Therapy For Erectile Dysfunction Research Articles

Indirect assessment of low-intensity shockwave therapy's energy density and pulse frequency for erectile dysfunction: a systematic review, bayesian network meta-analysis and meta-regression.

Shockwaves are thought to activate regenerative and angiogenic pathways, providing a possible therapeutic benefit for patients with erectile dysfunction. This study aimed to analyze the effectiveness of low-intensity extracorporeal shockwave therapy energy density and pulse frequency. In May 2022, a systematic search of online databases was performed to identify randomized clinical trials related to low-intensity extracorporeal shockwave therapy in erectile dysfunction. Eligible articles compared low-intensity extracorporeal shockwave therapy to controls or sham procedures. A Bayesian framework with 200,000 Markov chains was performed. We included a total of 1272 patients from 18 studies. The energy flux density measured in joules included 0.09 mJ/mm2 (mean difference 3.2 IIEF [95% CrI 2.8, 3.6]), 0.15 mJ/mm2 (mean difference 4.9 IIEF [95% CrI 2.8, 7.2]) and 0.20 mJ/mm2 (mean difference 1.2 IIEF [95% CrI 0.11, 2.3]). Of these, 0.15 mJ/mm2 had the greatest ranking (SUCRA = 0.983) compared with placebo. When analyzed by pulse frequency, significant increases were found in 500 pulses/session (mean difference 2.5 IIEF [CrI 1.9, 3.2]), 1500 pulses/session (mean difference 4.6 IIEF [95% CrI 3.9, 5.4]) and > 3000 pulses/session (mean difference 3.1 IIEF [95% CrI 2.1, 4.2]). Of these, 1500 pulses/session had the highest SUCRA, at 0.996. Our network meta-analysis suggests that low-intensity extracorporeal shockwave therapy is an effective intervention for erectile dysfunction, as measured by increases in the IIEF-EF. Sessions featuring 1500 pulses and an energy flux density of 0.15 mJ/mm2 appear to be the most effective.

Caveolin-1 scaffolding domain-derived peptide enhances erectile function by regulating oxidative stress, mitochondrial dysfunction, and apoptosis of corpus cavernosum smooth muscle cells in rats with cavernous nerve injury

AimIncreased corpus cavernosum smooth muscle cells (CCSMCs) apoptosis in the penis due to cavernous nerve injury (CNI) is a crucial contributor to erectile dysfunction (ED). Caveolin-1 scaffolding domain (CSD)-derived peptide has been found to exert potential antiapoptotic properties. However, whether CSD peptide can alleviate CCSMCs apoptosis and ED in CNI rats remains unknown. The study aimed to determine whether CSD peptide can improve bilateral CNI-induced ED (BCNI-ED) by enhancing the antiapoptotic processes of CCSMCs. Main methodsFifteen 10-week-old male Sprague-Dawley (SD) rats were randomly classified into three groups: sham surgery (Sham) group and BCNI groups that underwent saline or CSD peptide treatment respectively. At 3 weeks postoperatively, erectile function was assessed and the penis tissue was histologically examined. Furthermore, an in vitro model of CCSMCs apoptosis was established using transforming growth factor-beta 1 (TGF-β1) to investigate the mechanism of CSD peptide in treating BCNI-ED. Key findingsIn BCNI rats, CSD peptide significantly prevented ED and decreased oxidative stress, the Bax/Bcl-2 ratio, and the levels of caspase3. TGF-β1-treated CCSMCs exhibited severe oxidative stress, mitochondrial dysfunction, and apoptosis. However, CSD peptide partially reversed these alterations. SignificanceExogenous CSD peptide could improve BCNI-ED by inhibiting oxidative stress, the Bax/Bcl-2 ratio, and caspase3 expression in penile tissue. The underlying mechanism might involve the regulatory effects of CSD peptide on oxidative stress, mitochondrial dysfunction, and apoptosis of CCSMCs following CNI. This study highlights CSD peptide as an effective therapy for post-radical prostatectomy ED (pRP-ED).

Novel emerging therapy for erectile dysfunction: efficacy and safety of flat magnetic stimulation.

The erectile dysfunction (ED), which is the inability to achieve and/or sustain a penile erection sufficient to result in a satisfying sexual performance, represents a very common complaint. for men over forty years old. The aim of the study was to evaluate if Flat Magnetic Stimulation (FMS) technology could help individuals with symptomatic erectile dysfunction. Twenty patients with erectile dysfunction, underwent eight sessions of about 30 minutes each in a twice a week frequency with the study device. During treatments, every potential side effect was assessed. The International Index of Erectile Function (IIEF) was compiled by all patients at the beginning, after the eighth treatment and at 1 month from the end of the last treatment. The questionnaire scores were presented as median values along with the interquartile range (IQR) and we set the significance threshold at 0.01. After the treatment and at 1-month follow-up, the increase in questionnaire scores was statistically significant compared to the baseline, thus supporting the clinical usefulness of this treatment. In particular, the result of the study indicates a statistically significant difference between IIEF score before treatment (Median = 34) and IIEF score after the end of treatment (Median = 45) and between IIEF score before treatment and IIEF score at 1-month follow-up (Median = 54). The study findings showed that FMS represents a promising treatment option to individuals affected by symptomatic erectile dysfunction.

