Effects of Varicocele Repair on Testicular Endocrine Function: A Systematic Review and Meta-Analysis.

PURPOSE: The objective of this manuscript is to assess the effect of varicocele repair (VR) in patients with clinical varicoceles on serum total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin B serum levels. MATERIALS AND METHODS: The study was performed in compliance with the Meta-Analysis and Systematic Reviews of Observational Studies (MOOSE) guidelines and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). All eligible studies were selected following the PICOS (Population, Intervention, Comparison/Comparator, Outcomes, Study design) model. The values of each outcome measured after VR were compared to the before parameters and, when available, to the values on patients with unrepaired varicocele, and to those of healthy controls with no varicocele. For total testosterone, the values were sub-analyzed based on the mean total testosterone levels before VR (<300 ng/dL or >300 ng/dL), the fertility status, the time of follow-up and the technique used for VR. RESULTS: From a total of 460 abstracts retrieved, 48 articles were included in our meta-analysis. Serum total testosterone levels were significantly higher after VR compared to both pre-treatment levels (mean difference [MD] 82.45 ng/dL, 95% confidence interval [CI]: 64.14-100.76; p<0.00001) and to the levels of patients with unrepaired varicocele (MD 91.64 ng/dL, 95% CI: 62.30-120.99; p<0.00001). They did not differ from the levels of healthy controls with no varicocele (MD -22.01 ng/dL, 95% CI: -68.59-24.58; p=0.35). The increase resulted to be independent from the mean total testosterone levels before VR, fertility status, time of follow-up and type of VR. After VR, a trend toward lower serum LH levels was found compared to before values (MD -0.37 IU/L, 95% CI: -0.74-0.01; p=0.06). When compared to the levels of patients with unrepaired VR, LH levels after VR were significantly lower (MD -0.96 IU/L, 95% CI: -1.56 to -0.35; p=0.002). LH levels were not significantly higher than healthy men without varicocele (MD 0.84 IU/L, 95% CI: -0.68-2.36; p=0.28). Patients with VR had significantly lower FSH levels compared to their pre-treatment values (MD -1.43 IU/L, 95% CI: -1.82 to -1.04; p<0.00001), and also to those of patients with non-repaired varicocele (MD -2.35 IU/L, 95% CI: -4.06 to -0.65; p=0.007). When compared to healthy controls with no varicocele, FSH levels were significantly higher (MD 2.71 IU/L, 95% CI: 1.12-4.31; p=0.0009). Lastly, after VR no significant change in inhibin B serum levels was seen compared to pre-treatment levels (MD 11.76 pg/mL, 95% CI: -3.83-27.35; p=0.14). CONCLUSIONS: The present meta-analysis is the largest to date to assess the impact of VR on Leydig cell and Sertoli cell function using a before-after analysis for uncontrolled studies, and using data from patients with unrepaired varicoceles or healthy patients without varicocele as controls. VR was found to increase and restore to normality serum levels of total testosterone and LH. This evidence could be of value in considering the treatment of varicocele in patients with low testosterone or those who show a progressive decline in testosterone levels.

Prostate cancer survivorship of Australian men living with prostate cancer: Patient support programs in Australia.

BACKGROUND: Treatment for prostate cancer (PC) is associated with adverse effects, especially in patients receiving androgen deprivation therapy (ADT). The Australian Government, non-governmental organisations and pharmaceutical companies responsible for marketing ADT have initiated and sponsored various strategic support programs for patients diagnosed with PC. OBJECTIVE: This professional article provides an overview of available PC patient support programs in Australia to assist general practitioners (GPs) to direct patient referrals and optimise clinical care. DISCUSSION: These PC support programs provide useful assistance on educational materials, decision support, clinical care management and referral to specialised services (eg continence advice, sexual health counselling and psychological support). More concerted efforts and smarter investment in PC survivorship programs are necessary to engage, educate and improve the lives of men living with PC more effectively.

Further Insights into The Pathogenic Mechanisms of Haemotropic Mycoplasma ovis.

