Research progress on the therapeutic application of extracellular vesicles in erectile dysfunction.

Erectile dysfunction (ED) is one of the most common male sexual dysfunctions and is related to many pathogenic factors. However, first-line treatment, represented by phosphodiesterase 5 inhibitors, is unable to maintain long-term efficacy. Extracellular vesicles (EVs) have recently attracted the attention of researchers in the fields of cardiovascular disease, neurologic disease, and regenerative medicine and may become a treatment for ED. This article reviews recent applications of EVs in the treatment of ED from the aspects of the source, the therapeutic mechanism, and the strategies to enhance therapeutic efficacy. These research advances lay the foundation for further research and provide references for in-depth understanding of the therapeutic mechanism and possible clinical application of EVs in ED.

Penile Elastography Versus Penile Duplex Ultrasonography in Diagnosing Non-Responders to Intracavernosal Injection: A Prospective Cohort Study.

OBJECTIVES: The current study aims to investigate the value of penile elastography in assessing the fibrotic changes in the corpora cavernosa. PATIENTS AND METHODS: Eighty participants were included in the study. These were divided into two equal groups: a study group (group 1) included patients with ED who did not respond to intracavernosal injection (ICI), and an age-matched control group (group 2) included age-matched subjects with normal erection. All subjects answered an International Index of Erectile Function-5 (IIEF-5) questionnaire. The first group was evaluated by two ICI trials of 1 mL Quadmix, each took place 1 week apart, followed by a color duplex/Doppler ultrasonography (CDDU) scan using also a 1 mL Quadmix. All the above was done a week before the penile shear wave elastography (SWE) scan. It comprised a 12-section scan of both corpora cavernosa. Each corpus was scanned in three different segments (proximal, mid-shaft, and distal), and in both longitudinal and transverse axes. RESULTS: Comparisons of the laboratory data were non-significant, apart from the glycosylated hemoglobin which proved significant (P value <.001) in both groups. Also, the IIEF-5 scores were significantly lower in the study group (P value <.001). Significantly higher SWE readings (indicating higher fibrotic) were found in the study group compared with the control group in almost all of the scanned segments and their combinations (P value <.05). CONCLUSION: SWE can effectively assess the fibrotic changes occurring in the corpora cavernosa. Hence, SWE could be utilized as a modality that helps diagnose patients with ED.

Erectile response profiles of men using PDE5 inhibitors combined with intracavernosal injections as part of a penile rehabilitation program after radical prostatectomy.

BACKGROUND: Phosphodiesterase type 5 (PDE5) inhibitor labeling states that these agents should not be used in conjunction with other erectogenic medications for fear of priapism occurring. AIM: We explored the risk of priapism and prolonged erections in men in our post-radical prostatectomy (RP) penile injection program who were using regular PDE5 inhibitor and intracavernosal injections (ICIs) as part of their rehabilitation program. METHODS: The study cohort included men on penile injection therapy who (1) were taking tadalafil 5 mg daily or taking sildenafil 25 mg on noninjection days, (2) had an RP, (3) were using their respective PDE5 inhibitor regularly at the time of penile injection training, and (4) complied with the program instructions regarding penile injection use. Demographics, comorbidity details, PDE5 inhibitor dose and utilization, and injection dose and utilization data were collected. All patients underwent in-office injection training and used trimix (papaverine/phentolamine/prostaglandin E1) as the intracavernosal medication. OUTCOMES: Priapism was defined as a patient self-reported penetration hardness erection ≥4 hours in duration, while prolonged erection was defined as a penetration hardness erection lasting ≥2 hours. RESULTS: A total of 112 tadalafil users and 364 sildenafil users were compared. Mean age and duration post-RP were 62 ± 14 years and 5.2 ± 12 months, respectively, and there was no difference between tadalafil and sildenafil groups. The mean trimix dose was tadalafil 24 ± 24 units and sildenafil 31 ± 37 units (P < .05). Priapism occurred in 2 (1.7%) of 112 tadalafil users and 5 (1.4%) of 364 sildenafil users (P = .47). Excluding those men experiencing priapism on any occasion, those with any reported penetration hardness erection lasting ≥2 hours were 7 (6.3%) of 112 tadalafil users and 12 (3.3%) of 364 sildenafil users (P < .01). A total of 53% of these prolonged erections occurred within the first 6 injections at home (no difference between tadalafil and sildenafil groups). CLINICAL IMPLICATIONS: We emphasize the need for continued monitoring and education on proper injection techniques to minimize the risk of adverse events in ICI and PDE5 inhibitor combination therapy. STRENGTHS & LIMITATIONS: This study has a relatively large patient population with a considerable follow-up time. Additionally, the rigorous training, education, and monitoring of the participants, as well as the use of formal definitions for priapism and prolonged erections, enhances the accuracy and reliability of the results. However, there are some limitations, such as social desirability, confounding factors, and recall bias. CONCLUSION: There is no significant difference in the incidence of priapism in an ICI program in which men combine ICI with tadalafil or sildenafil. However, tadalafil patients had a higher rate of prolonged erections, which was found to occur mostly early during the titration phase.

