Triclocarban (TCC) is a broad-spectrum antimicrobial widely used in various personal care products, textiles, and children's toys. TCC has potential reproductive and developmental toxicity in animals. However, little is known regarding the effect of TCC on human sperm function. In this study, an in vitro assay was used to investigate the effects of TCC on normal human spermatozoa and the possible underlying mechanisms involved. Semen from healthy male donors was collected and cultured in complete Biggers, Whitten and Whittingham (BWW) and low-sugar BWW media, followed by treatment with TCC at concentrations of 0, 0.1 µmol l -1 , 1 µmol l -1 , 10 µmol l -1 , and 100 µmol l -1 for 4 h. TCC was found to reduce the sperm total motility and progressive motility. Moreover, the sperm kinematic parameters, straight-line velocity (VSL), average path velocity (VAP), and curvilinear velocity (VCL) were affected in a dose-dependent manner. After treatment with TCC at the lowest effective concentration of 10 µmol l -1 , TCC caused a significant decrease in mitochondrial adenosine triphosphate (ATP) production and mitochondrial membrane potential (MMP) and a significant increase in reactive oxygen species (ROS), similar to the observations with the positive control carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP), suggesting that TCC may decrease sperm motility by affecting the oxidative phosphorylation (OXPHOS) pathway. In a sugar-free and low-sugar BWW culture environment, TCC enhanced the damaging effect on sperm motility and ATP, MMP, and lactate decreased significantly, suggesting that TCC may also affect the glycolytic pathway that supplies energy to spermatozoa. This study demonstrates a possible mechanism of TCC toxicity in spermatozoa involving both the OXPHOS and glycolysis pathways.

Surgical methods for varicocele remain controversial. This study intends to evaluate the efficacy and safety of different surgical approaches for treating varicocele through a network meta-analysis (NMA). PubMed, Embase, Cochrane, and Web of Science databases were thoroughly searched. In total, 13 randomized controlled trials (RCTs) and 24 cohort studies were included, covering 9 different surgical methods. Pairwise meta-analysis and NMA were performed by means of random-effects models, and interventions were ranked based on the surface under the cumulative ranking curve (SUCRA). According to the SUCRA, microsurgical subinguinal varicocelectomy (MSV; 91.6%), microsurgical retroperitoneal varicocelectomy (MRV; 78.2%), and microsurgical inguinal varicocelectomy (MIV; 76.7%) demonstrated the highest effectiveness in reducing postoperative recurrence rates. In this study, sclerotherapy embolization (SE; 87.2%), MSV (77.9%), and MIV (67.7%) showed the best results in lowering the risk of hydrocele occurrence. MIV (82.9%), MSV (75.9%), and coil embolization (CE; 58.7%) were notably effective in increasing sperm motility. Moreover, CE (76.7%), subinguinal approach varicocelectomy (SV; 69.2%), and SE (55.7%) were the most effective in increasing sperm count. SE (82.5%), transabdominal laparoscopic varicocelectomy (TLV; 76.5%), and MRV (52.7%) were superior in shortening the length of hospital stay. The incidence rates of adverse events for MRV (0), SE (3.3%), and MIV (4.1%) were notably low. Cluster analyses indicated that MSV was the most effective in the treatment of varicocele. Based on the existing evidence, MSV may represent the optimal choice for varicocele surgery. However, selecting clinical surgical strategies requires consideration of various factors, including patient needs, surgeon experience, and the learning curve.

Multiple morphological abnormalities of the sperm flagella (MMAF), characterized by severe morphological sperm defects, such as absent, short, irregular caliber, and coiled flagella with extreme asthenoteratozoospermia, are the most prevalent cause of human male infertility. Previous studies have identified several genes linked to MMAF; however, the increasing incidence of infertility indicates that most affected individuals remain undiagnosed, prompting further investigation to uncover novel mutations and genes. Whole-exome sequencing (WES) was conducted on a consanguineous infertile family from Pakistan to investigate the potential monogenic inheritance pattern in individuals affected by asthenoteratozoospermia. WES identified novel homozygous variants (c.A4457G; p.K1486R, and c.C10624T; p.R3542*) in dynein heavy chain domain 1 (DNHD1) in the proband and his affected brother. Semen analysis revealed a low progressive motility and severe MMAF in both siblings. Hematoxylin and eosin staining, immunofluorescence, and transmission electron microscopy unveiled an abnormal axoneme structure characterized by missing central pairs, disorganized microtubule duplets, and severe mitochondrial sheath defects, which led to the low sperm progressive motility and infertility in the affected siblings. This study identified a novel biallelic nonsense variant in DNHD1 that caused MMAF in a Pakistani population, endorsing previous findings and expanding the spectrum of potential DNHD1 variants in the pathogenesis of asthenoteratozoospermia.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.

