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Dean S Elterman,1 Samir K Bhattacharyya,2 Michael Mafilios,3 Emily Woodward,2 Krista Nitschelm,2 Arthur L Burnett4 1University of Toronto, Toronto, ON, Canada; 2Boston Scientific Corporation, Marlborough, MA, USA; 3Health Economics Associates, San Diego, CA, USA; 4The Johns Hopkins University School of Medicine, Baltimore, MD, USACorrespondence: Michael MafiliosHealth Economics Associates, 1804 Garnet Avenue, Ste 412, San Diego, CA, 92109, USATel +1 858-367-9140Email info@hea-consulting.comAbstract: Erectile dysfunction (ED) is a common disorder in adult males that results in withdrawal from sexual intimacy, psychosocial problems (ie, poor self-esteem, depression, anxiety), decreased work productivity, and reduction in quality of life for both the men suffering from ED and their female partners. A pragmatic literature review was undertaken using PUBMED to identify original research studies published over the past 20 years that assessed the impact of ED on a male’s quality of life, the impact of ED on a female partner’s quality of life, or the economic impact of ED on employers. Twenty studies were selected for inclusion. This review showed that men with ED have a poorer quality of life than men without ED (n=9 studies). Results from a global burden of illness study showed that men with ED report substantially lower SF-36 Mental and Physical Component Summary scores and SF‐6D scores compared to men without ED (p< 0.001). Similarly, the partner is also negatively impacted by ED due to relationship difficulties and decreased sexual satisfaction (n=8 studies). Results from the Female Experience of Men’s Attitudes to Life Events and Sexuality study showed that females were significantly less satisfied and engaged in sexual activity less frequently after their partner developed ED (p< 0.001). ED also poses a substantial economic burden on employers (n=3 studies). An observational study in men aged 40– 70 showed that men with ED had significantly higher rates of absenteeism (2x) and work productivity impairment compared to men without ED (p< 0.001). Overall, this contemporary review demonstrated that ED imposes a substantial quality of life burden on men and their female partners as well as a significant economic burden on their employers. These findings underscore the need for more education and awareness of the burden of ED and greater access to appropriate ED treatments to help alleviate this burden.Keywords: erectile dysfunction, work productivity, absenteeism, burden, quality of life, economics, sexual partners, sexual dysfunction

Erectile dysfunction is a common condition in aging men and significantly affects their quality of life and interpersonal relationships. Its prevalence and incidence are associated with aging, lifestyle factors and cardiovascular comorbidities. Preoccupation withmale virility has been present for centuries, and a wide variety of herbs and potions have been used to treat any sexual deficiencies. Recent major advances in understanding of erectile physiology and pathophysiology led to development of currently available systemic and local pharmacotherapies. They are designed to work either centrally or peripherally and to either suppress anti-erectilemechanisms, enhance the pro-erectile ones or influence both. Since all the current formulations have variable safety and efficacy profiles, the search for highly specific, simple, convenient and clinically effective impotence treatments or prophylactics continues. [ABSTRACT FROM AUTHOR]

Introduction: Intracavernosal injection (ICI) therapy for erectile dysfunction (ED) carries a risk of corporal fibrosis, potentially making placement of an inflatable penile prosthesis more difficult. Prostate cancer treatment may also induce corporal fibrosis. Objective: To assess whether a history of ICI or prostate cancer treatment is associated with complications following IPP placement. Methods: A retrospective cohort study of primary IPP cases from 2016-2021 across 16 institutions. Patients were stratified by history of ICI and between-group differences in risk factors were assessed. Multivariable logistic regression was used to assess for predictors of intraoperative complications, postoperative non-infectious complications and postoperative infection. Results: A total of 2540 patients met inclusion criteria of which 781 (30.8%) had a history of ICI. Patients with a history of ICI tended to be older (mean 63 vs 64 years, p=0.002) and were more likely to have history of radical prostatectomy (21.0% vs. 32.1%, p<0.001) and/or radiation (5.51% vs 10.9%, p<0.001). On multivariable regression, a history of ICI, prostatectomy, and radiation were all significant predictors of intraoperative complications (OR 2.11, p=0.03; OR 2.27, p=0.03; OR 2.40, p=0.04, respectively). A history of ICI and patient age were predictors of non-infectious postoperative complications (OR 1.44, p=0.02, OR 1.02, p=0.004 respectively)). None of the variables were significant predictors of infection. Conclusions: In men undergoing IPP placement, a history of ICI is associated with an increased risk of both intraoperative and postoperative, non-infectious complications. Prostate cancer treatment with radiation or surgery is independently associated with increased risk of intraoperative complications. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: D.O. has served as a consultant for Coloplast, Intuitive Surgical, and Fidelis. P.P. has served as a consultant for Coloplast, Boston Scientific, and Urofill. M.S. has served as a consultant for Boston Scientific and Coloplast. J.S. has served as a consultant for Boston Scientific and Coloplast. F.A.Y. has served as a consultant for Coloplast, Cynosure, Antares Pharma, Clarus Pharmaceuticals, and Acerus Pharma. M.S.G. has served as a consultant for Coloplast. The other authors disclose no conflicts. [ABSTRACT FROM AUTHOR]

