World Journal of Mens Health最新文献

Purpose: Castration-resistant prostate cancer (CRPC) often progresses despite initial responses to enzalutamide owing to the development of resistance. Our study explored the mechanisms underlying resistance in enzalutamide-resistant prostate cancer cell lines, along with the role of phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchanger 1 (PREX1) in CRPC resistance.

Materials and methods: The sequencing of total RNA was performed to analyze the microarray gene expression profiles. In our colony formation assay, 1,000 cells per well were seeded into six-well plates to evaluate clonogenic survival. Phosphoprotein profiling was conducted to assess specific signaling pathways and estimate cell proliferation rates. Protein expression was analyzed by western blotting, and Rac GTPase activity was measured to evaluate the cellular responses to enzalutamide. Cell invasion was examined using Transwell migration assays. An in vivo model involving the subcutaneous implantation of tumor cells into mice was used to study tumorigenic potential under resistant conditions.

Results: RNA sequencing revealed activation of the cancer migration pathway in enzalutamide-resistant prostate cancer cells with significant upregulation of PREX1. PREX1 knockdown reduced the proliferation and colony formation rates of resistant cell lines. Mechanistically, PREX1 suppression inhibited both epidermal growth factor receptor and its downstream signaling pathways, including signal transducers and activators of transcription 5, thereby reducing cell migration and epithelial-mesenchymal transition, independent of Rac activation. In vivo, tumors derived from PREX1-knockdown cells exhibited significantly lower weights than those derived from control cells.

Conclusions: This study provides compelling evidence on the pivotal role of PREX1 in mediating enzalutamide resistance in CRPC. Our findings suggest that PREX1 is a promising therapeutic target that may modulate treatment efficacy and drug resistance in CRPC.

Purpose: Epidemiological studies have suggested that men are usually coupled with younger women. Parental age at first child have steadily increased over last decades. Accordingly, the age gap within partners has changed in the real-life setting over the same time frame. To analyze differences in partners' age (delta [Δ] age [M-F]) over a 20-year time frame among 1,605 men and their partners, seeking medical help for primary couple's infertility at a single center (2005-2024).

Materials and methods: Partners' age was recorded, Δage was calculated. Comorbidities were scored with Charlson Comorbidity Index (CCI). Educational status was recorded. Sexual dysfunctions were self-reported for all male patients. Descriptive statistics and linear regression analyses were applied.

Results: Median (interquartile range) patient's and partner's age were 37 (34-41) and 34 (31-37) years. Median Δage was 3 (0-6) years. Δage decreased by 1 point for each decade, being similar between 2005-2010 and 2011-2015, then decreasing from 2016-2020 to 2011-2015 and from 2021-2024 to 2011-2015 (all p<0.01). Similar values were found between 2021-2024 and 2016-2020, suggesting 2015 as a cutoff after which Δage decreased compared to earlier years, thus remaining afterwards stable. Δage change was related to increasing age bands of the female partner since male age was similar across the time frame. Men with low education status, with CCI ≥1 and with sedentary lifestyle had higher Δage (all p<0.01). Infertile men who self-reported erectile dysfunction had higher Δage than those with normal erectile function (p=0.01).

Conclusions: In infertile couples, age-difference relationships decreased over time due to female ageing at first parenthood. Greater Δage was linked to lower education, higher comorbidities, and a sedentary lifestyle in male partners. Erectile dysfunction was more common in couples with higher Δage.

Purpose: To perform a pilot study aiming at evaluating whether machine learning could be a useful model to evaluate semen analysis, improving the diagnostic work-up of male partner of infertile couples.

Materials and methods: A retrospective observational study was conducted using real-world data on male evaluated in routine andrological clinical practice at two Italian tertiary centers. The study utilized two distinct datasets: the first (UNIROMA) encompassed three distinct variables, including semen analysis, sex hormones, and testicular ultrasound parameters. The second dataset (UNIMORE) was constructed incorporating semen analysis, sex hormones, biochemical examinations, and parameters related to environmental pollution. The XGBoost analysis, as part of machine learning techniques, was applied separately to each dataset, as the two datasets did not share a significant overlap in terms of variables.

Results: The UNIROMA dataset comprised 2,334 male subjects. The XGBoost analysis exhibited the highest accuracy (area under the curve [AUC], 0.987) in predicting patients with azoospermia compared to other categories. Remarkably, our analysis revealed that among the most influential predictive variables, follicle-stimulating hormone serum levels (F-score=492.0), inhibin B serum levels (F-score=261), and bitesticular volume (F-score=253.0) stood out. The UNIMORE dataset consisted of 11,981 records. The XGBoost analysis demonstrated a good predictive accuracy (AUC, 0.668), especially for identifying the azoospermia group. Notably, the most crucial predictive variables were environmental pollution parameters (PM10, F-score=361; NO₂, F-score=299) and biochemical data (white blood cells, F-score=326; red blood cells, F-score=299).

