Therapeutic Advances in Urology最新文献

Male infertility accounts for a substantial proportion of global infertility, yet its molecular basis remains incompletely defined. Emerging evidence implicates epigenetic dysregulation in impaired spermatogenesis and abnormal sperm function. We synthesize genomic, transcriptomic, and single-cell studies to clarify how DNA methylation, histone modifications, and noncoding RNAs contribute to oligoasthenozoospermia. We also appraise single-cell RNA sequencing, single-cell assay for transposase-accessible chromatin using sequencing, and integrative multi-omics for resolving cell-type and stage-specific regulation. These approaches resolve germ-cell lineages, map gene-regulatory networks, and link chromatin states with transcription across spermatogenesis. Finally, we discuss translational implications for diagnostics, biomarkers, and therapeutic strategies, including antioxidant regimens, varicocele management, and assisted reproductive technologies outcomes. In conclusion, integrating epigenetics with single-cell technologies has enhanced our understanding of male germ cell development and identified potential research directions to improve reproductive health.

Background: Urolithiasis is a prevalent urological condition with high recurrence rates. Increasing evidence links metabolic syndrome (MetS) and its components to urinary stone disease, but the relationship between MetS and stone recurrence, including the roles of stone composition, residual fragments, urinary biochemistry, and lifestyle factors, remains underexplored.

Objectives: To investigate the association between MetS components and urinary stone recurrence in a retrospective cohort, with emphasis on stone composition, surgical residual fragments, urinary biochemical parameters, and lifestyle factors.

Design: A single-center retrospective case-control study.

Methods: We enrolled 542 patients with urinary stones (2019-2020) and followed them for up to 5 years (median follow-up 48 months). Baseline demographic, metabolic, lifestyle, urinary biochemical, surgical, and stone composition data were collected. Kaplan-Meier and Cox regression analyses were used to evaluate recurrence-free survival and independent predictors of recurrence.

Results: During follow-up, 211 patients (39%) experienced recurrence. The prevalence of MetS was significantly higher in the recurrence group (46.9% vs 28.7%). Cox regression identified hypertension (hazard ratio (HR) 1.31, 95% CI 1.04-1.65), hyperglycemia (HR 1.29, 1.01-1.64), hypertriglyceridemia (HR 1.38, 1.08-1.77), and residual fragments (HR 1.89, 1.47-2.43) as independent predictors. Stone composition analysis revealed higher recurrence in uric acid (52.3%), struvite (59.3%), and cystine (63.6%) stones compared with calcium oxalate (34.0%). Adverse urinary profiles (low pH, hypocitraturia, hyperuricosuria) and lifestyle factors (low fluid intake, high salt, high animal protein) were also associated with recurrence. Kaplan-Meier analysis showed shorter recurrence-free survival in patients with MetS (log-rank p < 0.001).

Conclusion: MetS and its components are independently associated with a higher risk of urinary stone recurrence. Stone composition, residual fragments, urinary biochemistry, and lifestyle factors further modify recurrence risk. These findings underscore the importance of comprehensive risk stratification and metabolic management in patients with urolithiasis.

Trail registration: Not applicable.

Background: Novel androgen receptor inhibitors (ARIs) have been recommended for patients with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC).

Objective: The present study aims to evaluate the cost-effectiveness of darolutamide, enzalutamide, apalutamide, and bicalutamide when combined with androgen deprivation therapy (ADT) for treating nmCRPC in the context of national drug price negotiations in China.

Design: A cost-effectiveness analysis.

Methods: A Markov model was developed to assess the cost-effectiveness of first-line therapy (darolutamide, enzalutamide, apalutamide, and bicalutamide) combined with ADT in nmCRPC patients, as well as second-line treatment options receiving chemotherapy after disease progression. The model included three health states: progression-free survival, progression survival, and death. The transfer probability per period was calculated using a Log-normal distribution. Drug costs were obtained from national price negotiations and relevant medical institutions, and health state utility values were obtained from the literature. Uncertainty was addressed through one-way sensitivity, probabilistic sensitivity, and scenario analyses.

Results: Compared with bicalutamide plus ADT, apalutamide, darolutamide, and enzalutamide provided incremental benefits of 3.52, 4.96, and 3.86 quality-adjusted life years (QALYs), respectively. This resulted in incremental cost-effectiveness ratios (ICERs) of $117,261, $166,618, and $238,170 in nmCRPC patients. Specifically, the ICERs of apalutamide, darolutamide, and enzalutamide were $33,357/QALY, $33,600/QALY, and $61,740/QALY, respectively.

Conclusion: Compared with bicalutamide plus ADT, apalutamide plus ADT and darolutamide plus ADT are more cost-effective under the willingness-to-pay threshold of $38,223/QALY. Nonetheless, enzalutamide plus ADT is not cost-effective compared with bicalutamide plus ADT.

