzed using random effects modeling. Thirteen observational studies involving 1243 patients met the criteria for inclusion in the meta-analysis. WHO grading of meningiomas was identified as the most powerful risk factor for recurrence. WHO grade II meningiomas (OR 11.61; 95% CI 4.43–30.43; P

BACKGROUND Meningioma growth rates are highly variable, even within benign subgroups, with some remaining stable, whereas others grow rapidly. OBJECTIVE To identify molecular-genetic markers for more accurate prediction of meningioma recurrence and better-targeted therapy. METHODS Microarrays identified microRNA (miRNA) expression in primary and recurrent meningiomas of all World Health Organization (WHO) grades. Those found to be deregulated were further validated by quantitative real-time polymerase chain reaction in a cohort of 172 patients. Statistical analysis of the resulting dataset revealed predictors of meningioma recurrence. RESULTS Adjusted and nonadjusted models of time to relapse identified the most significant prognosticators to be miR-15a-5p, miR-146a-5p, and miR-331-3p. The final validation phase proved the crucial significance of miR-146a-5p and miR-331-3p, and clinical factors such as type of resection (total or partial) and WHO grade in some selected models. Following stepwise selection in a multivariate model on an expanded cohort, the most predictive model was identified to be that which included lower miR-331-3p expression (hazard ratio [HR] 1.44; P

BACKGROUND MRI postcontrast nonenhanced brain tumors are found benign biologic entities with the better prognosis. The aim of this paper is to evaluate predictive features on MRI considered definite diagnosis occurrence, tumor progression, upgrading and postcontrast enhancement evolution on follow-up serial MRI. MATERIAL AND METHODS We retrospectively collected patients with the initially MRI postcontrast nonenhanced brain tumors, treated in our hospital from January 2009 to June 1, 2006. All tumors were converted into WHO 2016 IDH status classifications in accordance with current recommendations. Information about surgeries, patient clinical condition, MRI, and results of histological, immunohistochemical, molecular genetic, and cytogenetic investigations were gathered. Semiautomatic segmentations were performed using FSLeyes software (part of FSL package) on preoperative and followed-up 3D T1-w MPRAGE, T2-w or FLAIR scans. We focused on residual tumor volume, and time distribution of T2/FLAIR changes and T1-w postcontrast enhancement evolution. RESULTS Seventy-eight patients were enrolled in this study. There were 47 gliomas grade II 22 grade III and 9 grade IV. Glioma II comprised 35 diffuse astrocytomas (23 patients had IDH1 mutation). Nine gliomas grade III and 6 gliomas grade IV had IDH1 mutation. Overall survival in glioma group grade II, grade III, grade IV was 187.9 months, 71.1 months and 25.2 months, respectively. Oncotherapy underwent 14 gliomas grade II after first surgery, 13 patients had radiotherapy a 1 patient had neoadjuvant chemotherapy. Seventeen gliomas grade III were indicated to oncotherapy, 5 patients had radiotherapy and 12 had chemoradiotherapy. All patients with glioma grade IV experienced oncotherapy. Time to progression of non-contrast enhanced brain tumor was 5.8 years. Time to up-grading of non-contrast enhanced brain tumor was 16.8 months. Detailed time relations of glioma subgroup will be displayed in tables. CONCLUSION Regarding MRI postcontrast non-enhanced tumors, predominantly low grade gliomas (LGG), aggressive oncotherapy are reluctant to use but they are prone to repeat surgeries. Decision making issues are age, clinical patient status, histologic and genetic tumor characteristics, residual tumor volume, published guidelines for brain tumor treatment, and patient′s willing. Generally, hyposignal on the T1 postcontrast scans strictly relate to the better prognosis, even in HGG. Longer survival expectancy increases quality of life awareness. Prior to MRI postcontrast enhanced evolution and up-grading, T2/FLAIR changes have been demonstrated. T2/FLAIR scans considered also main role in LGG follow-up strategy. Individual tailored therapy is principal strategy. Supported by Ministry of Health of the Czech Republic, grant nr. NV19-04-00281 and grant nr. NU21-03-00195