Conclusions: This pilot study applies machine learning to two extensive datasets, suggesting that changes in semen analysis may be linked to other variables, such as testicular ultrasound characteristics, red blood cell count, and environmental pollution.

Purpose: In recent years, many genes have been associated with male infertility; however, testing of monogenic forms has not yet been clinically implemented in the diagnosis of severe forms of idiopathic male infertility, as the diagnostic utility has not been established yet. The aim of this study was therefore to answer if the implementation of genetic testing for monogenic forms of male infertility could contribute to the clinical diagnosis of men with severe forms of idiopathic male infertility.

Materials and methods: Based on the ClinGene curation protocol, we defined a panel of genes with sufficient evidence for the involvement with severe male infertility. We tested the 21-gene panel in a representative multicentric cohort of men with significantly impaired spermatogenesis. We performed whole exome sequencing on 191 infertile men with severe forms of idiopathic male infertility; non-obstructive azoospermia, and severe oligozoospermia (<5 million spermatozoa/mL). The control group consisted of 216 men who fathered a child. DNA was prepared based on the Twist CORE exome protocol and sequenced on the Illumina NovaSeq 6000 platform. Variants were classified using the Association for Clinical Genomic Science (ACGS) Best Practice Guidelines for Variant Classification in Rare Disease 2020.

Results: We identified potential monogenic disease-causing variants in four infertile men. Pathogenic/likely pathogenic variants in STAG3 (c.2776C>T, p.Arg926^*; c.2817delG, p.Leu940fs), MSH4 (c.1392delG, p.Ile465fs; c.2261C>T, p.Ser754Leu), TEX15 (c.6848_6849delGA, p.Arg2283fs; c.6271dupA, p.Arg2091fs), and TEX14 (c.1021C>T, p.Arg341^*) genes were found.

Conclusions: In the present multicentric cohort study, a monogenic cause in 2.1% of infertile men was identified. These findings confirm the utility of monogenic testing and suggest the clinical use of monogenic testing for men with severe forms of idiopathic male infertility.

Purpose: The K-FRAIL scale is a Korean version of the aging questionnaire that allows screening and diagnosis of easily observable aging in the elderly through a simple self-answer questionnaire. The objective of this study was to examine the relation between fraility and clinical symptoms of the lower urinary tract in elderly men using the K-FRAIL scale.

Materials and methods: A prospective study was conducted on 100 patients who underwent urological examination at our hospital from January 2021 to December 2021. Among them, 62 patients who met the study criteria completed the following questionnaires and lower urinary tract symptoms (LUTS) parameters: K-FRAIL, International Prostate Symptom Score (IPSS), prostate specific antigen, transrectal ultrasonography, and uroflowmetry. In this cross-sectional study, we compared the K-FRAIL scale parameters with various clinical examination parameters in elderly men presenting with LUTS. We also assessed the time required to complete the scale.

Results: The age of the subjects was 66.8±5.96 years in the normal group and 71.6±9.83 years in the frail group (p=0.027). In terms of IPSS indicators, the total scores of the natural patient group and the frail patient group were 13.24±5.48 and 20.44±9.67 (p=0.001); in terms of patient serum testosterone indicators, the scores of the natural patient group and the frail patient group were 4.32±1.52 and 3.74±1.64, respectively (p=0.163). The results indicated that IPSS item 7 and serum testosterone were significant predictors (odds ratio [OR]=4.679, p=0.29; OR=0.391, p=0.043, respectively).

Conclusions: The results of this study show that elderly men with fraility are more likely to develop nocturia and lower testosterone. When treating men with fraility, it will be helpful to know these characteristics and treat them.

The gay, bisexual, transgender, and queer + (LGBTQ+) community is underserved, and their needs are often misunderstood and/or overlooked. We aimed to analyze the current literature regarding prostate cancer's (PCa) impact on the quality of life (QoL) of LGBTQ+ patients with a focus on sexuality, identity, and psychosocial support. In June 2024, we searched the following databases, PubMed, Embase, and Clinicaltrials.gov, for relevant data regarding sexuality, identity, and psychosocial support of LGBTQ+ suffering from PCa using the keywords "Prostate Cancer AND Gay or Prostate Cancer AND LGBTQ+." In sum, there were only a few records on the subject with very few clinical trials. Major concerns of inadequate care included the impact on sexual intercourse, sexual identity and role, mental health, and psychological support. Two U.S. trials reported on the deep health-related quality of LGBTQ+ community members in dealing with PCa. These revealed significant sufferings and disparities in care access, delivery, perception, and satisfaction in the LGBTQ+ patients affected by PCa. Current data suggest that LGBTQ+ patients with PCa are an under-researched population whose QoL concerns and needs are often overlooked. PCa has a significant impact on the sexual, emotional, and social well-being of the LGBTQ+ community; this impact seems different than the non-LGBTQ+ community, underlying the need for focused research and interventions.