Introduction: The conventional approach for managing ischemic priapism (IP) involves a stepwise process that includes corporal aspiration and irrigation, intracavernosal sympathetic agent injection, shunt surgeries with or without snaking, and penile prosthesis implantation. It is crucial to determine the most appropriate surgical shunt procedure for patients who do not achieve detumescence with medical treatment, as complication rates are known to increase with ischemia time. Objective: This study compared the effectiveness and clinical outcomes of distal penile shunt procedures with or without corporal Burnett "Snake" maneuver in patients presenting with IP. Methods: We conducted a retrospective study involving patients who presented to our emergency department with IP and underwent surgical treatment at our institution between 2005 and 2021. The patients were divided into two groups: Group 1 (n = 26) underwent distal shunt + Burnett snake maneuver, and Group 2 (n = 56) underwent distal shunt-only. Clinical history, clinical parameters of IP, medical and surgical treatment details, and follow-up information, including IP recurrence, erectile function (EF), and complications, were determined through physician-patient interviews during preoperative assessment and postoperative visits. Successful priapism resolution was defined as pain relief, detumescence, and no further intervention required until discharge. Priapism recurrence was defined as a new presentation to the hospital with IP. EF was assessed before distal shunt surgeries and during post-op visits. EF was graded on a 4-point patient-reported scale: 1 = fully rigid, always capable of penetration, 2 = diminished erection, capable of penetration with phosphodiesterase-5 inhibitors, 3 = diminished erection, capable of penetration with intracavernosal/intraurethral injection or vacuum pump, 4 = insufficient erection despite non-surgical treatment methods. Results: The patient's demographic characteristics are shown in Table 1. IP resolution was observed in 24 out of 26 patients (92.3%) in Group 1 and in 30 out of 56 patients (53.6%) in Group 2 (p < 0.001) with a single surgical intervention. IP recurrence was observed in 1 out of 24 patients (4.2%) in Group 1 and in 18 out of 30 patients (60%) in Group 2 among those successfully treated with a single surgical intervention (p < 0.001). When comparing the EF status between groups, 6 out of 14 patients (42.8%) in Group 1 compared to 13 out of 26 patients (50%) in Group 2 had functional preservation of EF (level 1 + level 2) after priapism surgery, among those successfully treated with a single surgical intervention which had EF data in their charts (p = 0.66). Conclusions: Our study demonstrates that Burnett snake maneuver is more effective than distal shunt-only procedures in resolving acute IP. Furthermore, this technique shows greater success in preventing IP recurrences. Regarding EF recovery, Burnett snake maneuver is at least as successful as distal shunt-only procedures, even in cases with longer ischemia times. Disclosure: No. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the pre- and intraoperative variables that impact the integrity of the corporal bodies over time after inflatable penile prosthesis (IPP) placement, as predictors of intraoperative corporal perforation and delayed cylinder complications have not been well characterized., Patients and Methods: We retrospectively reviewed a 16-centre multi-institutional database of IPP surgeries performed by experienced implanters from 2016 to 2021. Poor corporal integrity (PCI) was defined as intraoperative (iPCI) corporal complications or postoperative (pPCI) corporal complications. Multivariable analysis was performed to identify independent predictors of PCI, iPCI, and pPCI. Primary outcomes included intra- and postoperative corporal complications., Results: We identified 5153 patients for analysis from 5406 IPP cases, finding 152 (2.95%) cases of PCI. On multivariable analysis, predictors of PCI included revision IPP surgery (odds ratio [OR] 8.16, 95% confidence interval [CI] 5.15-12.92; P < 0.001), sequential dilatation (OR 2.12, 95% CI 1.32-3.39; P = 0.002), coronary artery disease (CAD)/peripheral vascular disease (PVD) (OR 1.81, 95% CI 1.18-2.77; P = 0.006), older age (OR 1.02, 95% CI 1.01-1.04; P = 0.013), and corporal scarring (OR 1.58, 95% CI 1.0-2.5; P = 0.049). Predictors of iPCI included revision IPP surgery (OR 7.34, 95% CI 4.18-12.88; P < 0.001), corporal scarring (OR 2.77, 95% CI 1.64-4.69; P < 0.001), radiation therapy (OR 2.25, 95% CI 1.0-5.04; P = 0.049), and older age (OR 1.03, 95% CI 1.0-1.05; P = 0.025). Revision IPP surgery (OR 7.92, 95% CI 3.69-17.01; P < 0.001), sequential dilatation (OR 3.4, 95% CI 1.61-7.19; P = 0.001), CAD/PVD (OR 2.98, 95% CI 1.56-5.72; P = 0.001), and history of priapism (OR 3.59, 95% CI 1.08-11.99; P = 0.038) were predictive of pPCI., Conclusion: Coronary artery disease/PVD, being of older age, having corporal scarring, undergoing IPP revision surgery and sequential dilatation were predictive risk factors for complications associated with PCI. Identifying patients who are at risk of having PCI may improve patient-specific counselling, consideration of referral to more experienced implanters, and surgical planning to potentially promote longer-term device viability., (© 2024 BJU International.)