The aim of this study was to investigate the trend in testicular volume changes after orchiopexy in children with cryptorchidism. The clinical data of 854 children with cryptorchidism who underwent orchiopexy between January 2013 and December 2016 in Shenzhen Children's Hospital (Shenzhen, China) were retrospectively analyzed. The mean (standard deviation) age of the patients was 2.8 (2.5) years, and the duration of follow-up ranged from 1 year to 5 years. Ultrasonography was conducted preoperatively and postoperatively. The variables analyzed included age at the time of surgery, type of surgical procedure, laterality, preoperative testicular position, preoperative and postoperative testicular volumes, and the testicular volume ratio of them. The average testicular volumes preoperatively and at 1 year, 2 years, 3 years, and 5 years postoperatively were 0.27 ml, 0.38 ml, 0.53 ml, 0.87 ml, and 1.00 ml, respectively ( P < 0.001). The corresponding testicular volume ratios were 0.67, 0.76, 0.80, 0.83, and 0.84 ( P < 0.001). The mean volume of the undescended testes was significantly smaller than the mean normative value ( P < 0.001, lower than the 10 th percentile). The postoperative testicular volumes in children with cryptorchidism were generally lower than those in healthy boys but were still greater than the 10 th percentile and exhibited an increasing trend. The older the child is at the time of surgery, the larger the gap in volume between the affected and normal testes. Although testicular volume tends to gradually increase after orchiopexy for cryptorchidism, it could not normalizes. Earlier surgery results in affected testicular volumes closer to those of healthy boys.

Postoperative wound repair after transurethral resection of the prostate (TURP) in benign prostatic hyperplasia (BPH) patients is crucial for reducing complications and promoting recovery. Androgens, particularly dihydrotestosterone (DHT), influence prostatic development and wound healing, with type II 5α-reductase (5αR2) playing a key role in DHT synthesis. In this study, the effects of type II 5α-reductase inhibitors (5-ARIs) on postoperative healing, inflammation control, and fibrosis reduction were evaluated. A double-blinded randomized clinical trial was performed to assess 87 BPH patients treated with type II 5-ARIs (n = 47) or placebo (n = 42) over six months. The type II 5-ARIs group presented a 55.0% lower complication rate (P = 0.002), with reduced hematuria (0 vs 7.1%, P = 0.046) and catheter reintroduction (0 vs 9.5%, P = 0.025). An animal study using 12 beagles was performed, and molecular markers were analyzed via single-cell RNA sequencing, enzyme-linked immunosorbent assay (ELISA), and histology. 5αR2 inhibition accelerated urothelial regeneration, decreased inflammation, and reduced myofibroblast activation by 42.0% while increasing the expression of the urothelial marker uroplakin 3A (UPK3A) by 67.0%. Organoid experiments confirmed increased urothelial differentiation and reduced glandular epithelial expansion with type II 5-ARI treatment. These findings suggest that 5αR2 inhibition promotes TURP postoperative recovery in BPH patients by reducing inflammation, inhibiting fibrosis, and promoting wound repair. These findings support the use of type II 5-ARIs as potential adjuvant therapies for optimizing BPH patient postoperative outcomes.

In the evaluation of male infertility, precise assessment of sperm functional competence has surpassed the requirements of conventional semen parameters. Existing computer-aided analysis systems are deficient at the molecular diagnostic level and also face challenges in live-cell fluorescence quantification. To address these issues, we have developed a novel integrated computational-imaging platform that combines a fine-tuned You Only Look Once version 8 (YOLOv8) architecture, tailored for the EVISEN dataset, with dual-probe fluorescence microscopy image segmentation, enabling simultaneous quantification of intracellular pH (pHi) and mitochondrial DNA G-quadruplexes (mtDNA G4s). By automating the localization of fluorescent foci, our algorithm systematically discriminates between the fluorescent signatures of the sperm head and principal piece, revealing correlations between fluorescence intensity ratios and sperm functional outcomes. This study demonstrates the potential of artificial intelligence (AI)-enhanced multimodal sperm analysis for molecular phenotyping of sperm functional competence. Integrating deep learning with live-cell fluorescence imaging, our platform offers a transformative tool for mechanistically informed diagnostics of male infertility.