The main advantage of urinary biomarkers is their noninvasive character and the ability to detect multifocal prostate cancer (CaP). We have previously implemented a quadruplex assay of urinary markers into clinical practice (PCA3, AMACR, TRPM8 and MSMB with KLK3 normalization). In this study, we aimed to validate it in a larger cohort with serum PSA 2.5&ndash, 10 ng/mL and test other selected transcripts and clinical parameters, including the percentage of free prostate-specific antigen (PSA) (% free PSA) and inflammation. In the main cohort of 299 men, we tested the quadruplex transcripts. In a subset of 146 men, we analyzed additional transcripts (CD45, EPCAM, EZH2, Ki67, PA2G4, PSGR, RHOA and TBP). After a prostate massage, the urine was collected, RNA isolated from a cell sediment and qRT-PCR performed. Ct values of KLK3 (i.e., PSA) were strongly correlated with Ct values of other genes which play a role in CaP (i.e., PCA3, AMACR, TRPM8, MSMB and PSGR). AMACR, PCA3, TRPM8 and EZH2 mRNA expression, as well as % free PSA, were significantly different for BPH and CaP. The best combined model (% free PSA plus PCA3 and AMACR) achieved an AUC of 0.728 in the main cohort. In the subset of patients, the best AUC 0.753 was achieved for the combination of PCA3, % free PSA, EPCAM and PSGR. PCA3 mRNA was increased in patients with inflammation, however, this did not affect the stratification of patients indicated for prostate biopsy. In conclusion, the percentage of free PSA and urinary markers contribute to a more accurate indication for prostate biopsy.

High-risk human papillomavirus (hrHPV) infection is a cause of cervical cancer development. The addition of hrHPV testing to cervical cancer screening and monitoring of cervical intraepithelial neoplasia treatment improves the efficacy of screening and treatment, respectively. Self-sampling for hrHPV testing seems a promising tool for increasing patient participation in cervical cancer screening. In this project, 1198 cervical swabs obtained by physicians and 176 cervicovaginal swabs obtained by self-sampling (not collected in parallel) were analyzed for the presence of 14 hrHPV genotypes using three commercially available assays in comparison. HPV DNA was detected in 21.2% of all samples (21% of cervical swabs and 22.7% of cervicovaginal swabs). The cobas 4800 HPV Test was the most sensitive (0.983) and specific (0.992) for hrHPV detection overall. The PapilloCheck HPV-Screening and LMNX Genotyping Kit HPV GP had comparable specificity with that of the cobas (0.989 and 0.955, respectively), but lesser sensitivity (0.897 and 0.909, respectively). In physician-obtained cervical swabs, the cobas showed the highest sensitivity and specificity (0.980 and 0.994, respectively) for hrHPV detection, whereas in cervicovaginal swabs, the cobas had the highest sensitivity (1.00), but the PapilloCheck had the highest specificity (0.993). In conclusion, all of the detection methods evaluated were highly sensitive and specific for hrHPV detection from both clinician-collected cervical swabs and self-sampled cervicovaginal swabs.

Objective: The aims of this study were to determine the prevalence of human papillomavirus (HPV) infection in women treated for infertility and oocyte donors, and to investigate the possible influence of HPV infection on reproductive outcomes. Study design: In this observational laboratory-based study, cervical swabs were collected from oocyte donors (n = 207), and women treated for infertility (n = 945) and analysed for the presence of high-risk HPV (hrHPV) genotypes using the cobas® 4800 HPV Test and PapilloCheck® HPV-Screening. Associations between hrHPV positive status and fertility outcome or socio-behavioral and health characteristics were evaluated using R statistical software. Results: HrHPV prevalence was significantly higher in oocyte donors than in women treated for infertility (28.0% vs. 16.1%, P

Background and Objectives. Recently, we described an inverse association between cranberry supplementation and serum prostate specific antigen (PSA) in patients with negative biopsy for prostate cancer (PCa) and chronic nonbacterial prostatitis. This double blind placebo controlled study evaluates the effects of cranberry consumption on PSA values and other markers in men with PCa before radical prostatectomy. Methods: Prior to surgery, 64 patients with prostate cancer were randomized to a cranberry or placebo group. The cranberry group (n=32) received a mean 30 days of 1500 mg cranberry fruit powder. The control group (n=32) took a similar amount of placebo. Selected blood/urine markers as well as free and total phenolics in urine were measured at baseline and on the day of surgery in both groups. Prostate tissue markers were evaluated after surgery. Results: The serum PSA significantly decreased by 22.5% in the cranberry arm (n=31, P

