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The COVID-19 pandemic has disrupted surgical training worldwide, and reconstructive urology training has been neglected at the expense of more urgent life-saving procedures. To help address this problem, virtual reality must become a fundamental training aid in modern reconstructive urology surgery education.

The number of overweight, obese and diabetic patients is constantly increasing. Metabolic disorders may affect the pharmacokinetics of drugs, e.g., by altering the activity of cytochrome P450 (CYP) isoenzymes. Tramadol is a commonly used analgesic metabolised mainly via CYP2D6 to its active metabolite, O-desmethyltramadol. The aim of the study was to assess the influence of overweight, obesity and type 2 diabetes mellitus on tramadol and O-desmethyltramadol pharmacokinetics. All patients received a single oral dose (100 mg) of tramadol. The plasma concentrations of tramadol and O-desmethyltramadol were measured with the validated high-performance liquid chromatography method with fluorescence detection. The pharmacokinetic parameters of tramadol and O-desmethyltramadol were calculated by non-compartmental methods. After nephrectomy, the patients were divided into four groups—a control group (n= 12, mean [SD] age 61 [14] years, body mass index (BMI) 22 [2] kg/m2, CLcr(creatinine clearance) 74 [30] mL/min); an overweight group (n= 15, mean [SD] age 63 [11] years, BMI 27 [1] kg/m2, CLcr81 [35] mL/min); an obese group (n= 12, mean [SD] age 57 [8] years, BMI 33 [4] kg/m2, CLcr113 [51] mL/min); and an obese and diabetic group (n= 9, mean [SD] age 64 [10] years, BMI 33 [4] kg/m2, CLcr87 [35] mL/min). Apart from the time to first occurrence of maximal concentration (tmax), there were no significant differences in the pharmacokinetic parameters of tramadol and O-desmethyltramadol among the groups. Moreover, there were no significant differences in the O-desmethyltramadol/tramadol ratios among the four groups of patients after nephrectomy. No significant differences were found in the pharmacokinetics of tramadol and O-desmethyltramadol, indicating that the opioid can be administered to overweight, obese and diabetic patients without dosage adjustment.

Objectives: To preclinically evaluate drug-eluting biopsy needles (patent pending WO2016118026) as a new potential way of antimicrobial prophylaxis for transrectal prostate biopsy.Methods: Twenty steel biopsy needles have been coated with polyvinyl alcohol, ciprofloxacin, and amikacin. Modified biopsy needles have been randomly divided into 3 groups (1:2:1 ratio). Needles from group I were immersed for 30 minutes in dedicated test tubes containing saline. Needles from group II were immersed (one by one) for 5 seconds in a set of 12 test tubes containing saline. Then, each solution was analyzed using high-performance liquid chromatography. The results were compared with the susceptibility break points for Escherichia coli. Group III was incubated with E colistrains on Mueller-Hinton plate and then the bacterial inhibition zones surrounding needles were measured.Results: The average concentration of antibiotics eluted from needles (group I) was 361.98 ± 15.36 µg/mL for amikacin and 63.87 ± 5.95 µg/mL for ciprofloxacin. The chromatographic analysis revealed the gradual release of both antibiotics from needles (group II). The concentration of amikacin released from needles exceeded the break-point value from first to ninth immersion. Ciprofloxacin concentration was higher than break-point value in all immersions. The average bacterial inhibition zone minor axis was 42 ± 5.7 mm (group III).Conclusions: The use of drug-eluting biopsy needle could be a new potential way of antimicrobial prophylaxis for transrectal prostate biopsy. This study confirmed its biological activity as well as the gradual release of antibiotics from its surface. Confirmation of its preventive role, in terms of infectious complications after transrectal prostate biopsy, has to be evaluated in a clinical trial.

The aim of the study was to compare radioactive and fluorescent sentinel lymph node biopsy in bladder cancer. The study was conducted on 50 patients. We found that the sentinel lymph node biopsy technique is feasible and useful for the evaluation of lymph nodes in bladder cancer. The fluorescent technique may provide similar results to the radiocolloid method, although both have advantages and disadvantages.

We present a comparison of the 2 detection methods—radionuclide with technetium and fluorescent with indocyanine green—to identify sentinel lymph nodes for penile cancer. We obtained similar results in the identification of these nodes using 2 different detection techniques in 14 patients. Further studies are needed to assess the usefulness of a new technique.