Background: Preservation of erectogenic nerves during radical prostatectomy (RP) is hampered by limited understanding of their precise localization, due to their complex, intertwined paths, and the inherent individual variations across patients. Because erection utilizes a subset of cavernous nerves (CNs) that in response to sexual stimuli reveal phosphorylation of neuronal nitric oxide synthase (nNOS) on its stimulatory site Ser-1412, we hypothesized that delineation of nerves containing phosphorylated (P)-nNOS on Ser-1412 would establish the location of functional erectogenic nerves within the periprostatic region., Aim: To identify the distribution and quantity of functional erection-relevant ([P-nNOS]-containing) nerves in the periprostatic area and discriminate them among the CNs distribution. We further evaluated whether functional communication exists between contralateral CNs., Methods: Young adult male Sprague-Dawley rats underwent electrical stimulation of the CNs to induce penile erection via phosphorylation of nNOS on Ser-1412 (6 V for 2 min, n = 6). No stimulation group served as control (n = 6). The prostate and adjacent structures were collected and processed for whole-mount double-staining with TuJ1 antibody (a pan-axonal marker) and P-nNOS (n = 3 for stimulation, n = 3 for no stimulation), or total nNOS and P-nNOS (n = 3 for stimulation, n = 3 for no stimulation), followed by modified optical clearing and microscopic examination. Nerve quantification was done by systematic counting., Outcomes: Location and quantification of functional erectogenic nerves., Results: In the male rat, we obtained a map of P-nNOS-containing nerves in the periprostatic area, which are relevant for penile erection. Only 17.5% of all nerves, and only 28.4% of the total nNOS-containing nerves in the periprostatic region are functionally erectogenic nerves. Furthermore, there is no functional innervation between contralateral (stimulated and non-stimulated) CNs., Clinical Implications: This basic science study is expected to provide a foundation for subsequent studies at the human level. Understanding the erection-relevant nerve distribution in the periprostatic area is expected to advance nerve-sparing RP at the human level to improve sexual function outcomes., Strengths and Limitations: This is the first study to describe and quantitate a subset of functional erection-relevant (P-nNOS-containing) nerves in the periprostatic area. Our study differs from previous studies where nerves containing total nNOS were localized without specifying which nerves produce erection. However, because this study comprised a relatively small number of rats, further studies with a bigger sample size or other model animals are warranted., Conclusion: Only a subset of nerve fibers in the periprostatic region represent functional erectogenic nerves, characterized by the expression of P-nNOS (Ser-1412)., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Diabetes mellitus-induced erectile dysfunction (DMED) is a common urological complication of diabetes, and current drugs often fail to provide an effective treatment. Smad2/3 signaling-mediated corporal fibrosis has a critical role in the molecular basis of DMED., Aim: We investigated the effect of Niclosamide (Nic), an antihelmintic drug with antifibrotic effects, on erectile function in a rat DMED model., Methods: Male Sprague Dawley rats were injected intraperitoneally (i.p) with streptozotocin (75 mg/kg) to induce diabetes. At week 8, both diabetic and nondiabetic rats were treated with Nic (10 mg·kg-1/day; i.p) or vehicle for 4 weeks. At week 12, erectile function was evaluated as intracavernous pressure (ICP) response to the electrical stimulation of the cavernous nerve (CN). Penile tissues were harvested for Masson's trichrome staining or western blotting to determine corporal fibrosis and Smad2/3 pathway-related protein expression, respectively., Outcomes: At the end of the experimental protocol, in vivo erectile function was assessed by measuring the ratio of ICP/ mean arterial pressure (MAP) and total ICP following CN stimulation. Smooth muscle content and collagen fibers were evaluated by Masson's trichrome staining of the penile tissues. The expressions of fibrosis-related proteins (Smad2, Smad3, fibronectin) were determined using western blotting in the penile tissues., Results: Erectile function, as determined by the maximum ICP/MAP and total ICP/MAP ratios, was drastically decreased in diabetic rats. Corporal tissues of diabetic rats were severely fibrotic with a significant increase in collagen fibers and a marked reduction in smooth muscle content. Also, the protein expressions of phosphorylated (p-)Smad2, p-Smad3 and fibronectin were significantly increased in the penis of diabetic rats. Both functional and molecular alterations in DMED were effectively reversed by Nic-treated diabetic rats without a glycemic alteration., Clinical Implications: Nic could be a promising candidate for the treatment of DMED due to its antifibrotic effects., Strengths and Limitations: The present study provides the first evidence that Nic has beneficial effect on erectile dysfunction by attenuating corporal fibrosis in a rat model of DMED. The effect of Nic on penile endothelial function and the other potential underlying mechanisms needs to be further elucidated., Conclusions: Nic improved erectile function in DMED rats possibly suppressing penile fibrosis by inhibiting Smad2/3 signaling. These results suggest a potential therapeutic repurposing of Nic as an adjuvant treatment in DMED., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Priapism, a prevalent complication in sickle cell disease (SCD) patients, manifests as prolonged and painful erections unrelated to sexual arousal. The detailed mechanisms contributing to this condition, especially regarding sympathetic function in the corpus cavernosum that maintains penile flaccidity, remain to be elucidated. In this study, it was hypothesized that the pathways of the sympathetic nervous system would be down-regulated, thereby contributing to the development of ischemic priapism in sickle cell disease. This study aimed to investigate the contractions induced by stimulation of sympathetic terminals and the expression of tyrosine hydroxylase in the corpora cavernosa of Berkeley SCD mice. C57BL/6 mice (wild-type, WT) and Berkeley SCD mice were used. A total of 22 mice were used in this study, with 11 allocated to the WT group and 11 to the SCD group. Mice corpus cavernosum was dissected free and mounted in 7-mL organ baths containing Krebs solution. Noradrenergic contractions were obtained using electrical-field stimulation (4-32 Hz) in corpus cavernosum strips from WT and SCD mice. Measurements of tyrosine hydroxylase phosphorylated at Ser-31 and total tyrosine hydroxylase protein expressions in cavernosal tissues were also measured by western blot. The neurogenic contractions were significantly lower (P < 0.05) in the SCD group compared to WT group at all tested frequencies. The protein expression of both total tyrosine hydroxylase and tyrosine hydroxylase phosphorylated at Ser-31 was significantly decreased by approximately 46.28% (P = 0.01) and 55.32% (P = 0.03) in cavernosal tissues from the SCD group compared to the control group, respectively. In conclusion, sympathetic hypoactivity characterized by the downregulation of tyrosine hydroxylase contributes to the hypocontractility of the corpus cavernosum in Berkeley SCD mice. This suggests an impairment in the mechanism responsible for maintaining penile flaccidity, potentially predisposing to erections without sexual stimulation, similar to those observed in ischemic priapism. Pharmacological treatments aiming to restore sympathetic tone in the penis might hold promise for addressing ischemic priapism in SCD., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All experimental procedures were performed in accordance with the relevant guidelines and regulations. The study was approved by the Ethics Committee on Animal Use of the University of Campinas (CEUA/UNICAMP), under permit number 4754-1/2017. Consent to participate is not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Twenty percent of Americans live in non-urban areas, and the challenges in providing high-quality health care in rural areas are well described. These challenges are further exacerbated by the fact that rural citizens are often older and sicker than their urban colleagues, as well as by the ongoing workforce shortage in urology. This study aims to describe the current practice experiences of non-metropolitan urologists (NMUs) in the United States., Methods: Based on the results of the 2022 American Urological Association Census, a secondary questionnaire was developed and distributed electronically to urologists who self-identified in the Census as practicing in non-metropolitan areas. Multiple choice answers were summarized as proportions and free-text answers were collected and grouped by theme., Results: One hundred and thirteen of 552 (20.5%) urologists responded. Most respondents were male (92.9%), aged >55 years (76.1%), in practice >25 years, and in solo practice (25.5%) or a subspecialty group (20.8%). Stressors for NMUs included recruitment (61.3%), call concerns (59.3%), workforce issues (59.3%), difficulty interacting with tertiary medical centers (45.1%), and lack of resources (40.7%). Nearly half of respondents (48.5%) experience burnout more than once monthly, and 31.9% anticipate continuing their current practice and pace for the next five years. Call burden is the most likely reason to leave practice (40%)., Conclusions: Most urologists practicing in non-metropolitan areas are older, endorse high rates of burnout, and have active plans to leave or decrease practice within five years. Understanding contemporary stressors can inform policies to support current and future NMUs.