Background and Aims. Erythropoiesis is closely related to iron metabolism in a balanced homeostasis. Analyses of diverse erythroid and iron metabolism disorders have shown that disrupted erythropoiesis negatively affects iron homeostasis and vice versa. The aim of this study was to characterize the relationship between erythropoietic activity and iron homeostasis in pediatric patients with erythrocyte membrane defects and thalassemia traits. Methods. Selected markers of erythropoietic activity (erythropoietin, soluble transferrin receptor - sTfR and growth differentiation factor 15) and iron status parameters (serum iron, ferritin and hepcidin) were evaluated in pediatric patients with erythrocyte membrane defects and thalassemia traits. Results. The patients with erythrocyte membrane defects and thalassemia traits had altered iron homeostasis due to disturbed erythropoiesis. In comparison with healthy controls, they had a normal to low hepcidin/ferritin ratio and concomitantly elevated sTfR. Conclusion. The findings suggest that pediatric patients with erythrocyte membrane defects and thalassemia traits are more susceptible to iron overload than the general population and that the (hepcidin/ferritin)/sTfR ratio can be used to monitor any worsening of the disease.

Objectives Significant progress in treatment strategies improves the expectations of patients with extracranial cancers. Metastases are the primary consideration in patients with cancer history. In the case of neurologic disorders, the patient should undergo brain MRI. A rationale is presented for surgery, whole-brain or stereotactic radiotherapy, or chemotherapy. Recently, we have encountered misdiagnosed primary malignant brain tumours in patients with oncologic history who had been admitted for surgery for brain metastases. The aim of our study is to evaluate the incidence of concurrent cancers, to assess the relationship between previous cancer staging and primary brain tumour evaluation as well as to determine treatment efficiency. Methods From January 2007 to December 2011, we prospectively followed up patients with concurrent history of both extracranial cancer and subsequent glioblastoma multiforme. Information was collected on the clinical condition, imaging, history of extracranial cancer, previous and present surgical and oncologic procedures, and GBM histologic, cytogenetic, and molecular genetic investigations. Results Five patients were recruited: three females and two males. The average patient age at the time of GBM diagnosis was 65.6 years. Three patients had a history of breast carcinoma, one of renal carcinoma and one of colorectal carcinoma. Following the diagnosis of carcinoma, three patients received chemotherapy and radiotherapy, one patient had radiotherapy alone, and one had no adjuvant therapy. In all the cases, surgery revealed primary GBM, with a standard occurrence of genetic abnormalities ( Table 1 ). The average time from the diagnosis of extracranial cancer to that of GBM was 4 years. Four patients underwent chemoradiotherapy and one had palliative radiotherapy. Two patients completed oncotherapy and their OS was 27 months and 19 months, respectively. One patient had post-surgical progression of hemiparesis. One patient had pulmonary embolism during oncotherapy and one had paraplegia caused by a pathological fracture of vertebras T5 due to breast carcinoma metastases. The OS was 11.8 months (range 3–27 months). All the patients succumbed to GBM progression.

Background The optimal surgical strategy for treating internal carotid artery (ICA) blood blister-like aneurysms (BBAs) has remained unclear. Although some have preferred bypass surgery, others have favored less-demanding surgical methods. The aim of the present meta-analysis was to assess the efficacy, safety, and outcomes of bypass and non–bypass surgical methods when intended as primary treatment of ICA BBAs. Methods Studies reporting data on the outcomes of interest for surgically treated patients with ICA BBAs were searched for in the PubMed/MEDLINE, Evidence-Based Medicine Reviews, Cochrane Central, ProQuest, and Scopus databases. The data were analyzed using random effects modeling. Results Seven observational studies involving 140 patients met the inclusion criteria. The patients treated with bypass surgery, compared with those treated with non–bypass techniques, had lower odds of poor outcomes (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.28–2.02; P = 0.57; I2 = 0%), postoperative vasospasm (OR, 1.73; 95% CI, 0.38–7.92; P = 0.48; I2 = 19%), intraoperative bleeding (OR, 3.37; 95% CI, 0.82–13.90; P = 0.09; I2 = 0%), postoperative bleeding (OR, 1.91; 95% CI, 0.47–7.76; P = 0.36; I2 = 0%), and postoperative recurrence of BBAs (OR, 2.16; 95% CI, 0.54–8.66; P Conclusions For surgeons who use both bypass and non–bypass surgical strategies, the 2 methods seemed comparable in terms of the outcomes of interest, although the bypass technique appeared superior. However, comparisons with studies reporting bypass as the uniquely preferred technique have indicated that specialization in, and preference for, the bypass procedure has been associated with more favorable outcomes.