In this study, we examined the effects of experimental intraperitoneal infection with haemotropic Mycoplasma ovis (0.5 mL of blood containing 80% parasitaemia) on selected serum biomarkers and cellular pathology in mice. After infection, M. ovis cells appeared in the blood films within one week. A dose-dependent peak of parasitemia was observed during the 3rd-week post-infection (pi), with a significant decrease in mean PCV between treatment versus control group at week 3 (t 14 = -3.693, P < 0.02), week 5 (t 14 = -2.096, P = 0.055), and week 7 (t 14 = -4.329, P = 0.001). There was a significantly (t 8 = -2.330, P = 0.048) lower serum oestrogen in treatment (10.38 ± 5.07) than control (17.43 ± 4.48), while serum progesterone was significantly (t 8 = 5.415, P = 0.001) increased in treatment (27.37 ± 2.17) than control (15.92 ± 4.20). Serum haptoglobin was significantly (t 8 = 8.525, P < 0.01) lower in treatment (8.72 ± 1.49) than control (18.16 ± 1.98) while the SAA was significantly (t 8 = 3.362, P = 0.01) higher in treatment (16.79 ± 2.71) than control (11.59 ± 2.15). Prominent lesions observed in the ovary include degeneration, necrosis, vacuolation, and hypertrophy of the lutein cells in corpora lutea. In the lymph nodes, diffused cellular hyperplasia of the lymphoid tissue in the cortex. In the liver, degeneration and necrosis accompanied by leucocytic cellular infiltration and Kupffer cell proliferation within the sinusoids. There were diffused leucocytic infiltrations and proliferative lesions in the glomerulus of the kidneys. The disturbance in progesterone and ovarian pathology highlights the potential role of haemotropic M. ovis in reproductive disorders. The observed changes in biomarkers and cellular reactions following M. ovis infection in the mouse may be further advanced in sheep and goats.

Abstrak: Dalam kajian ini, kami mengkaji kesan jangkitan intraperitoneal eksperimen dengan Mycoplasma ovis hemotropik (0.5 mL darah yang mengandungi 80% parasitemia) pada biomarker serum terpilih dan patologi selular pada tikus. Selepas jangkitan, sel M. ovis muncul dalam filem darah dalam masa satu minggu. Kemuncak parasitemia yang bergantung kepada dos diperhatikan semasa minggu ke-3 selepas jangkitan (pi), dengan penurunan ketara dalam purata PCV antara rawatan berbanding kumpulan kawalan pada minggu ke-3 (t 14 = −3.693, P < 0.02), minggu ke-5 (t 14 = −2.096, P = 0.055), dan minggu 7 (t 14 = −4.329, P = 0.001). Terdapat estrogen serum yang jauh lebih rendah (t 8 = −2.330, P = 0.048) dalam rawatan (10.38 ± 5.07) daripada kawalan (17.43 ± 4.48), manakala progesteron serum adalah ketara (t 8 = 5.415, P = 0.001) meningkat dalam rawatan (27.37 ± 2.17) daripada kawalan (15.92 ± 4.20). Serum haptoglobin adalah ketara (t 8 = 8.525, P < 0.01) lebih rendah dalam rawatan (8.72 ± 1.49) daripada kawalan (18.16 ± 1.98) manakala SAA adalah ketara (t 8 = 3.362, P = 0.01) lebih tinggi dalam rawatan (16.79 ± 2.71) daripada kawalan (11.59 ± 2.15). Lesi yang menonjol yang diperhatikan dalam ovari termasuk degenerasi, nekrosis, vakuolasi dan hipertrofi sel lutein dalam corpora lutea. Di kelenjar getah bening, hiperplasia selular meresap tisu limfoid di korteks. Di dalam hati, degenerasi dan nekrosis disertai dengan penyusupan selular leukositik dan percambahan sel Kupffer dalam sinusoid. Terdapat penyusupan leukosit yang meresap dan lesi proliferatif dalam glomerulus buah pinggang. Gangguan dalam patologi progesteron dan ovari menyerlahkan potensi peranan hemotropik M. ovis dalam gangguan pembiakan. Perubahan yang diperhatikan dalam biomarker dan tindak balas selular berikutan jangkitan M. ovis pada tikus mungkin lebih maju pada biri-biri dan kambing.