Stem cell therapy for erectile dysfunction: a systematic review.

INTRODUCTION: Erectile dysfunction (ED) is a common condition that negatively affects men's quality of life. It can have various causes, including psychological, vascular, and neurologic factors. Existing treatments for ED mainly focus on symptom relief rather than addressing the underlying cause. Stem cells (SCs) have shown potential as a therapeutic approach for ED due to their anti-inflammatory properties. OBJECTIVES: This systematic review aims to assess the current status of trials and determine the potential impact of SCs on male sexual health. METHODS: A comprehensive search strategy was employed to gather relevant articles from 6 electronic databases. The search included articles published until March 2023. The reference lists of articles were manually reviewed to identify additional studies of relevance. The eligibility criteria for inclusion in the analysis focused on clinical trials involving humans that evaluated the safety and efficacy of SC therapy for ED. Exclusion criteria encompassed case reports, case series, abstracts, reviews, and editorials, as well as studies involving animals or SC derivatives. Data extraction was performed via a standardized form with a focus on erectile outcomes. RESULTS: A total of 2847 articles were initially identified; 18 were included in the final analysis. These studies involved 373 patients with ED and various underlying medical conditions. Multiple types of SC were utilized in the treatment of ED: mesenchymal SCs, placental matrix-derived mesenchymal SCs, mesenchymal SC-derived exosomes, adipose-derived SCs, bone marrow-derived mononuclear SCs, and umbilical cord blood SCs. CONCLUSION: SC therapy shows promise as an innovative and safe treatment for organic ED. However, the lack of standardized techniques and controlled groups in many studies hampers the ability to evaluate and compare trials.

Current status of intracavernosal injection therapy in erectile dysfunction.

INTRODUCTION: Erectile dysfunction (ED) is defined as the inability to attain and/or maintain a penile erection. The first introduction of intracavernosal injection (ICI) for the treatment of erectile failure was in 1982 by Virag who reported the positive effects of papaverine on erectile tissue, followed by Brindley concurrently conducting research on ICI therapy with alpha-blockade. ICI remains a viable option for the treatment of ED, even after FDA approval of phosphodiesterase type 5 inhibitors in 1998. The American Urological Association (AUA) and the European Association of Urology (EAU) both recommend ICI as a second-line therapy for the treatment of ED. We herein provide an overview of the current state of ICI therapy for the treatment of ED. AREAS COVERED: We performed a literature review from 1977-2022, using PubMed and the current AUA and EAU guidelines to discuss the current state of ICI for the treatment of ED. EXPERT OPINION: Although other oral agents are considered first line for the treatment of ED, the current guidelines and literature demonstrate that ICI is a safe and effective option for patients; however, careful patient selection and counseling should be performed to maximize the effectiveness and safety of this ED treatment.

Management of male erectile dysfunction: From the past to the future.

Erectile dysfunction is a common disease of the male reproductive system, which seriously affects the life quality of patients and their partners. At present, erectile dysfunction is considered as a social-psychological-physiological disease with complex etiology and various treatment methods. Oral PDE5I is the first-line treatment for erectile dysfunction with the advantages of high safety, good effect and non-invasiveness. But intracavernosal injection, hormonal replacement therapy, vacuum erection device, penile prosthesis implantation can also be alternative treatments for patients have organic erectile dysfunction or tolerance to PDE5I. With the rapid development of technologies, some new methods, such as low-intensity extracorporeal shock wave and stem cell injection therapy can even repair the organic damage of the corpora cavernosa. These are important directions for the treatment of male erectile dysfunction in the future. In this mini-review, we will introduce these therapies in detail.