Background: Ureteroscopy (URS) and laser lithotripsy are commonly used to treat kidney and ureteric stones. Post-operative infections, including urinary sepsis, can be a potentially serious complication of URS. We aimed to systematically review the incidence and predictors of post-ureteroscopy infections and sepsis.

Design: Systematic review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and registered prospectively with PROSPERO (CRD420251102349).

Data sources and methods: Only studies in the English language with over 500 patients were included. The Population, Intervention, Comparison, Outcome (PICO) framework for this study examined inpatients with stone disease who underwent ureteroscopy to investigate the incidence of urinary infections and urosepsis.

Results: Nineteen studies published between 2015 and 2024 were included, totalling 939,860 patients undergoing ureteroscopy for urolithiasis. Patient demographics varied, with a mean age range of 41.3-59.1 years and a male predominance (63.9%). Laser lithotripsy was the primary modality used, with a mean operative time of 53.4 min.The overall incidence of post-operative infectious complications was 7.8%, ranging from 0.8% to 18.2%. Fever (0.0%-16.2%) and urinary tract infections were the most commonly reported (0.0-12.3%), followed by sepsis (0.0%-7.0%) and septic shock (up to 1.9%). Identified risk factors included female gender, positive pre-operative urine cultures, pre-operative double-J stent placement, patient comorbidities and prolonged operative times.

Conclusion: Infectious complications predominate among post-ureteroscopy complications. Key factors for post-ureteroscopy infections included female gender, patient comorbidities, positive pre-operative cultures and longer operative times, highlighting the need for targeted management strategies to reduce complications.

Retroperitoneal fibroids are a rare condition that is often misdiagnosed preoperatively. It typically occurs in women with a history of hysterectomy or myomectomy for benign uterine smooth muscle tumors. In this case report, we present the case of a 50-year-old woman who presented with discomfort in the right perineal area. Imaging showed a large retroperitoneal tumor. The patient underwent robotic-assisted laparoscopic surgery to remove the mass, which was confirmed by histopathological analysis to be a uterine smooth muscle tumor of undetermined malignant potential (STUMP). The patient had no recurrence during the 2-year follow-up. The overall prognosis of STUMP is favorable, but more rigorous and long-term follow-up is required to monitor potential recurrence. Our case highlights that retroperitoneal masses in women with prior uterine fibroid surgery should raise suspicion for retroperitoneal fibroids. Robot-assisted laparoscopic surgery may be a safe and feasible minimally invasive option.

Background: Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has demonstrated efficacy in advanced urothelial carcinoma (UC) following platinum-based chemotherapy and immune checkpoint inhibitor (ICI) therapy. However, real-world evidence on its effectiveness and safety remains limited.

Methods: We conducted a multicenter retrospective study across Italian oncology centers to evaluate EV in patients with metastatic UC (mUC) who had progressed after prior platinum-based chemotherapy and ICI. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. We also assessed prognostic factors, including a composite index (HERO score) based on baseline hemoglobin and neutrophil-to-lymphocyte ratio (NLR).

Results: Fifty-three patients were included (median age 72 years; 41.5% ⩾75 years). The ORR was 34.0% (all partial responses), with a DCR of 58.5%. Median PFS and OS were 6.1 and 9.7 months, respectively. Multivariate analysis identified NLR ⩾ 4 and lung metastases as independent predictors of inferior PFS, while NLR ⩾ 4 remained independently associated with worse OS. Dose reductions and peripheral neuropathy were associated with improved outcomes. The HERO score significantly stratified patients by PFS and OS (p = 0.017 and p < 0.001, respectively). EV was generally well tolerated, with most adverse events being low-grade.

Conclusion: In this real-world cohort, EV confirmed its efficacy and manageable safety profile in mUC. The HERO score may provide a simple tool for risk stratification in clinical practice, though prospective validation is needed.

Background: Previous reviews evaluating biofeedback (BF)-assisted pelvic floor muscle (PFM) training (PFMT) with or without electrical stimulation (ES) for women with stress urinary incontinence (SUI) have reported conflicting results, and no consensus has been reached on the optimal parameters for this intervention.

Objectives: To (1) evaluate the effectiveness of non-invasive and invasive BF-assisted PFMT with or without ES for SUI in women and (2) investigate whether study design characteristics and intervention parameters affect treatment effects.

Design: Systematic review with meta-analysis and meta-regression.

Data sources and methods: Seven English and two Chinese databases were searched from inception to May 2025. Outcomes were synthesized as standardized mean differences (SMDs) or odds ratios (ORs) with 95% confidence intervals. Meta-regression was employed to investigate the impact of study design characteristics and intervention parameters on outcomes.