Purpose: Information retrieval (IR) and risk assessment (RA) from multi-modality imaging and pathology reports are critical to prostate cancer (PC) treatment. This study aims to evaluate the performance of four general-purpose large language model (LLMs) in IR and RA tasks.

Materials and methods: We conducted a study using simulated text reports from computed tomography, magnetic resonance imaging, bone scans, and biopsy pathology on stage IV PC patients. We assessed four LLMs (ChatGPT-4-turbo, Claude-3-opus, Gemini-Pro-1.0, ChatGPT-3.5-turbo) on three RA tasks (LATITUDE, CHAARTED, TwNHI) and seven IR tasks. It included TNM staging, and the detection and quantification of bone and visceral metastases, providing a broad evaluation of their capabilities in handling diverse clinical data. We queried LLMs with multi-modality reports using zero-shot chain-of-thought prompting via application programming interface. With three adjudicators' consensus as the gold standard, these models' performances were assessed through repeated single-round queries and ensemble voting methods, using 6 outcome metrics.

Results: Among 350 stage IV PC patients with simulated reports, 115 (32.9%), 128 (36.6%), and 94 (26.9%) belonged to LATITUDE, CHAARTED, and TwNHI high-risk, respectively. Ensemble voting, based on three repeated single-round queries, consistently enhances accuracy with a higher likelihood of achieving non-inferior results compared to a single query. Four models showed minimal differences in IR tasks with high accuracy (87.4%-94.2%) and consistency (ICC>0.8) in TNM staging. However, there were significant differences in RA performance, with the ranking as follows: ChatGPT-4-turbo, Claude-3-opus, Gemini-Pro-1.0, and ChatGPT-3.5-turbo, respectively. ChatGPT-4-turbo achieved the highest accuracy (90.1%, 90.7%,91.6%), and consistency (ICC 0.86, 0.93, 0.76) across 3 RA tasks.

Conclusions: ChatGPT-4-turbo demonstrated satisfactory accuracy and outcomes in RA and IR for stage IV PC, suggesting its potential for clinical decision support. However, the risks of misinterpretation impacting decision-making cannot be overlooked. Further research is necessary to validate these findings in other cancers.

Purpose: There is increased interest in regenerative therapies (RTs) to treat erectile dysfunction (ED). However, the need for society's guidelines has led to varied practices. This study aims to investigate current global practices, address the heterogeneity in treatment protocols and evaluations, and establish expert recommendations in clinical practice.

Materials and methods: Senior experts from the Global Andrology Forum (GAF) created a 32-question survey to evaluate the clinical aspects of various RT modalities and compare them with each other and with phosphodiesterase type 5 inhibitors (PDE5is). The survey was distributed worldwide to ED specialists through online Google Forms, the GAF website, international professional societies, and direct emails. The responses were analyzed and are presented as percentage frequencies. Additionally, an expert consensus on recommendations for RT use was reached at via a modified Delphi method.

Results: Out of 163 respondents from 39 countries, the majority (80.1%) were using low-intensity shockwave therapy (LISWT), followed by platelet-rich plasma (PRP) 61.3% and stem cell therapy (SCT) 17.8%. Efficacy comparisons revealed no perceived significant differences among RT modalities (p=0.124). Compared to PDE5is, the efficacy of LISWT and PRP was considered lower by the respondents, while SCT was rated better by almost half of those who used SCT. The duration of improvement varied (p=0.279), with most improvements lasting 1 to 6 months. The treatment protocols used for LISWT were mainly consistent but varied widely for PRP and SCT. Adverse effects were minimal, particularly for LISWT (p<0.001). The costs varied significantly (p<0.001), with SCT being the most expensive. The evidence for efficacy was rated as primarily moderate to strong for LISWT but poor for PRP and SCT (p=0.027).

Conclusions: Most respondents utilized LISWT, followed by PRP, with SCT being the least commonly utilized. The high break heterogeneity in treatment protocols and evaluation of RT underscores the need for further studies and guidelines to establish best practices.