The management of erectile dysfunction in men with diabetes mellitus unresponsive to phosphodiesterase type 5 inhibitors.

INTRODUCTION: Erectile dysfunction is associated with diabetes mellitus with an estimated prevalence of 52.5% in the diabetic population. The first-line therapy for erectile dysfunction is phosphodiesterase type 5 inhibitors, but data suggest that diabetic men may be less responsive than non-diabetic men. Thus, other treatments, including intracavernosal injections, intraurethral prostaglandin, vacuum erection devices and penile prosthetic surgery, should be considered in management of diabetic men with erectile dysfunction refractory to phosphodiesterase type 5 inhibitors. Furthermore, combination therapy of phosphodiesterase type 5 inhibitors and other oral treatments such as arginine or l-carnitine may have synergistic effects resulting in better outcomes. In addition, there are novel therapies such as low-intensity shockwave therapy and stem-cell therapy, which may also be effective in targeted treatment modalities. Furthermore, studies suggest that erectile dysfunction can be improved by targeting concurrent comorbidities or metabolic diseases such as depression, hypertension, hypogonadism, and dyslipidaemia. We present an evidence-based narrative review focusing on the management of erectile dysfunction in diabetic men who have not responded to phosphodiesterase type 5 inhibitors. CONCLUSIONS: Both clinicians and patients should be aware of the different management options in diabetic patients who have not responded to phosphodiesterase type 5 inhibitors.

Complication Rates in Patients Using Intracavernosal Injection Therapy for Erectile Dysfunction With or Without Concurrent Anticoagulant Use-A Single-Center, Retrospective Pilot Study.

BACKGROUND: Intracavernosal injection therapy (ICI) is an effective intervention used to treat erectile dysfunction (ED). It has been proposed that caution should be exercised when prescribing ICI to patients currently taking anticoagulants (AC) due to the theoretical increased risk of bleeding, however, there is limited literature describing complication rates of actively anticoagulated patients utilizing ICI. AIM: We sought to determine whether there was a difference in bleeding and other complications in a cohort of patients using ICI therapy with or without concurrent AC use. METHODS: We reviewed our institutional electronic health record and identified 168 patients who were seen in our clinic from January to August 2020 who had either currently or previously utilized ICI therapy for ED treatment. These patients were surveyed regarding their ICI therapy as well as given the erectile dysfunction inventory for treatment satisfaction questionnaire. Data from 85 patients was obtained; 43 concurrently using AC during ICI therapy and 42 with no AC use. Fisher's exact test for categorical variables and a 2-tailed t-test were used with P < .05 considered to be significant. OUTCOME: Documented bleeding events (eg, bruising, hematoma), complications, and mean erectile dysfunction inventory for treatment satisfaction scores were compared between the 2 groups. RESULTS: There were more absolute bleeding complications in the AC group vs the no AC group, with 3 of 43 AC patients (7%, 95% confidence interval: 2.4-18.6) and 0/42 no AC patients (0%, 95% confidence interval: 0-8.4) experiencing some type of bleeding complication on ICI. However, there was no statistically significant difference found in overall or stratified documented bleeding events and complications between the 2 groups. CLINICAL IMPLICATIONS: Patients with concurrent AC usage on ICI therapy reported a higher rate of absolute bleeding complications than our non-AC group. STRENGTHS AND LIMITATIONS: The strength of this study is addressing question of safety of ICI therapy in patients with concurrent AC usage. Limitations include single-center retrospective study design and underpowered sample size limiting confidence with which conclusions from data should guide future patient counseling regarding ICI risks. CONCLUSION: Findings from a single-center cohort of patients suggest that ICI therapy may be a safe and effective treatment modality for ED in patients with concurrent anticoagulant usage, however, given the higher rate of absolute bleeding events in our AC cohort, future assessment in a higher-powered study is warranted in determining a more accurate estimation of risk or propensity for bleeding complications in patients on AC using ICI therapy. Blum KA, Mehr JP, Green T, et al. Complication Rates in Patients Using Intracavernosal Injection Therapy for Erectile Dysfunction With or Without Concurrent Anticoagulant Use-A Single-Center, Retrospective Pilot Study. Sex Med 2022;10:100535.