A comprehensive history of injection therapy for erectile dysfunction, 1982-2023.

Although oral phosphodiesterase 5 inhibitors represent a first choice and long-term option for about half of all patients with erectile dysfunction (ED), self-injection therapy with vasoactive drugs remains a viable alternative for all those who are not reacting or cannot tolerate oral drug therapy. This current injection therapy has an interesting history beginning in 1982. To provide a comprehensive history of self-injection therapy from the very beginnings in 1982 by contemporary witnesses and some members of the International Society for Sexual Medicine's History Committee, a complete history of injection therapy is prepared from eyewitness accounts and review of the published literature on the subject, as well as an update of the current status of self-injection therapy. Published data on injection therapy, as a diagnostic and therapeutic tool for ED, were reviewed thoroughly by PubMed and Medline research from 1982 until June 2023. Early pioneers and witnesses added firsthand details to this historical review. Therapeutic reports of injection therapy were reviewed, and results of side effects and complications were thoroughly reviewed. The pioneers of the first hours were Ronal Virag (1982) for papaverine, Giles Brindley (1983) for cavernosal alpha-blockade (phentolamine and phenoxybenzamine), Adrian Zorgniotti (1985) for papaverine/phentolamine, and Ganesan Adaikan and N. Ishii (1986) for prostaglandin E1. Moxisylyte (thymoxamine) was originally marketed but later withdrawn. The most common side effect is priapism, with the greatest risk of this from papaverine, which has modified its use for therapy. Currently, prostaglandin E1 and trimixes continue to be the agents of choice for diagnostic and therapeutic use in ED. A recent agent is a mixture of a vasoactive intestinal polypeptide (aviptadil) and phentolamine. After 40years, self-injection therapy represents the medication with the highest efficacy and reliability rates and remains a viable option for many couples with ED. The history of this therapy is rich.

PDE5is-naïve versus non-naïve patients at first investigation for erectile dysfunction-findings from a long-term, real-life cross-sectional study.

Phosphodiesterase 5 inhibitors (PDE5is) represent a first-line pharmacological therapy for erectile dysfunction (ED). Men could obtain PDE5is for recreational purposes without any proper medical prescription. We aimed to analyze clinical characteristics of patients who already used any PDE5i for ED without previous formal medical prescription. Data from 2012 heterosexual, sexually active men seeking first medical help for ED at our outpatient clinic between 2005 and 2022 were analyzed. All patients were assessed with a comprehensive sexual and medical history and completed the International Index of Erectile Function (IIEF) at baseline. Comorbidities were scored with the Charlson comorbidity index (CCI). Thereof, according to exposure to any PDE5i before their first visit, patients were subdivided into: PDE5i-naïve and non-PDE5i-naïve patients. Descriptive statistics tested the sociodemographic and clinical characteristics of both groups. A logistic regression model predicted the likelihood of being PDE5i-naïve at the baseline. Linear regression analysis (LRA) estimated the likelihood of being PDE5i-naïve versus non-PDE5i-naïve over the analyzed timeframe. Lastly, local polynomial regression models graphically explored the likelihood of being PDE5i-naïve at the first clinical assessment over the analyzed timeframe, and the sensitivity analyses tested the probability of being PDE5i-naïve at baseline. Overall, 1,491 (70.9%) patients were PDE5i-naïve and 611 (29.1%) were non-PDE5i-naïve at the first assessment. PDE5is-naïve patients were younger, with a lower prevalence of CCI ≥ 1 and of normal erectile function (EF) than non-PDE5i-naïve men (all p<0.05). Multivariable logistic regression found that patients with lower BMI (OR: 0.99), higher IIEF-EF scores (OR: 1.02), lower rates of severe ED (OR: 0.94), and who had been assessed earlier throughout the study timeframe (OR: 1.27) were less likely to be PDE5i-naïve at baseline. Univariate LRA revealed that younger patients (Coeff: -0.02), with lower CCI (Coeff: -0.29) and higher alcohol intake per week (Coeff: 0.52) were more likely to be PDE5i-naïve over the analyzed timeframe. Moreover, for the same IIEF-EF score, patients with higher CCI had lower probability of being PDE5i-naïve. Self-prescription of PDE5is is an attitude presents in the general population, despite this phenomenon has decreased overtime. Current data outline the importance to keep promoting educational campaigns to promote PDE5is as effective and safe medicinal products, while avoiding their improper use.

Research Advances in Stem Cell Therapy for Erectile Dysfunction.

Erectile dysfunction (ED) is a common clinical condition that mainly affects men aged over 40 years. Various causes contribute to the progression of ED, including pelvic nerve injury, diabetes, metabolic syndrome, age, Peyronie's disease, smoking, and psychological disorders. Current treatments for ED are limited to symptom relief and do not address the root cause. Stem cells, with their powerful ability to proliferate and differentiate, are a promising approach for the treatment of male ED and are gradually gaining widespread attention. Current uses for treating ED have been studied primarily in experimental animals, with most studies observing improvements in erectile quality as well as improvements in erectile tissue. However, research on stem cell therapy for human ED is still limited. This article summarizes the recent literature on basic stem cell research on ED, including cavernous nerve injury, aging, diabetes, and sclerosing penile disease, and describes mechanisms of action and therapeutic effects of various stem cell therapies in experimental animals. Stem cells are also believed to interact with host tissue in a paracrine manner, and improved function can be supported through both implantation and paracrine factors. To date, stem cells have shown some preliminary promising results in animal and human models of ED.

