Diagnostics of infertile males in the 21st century - a traditional concept or a modern approach?

In developed countries, approximately 15% of couples suffer from infertility, i.e. they do not conceive within one year of a regular unprotected sexual intercourse. Since infertility is the only one diagnosis of a couple, and not of an individual, it is essential to examine the couple as the unit. Sperm analysis, i.e. native microscopic evaluation, has been used for decades as a golden standard for male fertile potential assessment. Sperm analysis, in its fundamental form, has been only morphological, and not functional evaluation of ejaculate, thus it might not give us reliable information about actual fertile potential of an individual male. On that account, new methods are being introduced to the clinical practice with a goal to improve diagnostics and subsequent treatment. The article presents these new methods, namely flow cytometry, and the impact of asymptomatic urogenital infections on fertility.

First experience in the Czech Republic with perirectal hydrogel injection before radiotherapy for prostate cancer.

PURPOSE: SpaceOAR® is a Food and Drug Administration approved hydrogel injection used to create space between the prostate and rectum before prostate radiotherapy (RT). This bio-degradable hydrogel was not available in the Czech Republic until 2019. We present our first experience as a new established SpaceOAR® centre. We namely focused on technical difficulties with a new procedure and possible medical complications. METHODS: We injected SpaceOAR® to 58 patients indicated for prostate RT due to prostate cancer. Prospectively and retrospectively, we monitored the learning curve and complication rate and we assessed the feasibility as an out-patient procedure in the Czech medical environment. RESULTS: The procedure is technically feasible as an out-patient procedure in a urological office. The learning curve with reasonable ultrasound experience and adequate equipment is acceptably short. The number of complications which might be associated with hydrogel injection was very low, with one exception in our centre - ulceration of the rectum. CONCLUSION: SpaceOAR® injection is a minimally invasive out-patient procedure with expected minimum complications and it is easy to learn.

DNA-linked Inhibitor Antibody Assay (DIANA) for sensitive and selective enzyme detection and inhibitor screening.

Human diseases are often diagnosed by determining levels of relevant enzymes and treated by enzyme inhibitors. We describe an assay suitable for both ultrasensitive enzyme quantification and quantitative inhibitor screening with unpurified enzymes. In the DNA-linked Inhibitor ANtibody Assay (DIANA), the target enzyme is captured by an immobilized antibody, probed with a small-molecule inhibitor attached to a reporter DNA and detected by quantitative PCR. We validate the approach using the putative cancer markers prostate-specific membrane antigen and carbonic anhydrase IX. We show that DIANA has a linear range of up to six logs and it selectively detects zeptomoles of targets in complex biological samples. DIANA's wide dynamic range permits determination of target enzyme inhibition constants using a single inhibitor concentration. DIANA also enables quantitative screening of small-molecule enzyme inhibitors using microliters of human blood serum containing picograms of target enzyme. DIANA's performance characteristics make it a superior tool for disease detection and drug discovery.

The aging effect on prostate metabolite concentrations measured by 1H MR spectroscopy.

OBJECTIVE: The effects of aging, magnetic field and the voxel localization on measured concentrations of citrate (Cit), creatine (Cr), cholines (Cho) and polyamines (PA) in a healthy prostate were evaluated. MATERIALS AND METHODS: 36 examinations at both 1.5T and 3T imagers of 52 healthy subjects aged 19-71 years were performed with PRESS 3D-CSI sequences (TE = 120 and 145 ms). Concentrations in laboratory units and their ratios to citrate were calculated using the LCModel technique. Absolute concentrations were also obtained after the application of correction coefficients. Statistical analysis was performed using a robust linear mixed effects model. RESULTS: Significant effects of aging, the magnetic field strength and the voxel position in central (CZ) or peripheral (PZ) zones on all measured metabolites were found. The concentrations (mmol/kg wet tissue) including prediction intervals in a range of 20-70 years were found: Cit: 7.9-17.2; Cho: 1.4-1.7; Cr: 2.8-2.5; PA (as spermine): 0.6-2.1 at 3T in CZ. In PZ, the concentrations were higher by about 10 % as compared to CZ. CONCLUSION: Increasing citrate and spermine concentrations with age are significant and correlate well with a recently described increase of zinc in the prostate. These findings should be considered in decision-making if the values obtained from a subject are in the range of control values.

Renal Abscess Caused by Extended-Spectrum Beta-Lactamase-Producing Bacteria and Complicated by the Perforation to a Cyst and to the Renal Pelvis.

We report a 50-year-old female patient with a left-sided renal abscess caused by extended-spectrum ß-lactamase-producing bacteria. According to the ORENUC classification she had phenotype N. The course was complicated by a perforation to an adjacent cyst and later to the renal pelvis. A primarily conservative approach of intravenous antibiotics had to be changed to an ultrasonography-guided percutaneous drainage of the lesion and insertion of a ureteral stent to stem a high volume of urine leakage. Drainage of a renal abscess is indicated if the size is larger than 3 cm according to EAU guidelines (relative size) or when the resolution does not occur after antibiotics. One-year follow-up showed the patient made a full recovery with no recurrence of a urinary tract infection or of any abscess.

Detection and quantitation of glutamate carboxypeptidase II in human blood.

