TPN171 is a potent phosphodiesterase type 5 inhibitor used to treat pulmonary arterial hypertension and erectile dysfunction, primarily metabolized by CYP3A4. This study aimed to evaluate its drug-drug interaction (DDI) potential and determine the optimal dosing when co-administered with CYP3A4 modulators. A physiologically based pharmacokinetic (PBPK) model was developed and validated using clinical DDI data for itraconazole (strong CYP3A4 inhibitor) and rifampin (strong CYP3A4 inducer). The model was then applied to predict DDIs with moderate (diltiazem, fluconazole) and mild (fluvoxamine) inhibitors, as well as moderate (efavirenz) and mild (zanubrutinib) inducers. Predicted AUC0-t ratios aligned with observed data: itraconazole (2.42-fold predicted vs. 2.67- fold observed) and rifampicin (0.14-fold predicted vs. 0.096-fold observed). For other modulators, geometric mean AUC0-t ratios were 2.40 with diltiazem, 3.27 with fluconazole (400 mg), 2.07 with fluconazole (100 mg), 1.16 with fluvoxamine, 0.53 with efavirenz, and 0.70 with zanubrutinib. These simulations indicate that strong and moderate CYP3A4 inhibitors and inducers significantly alter TPN171 exposure, whereas weak modulators have no clinically meaningful impact. These findings provide a scientific basis for dose recommendations when TPN171 is used with CYP3A4 modulators.

Morbid obesity (body mass index (BMI) ≥40 kg/m² or ≥35 kg/m² with comorbidities) predisposes patients to multiple urological disorders, including urinary incontinence, overactive bladder, erectile dysfunction, hypogonadism, nephrolithiasis, obesity-related kidney disease, renal cell carcinoma, and aggressive prostate cancer. Bariatric surgery is the most effective durable treatment for severe obesity. Glucagon-like peptide-1 receptor agonists, including semaglutide and tirzepatide, have revolutionised obesity pharmacotherapy. This systematic review evaluates the urological complications of morbid obesity and the effects of bariatric surgery and glucagon-like peptide-1 receptor agonists on these outcomes. We searched MEDLINE, Embase, Scopus, and the Cochrane Library (January 2000 to June 2025) for studies reporting urological outcomes in adults with BMI ≥35 kg/m². Two reviewers independently screened and extracted data. We assessed risk of bias using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) version 2 and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Eighty-four studies (>165,000 participants) met the inclusion criteria. Obesity increases renal cell carcinoma risk (relative risk: 1.5-2.0) and prostate cancer mortality (hazard ratio: 1.19-1.24) but paradoxically reduces prostate cancer incidence. Urinary incontinence and overactive bladder improve or resolve in 50-70% of women after bariatric surgery. Erectile dysfunction and hypogonadism improve after bariatric surgery, with International Index of Erectile Function (IIEF) scores increasing 4-6 points and testosterone rising 30-50%. Glucagon-like peptide-1 receptor agonists increase testosterone (standardised mean difference: 1.39 ng/mL) and improve erectile function. Tirzepatide reduces urinary albumin-to-creatinine ratio by 19-47% and preserves estimated glomerular filtration rate. Roux-en-Y gastric bypass increases nephrolithiasis risk 2.5-4-fold via enteric hyperoxaluria, whereas sleeve gastrectomy does not. Robot-assisted surgery in obese patients achieves complication rates comparable to those of non-obese patients after comorbidity adjustment. Bariatric surgery improves obesity-related urological morbidity, but Roux-en-Y gastric bypass increases stone risk. Glucagon-like peptide-1 receptor agonists offer a promising alternative with evidence for testosterone restoration, improved erectile function, and renal protection. Preoperative urological assessment, procedure selection, and multidisciplinary care are essential.

ObjectiveThe relationship between autoimmune diseases (ADs) and male reproductive health is easily neglected. Epidemiological studies indicated that multiple ADs may adversely affect male reproductive health. This study aimed to explore the causal relationship between ADs and erectile dysfunction (ED), abnormal spermatozoa, and sex hormones using Mendelian randomization (MR) analysis.MethodsWe selected 12 common ADs as exposures, with outcomes including ED, abnormal spermatozoa, and sex hormones. The selection of instrumental variables was based on summary statistics from European GWAS studies. A combination of multiple methods was performed for MR analysis of the above data, with the inverse-variance weighted method being the main method. We also conducted several sensitivity analyses to verify the reliability of the results.ResultsInflammatory bowel disease (IBD) and Crohn's disease (CD) were associated with an increased risk of ED (IBD, OR: 1.101, 95% CI: 1.016-1.194, P = 0.019; CD, OR: 1.086, 95% CI: 1.012-1.165, P = 0.022). Asthma was positively causally related to abnormal spermatozoa (OR: 1.270, 95% CI: 1.045-1.545, P = 0.017), but negatively causally related to total testosterone (β: -0.042, 95% CI: -0.057 - -0.027, P < 0.001). Detection of sensitivity analysis supported findings related to ED and abnormal spermatozoa.ConclusionCurrent genetic evidence suggested a potential causal effect of IBD and CD on the risk of ED. Furthermore, genetic liability to asthma was associated with abnormal spermatozoa and decreased total testosterone levels. Our results contributed to targeted prevention and management of these conditions, ultimately promoting male reproductive health.