Infertility is a global concern, and oligoasthenoteratozoospermia (OAT) is the most severe form of male infertility, characterized by reduced sperm count, decreased motility, and increased abnormal morphology. Multiple morphological abnormalities of the sperm flagella (MMAF) characterize the most severe type of OAT and are usually caused by loss-of-function mutations in the genes essential for vital aspects of sperm biology, including concentration, motility, and morphology. The fibrous sheath interacting protein 2 (FSIP2) plays an essential role in sperm flagellar structure and function by regulating such processes as intraflagellar transport and acrosome formation. The present study, employing whole-exome sequencing (WES), identified two FSIP2 mutations in one patient (patient 1), a homozygous missense (c.262C>A, p.P88T) and a homozygous frameshift mutation (c.10948_10951del, p.N3653Nfs*22), as well as a homozygous FSIP2 frameshift mutation (c.15982_15982del, p.I5328Lfs*33) in another patient (patient 2). The results of bioinformatics analysis indicate that the identified missense mutation (c.262C>A) is rare and predicted to have a deleterious effect on FSIP2. Transmission electron microscopy analysis of sperm revealed several abnormalities, including a disorganized mitochondrial sheath, absence of the central pair and some doublets of microtubules, and significant dysplasia of the fibrous sheath. Reverse transcription-polymerase chain reaction (RT-PCR) indicated significantly reduced FSIP2 messenger RNA (mRNA) levels in sperm lysate of the affected individuals. Immunofluorescence staining revealed a complete absence of FSIP2, A-kinase anchor protein 4 (AKAP4), sperm-associated antigen 6 (SPAG6), intraflagellar transport 20 (IFT20) and actin-like 7A (ACTL7A) proteins in the spermatozoa of patients. Thus, the novel FSIP2 variants identified in patient 1 and patient 2 are recognized as pathogenic mutations responsible for MMAF, providing valuable insights for genetic counseling and reproductive decision-making in affected males.

Erectile dysfunction is a complex and prevalent complication of diabetes, and effective treatments are lacking. Oxidative stress, fibrosis, and apoptosis are closely associated with the development of diabetes mellitus-related erectile dysfunction (DMED). Notably, ginsenoside Rb1 (Rb1) exerts antioxidant effects and displays promise in the treatment of DMED. This study evaluated the therapeutic efficacy of Rb1 in a rodent streptozotocin-induced DMED model. Thirty-two rats were randomly assigned to three groups: control group, DMED group, and DMED + Rb1 group. DMED was induced in male rats via an intraperitoneal injection of streptozotocin. After 8 weeks of Rb1 gavage, erectile function was assessed by the electrical stimulation of the cavernous nerve. In addition, western blot, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and Masson's trichrome staining were performed to verify the relevant factors and protein expression. Rb1 effectively improved the erectile function of the corpus cavernosum, decreased collagen content, and increased smooth muscle content in rats with diabetes. Rb1 decreased the levels of the pro-inflammatory factors (interleukin [IL]-6, tumor necrosis factor alpha [TNF-α], and IL-1β), and increased the levels of the anti-inflammatory factors (IL-10 and IL-4). Moreover, the activities of superoxide dismutase and catalase and levels of nitric oxide (NO) were increased, whereas malondialdehyde activity was decreased. Additionally, Rb1 activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) signaling pathway and inhibited cell apoptosis. Rb1 can improve erectile function in rats with DMED by increasing the activity of the PI3K/AKT/eNOS pathway, reducing oxidative stress, inhibiting inflammation and apoptosis, and alleviating corpus cavernosum fibrosis.

The management of data from computer-aided sperm analysis (CASA) systems is crucial for understanding sperm motility. CASA systems generate motility parameters derived from tracking individual sperm cells, producing raw data as spermatozoa coordinates, which form the basis for sperm trajectory construction. These parameters and trajectories allow statistical descriptions of motility and identification of sperm heterogeneity. The substantial information provided by CASA enables the application of artificial intelligence (AI) techniques to interpret their biological significance. However, the type and format of CASA data, whether raw or condensed, pose challenges for analysis using conventional statistical methods. Advances in machine learning and deep learning have addressed these limitations by leveraging motility parameters and trajectory representations for automated classification and clustering of motility patterns. These methods, including supervised and unsupervised learning, have been employed to identify kinematic subpopulations within sperm samples, offering deeper insights into sperm dynamics. Open-source tools and CASA systems have facilitated this progress by providing accessible platforms for AI applications in sperm motility analysis. Although the use of machine learning in this field remains limited, integrating CASA-derived data with AI techniques shows potential for automating sperm classification and identifying motility patterns, advancing reproductive biology and fertility assessments. This work reviews the traditional use of CASA data, the analytical constraints, and the promising role of machine learning in enhancing the understanding of the heterogeneity of sperm kinematics.