BACKGROUND: Glioblastoma (GBM) is the most common primary brain tumour in adults with nearly 100% mortality. Despite aggressive therapy, overall survival of GBM patients remains poor due to intrinsic or acquired resistance to maximal treatment modality based on combination of radiation and chemotherapy. The biological background behind GBM progression after first line therapy is mostly unknown and thus, there are only limited targeted therapeutic options for the second line treatment. The main goal of this study was to elucidate genetic landscape in paired samples of primary versus recurrent GBM and to validate prognostic and predictive value of the most significant differences in independent cohort of GBMs. MATERIAL AND METHODS: The cohort consists of 43 paired samples obtained during 1(st) surgery followed by radiochemotherapy (at least 54 Gy plus 3 cycles of temozolomide) and during the second palliative surgery. The analysis comprises genome copy number variations (24/43 samples) and fluorescent in situ hybridization determined gene and chromosomal region statuses for EGFR, p53, RB1, MDM2, CDKN2A and 1p, 19q, 10p. Methylation-specific PCR was used for analysis of MGMT promoter methylation and competitive amplification of differentially melting amplicons PCR for IDH1/2 mutations detection. The validation of the most relevant alterations was performed on independent cohort of non-paired 104 tumors. RESULTS: Statistically the most significant differences of GBM progression induced by combination of chemo and/or radiotherapy were: EGFR amplification, CDKN2A loss, MDM2 gain, PDGFRA gain and GSTT1 loss in primary tumors and GSTM1 gain in recurrent tumors. Univariate analysis of overall survival for significant copy number alterations proofs significantly worse prognosis for patients harboring GSTT1 deletion in primary tumor. The analysis revealed trend of better prognosis in patients with CDKN2A deletion and GSTM1 amplification in recurrent tumors. Significantly worse prognosis had GBM patients harboring GSTT1 gene aberrations and was also confirmed in independent validation cohort of unpaired GBMs in multivariate analysis adjusted for age and Karnofsky score. Full data with statistical analysis will be presented in the poster. CONCLUSION: The molecular genetic background of paired samples of primary and recurrent form of GBM revealed association with glutathione S-transferases genes. The significance of GSTT1 gene aberration was validated in independent group of GBM and thus supports the theory of in involvement of redox enzymes in GBM chemoradiation response and tumor progression. ACKNOWLEDGMENT: The financial support of grants TACR TE02000058, IGA_LF_2018_005 is gratefully acknowledged. Authors thank the collaborating neurosurgical centers from Ostrava (CGB laboratory), Brno (CEITEC) and Prague (Faculty Hospital Královské Vinohrady).

Most research on American cranberry in the prevention of urinary tract infection (UTI) has used juices. The spectrum of components in juice is limited. This study tested whether whole cranberry fruit powder (proanthocyanidin content 0.56%) could prevent recurrent UTI in 182 women with two or more UTI episodes in the last year. Participants were randomized to a cranberry (n = 89) or a placebo group (n = 93) and received daily 500 mg of cranberry for 6 months. The number of UTI diagnoses was counted. The intent-to-treat analyses showed that in the cranberry group, the UTIs were significantly fewer [10.8% vs. 25.8%, p = 0.04, with an age-standardized 12-month UTI history (p = 0.01)]. The Kaplan-Meier survival curves showed that the cranberry group experienced a longer time to first UTI than the placebo group (p = 0.04). Biochemical parameters were normal, and there was no significant difference in urinary phenolics between the groups at baseline or on day180. The results show that cranberry fruit powder (peel, seeds, pulp) may reduce the risk of symptomatic UTI in women with a history of recurrent UTIs.