Post-Vasectomy Semen Analysis: What's All the Fuss about?

Vasectomy is a reliable male contraceptive method with a success rate exceeding 98%. Despite its efficacy, vasectomy is not foolproof, with potential early and late failures requiring careful postoperative monitoring via post-vasectomy semen analysis (PVSA). Published guidelines emphasize the necessity of conducting PVSA to ensure clinical sterility. Despite these clear guidelines, discrepancies in adherence and interpretation persist, with significant mismatches between guidelines and actual practice. Recent shifts in societal attitudes toward reproductive autonomy, spurred by significant political events and socioeconomic factors, have increased vasectomy rates, particularly among younger, childless men. This demographic change calls for enhanced PVSA compliance and clear communication about the non-immediate contraceptive effect of vasectomy. Home test kits have emerged as a convenient, though not always reliable, method for conducting PVSAs, which may require reevaluation in clinical practice. Given the variations across clinical guidelines and the challenges in achieving consistent PVSA outcomes, further research is needed to harmonize PVSA protocols across different health systems. PVSA is typically conducted between 8 and 16 weeks post-vasectomy, depending on the surgeon's preference. Success is confirmed when a fresh, uncentrifuged sample exhibits either azoospermia, rare non-motile sperm (RNMS), or fewer than 100,000 non-motile sperm per milliliter. This effort will ensure that both patients and practitioners can rely on vasectomy as a safe and effective form of contraception. Effective patient counseling and strategic follow-up are crucial when it comes to managing expectations and ensuring compliance with post-vasectomy protocols, thereby minimizing the risk of unintended pregnancies post-procedure.

Pharmacological therapies for male infertility.

Male factor infertility is a multifaceted problem that affects approximately 50% of couples suffering from infertility. Causes of male infertility include endocrine disturbances, gonadotoxins, genetic abnormalities, varicocele, malignancies, infections, congenital or acquired urogenital abnormalities, iatrogenic factors, immunological factors, and idiopathic reasons. There are a variety of treatment options for male infertility, depending on the underlying cause(s). These can include surgical treatments, medical/hormonal therapies, and assisted reproductive techniques (ART), which can be combined with surgical sperm retrieval (SSR) if necessary. In this review article, the pharmacological therapies for male infertility are grouped by their underlying causes. Some of these therapies are targeted and specific, while others are used empirically to treat idiopathic male infertility. This will include treatments to optimize infertility in patients who have hypogonadism, ejaculatory dysfunction, infections, or idiopathic male infertility. Finally, we will provide an overview of the future directions of pharmacological therapies for male infertility. Significance Statement Male infertility is a significant worldwide problem. Detailed knowledge of the pharmacological therapies available will ensure the prescription of appropriate therapy and avoid the use of unnecessary or harmful treatments.

Narrative review: evolution in device technology and advances in surgical techniques on AMS 800 device in the last 50 years.