Pre- and Post-Injection Needle Pain in Patients Undergoing First Intracavernosal Injection.

BACKGROUND: Intracavernosal injections (ICI) are a well-established treatment option for men with erectile dysfunction (ED); however, the anticipation of pain with injection remains a significant barrier to the use of ICI. AIM: To evaluate the patient-anticipated degree of pain versus the experienced degree of pain pre- and post-ICI in men undergoing their first injection with an erectile agent. METHODS: We studied 51 patients who underwent their first ICI in our men's health clinic. Anticipated needle-associated pain was judged with a pre-injection score, and pain experienced during the injection was judged with a post-injection score. All patients graded their pre- and post-ICI pain using a standard 10-point scale (0-10). OUTCOMES: Pre- and post-ICI pain was defined with the visual analogue scale (0-10) in men undergoing their first penile injection. RESULTS: Medians and interquartile ranges (IQRs) of the patients' age [65 years (54.5-68.0)], pre-injection pain [5 (4-7)], and post-injection pain [1 (1-2)] were recorded. Most men in the study had erectile dysfunction (68.6%) and/or Peyronie's Disease (64.7%). The average pre-injection prediction pain score was 5.45 ± 2.15; the average post-injection perceived pain score was 1.20 ± 0.73. Thus, there was an average discrepancy of over 4 points in predicted pain vs perceived pain. A paired t-test was performed which showed a statistically significant difference between pre- and post-injection scores (P < .05). A Wilcoxson Signed Rank Test showed statistical significance in the difference between pre- and post-injection pain scores (P < .05). CLINICAL IMPLICATIONS: ICI is a safe, effective treatment for patients with ED and is associated with significantly less pain than is anticipated by patients. STRENGTHS & LIMITATIONS: This is the first report to describe the discrepancy between pre-ICI anticipated pain and post-ICI experienced pain. Limitations include an overall small sample size. CONCLUSION: Patients experience significantly less pain with ICI than they anticipate having. This represents an important factor to consider when counseling patients about available ED treatments. Baird B, Wajswol E, Ericson C et al. Pre- and Post-Injection Needle Pain in Patients Undergoing First Intracavernosal Injection. J Sex Med 2022;19:590-593.

Accurate and time-saving, two-step intracavernosal injection procedure to diagnose psychological erectile dysfunction.

BACKGROUND: The recognition of the erectile dysfunction pathogenesis is essential to identify the appropriate erectile dysfunction management. As vascular erectile dysfunction could be a manifestation of a systemic arterial damage, the watershed in the erectile dysfunction diagnostic framework is the discrimination between psychological erectile dysfunction and vascular erectile dysfunction. However, reliable tools to directly diagnose psychological erectile dysfunction are currently lacking. OBJECTIVE: To identify which parameters could predict psychological erectile dysfunction. Moreover, we suggest a new intracavernosal injection procedure to optimize the erectile dysfunction diagnostic workup. MATERIALS AND METHODS: A retrospective, real-world analysis was carried out including all men who underwent intracavernosal injection procedure at the Modena Andrology Unit from 2018 to 2021. A first intracavernosal injection procedure with 5 µg of prostaglandin E-1 (PGE-1) was performed. In the absence of a full drug-induced erection (immediate or delayed), an echo-color Doppler penile evaluation after administration of PGE-1 10 µg was conducted, measuring intracavernosal blood flows, to document a possible vascular etiology. Hormonal evaluations were performed. RESULTS: Out of 179 enrolled patients, 70.4% showed psychological erectile dysfunction, 21.7% vascular erectile dysfunction, and 7.8% hormonal genesis. Multinomial logistic regression analysis identified absence of cardiovascular disease (p = 0.017), presence of spontaneous morning erections (p = 0.018), and normal penile erections with masturbation (p = 0.035) as predictors of psychological erectile dysfunction. Clinically, normal intracavernosal injection test response was detected in 86 patients and abnormal response in 93 subjects. Among the latter, 54 patients experienced a delayed response. The combination of intracavernosal injection test with late penile erections evaluation was able to diagnose psychological erectile dysfunction (sensitivity 97%, specificity 100%), avoiding unnecessary retesting. DISCUSSION: We propose a two-step intracavernosal injection procedure that allows to recognize psychological erectile dysfunction with a high sensitivity/specificity, saving costs and time, and limiting adverse events. Moreover, the presence of spontaneous morning erections and valid penile erections after masturbation could guide the diagnostic workup, indirectly identifying those patients deserving of a deeper evaluation of vascular health.