The study aimed to examine the effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite, paracetamol glucuronide. Both drugs share metabolic pathways in the liver, and the drug interactions between sunitinib and paracetamol administered in higher doses were reported. These interactions resulted in hepatotoxicity. The adult New Zealand male rabbits were divided into three groups (6 animals each): rabbits receiving sunitinib and paracetamol (SUN + PC), rabbits receiving sunitinib (SUN), and a control group receiving paracetamol (PC). Sunitinib was administered orally (25 mg) and paracetamol was administrated intravenously (35 mg/kg). Blood samples for sunitinib and SU12662 assays were collected up to 96 h after drug administration and for paracetamol and paracetamol glucuronide up to 300 min after drug administration. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin were analysed before and after drug administration. A number of pharmacokinetic parameters were analysed. There were no differences in the levels of AST, ALT, and bilirubin among the groups at either time point. Significantly higher values of AUC0–t, AUC0–∞, and Cmaxand lower clearance and volume of distribution of paracetamol were observed in group PC vs. group SUN + PC (p< 0.01). The maximum plasma concentration of paracetamol glucuronide tended to be higher in group PC 213.27 μg/mL (90 % CI 1.06, 1.25; p= 0.0267). Statistically significant differences were revealed for paracetamol glucuronide mean residence time (MRT); MRT was higher in group SUN + PC than in group PC (p= 0.0375). The mean tmaxof paracetamol glucuronide was similar in both groups: SUN + PC and group PC (15 and 20 min, respectively). The mean tmaxof sunitinib was different in groups SUN + PC and SUN (10.0 and 7.0, respectively; p= 0.0134). At the studied doses, neither of the drugs, whether administered alone or together, had hepatotoxic effects. The present study was not able to confirm that sunitinib, administered at low doses in conjunction with paracetamol, displays a hepatoprotective effect. Significant differences were observed in some pharmacokinetic parameters of paracetamol.

Renal cell carcinoma (RCC) is a disease with no specific diagnostic method or treatment. Thus, the evaluation of novel diagnostic tools or treatment possibilities is essential. In this study, a multiplatform untargeted metabolomics analysis of urine was applied to search for a metabolic pattern specific for RCC, which could enable comprehensive assessment of its biochemical background. Thirty patients with diagnosed RCC and 29 healthy volunteers were involved in the first stage of the study. Initially, the utility of the application of the selected approach was checked for RCC with no differentiation for cancer subtypes. In the second stage, this approach was used to study clear cell renal cell carcinoma (ccRCC) in 38 ccRCC patients and 38 healthy volunteers. Three complementary analytical platforms were used: reversed-phase liquid chromatography coupled with time-of-flight mass spectrometry (RP-HPLC-TOF/MS), capillary electrophoresis coupled with time-of-flight mass spectrometry (CE-TOF/MS), and gas chromatography triple quadrupole mass spectrometry (GC-QqQ/MS). As a result of urine sample analyses, two panels of metabolites specific for RCC and ccRCC were selected. Disruptions in amino acid, lipid, purine, and pyrimidine metabolism, the TCA cycle and energetic processes were observed. The most interesting differences were observed for modified nucleosides. This is the first time that the levels of these compounds were found to be changed in RCC and ccRCC patients, providing a framework for further studies. Moreover, the application of the CE-MS technique enabled the determination of statistically significant changes in symmetric dimethylarginine (SDMA) in RCC.

Diabetes is one of the most common metabolic diseases in the world, which may influence changes in the pharmacokinetics and pharmacodynamics of drugs. Sunitinib is a tyrosine kinase inhibitor (TKI) broadly used for treatment of numerous cancers, which exhibits the side hypoglycaemic effect. The aim of the study was a comparison of concentrations and pharmacokinetics of sunitinib after a single administration in rabbits with hyperglycaemia and normoglycaemia (control group). Additionally, the effect of sunitinib on glucose levels was investigated.

Background: Diabetes is one of the most common metabolic diseases in the world, which may influence changes in the pharmacokinetics and pharmacodynamics of drugs. Sunitinib is a tyrosine kinase inhibitor (TKI) broadly used for treatment of numerous cancers, which exhibits the side hypoglycaemic effect. The aim of the study was a comparison of concentrations and pharmacokinetics of sunitinib after a single administration in rabbits with hyperglycaemia and normoglycaemia (control group). Additionally, the effect of sunitinib on glucose levels was investigated.

Background: Macrolides are the most widely prescribed antibiotics. Clarithromycin is a well-known inhibitor of cytochrome P450 CYP3A4 and causes numerous drug interactions that are not found for azithromycin. CYP3A4 is involved in the metabolism of the new oral multikinase inhibitor sunitinib and its active N-desethyl metabolite (SU012662). This study investigated the effects of oral single dose of clarithromycin or azithromycin on the pharmacokinetics of sunitinib. Methods: Rabbits were subjected to one of three study drug groups: sunitinib + clarithromycin (n = 6), sunitinib + azithromycin (n = 6), or sunitinib (n = 6). The rabbits were treated with sunitinib in the oral dose of 25 mg. Plasma concentrations of sunitinib were measured with validated HPLC method with UV detection. Results: Comparison of the sunitinib Cmaxfor the sunitinib + clarithromycin group with that of the sunitinib group gave a ratio of 94.4% [90% confidence interval (CI) (76.1, 117.1)]; for the sunitinib + azithromycin group, the ratio was 106.2% (90% CI 85.5, 131.7). Comparison of the sunitinib AUC0-tof the sunitinib + clarithromycin and sunitinib + azithromycin groups with that of the sunitinib group showed ratios of 86.86% (90% CI 69.7, 108.3) and 99.8% (90% CI 80.1, 124.5), respectively. Conclusions: No significant effect of the coadministration of clarithromycin or azithromycin on the pharmacokinetics of sunitinib in rabbits was found in this study.