Recent studies have begun to investigate the metabolic and microbiota profiles in semen, yet their association with abnormal sperm morphology, particularly in teratozoospermia, remains insufficiently characterized. Identifying specific metabolites and microbial taxa linked to this condition could improve diagnostics and management for male infertility. This study analyzed semen samples from 231 patients, including 30 patients with teratozoospermia and 30 patients with normal sperm morphology, collected over four seasons in Chongqing, China. Metabolomic profiling by gas chromatography-mass spectrometry (GC-MS) and microbiota composition analysis via 16S ribosomal ribonucleic acid (rRNA) sequencing revealed distinct seasonal metabolomic shifts, with significant changes in summer and autumn. After excluding seasonally affected metabolites, 14 key metabolites were associated with teratozoospermia, including reduced levels of 4-hydroxyphenylpyruvic acid, phenylpyruvic acid, and N-acetyl-L-aspartic acid. These metabolites are involved in pathways related to oxidative stress and energy metabolism in spermatozoa, suggesting that their depletion may contribute to sperm abnormalities. Proteobacteria, Firmicutes, and Actinobacteriota were predominant phyla across all seasons and groups, but significant genus-level fluctuations, such as Acinetobacter and Staphylococcus, were observed. In teratozoospermia, genera such as Lactobacillus and Limnochordaceae showed differential abundance, correlating with key metabolites and suggesting potential functional interactions. Limnochordaceae showed a significant positive correlation with undecanoic acid, whereas Lactobacillus showed a negative correlation. These findings highlight that while seasonal changes significantly influence semen metabolomics and microbiota composition, teratozoospermia is characterized by specific, season-independent metabolic and microbial signatures. Our study provides insights into the metabolic and microbial dynamics of semen, suggesting the possibility of developing novel diagnostic tools and therapeutic strategies for male infertility.

This study examines the global burden and prevalence of male infertility using data from the Global Burden of Disease Study 2021 (GBD 2021 Study), encompassing 204 countries from 1990 to 2021. By analyzing disability-adjusted life years (DALYs) and prevalence trends, alongside lifestyle, environmental, and disease-related factors, including the impact of coronavirus disease 2019 (COVID-19), we identified significant temporal and regional disparities. Using joinpoint regression, decomposition analysis, and Bayesian age-period-cohort models, the results revealed a rising global burden, with DALYs increasing from 15.8 to 18.6 per 100 000 and the age-standardized prevalence rising from 2752.5 to 3218.9 per 100 000 over three decades. Low- and middle-sociodemographic index (SDI) regions presented the highest burden, driven by demographic shifts and epidemiological challenges. The COVID-19 pandemic further exacerbated healthcare disparities, particularly in resource-limited settings. These findings underscore the urgent need to integrate male infertility into global health agendas, emphasizing tailored interventions and policy reforms to address socioeconomic impacts and mitigate rising burdens, especially in low- and middle-SDI regions.

Age-related erectile dysfunction (ARED) represents a significant clinical challenge due to the interplay between chronic comorbidities and age-related physiological decline. This study investigated the therapeutic potential of near-infrared photobiomodulation therapy (NIR-PBMT) in ARED mice, focusing on molecular and physiological mechanisms of complex erectile function restoration. Aged mice received NIR-PBMT (4 J cm-2) every 48 h for 2 weeks. Erectile function was evaluated using the maximum intracavernosal pressure/mean arterial pressure (ICPmax/MAP) ratio following cavernous nerve stimulation. Histological analysis and western blotting revealed significant improvements in penile tissue architecture, including increased smooth muscle content, reduced collagen deposition, and altered expression of senescence markers (p21 and phosphorylated H2A histone family member X [γ-H2A.X]) and endothelial nitric oxide synthase (eNOS). In vitro studies using human corpus cavernous endothelial cells (HCCECs) demonstrated that NIR-PBMT reduced cellular senescence (assessed via SA-β-galactosidase staining), enhanced nitric oxide (NO) production, and improved mitochondrial network integrity. Angiogenesis assays further confirmed the pro-angiogenic effects of NIR-PBMT. Collectively, these findings highlight NIR-PBMT as a promising non-invasive therapy for ARED, acting through multiple pathways to reverse pathological remodeling and restore endothelial function. Future translational research is necessary to validate its clinical efficacy and optimize treatment protocols.