Background and Objective: The current AMS 800 artificial urinary sphincter (AUS) device is designed to simulate the function of the biological urinary sphincter to prevent urinary flow through mucosal coaptation, compression, and pressure transmission. The challenges in designing the AMS 800 device involve not only the mechanical operation of the artificial sphincter device but also producing a device that is effective, safe, and durable for patients in the long term. The following article provides a narrative review regarding the evolution and development of the AMS 800 devices over the years and evaluates the advances in surgical techniques relating to AMS 800 implantation. Methods: Available literature pertaining to the AMS 800 device was reviewed from the MEDLINE and EMBASE databases between 1 January 2000 to 31 December 2022. Emphasis is placed on key scientific publications including previous reviews and clinical guidelines relevant to AMS 800 device(s) and surgical techniques. Key Content and Findings: From the engineering point of view, the current AMS 800 device is ingenious and has stood the test of time. The basic design of this modern AUS consists of 3 separate components namely a pressure regulating balloon (PRB), an inflatable cuff, and a control pump. Continued innovations in device design and technology, coupled with refinements in surgical techniques over the past 5 decades have ensured that the AMS 800 device is and remains the standard of care in male stress urinary incontinence. While the long-term AMS 800 efficacy, safety, and durability are well documented, it is not without its limitations and complications. Mechanical and non-mechanical complications can occur especially in high-risk populations (such as in radiated patients) despite strict adherence to surgical principles and manufacturer's guidelines. Conclusions: Continued innovations in device design, technology, and surgical techniques have ensured that the AMS 800 device is an effective and safe treatment for male stress urinary incontinence (SUI). Future directions in the treatment of male SUI likely reside in cellular regenerative therapy and nanotechnology to restore, replace, or simulate the damaged native urinary sphincter.

A narrative review on synchronous concurrent versus delayed sequential surgery in the artificial urinary sphincter and penile prosthesis implantation.

Background and Objective: In a patient who complains of both stress urinary incontinence (SUI) and erectile dysfunction (ED), prosthetic surgery with a urinary continence device and penile prosthesis implant can offer a definitive solution to address both problems. The AMS 800 artificial urinary sphincter (AUS) device is considered the standard of care to restore SUI while the inflatable penile prosthesis (IPP) device is thought to be superior to a malleable prosthesis to provide a more natural penile erection with higher patient satisfaction rates. The following article explores the current understanding of AMS 800 AUS surgery and IPP device in treating males with concurrent SUI and ED as well as evaluates the advantages and disadvantages of concurrent synchronous dual vs. delayed or staged device implantation. Methods: The available literature on AUS and IPP implantation was reviewed on PubMed and Embase databases between 1 January 2000 and 1 December 2022. This narrative review evaluates relevant key features pertaining to prosthetic surgery with an emphasis on arguments for concurrent synchronous dual vs. delayed sequential surgery for AUS and IPP devices. Additionally, this paper provides a brief surgical description of the techniques and potential complications relating to both prosthetic procedures. Key Content and Findings: While a great deal is known about the excellent outcomes of both AUS and IPP implantation, there is limited literature published on the outcomes of dual AUS and IPP surgery. The decision to proceed with concurrent synchronous dual vs. delayed sequential two-stage implants is likely determined by the patient's preference, the surgeon's expertise, and the availability of prostheses. In either situation, patients should be counselled regarding the advantages and disadvantages of undergoing synchronous concurrent vs. delayed sequential implants and associated surgical challenges are likely dependent on the patient's anatomy and the surgeon's preference. Conclusions: For carefully selected patients with SUI and ED, dual implantation of AUS and IPP provides a definitive treatment to address both conditions at the same time. Patients should be counselled regarding the advantages and disadvantages of synchronous concurrent vs. sequentially delayed implants while technical considerations regarding the sequence of prosthetic device surgery are likely dependent on the patient's factors and the surgeon's preference and surgical expertise.

The male slings: an effective and safe alternative surgical treatment to the artificial urinary sphincter for male stress urinary incontinence?-a narrative review.

Background and Objective: The ideal candidate for a male sling (MS) should have a mild to moderate degree of stress urinary incontinence (SUI). This narrative review article evaluates the current MS devices in the commercial market and examines the role of MS as an effective and safe alternative treatment option for male SUI. Methods: The available literature on MS was reviewed and relevant clinical studies pertaining to each MS were summarised with emphasis on device design and technology as well as specific surgical findings relating to clinical outcomes. Key Content and Findings: Over the past two decades, there have been considerable scientific advances in MS design and technology, and MS is an attractive alternative for patients who might not require or want an artificial urinary sphincter. The modern MS can be classified as adjustable or non-adjustable types and is placed either through a retropubic or transobturator (TO) approach. Strict patient selection and counselling, selection of MS with proven clinical records, and safe surgical practice are paramount to ensure a high continence rate, good patient satisfaction, and low postoperative complications. Published data on various MS materials and devices showed reasonable clinical efficacy and safety outcomes, although many of these synthetic MS devices may not be available worldwide due to a lack of regulatory approval in many countries. While the ideal MS is probably yet to be developed, continued scientific advances in slings design, mesh technology, and more refined surgical techniques will improve the continence rate and deliver better safety records. Conclusions: As clinical data matures with longer-term outcomes coupled with advances in scientific designs and technology, the ability to have and select the optimal MS for a particular patient will come to fruition.