The aim of this study was to evaluate the fatty acid (FA) profile in the plasma and erythrocyte membranes of apparently healthy men compared to male patients with various cardiovascular diseases (CVD). The plasma FA profiles were analyzed in five groups of subjects aged 37–57 years: groups 1 and 2 were male voluntary blood donors with a body mass index (BMI) 25.1 ± 1.6, (Group 1, N = 12) and a BMI 32.9 ± 4.5, (Group 2, N = 11) respectively, male patients with chronic heart failure due to dilated cardiomyopathy (Group 3, N = 10), chronic atrial fibrillation without heart failure or coronary heart disease (Group 4, N = 10) and patients after myocardial infarction (Group 5, N = 11). The FA profile in plasma and erythrocytes was measured by gas chromatography (GC) with flame ionization detection and basic plasma lipid parameters were then estimated. Deficiencies of eicosapentaenoic acid and docosahexaenoic acid were found in all the groups of CVD patients and in Group 2 (BMI 32.9 ± 4.5) of this Central European population. Unfavorable alterations in FA composition and clinical biochemistry parameters were found in patients with dilated cardiomyopathy (Group 3). Further, 75% of Group 1 (blood donors) had an average plasma PUFA level in the worst quartile for relative risk of cardiovascular events. Tailored n-3 PUFA supplementation should be recommended not only for secondary prevention in patients suffering from CVD but also for primary prevention in overweight and obese persons with a proven deficiency. Practical applications: Plasma and erythrocyte membrane n-3 polyunsaturated fatty acid (PUFA) levels are an important parameter of diet composition as well as a marker of cardiovascular risk. Regular sea fish intake or alternative supplementation with the n-3 PUFA recommendation is in all probability insufficiently realized, particularly in inland countries. In addition to contemporary guidelines and practice, research is providing data on the use of FA analysis for revealing people with an n-3 PUFA deficiency. This approach could benefit people suffering from CVD as well as for overweight and obese populations with demonstrated deficiency. Tailored n-3 PUFA supplementation should be recommended not only for secondary prevention in patients suffering from CVD but also for primary prevention in overweight and obese persons with a proven deficiency.

Background: Breast cancer (BC), the most frequent malignancy in women worldwide, is currently diagnosed in about 1.4 million female patients annually. Approximately 10-20% of BC is represented by triple negative breast cancer (TNBC) which is aggressive, the prognosis is poor and patients cannot benefit from targeted treatment based on hormonal or HER2 receptors. For this reason, search for markers that can predict the efficacy of chemotherapy in TNBC is a priority. Methods and Results: This review focuses on BCL2 protein as a prognostic marker in TNBC and its potential as a predictor of sensitivity to chemotherapy. Conclusion: BCL2 protein expression is a positive prognostic factor in BC. Better survival of patients with BCL2 positivity (BCL2+) has been explained by the correlation with estrogen receptor positive (ER+) status. BCL2+ is however not simply a surrogate marker for ER+. Moreover, BCL2 protein expression is also a positive prognostic marker in the TNBC subgroup. We and others show, that low BCL2 expression was associated with good outcome of TNBC patients treated with both adjuvant and neoadjuvant anthracycline-based chemotherapy. On the other hand, recent studies have shown that a subset of TNBC patients may benefit from the classical adjuvant CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimen. Given the heterogeneity of TNBC there is an urgent need to find and validate the sensitivity predictors to these regimens making them usable in clinical practice. BCL2 enrichment has been described in the mesenchymal stem-like (MSL) TNBC subgroup.

Background Meningioma growth rates are highly variable, even within benign subgroups, causing some cases to remain stable while others grow rapidly despite radiotherapy. Biomarkers that differentiate meningiomas by aggression and enable prediction of their biological behavior would therefore be clinically beneficial. Methods Microarrays were used to identify microRNA (miRNA) expression in primary recurrent, non-recurrent and secondary meningiomas of all grades. miRNAs found to be deregulated in the microarray experiments were validated by quantitative real-time PCR using samples from a cohort of 191 patients (median age 56). Statistical analysis of the resulting dataset revealed miRNA predictors of meningioma recurrence. Results miRNAs exhibiting differential expression (independently of histological grade) in primary recurrent, non-recurrent and secondary meningiomas were identified. The most effective predictive model included miR-331-3p, extent of tumor resection and its localization as predictive markers. The model with a recurrence probability cut-off of 28% and small number of the input data (7) had a high area under the curve (AUC) (0.829), sensitivity (75%), specificity (75%), and acceptable leave-one-out cross-validation (LOOCV) test error (23.2%). miR-18a-5p, miR-130b-3p, miR-146a-5p, miR-1271-5p, age at diagnosis, gender and histological grade showed to be supportive but not predictive factors in the tested models. Conclusions This model is a novel predictor of meningioma recurrence that could facilitate optimal postoperative management. Moreover, combining this model with information on the molecular processes underpinning recurrence could enable the identification of distinct meningioma subtypes and targeted therapies. Legal entity responsible for the study The authors. Funding Ministry of Health of the Czech Republic (15-29021A); Palacky University Olomouc (LF 2019_003); Ministry of Education, Youth and Sports of the Czech Republic (LO1304, LM2015091); European Regional Development Fund (ENOCH CZ.02.1.01/0.0/0.0/16_019/0000868). Disclosure All authors have declared no conflicts of interest.