BMP4 and GREM1 are targets of SHH signaling and downstream regulators of collagen in the penis.

Cavernous nerve (CN) injury, caused by prostatectomy and diabetes, initiates a remodeling process (smooth muscle apoptosis and increased collagen) in the corpora cavernosa of the penis of patients and animal models that is an underlying cause of erectile dysfunction (ED), and the Sonic hedgehog (SHH) pathway plays an essential role in the response of the penis to denervation, as collagen increases with SHH inhibition and decreases with SHH treatment. We examined if part of the mechanism of how SHH prevents penile remodeling and increased collagen with CN injury involves bone morphogenetic protein 4 (BMP4) and gremlin1 (GREM1) and examined the relationship between SHH, BMP4, GREM1, and collagen in penis of ED patients and rat models of CN injury, SHH inhibition, and SHH, BMP4, and GREM1 treatment. Corpora cavernosa of Peyronie's disease (control), prostatectomy, and diabetic ED patients were obtained (N= 30). Adult Sprague Dawley rats (n = 90) underwent (1) CN crush (1-7days) or sham surgery; (2) CN injury and BMP4, GREM1, or mouse serum albumin (control) treatment via Affi-Gel beads or peptide amphiphile (PA) for 14days; (3) 5E1 SHH inhibitor, IgG, or phosphate-buffered saline (control) treatment for 2 to 4days; or (4) CN crush with mouse serum albumin or SHH for 9days. Immunohistochemical and Western analysis for BMP4 and GREM1, and collagen analysis by hydroxyproline and trichrome stain were performed. BMP4 and GREM1 proteins were identified in corpora cavernosa smooth muscle of prostatectomy, diabetic, and Peyronie's patients, and in rat smooth muscle, sympathetic nerve fibers, perineurium, blood vessels, and urethra. Collagen decreased 25.4% in rats with CN injury and BMP4 treatment (P = .02) and increased 61.3% with CN injury and GREM1 treatment (P = .005). Trichrome stain showed increased collagen in rats treated with GREM1. Western analysis identified increased BMP4 and GREM1 in corpora cavernosa of prostatectomy and diabetic patients, and after CN injury (1-2days) in our rat model. Localization of BMP4 and GREM1 changed with SHH inhibition. SHH treatment increased the monomer form of BMP4 and GREM1, altering their range of signaling. A better understanding of penile remodeling and how fibrosis occurs with loss of innervation is essential for development of novel ED therapies. The relationship between SHH, BMP4, GREM1, and collagen is complex in the penis. BMP4 and GREM1 are downstream targets of SHH that impact collagen and may be useful in collaboration with SHH to prevent penile remodeling and ED.

SHH regulates penile morphology and smooth muscle through a mechanism involving BMP4 and GREM1.

The cavernous nerve (CN) is frequently damaged in prostatectomy and diabetic patients with erectile dysfunction (ED), initiating changes in penile morphology including an acute and intense phase of apoptosis in penile smooth muscle and increased collagen, which alter penile architecture and make corpora cavernosa smooth muscle less able to relax in response to neurotransmitters, resulting in ED. Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle, and SHH treatment suppresses penile remodeling after CN injury through an unknown mechanism; we examine if part of the mechanism of how SHH preserves smooth muscle after CN injury involves bone morphogenetic protein 4 (BMP4) and gremlin1 (GREM1). Primary cultures of smooth muscle cells were established from prostatectomy, diabetic, hypertension and Peyronie's (control) (N= 18) patients. Cultures were characterized by ACTA2, CD31, P4HB, and nNOS immunohistochemical analysis. Patient smooth muscle cell growth was quantified in response to BMP4 and GREM1 treatment. Adult Sprague Dawley rats underwent 1 of 3 surgeries: (1) uninjured or CN-injured rats were treated with BMP4, GREM1, or mouse serum albumin (control) proteins via Affi-Gel beads (N = 16) or peptide amphiphile (PA) (N = 26) for 3 and 14days, and trichrome stain was performed; (2) rats underwent sham (N = 3), CN injury (N = 9), or CN injury and SHH PA treatment for 1, 2, and 4days (N = 9). Western analysis for BMP4 and GREM1 was performed; (3) rats were treated with 5E1 SHH inhibitor (N = 6) or IgG (control; N = 6) for 2 and 4days, and BMP4 and GREM1 localization was examined. Statistics were performed by analysis of variance with Scheffé's post hoc test. BMP4 increased patient smooth muscle cell growth, and GREM1 decreased growth. In rats, BMP4 treatment via Affi-Gel beads and PA increased smooth muscle at 3 and 14days of treatment. GREM1 treatment caused increased collagen and smooth muscle at 3days, which switched to primarily collagen at 14days. CN injury increased BMP4 and GREM1, while SHH PA altered Western band size, suggesting alternative cleavage and range of BMP4 and GREM1 signaling. SHH inhibition in rats increased BMP4 and GREM1 in fibroblasts. Understanding how SHH PA preserves and regenerates penile morphology after CN injury will aid development of ED therapies. SHH treatment alters BMP4 and GREM1 localization and range of signaling, which can affect penile morphology. Part of the mechanism of how SHH regulates corpora cavernosa smooth muscle involves BMP4 and GREM1.