Objective: To evaluate predictors of implant length for men undergoing primary IPP placement., Methods: A multicenter, retrospective cohort study was performed for men undergoing primary IPP placement at 16 high-volume surgical centers. Patient demographics, comorbidities, operative approach, and implanted cylinder and rear-tip extender length were recorded. Associations between potential preoperative and intraoperative predictors of total device length were tested using non-parametric correlation and Kruskal-Wallis tests, followed by multiple regression., Results: Of 3951 men undergoing primary IPP placement from July 2016 to July 2021, the median implant length was 20 cm (IQR: 19-22). Shorter implant length was associated with increasing age in years (β = -0.01, P = .009), Asian ethnicity (β = -2.34, P = .008), history of radical prostatectomy (β = -0.35, P = .001), and use of an infrapubic surgical approach (β = -1.02, P <.001). Black or African American ethnicity was associated with the implantation of longer devices (β = 0.35, P <.001). No significant associations were recorded with BMI, history of intracavernosal injections, diabetes mellitus, tobacco use, radiation therapy, Peyronie's disease, priapism, or cavernosal dilation technique., Conclusion: The length of an implanted penile prosthesis was found to be associated with preoperative and intraoperative factors including history of radical prostatectomy and operative approach. The knowledge of these associations may assist in the preoperative counseling of patients receiving IPP and help create accurate postoperative expectations., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JAM, MH, EA, KG, GH, JMH, TH, JMJ, VM, SHP, IP, HSN, AS, MS, KVR, NW, DWB - no disclosures; MSG-consultant Coloplast; AL-speaker, consultant, preceptor for Boston Scientific and Coloplast; DO-consultant Coloplast, Intuitive Surgical, Fidelis; PP-consultant Coloplast. Boston Scientific, Urofill; JS-consultant Boston Scientific and Coloplast; FAY- consultant for Coloplast, Cynosure, Antares Pharma, Clarus Pharmaceuticals, Acerus Pharma; MZ- consultant Endo Pharma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Patients with sickle cell disease (SCD) experience intravascular hemolysis, leading to elevated plasma heme levels. This phenomenon has been associated with increased priapism in men with SCD. The heme group can be metabolized by heme oxygenase (HO), generating carbon monoxide (CO), which is known to promote smooth muscle relaxation via soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP). However, the effects of heme on the relaxation responses of corpus cavernosum (CC) have not been investigated., Objectives: To evaluate the functional and biochemical effects of the heme group on mouse CC smooth muscle in vitro., Materials and Methods: Male C57BL/6 mice were used. CC tissues were mounted in organ baths. Measurement of cGMP in mice CC was evaluated., Results: The cumulative addition of heme concentrations promoted the relaxation of CC. HO inhibitor (1J, 100 μM) or sGC inhibitor (ODQ, 10 μM) blocked the relaxing effect of the heme group. Pre-incubation of CC with heme (100 μM) enhanced relaxation induced by acetylcholine, sodium nitroprusside, and nitrergic relaxation (electrical field stimulation), which was abolished by 1J or ODQ. The heme group increased the cGMP production in CC, which was abolished by 1J or ODQ. cGMP levels were significantly higher in CC treated with heme, and pre-incubation with compound 1J or ODQ abolished the effect of heme in raising cGMP levels., Discussion and Conclusion: The HO-CO-sGC-cGMP pathway appears to play a crucial role in promoting CC relaxation. Our study provides novel insight into the role of group heme in CC relaxation and its potential contribution to priapism in SCD. Heme may serve as a pharmacological target for new therapies to prevent priapism., (© 2024 American Society of Andrology and European Academy of Andrology.)