BACKGROUND: Glutamate carboxypeptidase II (GCPII) is a transmembrane enzyme that cleaves N-acetyl-L-aspartyl-L-glutamate (NAAG) in the brain. GCPII is highly expressed in the prostate and prostate cancer and might be associated with prostate cancer progression. Another exopeptidase, plasma glutamate carboxypeptidase (PGCP), was reported to be similar to GCPII and to share its NAAG-hydrolyzing activity. METHODS: We performed a radioenzymatic assay with [(3) H]NAAG as a substrate to detect and quantify the enzymatic activity of GCPII in plasma. Using a specific antibody raised against native GCPII (2G7), we immunoprecipitated GCPII from human plasma. We also cloned two PGCP constructs, expressed them in insect cells, and tested them for their NAAG-hydrolyzing activity. RESULTS: We detected GCPII protein in human plasma and found that its concentration ranges between 1.3 and 17.2 ng/ml in volunteers not diagnosed with prostate cancer. Recombinant PGCP was enzymatically active but exhibited no NAAG-hydrolyzing activity. CONCLUSION: GCPII is present in human blood, and its concentration within a healthy population varies. Recombinant PGCP does not hydrolyze NAAG, suggesting that GCPII alone is responsible for the NAAG-hydrolyzing activity observed in human blood. The potential correlation between GCPII serum levels and the disease status of prostate cancer patients will be further investigated.

Efficacy and safety of solifenacin plus tamsulosin OCAS in men with voiding and storage lower urinary tract symptoms: results from a phase 2, dose-finding study (SATURN).

BACKGROUND: Storage symptoms are often undertreated in men with lower urinary tract symptoms (LUTS). OBJECTIVE: To evaluate the combination of an antimuscarinic (solifenacin) with an α-blocker (tamsulosin) versus tamsulosin alone in the treatment of men with LUTS. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, 12-wk, phase 2 study in 937 men with LUTS (≥ 3 mo, total International Prostate Symptom Score [IPSS] ≥ 13, and maximum urinary flow rate 4.0-15.0 ml/s). INTERVENTION: Eight treatment groups: tamsulosin oral controlled absorption system (OCAS) 0.4 mg; solifenacin 3, 6, or 9 mg; solifenacin 3, 6 or 9 mg plus tamsulosin OCAS 0.4 mg; or placebo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary efficacy end point was change from baseline in total IPSS. Secondary end points included micturition diary and quality-of-life (QoL) parameters. Post hoc subgroup analyses were performed by severity of baseline storage symptoms, with statistical comparisons presented only for tamsulosin OCAS alone versus combination therapy, due to the small sample size of the solifenacin monotherapy and placebo subgroups. RESULTS AND LIMITATIONS: Combination therapy was associated with significant improvements in micturition frequency and voided volume versus tamsulosin OCAS alone in the total study population; improvements in total IPSS were not significant. Statistically significant improvements in urgency episodes, micturition frequency, total urgency score, voided volume, IPSS storage subscore, IPSS-QoL index, and Patient Perception of Bladder Condition were observed in a subpopulation of men with two or more urgency episodes per 24h (Patient Perception of Intensity of Urgency Scale grade 3 or 4) and eight or more micturitions per 24h at baseline (storage symptoms subgroup) with combination therapy versus tamsulosin OCAS alone (p ≤ 0.05 for the dose-response slope, all variables). Combination therapy was well tolerated, and adverse events were consistent with the safety profiles of both compounds. CONCLUSIONS: Solifenacin plus tamsulosin OCAS did not significantly improve IPSS in the total study population but offered significant efficacy and QoL benefits over tamsulosin OCAS monotherapy in men with both voiding and storage symptoms at baseline. Combination therapy was well tolerated. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT00510406.

A proof-of-concept study: mirabegron, a new therapy for overactive bladder.

AIMS: To evaluate the potential of mirabegron, a selective ß3-adrenoceptor agonist, for treatment of overactive bladder (OAB) symptoms. METHODS: A multicenter, randomized, double-blind, double-dummy, parallel group, placebo and active-controlled, Phase 2, proof-of-concept study was conducted. Eligible patients (n = 314) were enrolled into a single-blind, 2-week placebo run-in period followed by a randomized, double-blind, placebo-controlled treatment period. Patients received mirabegron 100 or 150 mg twice-daily (BID), placebo or tolterodine 4 mg extended release (ER) once-daily for 4 weeks. Primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes per 24 hr. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes per 24 hr; severity of urgency; nocturia, and quality of life measures. Safety parameters included adverse events, laboratory tests, electrocardiogram parameters and post-void residual volume. RESULTS: Mirabegron 100 and 150 mg BID resulted in a statistically significant improvement versus placebo in mean change from baseline to end-of-treatment in the primary endpoint of micturition frequency (2.2 micturitions/24 hr vs. 1.2 micturitions/24 hr for both doses, adjusted P ≤ 0.01 for both comparisons). Mirabegron had a statistically significant effect versus placebo for most secondary endpoints, including quality of life variables. Despite a small increase in pulse rate, mirabegron demonstrated good safety and tolerability. CONCLUSIONS: Mirabegron was efficacious and well tolerated in patients with OAB symptoms and heralds the first of a new class of oral pharmacological therapy for OAB for more than 30 years.