(103) Prior Intracavernosal Injection Therapy and Prostate Cancer Treatment are Both Independently Associated with Increased Risks of Complications in Men Undergoing Inflatable Penile Prosthesis Placement

Abstract 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&amp;lt;0.001) and/or radiation (5.51% vs 10.9%, p&amp;lt;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.

Bibliometric and Visualization Analysis of Stem Cell Therapy for Erectile Dysfunction.

As a common male disease, erectile dysfunction (ED) seriously affects the physical and mental health of patients. In recent years, studies have continued to point out the great potential of stem cell therapy (SCT) in the treatment of ED. The purpose of this study is to comprehensively analyze the research of SCT for ED and understand the development trends and research frontiers in this field. Publications regarding SCT and ED were retrieved and collected from the Web of Science Core Collection. CiteSpace and VOSviewer software were then utilized for bibliometric and visualization analysis. A total of 524 publications were eventually included in this study. The annual number of publications in this field was increasing year by year. China and the USA were the two most productive countries. Lin GT, Lue TF and Lin CS, and the University of California San Francisco where they worked were the most productive research group and institution, respectively. The journal with the largest number of publications was The Journal of Sexual Medicine, and the following were mostly professional journals of urology and andrology. Diabetes mellitus-induced ED and cavernous nerve injury-related ED were the two most commonly constructed models of ED in studies. Concerning the types of stem cells, mesenchymal stem cells derived from adipose and bone marrow were most frequently used. Moreover, future research would mainly focus on exosomes, tissue engineering technology, extracorporeal shockwave therapy, and clinical translation. The research of SCT for ED will receive increasing global attention in the future. Our study provided bibliometric and visualization analysis of published literature, helping researchers understand the global landscape and frontiers in this field. More preclinical and clinical studies should be conducted to more deeply explore the underlying mechanisms of treatment and promote clinical translation.

Artificial cavernosa-like tissue based on multibubble Matrigel and a human corpus cavernous fibroblast scaffold.

Ex vivo tissue culture of the human corpus cavernosum (CC) can be used to explore the tissue structural changes and complex signaling networks. At present, artificial CC-like tissues based on acellular or three-dimensional (3D)-printed scaffolds are used to solve the scarcity of primary penis tissue samples. However, inconvenience and high costs limit the wide application of such methods. Here, we describe a simple, fast, and economical method of constructing artificial CC-like tissue. Human CC fibroblasts (FBs), endothelial cells (ECs), and smooth muscle cells (SMCs) were expanded in vitro and mixed with Matrigel in specific proportions. A large number of bubbles were formed in the mixture by vortexing combined with pipette blowing, creating a porous, spongy, and spatial structure. The CC FBs produced a variety of signaling factors, showed multidirectional differentiation potential, and grew in a 3D grid in Matrigel, which is necessary for CC-like tissue to maintain a porous structure as a cell scaffold. Within the CC-like tissue, ECs covered the surface of the lumen, and SMCs were located inside the trabeculae, similar to the structure of the primary CC. Various cell components remained stable for 3 days in vitro, but the EC content decreased on the 7th day. Wingless/integrated (WNT) signaling activation led to lumen atrophy and increased tissue fibrosis in CC-like tissue, inducing the same changes in characteristics as in the primary CC. This study describes a preparation method for human artificial CC-like tissue that may provide an improved experimental platform for exploring the function and structure of the CC and conducting drug screening for erectile dysfunction therapy.

(232) The Use of Restorative Therapies for Erectile Dysfunction: A Review of the Current Canadian Landscape

Abstract Introduction Erectile dysfunction (ED) is the inability to achieve or maintain an erection that is sufficient for sexual performance. Restorative therapies are heralded as options to restore one’s natural, spontaneous erection without the need for pharmacologic therapy. There is a growing interest in these therapies including low-intensity shockwave therapy (Li-EST), platelet-rich plasma (PRP) and stem cells for the treatment of ED. However, limited data exists to support their routine clinical use. With direct-to-consumer marketing, numerous clinics across Canada now offer this therapy. We sought to investigate the landscape of restorative therapies for ED across Canada. Objective The objective is to evaluate how restorative therapies for ED are being marketed and administered to patients. Our study hopes to analyze cost, indications for treatment, equipment utilized, treatment protocol, clinic ownership, level of training for staff, and whether a urologic consult is required prior to treatment. Methods Searches were made on a private Google browser with queries that include phrases “Shockwave therapy for erectile dysfunction in Province/Territory”, “PRP therapy for erectile dysfunction in Province/Territory”, among others. Searches were also made to include any stem cell regenerative therapies for ED. Clinics advertising their services online had their public website analysed for preliminary data collection. Our team captured data on costs, treatment duration, success rates, adjuvant therapies administered and more. Data obtained was then compared against existing literature to assess the accuracy of marketing towards patients. Results To date, we have obtained preliminary results from 107 clinics across Canada offering a form of restorative therapy for ED. We hope to contact every clinic offering these services in Canada by the end of the study period in August of 2023. Out of the identified clinics thus far, 72.9% are offering SWT and 49.5% are offering PRP treatment for ED, with 27.1% of clinics offering both. Our team was unable to identify any clinics providing stem cell therapy for ED. The average cost of SWT from the data we have collected thus far is $1701.92, ranging from $500 to $3500 for a six-treatment protocol that a majority of clinics opt for. Similarly, the average cost of PRP is $1458.22, ranging from $875 to $2000 per treatment. 15% of clinics reported a success rate for SWT, with a mean of 76.81% (ranges 50-100%). A singular clinic has quoted the success rate of PRP at 75% currently. Out of the 107 clinics contacted, 74 of them listed their ownership and staff. 12.2% of the clinics that listed their staff had a urologist present, 56.8% of them had a non-urologist MD employed on staff, and 31.1% did not have an MD present at the clinic. Conclusions Our study has so far found that Li-SWT and PRP for restorative therapies are being largely marketed directly-to-consumer with very little urologic intervention prior to treatment throughout Canada. The study highlights similar trends found in the US, taking advantage of the psychosocial burden faced by patients that suffer from ED, tacking on substantial financial costs for restorative therapies. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific.