Background: Artificial urinary sphincter (AUS) placement remains the gold-standard treatment for post-prostatectomy urinary incontinence (PPUI), despite their need for periodic surgical revision., Objective: To understand the experiences of patients who undergo repeat AUS revisions., Design: Mixed design including quantitative surveys and qualitative interviews for thematic analysis., Methods: Men with ⩾2 revisions were collected from a single-institution, retrospective database of AUS patients. Participants were interviewed about their prostatectomy, incontinence, AUS placement, and revisions. A survey was administered utilizing validated tools (e.g., Decision Regret Scale (DRS), Incontinence Impact Questionnaire-7) for quantitative analysis. Interview transcripts were used for qualitative thematic analysis., Results: Of 26 respondents, 20 completed the interview. Twenty-three men completed the survey. The mean DRS score for prostatectomy was 24 (standard deviation (SD) = 27), indicating low regret. Median Incontinence Impact Questionnaire score was 54 (SD = 27), with 70% of participants describing their PPUI as "severe." Participants experienced a significant decrease in daily pad usage with AUS placement (5.5 pre-AUS vs 1.4 post-AUS, p  < 0.0001). Qualitative analysis revealed themes involving prostatectomy urgency, physician-patient relationships, expectation setting, and quality of follow-up. Most participants (96%) were satisfied with their initial AUS placement and endorsed a positive relationship with their urologist. However, 22% of participants were unaware of device limitations, including the need for revision. Some participants (26%) were uncertain of the status of their AUS, while some participants (35%) desired improved follow-up., Conclusions: Initial improvement and positive experiences with urologists motivate patients to undergo AUS repeat revision. Urologists should emphasize the limitations of the AUS before placement and follow up with patients to evaluate their needs for future care., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Introduction: Prior consensus meetings have addressed the relationship between phosphodiesterase type 5 (PDE5) inhibition and cardiac health. Given significant accumulation of new data in the past decade, a fourth consensus conference on this topic was convened in Pasadena, California, on March 10 and 11, 2023., Objectives: Our meeting aimed to update existing knowledge, assess current guidelines, and make recommendations for future research and practice in this area., Methods: An expert panel reviewed existing research and clinical practice guidelines., Results: Key findings and clinical recommendations are the following: First, erectile dysfunction (ED) is a risk marker and enhancer for cardiovascular (CV) disease. For men with ED and intermediate levels of CV risk, coronary artery calcium (CAC) computed tomography should be considered in addition to previous management algorithms. Second, sexual activity is generally safe for men with ED, although stress testing should still be considered for men with reduced exercise tolerance or ischemia. Third, the safety of PDE5 inhibitor use with concomitant medications was reviewed in depth, particularly concomitant use with nitrates or alpha-blockers. With rare exceptions, PDE5 inhibitors can be safely used in men being treated for hypertension, lower urinary tract symptoms and other common male disorders. Fourth, for men unresponsive to oral therapy or with absolute contraindications for PDE5 inhibitor administration, multiple treatment options can be selected. These were reviewed in depth with clinical recommendations. Fifth, evidence from retrospective studies points strongly toward cardioprotective effects of chronic PDE5-inhibitor use in men. Decreased rates of adverse cardiac outcomes in men taking PDE-5 inhibitors has been consistently reported from multiple studies. Sixth, recommendations were made regarding over-the-counter access and potential risks of dietary supplement adulteration. Seventh, although limited data exist in women, PDE5 inhibitors are generally safe and are being tested for use in multiple new indications., Conclusion: Studies support the overall cardiovascular safety of the PDE5 inhibitors. New indications and applications were reviewed in depth., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative symposium dedicated to optimizing sexual function and preserving cardiovascular health. The Fourth Princeton Consensus Conference was convened on March 10-11, 2023, at the Huntington Medical Research Institutes in Pasadena, California. Princeton panels I to III addressed the clinical management of men with erectile dysfunction (ED) who also had cardiovascular disease. Thirteen years since Princeton III, Princeton IV builds on previous foundations in several key areas. Mounting evidence supports the need for providers to treat men with ED as being at risk for cardiac events until proven otherwise. Algorithms for the diagnosis and treatment of ED are updated with new recommendations for coronary artery calcium scoring for advanced cardiovascular risk stratification. Optimization of oral phosphodiesterase type 5 inhibitors in the treatment of men with ED and cardiovascular disease is thoroughly explored, including recent evidence of potential cardioprotective effects of these drugs., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Peyronie's disease (PD) is a connective tissue disorder that affects the penis and is characterized by abnormal collagen structure in the penile tunica albuginea, resulting in plaque formation and penile deformity. PD's overall prevalence is estimated at 3.2% to 8.9%, with rates as high as 20.3% among men with type 2 diabetes mellitus (DM). However, the characteristics of DM associated with PD complications remain unclear., Aim: To explore clinical associations between DM characteristics and PD complications., Methods: We conducted a retrospective analysis of patients with DM and PD who presented at our institution between 2007 and 2022. We examined patients' clinical histories, DM- and PD-related clinical parameters, and complications. Penile deformities were assessed through physical examination, photographs, and penile Doppler ultrasound. Patients were categorized into subgroups based on age of DM onset: early (<45 years), average (45-65 years), and late (>65 years)., Outcomes: Outcomes included effects of DM characteristics on PD development, progression, and severity., Results: In total, 197 patients were included in the evaluation. Early-onset diabetes and elevated hemoglobin A1c (HbA1c) levels exhibited significant correlations with the early development of PD (ρ = 0.66, P < .001, and ρ = -0.24, P < .001, respectively). Furthermore, having DM at an early age was associated with the occurrence of penile plaque (ρ = -0.18, P = .03), and there were no significant differences in plaque dimensions (ρ = -0.29, P = .053). A rise in HbA1c levels after the initial PD diagnosis displayed positive correlations with the formation of penile plaque (ρ = 0.22, P < .006)., Clinical Implications: These findings emphasize