Rigicon ContiClassic and ContiReflex artificial urinary sphincter devices.

The modern AMS 800 artificial urinary sphincter (AUS) is often considered the standard of care for the treatment of moderate to severe stress urinary incontinence in male patients. Nonetheless, the AMS 800 device has several inherent limitations, and these factors can potentially impact its clinical utility and impede excellent clinical outcomes. The new Rigicon AUS devices such as ContiClassic and ContiReflex urinary sphincters are designed to overcome some of the existing issues pertaining to the AMS 800 device. The ContiClassic device is similar in terms of device design to the AMS 800 apart from the inclusion of a hydrophilic coating, has a greater range of cuff sizes with 0.25-cm diameter increments, and an Easy Clink Connectors which negates the need for an assembly tool. In contrast, The ContiReflex device differs from the ContiClassic model in that it features an extra stress relief balloon (SRB) to provide a safeguard on the urethral occlusive mechanism against any sudden increase in intra-abdominal pressure, and a larger pump system that is responsible to cycle fluid between the higher pressure two-balloon system and the sphincteric cuff. The following brief report evaluates the current device design and technology of the Rigicon ContiClassic and ContiReflex AUS devices.

Changes in Testosterone Levels Following Surgical Sperm Retrieval in Men with Non-Obstructive Azoospermia: Systematic Review and Meta-Analysis.

PURPOSE: Surgical sperm retrieval (SSR) is used to extract spermatozoa for use with intracytoplasmic sperm injection in men with obstructive and non-obstructive azoospermia (NOA). The procedure may lead to segmental devascularization, postoperative fibrosis, and atrophy with a subsequent decrease in testosterone. The aim of the study is to investigate the impact of SSR on serum levels of total testosterone (TT), follicle-stimulating hormone (FSH), luteinizing hormone (LH) testicular volume, and sexual function in infertile azoospermic men. MATERIALS AND METHODS: In this systematic review and meta-analysis (SRMA), we searched articles in "PubMed" and "Scopus" exploring the impact of SSR on TT, FSH, LH, and testicular volume. The full-text articles were screened to assess eligibility before data extraction, quality assessment, and meta-analysis. RESULTS: Seventeen studies meeting the inclusion criteria were finally analyzed and included 1,685 infertile, azoospermic men. Patients underwent SSR and were followed in the postoperative period (one week to 32 months). The analysis showed a significant reduction in TT (mean difference [MD] 3.81 nmol/L, 95% confidence interval [CI] 0.55:7.06; p=0.02) compared to pre-SSR values. We also observed insignificant differences in serum FSH (MD 5.08 IU/L, 95% CI -5.6:15.8; p=0.35), LH (MD -2.96 IU/L, 95% CI -6.31:0.39; p=0.08), and no change in testicular volume (MD 0.07 mL, 95% CI -1.92:2.07; p=0.94) after SSR. Sexual dysfunction was associated with hypogonadism, depression, and anxiety, especially in men with unsuccessful SSR and Klinefelter syndrome. CONCLUSIONS: The results of this SRMA indicate a significant reduction in TT after SSR. Sexual dysfunction after testicular sperm extraction and the potential negative impact of future SSR repeat should be considered during preoperative counseling.

Regenerative Therapy in Erectile Dysfunction: A Survey on Current Global Practice Trends and GAF Expert Recommendations.