The aim of this double-blind, placebo controlled clinical trial was to assess the effects of a combination of selenium and silymarin in men with lower urinary tract symptoms, benign prostatic hyperplasia and a prostate specific antigen (PSA) ≤2.5ng/ml. The volunteers were randomized to two groups: the first one (n=26) received 240μg selenium (in the form of yeast l-selenomethionine) plus 570mg silymarin daily for 6 months and the second (n=29) received placebo. Outcome measures were changes in the International Prostate Symptom Score (IPSS), bladder volume (V), urinary flow rate, ultrasound estimated postvoid residual urine volume (RV), serum PSA, testosterone and selenium levels, safety clinical biochemistry, hematology and oxidative stress parameters at baseline and on day 180. The results showed statistically significant differences (p

Lower urinary tract symptoms (LUTS) are a common condition in older men. The objective of the present study was to evaluate the efficacy and tolerability of cranberry (Vaccinium macrocarpon) powder in men at risk of prostate disease with LUTS, elevated prostate-specific antigen (PSA), negative prostate biopsy and clinically confirmed chronic non-bacterial prostatitis. Forty-two participants received either 1500 mg of the dried powdered cranberries per d for 6 months (cranberry group;n21) or no cranberry treatment (control group;n21). Physical examination, International Prostate Symptom Score, quality of life (QoL), five-item version of the International Index of Erectile Function (IIEF-5), basic clinical chemistry parameters, haematology, Se, testosterone, PSA (free and total), C-reactive protein (CRP), antioxidant status, transrectal ultrasound prostate volume, urinary flow rate, ultrasound-estimated post-void residual urine volume at baseline, and at 3 and 6 months, and urineex vivoanti-adherence activity were determined in all subjects. In contrast to the control group, patients in the cranberry group had statistically significant improvement in International Prostate Symptom Score, QoL, urination parameters including voiding parameters (rate of urine flow, average flow, total volume and post-void residual urine volume), and lower total PSA level on day 180 of the study. There was no influence on blood testosterone or serum CRP levels. There was no statistically significant improvement in the control group. The results of the present trial are the first firm evidence that cranberries may ameliorate LUTS, independent of benign prostatic hyperplasia or C-reactive protein level.