the need for comprehensive assessments and personalized treatment strategies for individuals with DM and PD. Enhanced management approaches can improve outcomes for those facing both challenges., Strengths and Limitations: Limitations include the single-site retrospective design with potential selection bias, inaccuracies in medical record data, and challenges in controlling confounding variables., Conclusions: This study highlights that early-onset diabetes and poor diabetes control, as indicated by a subsequent rise in HbA1c levels following PD diagnosis, are significantly correlated with the onset and severity of PD. Revealing the mechanisms behind these findings will help us develop better management strategies for individuals with DM and PD., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Major ischemic priapism (IP) is defined as a persistent penile erection for >4 hours. IP may cause serious complications, especially if prompt resolution is not achieved. Therefore, selecting the most effective and usable shunt technique is crucial in IP cases that are refractory to medical therapy., Aim: To compare the effectiveness and complication risks of distal corporoglanular shunt procedures with and without the Burnett "snake" maneuver., Methods: We conducted a retrospective study of patients who presented with IP and underwent surgical treatment at our institution between 2005 and 2021. The patients were categorized into 2 groups: group 1 (n = 26) underwent distal shunt + Burnett snake maneuver, and group 2 (n = 56) underwent distal shunt-only. Clinical history, parameters of IP, details of medical and surgical treatments, and follow-up information were evaluated., Outcomes: Outcomes included differences in IP resolution and recurrence, functional erections, and complications between corporoglanular shunt procedures with and without the Burnett snake maneuver., Results: In group 1, 24 of 26 patients (92.3%) experienced priapism resolution with a single surgical intervention, while this outcome was observed in 30 of 56 patients (53.6%) in group 2 (P < .001). Notably, priapism recurrence was significantly lower in group 1, occurring in 1 of 24 patients (4.2%), as opposed to 8 of 30 patients (26.6%) in group 2 (P < .001). Of the patients with documented sexual function status at follow-up, functional erections (capable of penetration with or without phosphodiesterase 5 inhibitors) were noted in 6 of 14 patients (42.8%) in group 1 and 13 of 26 patients (50%) in group 2 (P = .66)., Clinical Implications: This study provides valuable insights regarding technical aspects of distal shunt procedures with and without the Burnett snake maneuver for treating major IP episodes. These results can help surgeons with clinical decision making for patients who present with IP., Strength and Limitations: Limitations include the single-site retrospective design with potential selection bias, inaccuracies in medical record data, challenges in controlling confounding variables, and the lack of validated questionnaire scores for erectile function evaluation., Conclusion: Our study demonstrates that modifying distal shunt procedures using the Burnett snake maneuver significantly improves priapism resolution and effectively prevents further priapism episodes without introducing additional complications or erectile function loss, thereby distinguishing it from distal shunt-only procedures., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Patients with sickle cell disease (SCD) display an overactive bladder (OAB). Intravascular hemolysis in SCD is associated with various severe SCD complications. However, no experimental studies have evaluated the effect of intravascular hemolysis on bladder function. This study aimed to assess the effects of intravascular hemolysis on the micturition process and the contractile mechanisms of the detrusor smooth muscle (DSM) in a mouse model with phenylhydrazine (PHZ)-induced hemolysis; furthermore, it aimed to investigate the role of intravascular hemolysis in the dysfunction of nitric oxide (NO) signaling and in increasing oxidative stress in the bladder. Mice underwent a void spot assay, and DSM contractions were evaluated in organ baths. The PHZ group exhibited increased urinary frequency and increased void volumes. DSM contractile responses to carbachol, KCl, α-β-methylene-ATP, and EFS were increased in the PHZ group. Protein expression of phosphorylated endothelial NO synthase (eNOS) (Ser-1177), phosphorylated neuronal NO synthase (nNOS) (Ser-1417), and phosphorylated vasodilator-stimulated phosphoprotein (VASP) (Ser-239) decreased in the bladder of the PHZ group. Protein expression of oxidative stress markers, NOX-2, 3-NT, and 4-HNE, increased in the bladder of the PHZ group. Our study shows that intravascular hemolysis promotes voiding dysfunction correlated with alterations in the NO signaling pathway in the bladder, as evidenced by reduced levels of p-eNOS (Ser-1177), nNOS (Ser-1417), and p-VASP (Ser-239). The study also showed that intravascular hemolysis increases oxidative stress in the bladder. Our study indicates that intravascular hemolysis promotes an OAB phenotype similar to those observed in patients and mice with SCD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Silveira, Pereira, Pereira, Calmasini, Burnett, Costa and Silva.)

Patients with sickle cell disease (SCD) display priapism, a prolonged penile erection in the absence of sexual arousal. The current pharmacological treatments for SCD-associated priapism are limited and focused on acute interventions rather than prevention. Thus, there is an urgent need for new drug targets and preventive pharmacological therapies for this condition. This review focuses on the molecular mechanisms linked to the dysfunction of the NO-cyclic guanosine monophosphate (cGMP)-phosphodiesterase type 5 (PDE5) pathway implicated in SCD-associated priapism. In murine models of SCD, reduced nitric oxide (NO)-cGMP bioavailability in the corpus cavernosum is associated with elevated plasma hemoglobin levels, increased reactive oxygen species levels that inactive NO, and testosterone deficiency that leads to endothelial nitric oxide synthase downregulation. We discuss the consequences of the reduced cGMP-dependent PDE5 activity in response to these molecular changes, highlighting it as the primary pathophysiological mechanism leading to excessive corpus cavernosum relaxation, culminating in priapism. We also further discuss the impact of intravascular hemolysis on therapeutic approaches, present current pharmacological strategies targeting the NO-cGMP-PDE5 pathway in the penis, and identify potential pharmacological targets for future priapism therapies. In men with SCD and priapism, PDE5 inhibitor therapy and testosterone replacement have shown promising results. Recent preclinical research reported the beneficial effect of treatment with haptoglobin and NO donors. SIGNIFICANCE STATEMENT: This review discusses the molecular changes that reduce NO-cGMP bioavailability in the penis in SCD and highlights pharmacological targets and therapeutic strategies for the treatment of priapism, including