PURPOSE: This study aimed to examine current global practices in regenerative therapy (RT) for erectile dysfunction (ED) and to establish expert recommendations for its use, addressing the current lack of solid evidence and standardized guidelines. MATERIALS AND METHODS: A 39-question survey was developed by senior Global Andrology Forum (GAF) experts to comprehensively cover clinical aspects of RT. This was distributed globally via a secure online Google Form to ED specialists through the GAF website, international professional societies, and social media, the responses were analyzed and presented for frequencies as percentages. Consensus on expert recommendations for RT use was achieved using the Delphi method. RESULTS: Out of 479 respondents from 62 countries, a third reported using RT for ED. The most popular treatment was low-intensity shock wave therapy (54.6%), followed by platelet-rich plasma (24.5%) and their combination (14.7%), with stem cell therapy being the least used (3.7%). The primary indication for RT was the refractory or adverse effects of PDE5 inhibitors, with the best effectiveness reported in middle-aged and mild-to-moderate ED patients. Respondents were confident about its overall safety, with a significant number expressing interest in RT's future use, despite pending guidelines support. CONCLUSIONS: This inaugural global survey reveals a growing use of RT in ED treatment, showcasing its diverse clinical applications and potential for future widespread adoption. However, the lack of comprehensive evidence and clear guidelines requires further research to standardize RT practices in ED treatment.

Seroprevalence and contributing factors of transboundary animal diseases in sheep and goats: a study in Peninsular Malaysia.

Diseases caused by small ruminant lentiviruses, Mycobacterium avium ssp. paratuberculosis (MAP), Schmallenberg virus, and peste des petits ruminants virus (PPR) is globally recognised as serious threats to the ruminant industry due to their potential to spread rapidly across boundaries. Despite their global distribution and negative impacts on ruminant production, there is a gap in knowledge of the current trends in their epidemiology among sheep and goat populations in Peninsular Malaysia. This study was therefore designed to fill the gap of knowledge concerning the seroprevalence and contributing factors of CAEV, paratuberculosis, SBV, and PPRV among small ruminants from selected flocks in Selangor, Negeri Sembilan, and Pahang states in Peninsular Malaysia. A cross-sectional study design was used to collect animal data and blood samples for serological assays simultaneously. The ID Screen (ID.VET, France) indirect ELISA screening tests were used to detect serum antibodies directed against CAEV/MVV (VISNAS Ver 0922), paratuberculosis (PARAS Ver 0516), SBV (SBVC Ver 1114) and PPRV (PPRC Ver 0821). There was 45.4% (95% CI = 40.74-50.74), 6.8% (95% CI = 4.66-9.69), 27.8% (95% CI = 23.35-32.77), and 2.6% (95% CI = 1.11-0.51) true seroprevalence for CAEV, paratuberculosis, SBV, and PPR, respectively. Geographical location and species were the risk factors for CAEV and paratuberculosis, while the management system and age of small ruminants were the risk factors for SBV. The present study is the first to document a large-scale seroprevalence of MAP and PPR infection among sheep and goat flocks in Peninsular Malaysia. The presence of PPRV and MAP antibodies among small ruminant flocks is signalling current or previous exposure to the pathogens or cross reactions with similar antigens. This finding further suggests the potential for future outbreaks of these devastating diseases among sheep and goats in Malaysia. The high seroprevalence of CAEV and SBV among small ruminants indicates high levels of exposure to the viruses in the environment, which is a potential threat to production.

Complications and adverse events in lymphadenectomy of the inguinal area: worldwide expert consensus.