(176) Prior Intracavernosal Injection Therapy and Prostate Cancer Treatment are Both Independently Associated with Increased Risks of Complications in Men Undergoing Inflatable Penile Prosthesis Placement

Abstract 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&amp;lt;0.001) and/or radiation (5.51% vs 10.9%, p&amp;lt;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.

(021) ChatGPT's Ability to Assess Quality and Readability of Online Medical Information

Abstract Introduction Health literacy plays a crucial role in enabling patients to understand and effectively use medical information. As technology rapidly advances, the significance of health literacy becomes even more pronounced, particularly in comprehending complex medical information. Artificial Intelligence (AI) platforms have garnered significant attention for their remarkable ability to generate automated responses to a wide range of prompts. However, their capacity to assess the quality and readability of provided text remains uncertain. Given the growing prominence of AI web assistant tools, we hypothesized that integrating these tools into patients' web searches could enhance the retrieval of accurate medical information. Objective To evaluate the proficiency of Conversational Generative Pre-Trained Transformer (ChatGPT) in assessing readability, and utilizing the DISCERN tool to assess quality of online content regarding shock wave therapy for erectile dysfunction. Methods Websites were generated using a Google search of “shock wave therapy for erectile dysfunction” with location filters disabled. Readability was analyzed using the Readable software (Readable.com, Horsham, United Kingdom). Quality was assessed independently by three reviewers using the DISCERN tool. The same plain text files collected were inputted into ChatGPT to determine whether it produced comparable metrics for readability and quality. Results The study results revealed a notable disparity between ChatGPT's readability assessment and that obtained from a reliable tool, Readable.com (p&amp;lt;0.05). This indicates a lack of alignment between ChatGPT's algorithm and that of established tools, such as Readable.com. Similarly, the DISCERN score generated by ChatGPT differed significantly from the scores generated manually by human evaluators (p&amp;lt;0.05), suggesting that ChatGPT may not be capable of accurately identifying poor-quality information sources regarding shock wave therapy as a treatment for erectile dysfunction. Conclusions ChatGPT’s evaluation of the quality and readability of online text regarding shockwave therapy for erectile dysfunction differs from that of human raters and trusted tools. ChatGPT's current capabilities were not sufficient for reliably assessing the quality and readability of textual content. Further research is needed to elucidate the role of AI in the objective evaluation of online medical content in other fields. Continued development in AI and incorporation of tools such as DISCERN into AI software may enhance the way patients navigate the web in search of high-quality medical content in the future. Disclosure No.

(061) Analysis of BMP4 and GREM1 as Targets of SHH Signaling and Downstream Regulators of the Collagen Axis in the Penis

Abstract Introduction Cavernous nerve (CN) injury caused by prostatectomy and diabetes, initiates a remodeling process (smooth muscle apoptosis and increased collagen) in the corpora cavernosa of the penis of patients and animal models that is an underlying cause of erectile dysfunction (ED). The Sonic hedgehog (SHH) pathway plays an essential role in the response of the penis to denervation, as collagen increases with SHH inhibition and decreases with SHH treatment. Part of the mechanism of how SHH impacts collagen may involve bone morphogenetic protein four (BMP4) and GREMLIN (GREM1). Microarray analysis identified increased GREM1 (BMP4 antagonist) in corpora cavernosa of ED patients and SHH is a regulator of GREM1 in the limb bud. Objective We will examine the relationship between SHH, BMP4, GREM1 and collagen in penis of ED patients and rat models of CN injury, SHH inhibition, and SHH, BMP4 and GREM1 treatment. Methods Corpora cavernosa of Peyronie’s (control), prostatectomy and diabetic ED patients was obtained (n=26). Adult Sprague Dawley rats (n=90) underwent either: 1. CN crush (1-7 days) or sham control, 2. CN injury and BMP4, GREM1 or MSA (control) protein treatment via Affi-Gel beads or peptide amphiphile (PA) for 14 days, 3. 5E1 SHH inhibitor, IgG and PBS (controls), or SHH protein treatment for 2-4 days. Immunohistochemical and western analysis for BMP-4 and GREM1, and collagen analysis by hydroxyproline and trichrome stain were performed. Results BMP4 and GREM1 proteins were identified in corpora cavernosal smooth muscle of prostatectomy, diabetic and Peyronie’s patients, and in rat penis, sympathetic nerve fibers, perineurium, blood vessels, and urethra. Collagen decreased 25.4% in rats with CN injury and BMP4 PA treatment (p=0.02) and increased 61.3% with CN injury and GREM1 treatment (p=0.005). Trichrome showed increased collagen in rats treated with GREM1. BMP4 increased smooth muscle. Western identified increased BMP4 and GREM1 in corpora cavernosa of prostatectomy and diabetic patients, and after CN injury (1-2 days) in our rat model. Localization of BMP4 and GREM1 changed with SHH inhibition. SHH treatment increased BMP4 and GREM1. Aging did not impact BMP4 and GREM1 localization. Conclusions BMP4 and GREM1 are downstream targets of SHH that impact collagen and may be useful in collaboration with SHH to prevent penile remodeling and ED. Better understanding of penile remodeling and how fibrosis occurs is essential for development of novel therapies for ED. Disclosure No.