Background: Glioblastoma (GBM) is the most frequent and the most malignant brain tumor in adults. Despite aggressive therapy, overall survival of GBM patients remains poor due to intrinsic or acquired resistance to combined radiation and chemotherapy. Underlying biology behind GBM progression after first line therapy is mostly unknown and thus, there are only limited targeted therapeutic options for the 2nd line treatment. The aim of this study was to investigate genetic landscape in paired samples of primary versus recurrent tumors and to validate prognostic and predictive value of the most significant differences in independent cohort of GBMs. Patients and methods: 43 paired tumor samples were obtained during the 1st surgery followed by radiochemotherapy and after tumor recurrence during the 2nd palliative surgery. 24/43 paired samples were analyzed for whole genome copy number variations (CNV), 23/43 by fluorescent in situ hybridization for determination of EGFR, p53, RB1, MDM2, CDKN2A, 1p, 19q and 10p statuses. Methylation-specific PCR was used for analysis of MGMT promoter methylation and competitive amplification of differentially melting amplicons PCR for IDH1/2 mutations detection. The impact of most relevant alterations identified in paired GBMs was then validated in independent cohort of unpaired 104 tumors. Results: The most significant differences induced by chemoradiotherapy and/or GBM progression in primary versus recurrent tumors were EGFR amplification (19/24 primary tumors, 16/24 recurrent tumors), CDKN2A loss (18/24 primary tumors, 16/24 recurrent tumors), MDM2 gain (4/24 primary tumors), PDGFRA gain (3/24 recurrent tumors) and GSTT1 loss in primary tumors (7/24) and GSTM1 gain in recurrent tumors (7/24). Univariate analysis of overall survival for significant copy number alterations shown significantly worse prognosis for patients with GSTT1 deletion (HR = 5.356, CI = 1.161-24.701, p = 0.031) in primary tumor and trend for better prognosis in patients with CDKN2A deletion (HR = 0.391, CI = 0.124-1.229, p = 0.108) and GSTM1 amplification (HR = 0.341, CI = 0.090-1.288, p = 0.112) in recurrent tumors. Significantly worse prognosis for GBM patients with aberrations of GSTT1 gene was also confirmed in independent validation cohort of unpaired GBMs in multivariate analysis adjusted for age and Karnofsky score (gain: HR = 1.95, CI = 1.116-3.260, p = 0.011; loss: HR = 2.15, CI = 1.185-3.900, p = 0.012). Conclusion: Molecular genetic profiling of 24 recurrent GBM showed association between recurrence and status of glutathione S-transferases genes. Significance of GSTT1 gene aberration was validated in independent group of glioblastomas and indicates involvement of redox enzymes in GBM chemoradiation response and tumor progression. Acknowledgment: The financial support of grants TE02000058, IGA UP LF_2017_013 is gratefully acknowledged. Citation Format: Magdalena Houdova Megova, Zuzana Sporikova, Radek Trojanec, Ondrej Kalita, Jana Vrbkova, Jiri Drabek, Vladimira Koudelakova, Marian Hajduch. Mapping of molecular landscape underlying drug resistance and recurrence in glioblastoma: Paired analysis of primary and recurrent tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3695.

The study aimed at assessing the potential use of lower total and HMW adiponectin levels for predicting cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). Concentrations of total adiponectin or high molecular weight (HMW) adiponectin decrease in association with the development of metabolic dysfunction such as obesity, insulin resistance, or T2DM. Increased adiponectin levels are associated with a lower risk for coronary heart disease. A total of 551 individuals were assessed. The first group comprised metabolically healthy participants (143 females, and 126 males) and the second group were T2DM patients (164 females, and 118 males). Both total adiponectin and HMW adiponectin in diabetic patients were significantly lower when compared with the group of metabolically healthy individuals. There was a weak monotonic correlation between HMW adiponectin levels and triglycerides levels. Binary logistic regression analysis, gender adjusted, showed a higher cardiovascular risk in diabetic persons when both total adiponectin (OR = 1.700) and HMW adiponectin (OR = 2.785) levels were decreased. A decrease in total adiponectin levels as well as a decrease in its HMW adiponectin is associated with a higher cardiovascular risk in individuals with T2DM. This association suggests that adiponectin levels may be potentially used as an epidemiological marker for cardiovascular risk in diabetic patients.

Neither targeted therapies nor predictors for chemotherapy sensitivity are available for triple-negative breast cancer (TNBC). Our study included 187 patients with TNBC, 164 of whom were treated with anthracycline-based adjuvant chemotherapy. Eleven molecular biomarkers were analyzed. BCL2, epidermal growth factor receptor (EGFR), MYC, TOP2A, and Ki-67 protein expression was evaluated by immunohistochemistry. The status of the EGFR, MYC, and TOP2A genes and chromosomes 7, 8, and 17 was assessed using fluorescence in situ hybridization. High BCL2 expression predicted poor relapse-free survival (RFS) in patients treated with anthracycline-based adjuvant chemotherapy (p = 0.035), poor breast cancer-specific survival (BCSS) (p = 0.048), and a trend to poor overall survival (OS) (p = 0.085). High levels of BCL2 expression predicted poor OS in basal-like (BL) TNBC patients treated with adjuvant anthracycline-based regimens (log-rank p = 0.033, hazard ratio (HR) 3.04, 95 % confidence interval (CI) 1.04–8.91) and a trend to poor RFS (log-rank p = 0.079) and poor BCSS (log-rank p = 0.056). Multivariate analysis showed that BCL2 status, tumor size, and nodal status all had independent predictive significance for RFS (p = 0.005, p = 0.091, p = 0.003, respectively; likelihood ratio test for the whole model, p = 0.003), BCSS (p = 0.012, p = 0.077, p = 0.01, respectively; likelihood ratio test for the whole model, p = 0.016), and OS (p = 0.008, p = 0.004, p = 0.004, respectively; likelihood ratio test for the whole model, p = 0.0006). Similarly, multivariate analysis for BL TNBC showed BCL2, tumor size, and nodal status all had independent predictive significance for RFS (likelihood ratio test for the whole model, p = 0.00125), BCSS (p = 0.00035), and OS (p = 0.00063). High EGFR expression was associated with poor BCSS (p = 0.039) in patients treated with anthracycline-based adjuvant chemotherapy. Patients who underwent anthracycline-based adjuvant chemotherapy and exhibited CMYC amplification had a trend to worse BCSS (p = 0.066). In conclusion, high BCL2 expression is a significant independent predictor of poor outcome in TNBC patients treated with anthracycline-based adjuvant chemotherapy, and this is the first study showing the BCL2 prediction in BL TNBC. BCL2 expression analysis could facilitate decision making on adjuvant treatment in TNBC patients.