Recent data from clinical trials have shown that neoadjuvant therapies significantly improve the pathological outcomes of prostate cancer patients. This study aimed to assess the specific pathological and prognostic effects of these therapies in a real-world, multicenter cohort. Additionally, we explored how factors such as the duration of neoadjuvant therapy and pretreatment imaging modality impact overall treatment outcomes within this therapeutic framework. Data were collected from 407 patients with locally advanced prostate cancer (LAPC) who underwent radical prostatectomy following neoadjuvant therapy. Kaplan‒Meier estimates were used to evaluate the four primary clinical endpoints. The log-rank test was used to assess whether significant differences existed between patients grouped according to neoadjuvant therapy duration and pretreatment imaging modality. After a median follow-up period of 36 months, the median progression-free survival (PFS) for the entire cohort was 19 months. An analysis of different durations of neoadjuvant therapy revealed that compared with a 3-month regimen, a 6-month regimen was significantly associated with a greater extent of pathological downstaging and more favorable values for drug response indicators (Pearson test, P = 0.018). Additionally, the 6-month regimen significantly improved the clinical endpoints of PFS (log-rank test, P = 0.0075) and metastasis-free survival (MFS; log-rank test, P = 0.0069). Kaplan‒Meier analysis of patients grouped according to preoperative imaging modality revealed that the use of 68Ga-labeled prostate-specific membrane antigen-directed positron emission tomography/computed tomography (68Ga-PSMA PET/CT) before treatment, as opposed to traditional imaging, led to significant improvements in the clinical endpoints of PFS (log-rank test, P = 0.0059) and radiographic progression-free survival (rPFS; log-rank test, P = 0.016).

Accurate classification between non-clinically significant prostate cancer (non-csPCa) and clinically significant prostate cancer (csPCa) is essential for effective risk stratification and optimal management of prostate cancer. This study aimed to evaluate the consistency between preoperative and postoperative assessments of non-csPCa, and identify preoperative variables that can effectively predict the risk of csPCa. We analyzed data from 277 patients initially classified as non-csPCa after biopsy who underwent radical prostatectomy (RP) between August 2015 and January 2024. Univariate and multivariate logistic regression analyses were performed to identify predictors of csPCa. Receiver operating characteristic curves, calibration curves, and decision curve analyses were used to evaluate the performance of the nomogram model. Differences in biochemical recurrence rates between the non-csPCa group and csPCa group were analyzed using the log-rank test. Overall, 183 (66.1%) patients were reclassified as csPCa on the basis of postoperative pathology, with this group showing a higher incidence of biochemical recurrence versus non-csPCa (14 cases vs 0; P = 0.004). The following factors were independent predictors of csPCa: age, free prostate-specific antigen (fPSA)/total prostate-specific antigen (tPSA) ratio, cumulative cancer length, clinical tumor stage, and PSA density. In addition, a nomogram was developed with good predictive accuracy (area under the curve: 0.782). The substantial inconsistency between biopsy and RP pathology findings in the classification of non-csPCa highlights the limitations of biopsy-only management. The developed nomogram predicting the risk of csPCa provides urologists with a valuable tool for improved risk stratification and PCa management.

The tripartite motif-containing protein 26 (TRIM26) is an E3 ubiquitin ligase with strong oncogenic activity in various cancers. However, its role and molecular mechanism in prostate cancer (PCa) remain elusive. To clarify its role in promoting PCa progression, we evaluated TRIM26 expression in cells and clinical specimens using immunohistochemistry and found that TRIM26 was significantly upregulated in PCa tissue. Moreover, high TRIM26 levels predicted a poor prognosis in patients with PCa. Ectopic overexpression of TRIM26 increased PCa cell proliferation and migration, and this activity was suppressed by TRIM26 knockdown. Notably, TRIM26 activated both protein kinase B (AKT)/mammalian target of the rapamycin (mTOR) and the epithelial-mesenchymal transition (EMT) signaling pathways in PCa cells. Consistent with these findings, TRIM26 knockdown led to decreased activation of these signals. Furthermore, the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway activated by TRIM26 was attenuated by the PI3K inhibitor S14161. Similarly, cisplatin, a commonly used anti-PCa drug, downregulated TRIM26 and AKT/mTOR activation, while TRIM26 overexpression reversed AKT/mTOR inactivation. Finally, this finding was also demonstrated TRIM26 expression strikingly promoted tumor growth and activated AKT/mTOR signaling in a PCa xenograft. In conclusion, TRIM26 drives PCa malignancy and may be an attractive target for PCa treatment.