Results: This review included 21 studies involving 2373 participants. Meta-analyses revealed significant effects of invasive BF-assisted PFMT on PFM strength (SMD 0.71 (0.29, 1.14), p = 0.001), urinary incontinence (UI) symptom severity (SMD -0.33 (-0.63, -0.03), p = 0.032), quality of life (QoL; SMD -1.10 (-1.78, -0.41), p = 0.002), and improvement/cure rate (OR 2.02 (1.25, 3.26), p = 0.004). Meta-analyses also revealed significant effects of both invasive (SMD -1.23 (-1.93, -0.52), p = 0.001) and non-invasive (SMD -1.23 (-1.77, -0.68), p < 0.001) BF-assisted PFMT on urine loss severity. Meta-regression analysis revealed higher improvement/cure rates when BF-assisted PFMT involved mildly challenging exercises, tailoring to patients' abilities, therapist supervision, sessions of <10 min, durations of >1 h/week for ⩾8 weeks, and ⩾80%-95% adherence.

Conclusion: Invasive BF-assisted PFMT can improve PFM strength, reduce urine loss and UI symptom severity, enhance QoL, and increase the improvement/cure rate. Non-invasive BF-assisted PFMT can reduce urine loss severity. However, these results must be interpreted cautiously due to methodological flaws, risks of bias, and substantial heterogeneity across the included studies. Further high-quality studies are warranted to confirm the effectiveness of invasive or non-invasive BF-assisted PFMT with or without ES for treating SUI in women. The recommended parameters may optimize treatment effects.

Trial registration: PROSPERO (CRD42023473798).

Background: High sodium intake is associated with cardiovascular and kidney disease, as well as the development of lower urinary tract symptoms (LUTS). The amount of salt intake can influence the development of symptoms, but reduction may benefit patients by lowering the presentation of LUTS. However, there is a lack of systematization of evidence between salt intake and LUTS.

Objectives: Determine the relationship between a high salt intake and LUTS, and the impact of salt intake reduction on the development of LUTS.

Design: Systematic review.

Data sources and methods: We included observational studies and clinical trials that assessed any clinical manifestations of LUTS and any method of measuring salt intake to establish a comparison between high and low salt intake. A search was conducted on PubMed, Scopus, Ovid-Medline, WOS, and Embase databases in February 2024, including studies published at any time until the date of the search. Risk of bias was assessed using the Newcastle-Ottawa Scale and risk of bias in non-randomized studies of interventions. A qualitative synthesis of the included studies was performed, and a meta-analysis was not conducted due to the heterogeneity of how LUTS and salt intake were measured.

Results: We obtained 3085 articles, from which 10 were included in this review. In regards to urinary incontinence and general LUTS, patients who had a salty diet had more frequency and severe symptoms according to the Overactive Bladder Symptom score (H: 286, 1% vs N: 356, 0.6% vs N: 225, 0.8%; p < 0.001) and International Prostate Symptom score (H: 688, 2.5% vs N: 670, 1.7% vs B: 419, 2.3%; p < 0.001) respectively, compared to patients who had neutral or bland diets.

Conclusion: Some evidence suggests a possible association between a high salt intake and LUTS, and lowering salt intake might help to improve symptoms. We suggest that future studies improve clinical trial designs to clarify the relationship and methods to assess salt intake and measurement of LUTS.

Background: Artificial intelligence (AI) is increasingly used in patient education, especially with the rise in popularity of large language models (LLMs) such as ChatGPT, Microsoft Copilot, and DeepSeek, offering quick, accessible answers to health-related queries. Yet, in female sexual health, a field historically under-researched and stigmatized, AI's role in patient-facing education has yet to be thoroughly explored.

Objectives: To evaluate the accuracy and relevance of responses from ChatGPT, Copilot, and DeepSeek to common female sexual health questions, comparing them to the Prosayla website and to each other.

Design and methods: Twelve questions were developed based on content from the Prosayla website, covering topics ranging from menopause to sexual dysfunction. Responses were collected from the three LLMs and Prosayla. Two female sexual medicine experts independently rated each response for accuracy and relevance utilizing a six-point Likert scale (0-5) with a double-blind design being used to minimize bias. One-way ANOVA and Bonferroni post hoc analyses were used to assess statistical significance (p < 0.05).

Results: No significant differences in accuracy scores were observed across the four sources for Physician A (p = 0.558) or Physician B (p = 0.052), although ChatGPT was rated significantly more accurate than Prosayla in post hoc analysis by Physician B (p = 0.044). Relevance scores differed by rater: Physician A found no differences across sources (p = 0.771), while Physician B rated all three AI models significantly higher in relevance than Prosayla (p < 0.001).

Conclusion: AI models demonstrated comparable accuracy to Prosayla (a trusted patient education source), with the models being more relevant for one of the raters. These findings suggest that AI tools may complement traditional educational materials and support patient learning. However, expert oversight remains essential to ensure content quality and appropriateness. Future efforts should develop structured strategies and implementation frameworks to responsibly integrate AI into patient education, particularly in sensitive areas like women's sexual health.