Cranberry (Vaccinium macrocarpon) is being studied for use in the prevention of recurrent urinary tract infection (rUTI) where it affects the adhesion Escherichia coli to the uroepithelium. This 6 month, randomized, double-blind, placebo-controlled trial aimed to evaluate whether a daily dose of 500 mg Pacran® could prevent UTI occurrences in sexually active women with a medical history of at least 2 symptomatic UTI in the previous 12 months. Study participants were randomized to the Pacran® or the placebo group and were followed up for 6 months. The intent-to-treat analysis included 176 participants (n=93 in placebo and n=83 in Pacran® group). In the Pacran® group, the proportion of women experiencing at least one UTI was significantly lower than in the placebo group [10.8% versus 25.8%, respectively, p=0.04, with age adjusted 12-month UTI history (p=0.01), age (p=0.73), and age-squared (p=0.05) also included in the model]. There was a similar finding when risk of an E. coli UTI was assessed (p=0.03). Wh...

Background. Silymarin, a milk thistle flavonolignan mixture, has anti-proliferative and anti-angiogenic activities in xenografts of human prostate cancer (PCa). Low dietary selenium on the other hand has been associated with increased incidence of PCa. The purpose of the current trial was to determine whether a daily administration of a silymarin and selenium (SM-Se) combination for 6 months would alter basic clinical chemistry and oxidative stress markers, and improve the quality of life score (QoL) in men after radical prostatectomy (RP). Methods. Thirty seven participants, 2–3 months after RP, were randomly assigned to receive 570 mg of silymarin and 240 μg of selenium as selenomethionine (n = 19, SM-Se group) or placebo (n = 18, Placebo group) daily for six months. Both groups had similar clinical and demographic characteristics. Physical examination, QoL score, haematology, basic clinical chemistry and oxidative stress markers, selenium and testosterone levels, antioxidant status were evaluated at baseline, at 3 and 6 months. Results. The six months administration of silymarin and selenium improved the QoL score, decreased low density lipoproteins (LDL) and total cholesterol and, increased serum selenium levels. The combination had no effect on blood antioxidant status and no influence on testosterone level. No adverse events were recorded. No improvement was found in the placebo group. Conclusions. The selected combination of silymarin and selenium significantly reduced two markers of lipid metabolism known to be associated with PCa progression, LDL and total cholesterol in the blood of men after RP. This suggests that this combination may be effective in reducing PCa progression.

Myocardial revascularization belongs among the most frequent cardiosurgery operations. Perioperative and longterm survival depend on the patency of the graft used and the anastomotic quality. Haemodynamical characteristics measured during a coronary artery bypass graft (CABG) surgery help verify anastomotic quality and also affect longterm graft patency. During CABG surgery (on a heart bypass machine with extracorporal circulation), a surgeon measures blood flow through the bypass at the time the cross clamp is applied to the ascending aorta (blood is not flowing through coronary vessels, rather through the bypass) and later at the same place after removal of the cross clamp. The aim of this article is to find a statistical model for prediction of blood flow through the bypass after removal of the cross clamp based on the blood flow value when the cross clamp is placed on the aorta. When this prediction is good, we will be able to decrease a number of measurements with keeping whole information about an object.

1132 Background: The role of BRCA mutation status as a predictor in TNBC is unclear. Data show an association of high BCL2 expression and resistance to anthracyclines. BCL2, size and nodal status a...