Background: Renal cell carcinoma (RCC) is the most common form of kidney cancer. Surgery is a standard procedure to resect the tumor during total (TN) or partial (nephron-sparing) nephrectomy (PN). Ciprofloxacin is most often administered at the usual intravenous dose of 100–400 mg/12 h. The application of such low doses of ciprofloxacin as 200 mg/24 h carries the risk of achieving subtherapeutic concentrations even in patients with limited renal function. The aim of the study was a comparison of concentrations and pharmacokinetics for ciprofloxacin at steady-state in patients after total and partial nephrectomy and evaluation of the effectiveness of the ivdose 200 mg/24 h against the theoretical value of MIC, 0.5 µg/ml. Methods: The research was carried out on two groups of patients after nephrectomy: total (group 1, n = 21; mean [SD], age, 62.9 [14.4] years; weight, 76.0 [14.6] kg; creatinine clearance, CLCR, 90.7 [22.2] ml/min) and partial (group 2, n= 15; 61.7 [9.3] years; 87.8 [16.4] kg; CLCR, 107.8 [36.4] ml/min). The patients were treated with ciprofloxacin in the dose of 200 mg/24 h (iv).Plasma concentrations of ciprofloxacin at steady state were measured with validated HPLC method with UV detection. Results: The mean values of plasma concentrations of ciprofloxacin at steady state in group 1 and 2 were: Cssmax, 2.012 and 1.345; Cssmin, 0.437 and 0.244 µg/ml, respectively. The main pharmacokinetic parameters for ciprofloxacin in group 1 and 2 were as follows: AUC(0-last), 30.9 [17.9] and 19.5 [8.7] µgh/ml; AUMC(0-last), 177.91 [11.1] and 91.9 [66.5] µgh2/ml; t1/2ß, 13.9 [7.7] and 9.8 [3.3] h; MRT, 16.5 [12.1] and 9.77 [5.4] h; Vd, 115.0 [67.2] and 142.2 [78.7] l; CL, 6.2 [3.3] and 10.8 [5.7] l/h, respectively. With the assumed MIC = 0.5 µg/ml, the values of Cssmax/MIC &lt; 10 and AUC/MIC &lt; 125 were obtained in all the patients. Conclusion: In our patients we observed significant differences in some pharmacokinetic parameters of ciprofloxacin after two types of nephrectomy.

Schoemaker's scenario planning is a suitable method for decision making in the context of emerging mobile services. The main challenges in using the method are related to avoiding subjective bias, identifying the most relevant trends, uncertainties and stakeholders and building consistent and coherent scenarios. The method is a systematic way to assess possible future outcomes, but does not provide a detailed understanding of them. Scenario planning serves as a structure for brainstorming sessions, and as a basis for a more detailed analysis using quantitative methods. We applied Schoemaker's scenario planning to the emerging mobile Peer-to-Peer Session Initiation Protocol (P2PSIP) communications services. According to our analysis, a potential P2PSIP stakeholder should seek settings where network and legal aspects are the most favourable: ad hoc and private environments without interconnectivity to the internet. A stakeholder considering global service provisioning should evaluate the semi-centralised public global scenario.

In the present study we correlate the p53 gene mutations in tumour tissue with urine sediment using a functional assay in yeast, and relate the p53 status to the outcome in a group of patients with transitional cell carcinoma of the bladder. The p53 mutations were found in three of 30 (10%) Ta/T1 tumour tissue samples and in two of 20 (10%) corresponding urine sediments. In the stage T2–T4 tumour p53 mutations were found in tumour tissues and urine sediments in 13 of 31 (42%) and in seven of 18 (39%) samples, respectively. In 80% (8/10) of cases, the p53 mutations found in tumour tissue were re-detected in urine sediment. Median follow-up was at 20 months. Disease recurred in 18 of the 61 patients (30%) with a median time of 5 months. In Ta/T1 tumours the frequency of recurrence was 37% (11/30) compared with 23% (7/31) of T2–T4 tumours. The 3-year overall survival (OS) was 82% (50/61). The p53 status was significantly associated with stage (P = 0.0077, two-sided Fisher's exact test), grade (P < 0.001) and lymph node involvement (P = 0.027). There was an association between the p53 mutations and shorter OS (P = 0.033; log-rank test); however in a multivariate analysis adjusted for stage, grade, lymph node status and age the p53 mutation was not an independent predictor of survival. There was no correlation of the p53 status with decreased disease-free survival (P = 0.8; log-rank test). The data presented indicate that the yeast functional assay is a useful method for p53 gene mutation analysis in tumour tissue and p53 mutation can be re-detected in urine sediment, but further validation of the assay in non-invasive screening for p53 mutations is needed.