The circadian clock is strongly influenced by the sun exposure and prostate cancer has been shown to be inversely proportional to it. We investigated whether PCa aggressiveness in Montreal, Quebec, Canada, differs over the months during or following potentially longer exposure to sunlight. We analyzed 3447 patients treated between January 1995 and December 2023 with primary radiotherapy for localized PCa. We investigated whether the month when diagnostic biopsy was performed was associated with a more frequent diagnosis of a primary Gleason score (pGS) of 4 or 5. We grouped the months of biopsy into the four quarters (Q1-4) of the year. Multivariable logistic regression was used to predict a pGS of 4 or 5, adjusted for age and year of biopsy. There were significantly fewer biopsies (P = 0.027) with pGS 4 or 5 in the last 3 months of the year (Q4; 19.0%) than those in Q1-3 (22.9%). Age, prostate-specific antigen (PSA) level, and the number of positive biopsies were not significantly different between Q4 versus Q1-3. In multivariate logistic regression analysis, a biopsy in Q4 was significantly predictive of a lower risk of pGS 4 or 5 (odds ratio [OR]: 0.77, 95% confidence interval [CI]: 0.63-0.93, P = 0.007), as was older age (P < 0.001), but not the year of biopsy (P = 0.76). In conclusion, patients biopsied during Q4 had a 23% lower risk of a pGS 4 or 5 on diagnostic biopsy than those biopsied during the previous 9 months. Our results are not a proof of causality.

Erectile dysfunction (ED) is a common condition affecting men worldwide. The U.S. Food and Drug Administration (FDA) has approved phosphodiesterase type 5 inhibitors (PDE5Is), including sildenafil, tadalafil, vardenafil, and avanafil, for treating ED. However, real-world studies on adverse events (AEs) linked to PDE5Is are limited. This study comprehensively assessed the safety of PDE5Is based on reports from the FDA adverse event reporting system (FAERS) database from January 2004 to June 2024. The disproportionality analysis was used to evaluate the safety profiles of PDE5Is. Based on demographic stratification, correlational analysis and signal differences examination in subgroups were performed in different PDE5Is. Among the 53 517 AEs reports collected from the FAERS database, we identified 135, 73, 72, and 7 preferred terms associated with sildenafil, tadalafil, vardenafil, and avanafil, respectively. The study detected AEs listed on the FDA-approved label of each PDE5I. However, some AEs not listed on the labels were also identified. Some AEs listed by the FDA for PDE5Is were insignificant signals in our analysis. Significant differences were found among PDE5Is across age, weight, and onset time categories. We detected AEs related to the nervous, cardiovascular, and ocular systems that were not listed on the labels of the four PDE5Is, warranting further research on the underlying mechanisms. Additionally, significant differences in PDE5I-associated AEs were observed across age, weight, and onset time, highlighting the need for tailored patient management.

The transurethral route is the access of choice for benign prostatic hyperplasia (BPH) surgical treatment. Transurethral resection of the prostate (TURP) has been the gold standard in surgical intervention for BPH; however, the advent of novel surgical techniques and the exploration of new energy sources in recent decades have seen this primacy contested. Nevertheless, the transurethral route harbors numerous challenges and pitfalls that can pose significant risks even for the most experienced endoscopic urologists. Complications associated with transurethral access are well documented yet often underestimated by endoscopic surgeons, primarily because the pathological conditions arising from transurethral surgery typically fall within the realm of those specializing in genitourinary reconstructive surgery. This narrative review describes and critically discusses the specific pitfalls associated with transurethral surgery for BPH. Urethral strictures, transient or permanent postoperative incontinence, reintervention, and de novo/persistent lower urinary tract symptoms (LUTS) represent the main complications of transurethral treatments for BPH. These problems still stand as the foremost challenge for all endoscopists despite recent technological advancements. The use of increasingly miniaturized instruments, more mindful energy application, sphincter-sparing enucleation techniques, and the advent of so-called minimally invasive surgical techniques (MISTs) all contribute to a more conscious and anatomically respectful transurethral approach. An endoscopic transvesical suprapubic access may be another alternative strategy to minimize the complications of transurethral route in the future.