Severe Peyronie's disease with concomitant erectile dysfunction remains surgically challenging, particularly in patients with significant curvature and penile shortening undergoing inflatable penile prosthesis implantation. We describe the SAPOC (Slices Around the Point of maximal Curvature) technique, a modification of the Multiple-Slit Technique, designed to permit length restoration while limiting large tunical defects and potentially reducing the need for structural grafting. Between October 2018 and December 2023, 64 patients with medically refractory erectile dysfunction and severe Peyronie's disease underwent inflatable penile prosthesis placement with SAPOC reconstruction by a single surgeon at a single academic center. Mean preoperative curvature was 72.0° ± 20.8° and mean stretched penile length increased from 14.2 ± 1.36 cm to 15.3 ± 1.2 cm (mean gain 1.05 ± 0.62 cm; p < 0.001). Complete intraoperative curvature correction was achieved in 73.4% of cases, with residual curvature <20° (mean postoperative curvature 3.3°) in the remainder. At median follow-up of 13.5 months (IQR: 9-22 months), 96.9% had no functionally significant curvature. Structural grafting (Cadaveric Pericardium) was required in only 7.8% of cases. Complications included one infection and no cases of glans necrosis. These findings suggest that SAPOC may represent a feasible reconstructive adjunct during inflatable penile prosthesis implantation that preserves tunical integrity while facilitating length restoration in selected patients. Further multicenter and comparative studies are needed to better define its safety profile and reproducibility.

Background/Objectives: Iatrogenic nerve injury is a significant challenge in urologic surgery, with radical prostatectomy posing a high risk due to complex pelvic neural anatomy. Despite advances in robotic-assisted and nerve-sparing techniques, postoperative urinary incontinence and erectile dysfunction remain prevalent, adversely affecting patients' quality of life and imposing substantial healthcare costs. Methods: A narrative review was conducted using PubMed, MEDLINE, and the Cochrane Library (searches through February 2026) for studies on radical prostatectomy epidemiology, mechanisms of nerve injury, functional outcomes, and economic burden. Emerging intraoperative fluorescence imaging technologies, surgical strategies to mitigate iatrogenic nerve injuries, and the financial costs of post-prostatectomy complications were assessed. Results: Robotic-assisted radical prostatectomy now accounts for >80% of procedures in the United States, and has been associated in observational studies with improved early recovery of erectile function compared with open and laparoscopic approaches. However, the lack of real-time nerve visualization remains a limiting factor. Recent milestones (January 2026) include the Food and Drug Administration Investigational New Drug clearance for the nerve-specific fluorophore LGW16-03 (NerveTrace), which enables real-time identification of sub-millimeter nerve branches, and the 510(k) premarket clearance of Dendrite imaging (November 2025). Conclusions: Enhanced intraoperative nerve discrimination via molecularly targeted imaging has the potential to reduce iatrogenic complications and improve long-term functional and economic outcomes in prostate cancer surgery, although these benefits have yet to be demonstrated in prospective clinical and health-economic studies.

Background/Objective: The psychosexual burden of human papillomavirus (HPV)-induced genital warts (GWs) in men remains underexplored. This study aimed to determine the prevalence of sexual dysfunction in men with GWs and to evaluate the effects of disease duration and condom use on the sexual cycle using the International Index of Erectile Function (IIEF-15). Methods: This single-center, cross-sectional study was conducted in the dermatology outpatient clinic of Kayseri City Education and Research Hospital between May and June 2026 and enrolled 150 sexually active male patients with clinically diagnosed, currently present genital wart lesions. To minimize reading comprehension and social desirability biases, a two-stage protocol was implemented. First, a clinician explained each IIEF-15 item face-to-face. Patients then completed the questionnaire independently and submitted it in a sealed envelope. Associations were analyzed using Spearman's rank correlation, and group comparisons used the Mann-Whitney U and Kruskal-Wallis tests. Results: The median age was 30.0 years (IQR 25.0-36.0) and the median disease duration was 18.0 months (IQR 8.0-35.8). Erectile dysfunction (ED) of varying severity was detected in 84.7% (n = 127) of patients. In unadjusted analysis, longer disease duration was associated with lower sexual function scores; however, these associations did not remain significant after adjustment for age. As ED severity increased, all other sexual function domains declined concurrently and strongly (Spearman rho ranging from -0.679 to -0.821; p < 0.0001). Condom users exhibited higher total sexual function scores than non-users (median 55.5, IQR 43.2-61.0 vs. median 49.5, IQR 37.0-60.0); however, this difference did not reach statistical significance (p = 0.076). Conclusions: Genital warts in men constitute a major psychosexual condition that disrupts multiple phases of the sexual response cycle, not merely a dermatological lesion. Our cross-sectional findings suggest that lesion-directed treatment alone may not fully address this psychosexual burden: whether the proactive integration of multidisciplinary sexual counseling improves outcomes should be tested in controlled, longitudinal studies.