(239) Stem Cell Therapy for Erectile Dysfunction Across States – Fact or Fiction?

Abstract Introduction While conventional treatments exist for erectile dysfunction (ED), the growing interest in alternative therapies has brought stem cell therapy to the forefront. Stem cells, with their regenerative potential, hold promise for addressing a wide range of diseases, including ED. However, the overall efficacy and potential risks of stem cell therapy for ED remain uncertain. Despite the limited evidence, an increasing number of clinics in the US offer these treatments. This study aims to analyze businesses marketing stem cell therapies and public interest in them. Objective To quantify data in the treatment of erectile dysfunction (ED) with stem cell therapy as marketed by U.S. companies. By querying Google trends, this study provides a novel epidemiological tool for geographically mapping search intent in relation to stem cell use and ED. Methods Google trends were extracted to trace stem cell related search intents combined with ED related searches within past 5 years in U.S. Weather related searches are predicted to remain consistent across time, thus were implemented as a control of Google searches. In addition, data collected regarding stem cell search trends were regressed on state GDP to correlate the degree to which price influences those interested in the novel treatment. The derived data was then implemented into a nationwide heat map to determine which states harbor the most interest (Figure 1). Individual Income Tax Statistics- Zip Code Data (SOI) were used to further explore correlation of public interest with individual’s annual income in the top 4 searched states. Results From the available patient websites, there were 6 practicing clinics within the U.S. that offer stem cells for ED, with out-of-pocket expenses averaging $5000 to $10000 per treatment. The types of stem cells advertised on these websites included umbilical derived, adipose derived, bone marrow derived and blood derived stem cells. Using the heat map, states with the highest search intents were in Florida, California, Massachusetts, New York, and Arizona. While stem cell average search intent exponential increase was observed over the past 5 years relative to platelet rich plasma (PRP), it was not as high as that of low-intensity shockwave therapy increase: stem cell= 11.3 Arbitrary Units (A.U), shockwave= 35.4 A.U, and PRP= 10.8 A.U. Using linear regression, a correlation of r = 0.132 was observed between a higher State GDP per capita and a higher search intent (Figure 2). Furthermore, SOI was analyzed for the highly searched states to explore the specific search interest for the public with corresponding zip codes of an annual income &amp;gt; $200,000. In Arizona, for example, a conspicuously great number of individuals who make &amp;gt;$200,000 annually demonstrated an even increasing higher correlation regarding interest in stem cell treatment for ED. Conclusions With different sites offering such therapy across the US, there is a growing interest in stem cells and other regenerative therapies for ED with the affluent areas having more interest in these therapies, likely due to the high cost of treatment Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Advisory board and speaker for Coloplast; consultant for Cynosure; advisory board and speaker for Halozyme; intellectual property with Masimo; advisory board for Promescent; consultant for Sprout; advisory board for Xialla.

(151) Safety and Feasibility of the COCKTAIL (Combining Shockwave Therapy and Platelet-Rich Plasma for Erectile Dysfunction) Trial: A Single Center, Randomized, Double-Blind, Sham-Controlled Study Update