Dual effect of chitosan activated platelet rich plasma (cPRP) improved erectile function after cavernous nerve injury.

BACKGROUND: The intracavernosal (IC) injection of chitosan activated platelet rich plasma (cPRP) has shown to improve the erectile dysfunction in cavernous nerve injury rat model. However, the action target of PRP in improving neurogenic erectile dysfunction remains unclear. We aimed to determine the effect of cPRP action at early stage that further mediates its effect on erectile function (EF) recovery in the bilateral cavernous nerve crushing (BCNC) injury rat model. METHODS: Fifty-four rats were randomly divided into two equal groups: intracavernosal ( IC) injection of saline after BCNC (group 1) and IC injection of cPRP after BCNC (group 2). Five animals in each group were euthanized at 3, 7 and 14 day (d) post-injection, and the tissues were harvested to conduct transmission electron microscopy and histological assays. Six animals in each group were used to determine the recovery of EF at 14 and 28 d post-injury. RESULTS: IC injections of cPRP increased all EF parameters at 28 d and 14 d post-injury (p < 0.05). cPRP injections simultaneously prevented the loss of neuronal nitric oxide synthase-positive neurons (p < 0.05) and nerve fibers (p < 0.05) in the major pelvic ganglion and cavernous nerve (CN), respectively, compared with saline injections. This simultaneous accelerated the regeneration of myelinated axons of the CN, reduced apoptosis, and enhanced the proliferation of the corporal smooth muscle cells at an earlier stage. CONCLUSION: These results suggest that the application of cPRP was beneficial to restore EF via neuroprotective and tissue-protective effects at early stage.

Hard Times: Prostate Cancer Patients' Experiences with Erectile Aids.

BACKGROUND: Prostate cancer (PCa) treatments commonly lead to erectile difficulties. While the mainstay treatment is erectile aids (EAs) to promote erectile recovery, some men never use these treatments and those whose do use EAs often abandon them in the long-term. AIM: The goal of this study was to examine PCa patients' experiences with EAs, to elucidate relationships between experiences with EAs on psychological and sexual well-being, and to explore benefits and drawbacks to EA use. METHODS: A self-report survey including validated questionnaires was administered to examine PCa patients' use and perceptions of helpfulness of EAs, and to characterize associations between use, perceived helpfulness, and psychological and sexual well-being. The survey was followed by an open-ended prompt to explore participants' experiences with EAs. OUTCOMES: We surveyed 260 North American men, up to 25 years after receiving treatment for PCa. Three groups of patients were observed, including those who used EAs and perceived them to be helpful, those who used EAs and perceived them to be unhelpful, as well as a smaller group of patients who never used EAs. RESULTS: Around 80% of the sample were using or had used EAs. Despite the high frequency of use, not all men found EAs helpful. Men who used EAs and found them unhelpful reported poorer psychological and sexual well-being compared to men who didn't use aids or who used EAs but found them helpful. Results indicated both benefits and drawbacks to the use of EAs. Benefits related largely to the efficacy of the aid in promoting erections. A wide range of drawbacks were also reported. CLINICAL IMPLICATIONS: Given the negative sexual and psychological impacts associated with using EAs and finding them unhelpful, we suggest that researchers and health care providers should take care to proactively address potential challenges that are common with EA use, and also to consider the risks of failed attempts with EAs. STRENGTHS & LIMITATIONS: By using both scaled and open-ended questions, a more nuanced picture of the relative benefits and limitations of EA use within the PCa population is presented. As responses were not mandatory, a subset of participants provided comments about the use of EAs. Additionally, the sample was quite homogenous, with mostly white, American and well-educated participants, so it therefore lacks generalizability to other populations. CONCLUSION: This paper illustrates several challenges to EA use, while providing insight into reasons for abandonment of use of EAs. Walker LM, Sears CS, Santos-Iglesias P, et al. Hard Times: Prostate Cancer Patients' Experiences with Erectile Aids. J Sex Med 2021;18:1775-1787.