PDE5 inhibitors, hormonal modulators, NO donors, hydroxyurea, soluble guanylate cyclase stimulators, haptoglobin, hemopexin, and antioxidants., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: Variations in climate have been associated with a greater risk of surgical site infections, urinary tract infections, and changes in the skin microbiome; however, limited data exist on the impact of climate on inflatable penile prosthesis (IPP) infections., Aim: We sought to evaluate the impact of climate on the risk of IPP infections in a large international, multicenter cohort., Methods: We performed a multi-institutional, retrospective study of patients undergoing IPP surgery. We then evaluated whether the month or season, during which surgery was performed, affected device infections. Implant infections were defined as infections requiring device explantation. A univariate logistic regression analysis was undertaken., Outcomes: Our primary outcome was implant infection., Results: A total of 5289 patients with a mean age of 62.2 ± 10.8 years received IPP placement. There was a fairly even distribution of implants performed in each season. A total of 103 (1.9%) infections were recorded. There were 32 (31.1%) IPP infections in patients who underwent surgery in the summer, followed by 28 (27.2%) in the winter, 26 (25.2%) in the spring, and 17 (16.5%) in the fall. No statistically significant differences were recorded in terms of season (P = .19) and month (P = .29). The mean daily temperature (P = .43), dew point (P = .43), and humidity (P = .92) at the time of IPP placement was not associated with infection., Clinical Implications: These findings provide reassurance to prosthetic urologists that infection reduction strategies do not need to be tailored to local climate., Strengths and Limitations: Climate data were not directly recorded for each hospital, but rather based on the monthly averages in the city where the surgery was performed., Conclusion: The climate at time of IPP placement and time of year of surgery is not associated with IPP infection risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Our objective was to analyze the rates of erectile dysfunction and Peyronie's disease following a penile fracture using a large, multi-institutional claims database. Inclusion criteria included men ages 15 or older with a diagnosis of penile fracture and any office visit within 5 years of the penile fracture. Exclusion criteria included prior erectile dysfunction, prescription of erectile aids, or penile prosthesis placement. Our primary outcome was the diagnosis of erectile dysfunction or prescription of phosphodiesterase-5 inhibitors within 5 years. A secondary analysis assessed rates of Peyronie's disease following penile fracture. 1242 men were identified with penile fracture and subsequently matched to men without penile fracture, resulting in equal cohorts of 1227 men. Men with a history of penile fracture were more likely to receive a diagnosis of erectile dysfunction or require phosphodiesterase-5 inhibitors (RR 3.18, 95% CI: 2.30-4.40). Men who did not undergo immediate repair had higher rates of erectile dysfunction or treatment (RR: 1.84, 95% CI: 1.22-2.78). Men over the age of 45 years who had a penile fracture were more likely to develop erectile dysfunction or treatment compared to men under 45 years (RR: 1.65, 95% CI: 1.14-2.39). Rates of Peyronie's disease were higher in men with a history of penile fracture (5.8% vs 0%, p < 0.0001). Rates of Peyronie's disease were lower if immediate repair of the fracture was performed (RR: 0.20, 95% CI: 0.10-0.41). Men over the age of 45 years with penile fracture were more likely to develop Peyronie's Disease within 5 years compared to men under the age of 45 years penile fracture (RR: 3.72, 95% CI: 1.94-7.16). Penile fracture increases the risk of both erectile dysfunction and Peyronie's disease, especially those treated with conservative measures or over the age of 45 years compared to patients under 45 years with a penile fracture., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: To investigate the racial and socioeconomic (income) differences in receipt of and time to surgical care for urinary incontinence (UI) and erectile dysfunction (ED) occurring post-radical prostatectomy (RP) and/or radiation therapy (RT)., Materials and Methods: Utilizing the Medicare Standard Analytical Files (SAF), a retrospective cohort study was performed on data of patients diagnosed with prostate cancer (PCa) from 2015 to 2021. Patients who underwent RP and/or RT and who subsequently developed UI and/or ED were grouped into four cohorts: RP-ED, RP-UI, RT-ED and RT-UI. County-level median household income was cross-referenced with SAF county codes, classified into income quartiles, and used as a proxy for patient income status. The rate of surgical care was compared between groups using two-sample t-test and log-rank test. Cox proportional hazards modelling was used to determine covariate-adjusted impact of race on time to surgical care., Results: The rate of surgical care was 6.8, 3.61 3.07, and 1.54 per 100 person-years for the RP-UI, RT-UI, RP-ED, and RT-ED cohorts, respectively. Cox proportional 'time-to-surgical care' regression analysis revealed that Black men were statistically more likely to receive ED surgical care (RP-ED AHR:1.79, 95% CI:1.49-2.17; RT-ED AHR:1.50, 95% CI:1.11-2.01), but less likely to receive UI surgical care (RP-UI AHR:0.80, 95% CI:0.67-0.96) than White men, in all cohorts except RT-UI. Surgical care was highest among Q1 (lowest income quartile) patients in all cohorts except RT-UI., Conclusions: Surgical care for post-PCa treatment complications is low, and significantly impacted by racial and socioeconomic (income) differences. Prospective studies investigating the basis of these results would be insightful., Competing Interests: Support for this research was provided by Boston Scientific, Marlborough, MA. Sirikan Rojanasarot and Alysha McGovern are full‐time employees of Boston Scientific. Oluwafolajimi Adesanya has no conflicts of interest to disclose. Arthur Burnett is a research award recipient from Boston Scientific. Oluwafolajimi Adesanya and Arthur Burnett were not compensated for their participation in this study., (© 2024 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Background: In 1999, 1 year after the approval of the first oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), the first Princeton Consensus Conference was held to address the clinical management of men with ED who also had cardiovascular disease. These issues were readdressed in the second and third conferences. In the 13 years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug-drug interactions, but also a potential cardioprotective effect of these drugs., Aim: In March 2023, an interdisciplinary group of scientists and practitioners met for the fourth Princeton Consensus Guidelines at the Huntington Medical Research Institutes in Pasadena, California, to readdress the cardiovascular workup of men presenting with ED as well as the approach to treatment of ED in men with known cardiovascular disease., Method: A series of lectures from experts in the field followed by Delphi-type discussions were developed to reach consensus., Outcomes: Consensus was reached regarding a number of issues related to erectile dysfunction and the interaction with cardiovascular health and phosphodiesterase-5 inhibitors., Results: An algorithm based on recent recommendations of the American College of Cardiology and American Heart Association, including the use of computed tomography coronary artery calcium scoring, was integrated into the evaluation of men presenting with ED. Additionally, the issue of nitrate use was further considered in an algorithm regarding the treatment of ED patients with coronary artery disease. Other topics included the psychological effect of ED and the benefits of treating it; the mechanism of action of the PDE5 inhibitors; drug-drug interactions; optimizing use of a PDE5 inhibitors; rare adverse events; potential cardiovascular benefits observed in recent retrospective studies; adulteration of dietary supplements with PDE5 inhibitors; the pros and cons of over-the-counter PDE5 inhibitors; non-PDE5 inhibitor therapy for ED including restorative therapies such as stem cells, platelet-rich plasma, and shock therapy; other non-PDE5 inhibitor therapies, including injection therapy and penile prostheses; the issue of safety and effectiveness of PDE5 inhibitors in women; and recommendations for future studies in the field of sexual dysfunction and PDE5 inhibitor use were discussed., Clinical Implications: Algorithms and tables were developed to help guide the clinician in dealing with the interaction of ED and cardiovascular risk and disease., Strengths and Limitations: Strengths include the expertise of the participants and consensus recommendations. Limitations included that participants were from the United States only for this particular meeting., Conclusion: The issue of the intersection between cardiovascular health and sexual health remains an important topic with new studies suggesting the cardiovascular safety of PDE5 inhibitors., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Introduction: Preserving the cavernous nerves, the main autonomic nerve supply of the penis, is a major challenge of radical prostatectomy. Cavernous nerve injury during radical prostatectomy predominantly accounts for post-radical prostatectomy erectile dysfunction. The cavernous nerve is a bilateral structure that branches in a weblike distribution over the prostate surface and varies anatomically in individuals, such that standard nerve-sparing methods do not sufficiently sustain penile erection ability. As a consequence, researchers have focused on developing personalized cavernous nerve mapping methods applied to the surgical procedure aiming to improve postoperative sexual function outcomes., Objectives: We provide an updated overview of preclinical and clinical data of cavernous nerve mapping methods, emphasizing their strengths, limitations, and future directions., Methods: A literature review was performed via Scopus, PubMed, and Google Scholar for studies that describe cavernous nerve mapping/localization., Results: Several cavernous nerve mapping methods have been investigated based on various properties of the nerve structures including stimulation techniques, spectroscopy/imaging techniques, and assorted combinations of these methods. More recent methods have portrayed the course of the main cavernous nerve as well as its branches based on real-time mapping, high-resolution imaging, and functional imaging. However, each of these methods has distinctive limitations, including low spatial accuracy, lack of standardization for stimulation and response measurement, superficial imaging depth, toxicity risk, and lack of suitability for intraoperative use., Conclusion: While various cavernous nerve mapping methods have provided improvements in identification and preservation of the cavernous nerve during radical prostatectomy, no method has been implemented in clinical practice due to their distinctive limitations. To overcome the limitations of existing cavernous nerve mapping methods, the development of new imaging techniques and mapping methods is in progress. There is a need for further research in this area to improve sexual function outcomes and quality of life after radical prostatectomy., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Since 2006, five penis transplants have been performed worldwide. Mixed outcomes have been reported, and two of the five penile transplants have required explantation. However, the long-term outcomes have been encouraging when compliance is implemented, whether standard induction and triple therapy maintenance, or single therapy maintenance. Follow-up monitoring of transplant recipients has enabled a synthesis of technical considerations for surgical success and has shown stable leukocyte counts and renal function after a donor bone-marrow-based immunomodulatory regimen followed by tacrolimus monotherapy as long as 3 years post-transplant, as well as continuous nerve regeneration of penile allografts 3 years post-transplant. Areas of uncertainty include the ethics of donor-recipient colour mismatch, surveillance for sexually transmitted infections and how to optimize patient compliance. Questions also remain with respect to the long-term immunological sequelae of penile tissue, functional outcomes, psychosocial implications and patient selection. Patient counselling should be modified to mention the possibility of long-term improvement in nerve regeneration and sufficient renal function with single-therapy maintenance, and to build a longitudinal dialogue and partnership between the patient and the multidisciplinary care team regarding the risks of sexually transmitted infection instead of surveillance., (© 2023. Springer Nature Limited.)

Despite substantial advances in early detection/prevention and treatments, and improved outcomes in recent decades, prostate cancer continues to disproportionately affect Black men and is the secondleading cause of cancer death in this subgroup. Black men are substantially more likely to develop prostate cancer and are twice as likely to die from the disease compared with White men. In addition, Black men are younger at diagnosis and face a higher risk of aggressive disease relative to White men. Striking racial disparities endure along the continuum of prostate cancer care, including screening, genomic testing, diagnostic procedures, and treatment modalities. The underlying causes of these inequalities are complex and multifactorial and involve biological factors, structural determinants of equity (i.e., public policy, structural and systemic racism, economic policy), social determinants of health (including income, education, and insurance status, neighborhood/physical environment, community/social context, and geography), and health care factors. The objective of this article is to review the sources of racial disparities in prostate cancer and to propose actionable recommendations to help address these inequities and narrow the racial gap., (Copyright © 2023. Published by Elsevier Inc.)