Abstract Introduction Therapeutic approaches focusing on tissue neovascularization play a crucial role in the development of treatments for erectile dysfunction (ED). Autologous Platelet-Rich Plasma (PRP) and Low-Intensity Shockwave Therapy (SWT) are two restorative therapies that potentially target underlying causes of ED. Pre-clinical evidence suggests their angiogenic and regenerative properties, indicating a potential synergistic pathway to improve vasculogenic ED. Objective The primary objective aims to investigate and compare the treatment efficacy of PRP injection and SWT vs placebo injection/SHAM treatment in men with mild-moderate ED, as measured by IIEF. The secondary objective aims to study incidence of adverse events and safety of PRP injection and SWT treatment in men with mild-moderate ED, as measured by IIEF. Methods The COCKTAIL (Combining Shockwave Therapy and Platelet Rich Plasma) trial is a Phase II, single-center study assessing the safety and efficacy of PRP and SWT in combination for ED (NCT05048667). Thirty-five men with mild to moderate ED were enrolled based on International Index of Erectile Function-EF subdomain (IIEF-EF) questionnaire (12-25). Data from a cohort of men treated with PRP and SWT were analyzed, comparing it to men who received placebo saline injections and sham SWT. Patients received two PRP or placebo injections directly into the corpus cavernosum and penile SWT every week for 5 weeks. Assessment included pain scale evaluations, immediate post-procedure examination, and follow-up for complications. IIEF scores were recorded at baseline, 3-month, and 6-month follow-up visits. All statistics and analyses were conducted with IBM SPSS Statistics 27.0.1. Non-parametric tests were used for analysis. Mann-Whitney U test was used to compare independent groups (Group A vs. Group B) at different time points. Related Samples Wilcoxon -Signed Rank test was used for dependent repeated groups, the serial measurements of IIEF-EF scores at different time points for each patient within a specific group. Findings at p&amp;lt; 0.05 were considered statistically significant. Results The primary endpoint of this study was to investigate the incidence of Serious Adverse Events (SAEs). Encouragingly, no adverse events were reported, suggesting that the procedure appears to be safe for the participants. The median baseline IIEF scores for patients in Group A were 17 (±4), and at the three-month follow-up, the scores increased to 19 (±4), slightly dropping to 18 (±8) at six months. In Group B, the median baseline IIEF scores were 19.50 (±4), which improved to 20 (±7) at the three-month follow-up and further increased to 21 (±10) at six months. No statistical differences were found likely because this is an ongoing study, and we only have complete data for 12 men. We aim to accrue a total of 30 men in each arm and plan to complete the recruitment by January 2024 and complete the study by July 2024. Currently, both the investigators and the patients remain blinded. Conclusions The combination of PRP and SWT appears to be safe, as no adverse events were reported. Although preliminary data do not show differences between the treatment and sham groups currently, we intend to complete the trial to perform a comprehensive statistical calculation for efficacy. Disclosure No.

(069) Markers of Neovascularization and Neurogenesis May Change After Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction

Abstract Introduction Low-intensity extracorporeal shockwave therapy (LiESWT) is thought to treat erectile dysfunction (ED) but the mechanism remains elusive. It is believed that LiESWT may work by stimulating neovascularization and nerve regeneration as demonstrated in animal models by histologically increased angiogenesis-related growth factors and neuronal factors including vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS) and brain derived-neurotropic factor (BDNF). Given its prolific use, a thorough understanding of the mechanism of action of this therapy at a cellular level is critical prior to recommendation of this therapy on a larger scale. Objective Objective data post LiESWT is sparse. In this study, we aimed to determine whether markers for neovascularization and nerve regeneration can be detected in the serum of penile tissue in men following LiESWT treatment. We hypothesized that LiESWT results in appreciable increases in vascular and neuronal factors post therapy. Methods Patients were prospectively enrolled in a clinical trial of LiESWT for ED. Patients received 12 bi-weekly LiESWT treatments of 0.2mJ/mm2 at 5Hz, 1500 shocks delivered per treatment, with follow up at 1-2 weeks, 4-6 weeks, 3 months and 6 months post-treatment. Cavernosal penile blood samples were obtained prior to treatment and at each visit post-treatment. The concentrations of eNOS, nNOS, VEGF, and BDNF in penile plasma samples were measured using Enzyme-Linked Immunosorbent Assay (ELISA) with specific commercial kits, following the protocols provided by the manufacturer. Results Twenty-five patients completed all five study visits. Mean patient age was 63. Mean baseline IIEF-EF score prior to treatment was 14.24 (±1.21). At the time of data analysis, plasma samples from 9 men were analyzed for BDNF, eNOS, and nNOS levels using the ELISA assay, and samples from all 25 men were analyzed for VEGF. BDNF levels demonstrated a sustained decrease after the first treatment (P = 0.0001, Figure 1A). Levels of eNOS were noted to trend upward, but no significant changes in eNOS, nNOS or VEGF levels were noted. Conclusions To our knowledge, this is the first study in human tissues to attempt to quantify objective measures of neurogenesis and neovascularization in penile tissue following LiESWT for ED. Though our N is small, our results suggest that LiESWT may decrease BDNF levels after initial LiESWT treatment while VEGF, eNOS and nNOS levels remain unchanged. The clinical significance of these findings is currently unknown, as our findings are not consistent with histological studies in animals which demonstrate upregulation of these markers in penile tissues. However, we believe this represents a promising first step in attempting to understand the effect of LiESWT at a tissue level in men undergoing LiESWT. Disclosure No.