BACKGROUND: Inguinal lymph node dissection plays an important role in the management of melanoma, penile and vulval cancer. Inguinal lymph node dissection is associated with various intraoperative and postoperative complications with significant heterogeneity in classification and reporting. This lack of standardization challenges efforts to study and report inguinal lymph node dissection outcomes. The aim of this study was to devise a system to standardize the classification and reporting of inguinal lymph node dissection perioperative complications by creating a worldwide collaborative, the complications and adverse events in lymphadenectomy of the inguinal area (CALI) group. METHODS: A modified 3-round Delphi consensus approach surveyed a worldwide group of experts in inguinal lymph node dissection for melanoma, penile and vulval cancer. The group of experts included general surgeons, urologists and oncologists (gynaecological and surgical). The survey assessed expert agreement on inguinal lymph node dissection perioperative complications. Panel interrater agreement and consistency were assessed as the overall percentage agreement and Cronbach's α. RESULTS: Forty-seven experienced consultants were enrolled: 26 (55.3%) urologists, 11 (23.4%) surgical oncologists, 6 (12.8%) general surgeons and 4 (8.5%) gynaecology oncologists. Based on their expertise, 31 (66%), 10 (21.3%) and 22 (46.8%) of the participants treat penile cancer, vulval cancer and melanoma using inguinal lymph node dissection respectively; 89.4% (42 of 47) agreed with the definitions and inclusion as part of the inguinal lymph node dissection intraoperative complication group, while 93.6% (44 of 47) agreed that postoperative complications should be subclassified into five macrocategories. Unanimous agreement (100%, 37 of 37) was achieved with the final standardized classification system for reporting inguinal lymph node dissection complications in melanoma, vulval cancer and penile cancer. CONCLUSION: The complications and adverse events in lymphadenectomy of the inguinal area classification system has been developed as a tool to standardize the assessment and reporting of complications during inguinal lymph node dissection for the treatment of melanoma, vulval and penile cancer.

What to do about recurrent urinary tract infections: A review of evidence behind emerging therapies.

BACKGROUND: Recurrent urinary tract infections (rUTIs) can be debilitating for patients and pose an increasing challenge in the primary care setting. An efficient approach enables timely access and effective care for patients. Recent research and pharmaceutical developments have provided new avenues for treating this common condition. OBJECTIVE: A narrative review was conducted to provide a targeted overview of contemporary management strategies in rUTIs to assist primary care physicians in managing patients with rUTIs efficiently and effectively. DISCUSSION: Recurrent urinary tract infections require investigation and risk factor identification. Appropriate patient education in the primary care setting, behavioural modifications and commencement of non-antibiotic treatment might reduce rUTI. Certain patients might require referral to a urologist for consideration of other treatment strategies and further investigation.

TGF-ß signalling limits effector function capacity of NK cell anti-tumour immunity in human bladder cancer.

BACKGROUND: Natural killer (NK) cells are important innate immunity players and have unique abilities to recognize and eliminate cancer cells, particularly in settings of antibody-opsonization and antibody-dependant cellular cytotoxicity (ADCC). However, NK cell-based responses in bladder cancers to therapeutic antibodies are typically immunosuppressed, and these immunosuppressive mechanisms are largely unknown. METHODS: Single cell RNA sequencing (scRNA-seq) and high-dimensional flow cytometry were used to investigate the phenotype of tumour-infiltrating NK cells in patients with bladder cancer. Further, in vitro, and in vivo models of this disease were used to validate these findings. FINDINGS: NK cells within bladder tumours displayed reduced expression of FcγRIIIa/CD16, the critical Fc receptor involved in ADCC-mediated cytotoxicity, on both transcriptional and protein levels. Transcriptional signatures of transforming growth factor (TGF)-ß-signalling, a pleiotropic cytokine known for its immunosuppressive and tissue residency-inducing effects, were upregulated in tumour-infiltrating NK cells. TGF-ß mediated CD16 downregulation on NK cells, was further validated in vitro, which was accompanied by a transition into a tissue residency phenotype. This CD16 downregulation was also abrogated by TGF-ßR signalling inhibition, which could also restore the ADCC ability of NK cells subject to TGF-ß effects. In a humanized mouse model of bladder cancer, mice treated with a TGF-ß inhibitor exhibited increased ADCC activity compared to mice treated only with antibodies. INTERPRETATION: This study highlights how TGF-ß-rich bladder cancers inhibit NK cell-mediated ADCC by downregulating CD16. TGF-ß inhibition represents new avenues to reverse immunosuppression and enhance the tumoricidal capacity of NK cells in bladder cancer. FUNDING: The Guimaraes Laboratory is funded by a US Department of Defense-Breast Cancer Research Program-Breakthrough Award Level 1 (#BC200025), a grant (#2019485) awarded through the Medical Research Future Fund (MRFF, with the support of the Queensland Children's Hospital Foundation, Microba Life Sciences, Richie's Rainbow Foundation, Translational Research Institute (TRI) and UQ), and a grant (#RSS_2023_085) funded by a Metro South Health Research Support Scheme. J.K.M.W. is funded by a UQ Research Training Program PhD Scholarship and N.O. is funded by a NHMRC Postgraduate Scholarship (#2021932).

Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit. CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

Systematic review and network meta-analysis of re-intervention rates of new surgical interventions for benign prostatic hyperplasia.

OBJECTIVE: To assess the re-intervention rates of new surgical benign prostatic hyperplasia (BPH) interventions, as the clinical durability of new surgical interventions for BPH is not widely known. METHODS: A critical review of new surgical BPH therapies namely 'UroLift®', 'Aquablation', 'Rezum', 'prostatic artery embolisation (PAE)' and 'temporary implantable nitinol device (iTIND)' was performed on PubMed, the Cochrane Library, and Embase databases between May 2010 and December 2022 according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. All relevant articles were reviewed, and the risk of bias was evaluated using the Cochrane risk assessment tool and Newcastle-Ottawa Scale. RESULTS: Of the 32 studies included, there were 10 randomised controlled trials and 22 prospective observational cohorts. A total of 2400 participants were studied with a median patient age of 66 years, a median prostate volume of 51.9 mL, and a median International Prostate Symptom Score of 22. The lowest re-intervention rate at 12 months was for Aquablation at 0.01%, followed by Rezum at 0.02%, iTIND at 0.03%, and PAE at 0.05%. Network meta-analysis (NMA) showed that the best-ranked treatment at 12 months was transurethral resection of the prostate (TURP), followed by Aquablation, iTIND, Rezum, and UroLift. Re-intervention rates with these new BPH interventions are comparable, although some interventions reported better outcomes than TURP in the shorter term. CONCLUSIONS: While this systematic review and NMA showed that the re-intervention rate with these new surgical BPH interventions appears to be comparable to TURP in the short term, further studies are required to directly compare these various BPH procedures.

The effect of three years of vitamin D supplementation on erectile dysfunction: Results from the randomized placebo-controlled D-Health Trial.

BACKGROUND & AIMS: Erectile dysfunction is common among older men and has been associated with low serum 25-hydroxy vitamin D concentration. However, this association may be due to uncontrolled confounding, and there is a paucity of evidence from interventional studies. We aimed to examine the effect of vitamin D supplementation on the prevalence of erectile dysfunction, in an exploratory analysis using data from a large randomized controlled trial. METHODS: The D-Health Trial recruited Australians aged 60-84 years between January 2014 and May 2015 and randomly assigned them to supplementation with 60,000 IU of vitamin D or placebo per month for up to 5 years. Blood samples were collected annually from randomly selected participants (total N = 3943). We assessed erectile dysfunction at the end of the third year of follow-up. We used log-binomial regression to examine the effect of vitamin D on the prevalence of erectile dysfunction overall, and within sub-groups. RESULTS: Of the 11,530 men enrolled, 8920 (77.4 %) completed the erectile dysfunction question and were included in the analysis. After three years of supplementation, the mean serum 25-hydroxy vitamin D concentration was 76 nmol/L (standard deviation (SD) 24.94) in the placebo group and 106 nmol/L (SD 26.76) in the vitamin D group (p < 0.0001). The prevalence of erectile dysfunction was 58.8 % and 59.0 % in the vitamin D and placebo groups, respectively (prevalence ratio 1.00, 95 % CI 0.97, 1.03); there was no evidence of an effect of vitamin D in any subgroup analyses. CONCLUSION: Supplementing older men with vitamin D is unlikely to prevent or improve erectile dysfunction. CLINICAL TRIALS REGISTRY: (ACTRN12613000743763).