Penile Rehabilitation and Treatment Options for Erectile Dysfunction Following Radical Prostatectomy and Radiotherapy: A Systematic Review.

After radical prostatectomy (RP) or radiotherapy (RT) for prostate cancer, erectile dysfunction (ED) is the main complication next to urinary incontinence, affecting quality of life. The pathophysiology of ED after these treatments is believed to include neuropraxia causing reduced oxygenation and structural changes of the tissue in the corpora cavernosa. Next to the option of sparing the nerves during RP, research has been focusing on methods for penile rehabilitation after RP and RT, since it occurs often, even after nerve-sparing techniques were used. In animal studies, the use of phosphodiesterase type 5 inhibitors (PDE5i) after cavernous nerve damage is supported, but results in human studies are contradictory. Non-medical treatment options such as vacuum device therapy, hyperbaric oxygen therapy, yoga, aerobic, or pelvic floor training may be helpful, but evidence is scarce. Clear guidelines for penile rehabilitation are not yet available. However, care and support for ED after RP and RT is highly demanded by a large group of patients, so measures have to be taken even though the evidence is not strong yet. In this systematic review, an overview of the literature for penile rehabilitation and treatment options for ED after RP and RT is provided, using only randomized controlled trials (RCT).

Patient Education Is Associated With Reduced Delay to Presentation for Management of Ischemic Priapism: A Retrospective Review of 123 Men.

BACKGROUND: Adverse outcomes secondary to ischemic priapism (IP) are associated with time to presentation and management. AIM: To characterize patterns in presentation delay as a function of etiology and patient education regarding IP risk. METHODS: Following institutional review board approval, charts of IP patients presenting to our institution from 2010 to 2020 were reviewed. One episode of IP per patient was included for analysis. OUTCOMES: Priapism duration in patients presenting with IP. RESULTS: We identified 123 unique patients with IP. Common etiologies included erectogenic intracavernosal injection (24%), trazodone (16%), and other psychiatric medications (16%). Patients with sickle cell anemia or trait and intracavernosal injection-related IP presented sooner than idiopathic cases and those from psychiatric medication (P < .001). Etiology and provider education on IP risk were associated with presentation ≥ 24 hours. Upon multivariate analysis, only a lack of provider education was independently associated with presentation ≥ 24 hours. CLINICAL IMPLICATIONS: Men who received provider-based education on the risk of IP associated with their condition or medication regimen were more likely to seek prompt medical attention for IP and, therefore, less likely to require surgery. STRENGTHS & LIMITATIONS: This manuscript represents one of the largest series on priapism, an area of urologic practice in need of more evidence-based guidance. The numbers are not inflated by including multiple episodes per patient, and the data collected include etiology, time to presentation, and treatment. Limitations include a retrospective chart review study design at a single institution. CONCLUSION: Educational initiatives on the risk of IP associated with particular disease states and medications should target at-risk individuals, as well as prescribers of medications associated with IP. Dutta1 R, Matz1 EL, Overholt TL, et al. Patient Education Is Associated With Reduced Delay to Presentation for Management of Ischemic Priapism: A Retrospective Review of 123 Men. J Sex Med 2021;18:385-390.

Administration of secretome from human placental stem cell-conditioned media improves recovery of erectile function in the pelvic neurovascular injury model.

Human placental stem cells (PSCs) enhance histological and functional recovery in a rodent erectile dysfunction (ED) model. We tested the hypothesis that bioactive factors secreted by PSC (i.e., the secretome) mediate functional recovery and that acellular-conditioned media (CM) from PSC culture (PSC-CM) could be used independently to facilitate functional and histological recovery. To identify factors relative to efficacy of PSC, a comparison of CM from PSC and three additional human stem cell populations was performed. CM from human PSC, amniotic fluid stem cells (AFSCs), adipose-derived stem cells (ADSC), and human umbilical vein endothelial cells (HUVECs) was assayed using a semi-quantitative human cytokine antibody array. Male rats, after surgically created ED by neurovascular injury, were randomly divided into four groups: vehicle control (phosphate-buffered saline [PBS]), PSC, PSC-CM, and serum-free media control (SFM) as control. Functional data on intracorporal and mean arterial pressure were obtained, and histological architecture was examined 6 weeks after single injection. PSCs were found to secrete at least 27 cytokines and growth factors at a significantly higher level than the other three cell types. Either single injection of PSC-CM or PSC significantly improved erectile functional recovery and histological architecture compared with SFM or PBS. Injection of the secretome isolated from human PSC improves erectile functional recovery and histological structure in a rat model of neurovascular injury-induced ED. Further characterization of the unique protein expression within the PSC-CM may help to identify the potential for a novel injectable cell-free therapeutic for applicable patients.