(228) Cell-Based Therapy Can Restore Erectile Function in Men with Type 2 Diabetes and Metabolic Syndrome by Promoting Angiogenesis and Endothelial Repair

Abstract Introduction Although there has been a growing interest in restorative therapies for erectile dysfunction (ED) in recent years, there is still limited mechanistic evidence to support their effectiveness in the clinical setting. Objective The goal of this research was to investigate the mechanistic impact of cell-based therapy in men with ED secondary to Type 2 Diabetes Mellitus (DM2) and Metabolic Syndrome (MetS) through analysis of plasma biomarkers. Methods International Index of Erectile Function (IIEF) was completed by all men in the ACESO (NCT02886884) and CERES (NCT03059355) clinical trials. ACESO and CERES were both randomized, blinded, pilot phase clinical trials in which all participants received cellular therapy at varying doses and sources to treat endothelial dysfunction secondary to either DM2 or MetS, respectively. The intervention in both trials was peripheral intravenous infusion of allogeneic Mesenchymal Stem Cells (MSCs) of either 20 or 100 million cells derived from either bone marrow (BM) or umbilical cord tissue (UC). Follow-up was for 1 year. Endothelial function was measured via Brachial Artery Flow Mediated Vasodilation (FMD) and Endothelial Progenitor Cell-Colony Forming Units (EPC-CFU) assay. Plasma aliquots were isolated from blood samples and subjected to multiplex ELISA assay for analysis of angiogenic biomarkers. Results Data was pooled from all 20 men in the ACESO and CERES clinical trials. Overall, 7 received 20 million BM-MSCs, 9 received 100 million BM-MSCs, 2 received 20 million UC-MSCs, and 2 received 100 million UC-MSCs. There were no treatment emergent serious adverse effects (TE-SAEs) within 30 days following infusion in any of the participants. Among men with ED (IIEF-EF&amp;lt;25), 31.25% achieved MCID in erectile function. Participants with mild or moderate ED at baseline showed greater improvements in erectile function and endothelial function compared to those with severe ED. Participants who achieved MCID following cell therapy also experienced statistically significant improvements in FMD (P=0.05), whereas those who did not achieve MCID or had normal erectile function at baseline did not experience an improvement in FMD. Furthermore, men with Metabolic Syndrome who met MCID criteria were found to have increased Angiopoietin 1 and decreased Angiopoietin 2 following cell therapy. Conclusions The findings of this study demonstrate the potential of cell-based therapies in improving erectile function, angiogenic, and endothelial function. Future studies should aim to identify the causative mechanisms underlying these restorative effects in humans, paving the way for enhanced understanding and optimization of such therapies. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Longeveron LLC.

(230) Investigating the Efficacy, Satisfaction, and Predictors of Response to Low-Intensity Shockwave Therapy for Erectile Dysfunction

Abstract Introduction Erectile dysfunction (ED) affects 52% of men in the US, with treatment modalities varying significantly in their degree of invasiveness. Low-intensity shockwave therapy (LI-SWT) is an emerging non-invasive therapy that uses acoustic waves to improve cavernosal arterial flow by inducing microtrauma and subsequent angiogenesis, in addition to enhancing tissue regeneration and reducing local inflammation. Objective Our objective is to investigate the efficacy of LI-SWT, identify factors predictive of response, and explore patient satisfaction and attitudes towards the therapy. Methods An IRB-approved retrospective chart review and survey study was conducted, examining 102 men who underwent LI-SWT for ED between 2009-2022 at a single tertiary referral center. Univariate and multivariate analyses were performed in JMP. Results Out of 102 men, 50 (49.0%) subjects responded to the survey. 22 (44.0%) men reported clinical responses to LI-SWT, with an average improvement of 1.46 on the validated Erection Hardness Score (EHS; scale 0-5). Clinical responders noticed their first response after a mean of 3.53 treatments. 48 of the respondents (96.0%) had previously trialed PDE5 inhibitors, while 18 (36.0%) men previously trialed intracavernosal injections (ICI). On univariate analysis, alcohol use (OR 0.23, 95% CI 0.07-0.77, p =0.015) and prior ICI (OR 0.23, 95% CI 0.05-0.95, p=0.036) use were both associated with lower odds of response to LI-SWT. Interestingly, history of radical prostatectomy (RP) did not correlate with LI-SWT response (p=0.117). These results were redemonstrated on multivariate logistic regression, with alcohol use (OR 0.23, p=0.039) and prior ICI use (OR 0.17, p=0.047) again predicting lower odds of LI-SWT response. Of 28 men who did not benefit from LI-SWT, 5 (18%) progressed to ICI, and 3 (11%) progressed to inflatable penile prosthesis (IPP). Out of all respondents, only 2 men (4%) experienced side effects, which consisted of mild transient pain/paresthesia. No hematomas or bruising were reported, including 8 men on anticoagulants. Clinical responders demonstrated a higher mean satisfaction score of 7.1 on the 10-point Likert scale (somewhat satisfied) compared to non-responders who scored an average satisfaction score of 2.3 (somewhat dissatisfied). Surprisingly, the majority (66%) of the survey respondents were willing to try LI-SWT again, including 54% of first time non-responders. Conclusions Patients with a history of alcohol use and/or prior ICI use were associated with a lower likelihood of response to LI-SWT. LI-SWT demonstrated promising results as a non-invasive option for ED treatment, including treatment refractory ED as well as post-prostatectomy ED, with minimal adverse events. Responders viewed LI-SWT favorably as a modality for treating ED, and the majority of patients who had undergone LI-SWT were willing to try it again. These findings support the use of LI-SWT before resorting to more invasive ED therapies, including surgery. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Mohit Khera - consultant for Endo, Petros, AbbVie, Tolmar, Marius, Halozyme, Boston Scientific.