Revisiting the Regenerative Therapeutic Advances Towards Erectile Dysfunction.

Erectile dysfunction (ED) is an inability to attain or maintain adequate penile erection for successful vaginal intercourse, leading to sexual and relationship dissatisfaction. To combat ED, various surgical and non-surgical approaches have been developed in the past to restore erectile functions. These therapeutic interventions exhibit significant impact in providing relief to patients; however, due to their associated adverse effects and lack of long-term efficacy, newer modalities such as regenerative therapeutics have gained attention due to their safe and prolonged efficacy. Stem cells and platelet-derived biomaterials contained in platelet-rich plasma (PRP) are thriving as some of the major therapeutic regenerative agents. In recent years, various preclinical and clinical studies have evaluated the individual, as well as combined of stem cells and PRP to restore erectile function. Being rich in growth factors, chemokines, and angiogenic factors, both stem cells and PRP play a crucial role in regenerating nerve cells, myelination of axons, homing and migration of progenitor cells, and anti-fibrosis and anti-apoptosis of damaged cavernous nerve in corporal tissues. Further, platelet-derived biomaterials have been proven to be a biological supplement for enhancing the proliferative and differentiation potential of stem cells towards neurogenic fate. Therefore, this article comprehensively analyzes the progresses of these regenerative therapies for ED.

Intraoperative Intracavernosal Liposomal Bupivacaine (Exparel) Injection Does Not Affect Systemic Hemodynamics.

INTRODUCTION: The systemic effect of intracavernosal liposomal bupivacaine (Exparel) injection during inflatable penile prosthesis (IPP) implantation on systemic hemodynamics has not been clarified. AIM: To evaluate whether intraoperative intracavernosal Exparel injection affects systemic hemodynamics. METHODS: We studied 56 consecutive patients who underwent IPP implantation under general anesthesia using the transverse scrotal approach. Exparel [10 mL of 1.3% (13.3 mg/mL)] was instilled bilaterally intracavernosally via a 25-gauge needle around 30 min after starting the surgery. All patients graded their postoperative pain using a standard 10-point scale. MAIN OUTCOME MEASURE: Perioperative vital signs at defined time intervals and postoperative pain were monitored. The degree of postoperative pain were analyzed using a standard 10-point scale. RESULTS: Medians and interquartile ranges (IQRs) of the patients' age [64 years (57.3-69.3)], operation time [85 min (78-96)], and estimated blood loss [75 mL (29-100)] were recorded. Although the median preoperative systolic noninvasively measured blood pressure of 131 mm/Hg (IQR: 122-139) fell by 25% to 98 mm/Hg (IQR: 90-100) (P < .001) after anesthesia started, there was no significant decrease in blood pressure between before and after Exparel injection. The perioperative pulse rate and pulse oximetry oxygen saturation were stable. Neither arrhythmia nor convulsion occurred. Patients reported postoperative pain as 0 (IQR: 0-2.25) on a scale of 0-10. CLINICAL IMPLICATIONS: Intraoperative intracavernosal Exparel injection is safe and effective in patients undergoing IPP implantation surgery. STRENGTH & LIMITATIONS: This is the first report to describe systemic hemodynamics of intracavernosal Exparel injection. Limitations are lack of blood concentration of Exparel at various time points and long-term follow-up for pain assessment. CONCLUSION: Although limited by a lack of the blood concentration of Exparel and short follow-up for pain assessment, we concluded that intraoperative intracavernosal Exparel injection does not affect systemic hemodynamics. Taniguchi H, Mulhall JP. Intraoperative Intracavernosal Liposomal Bupivacaine (Exparel) Injection Does Not Affect Systemic Hemodynamics. J Sex Med 2020;17:526-530.

Is topical alprostadil an usable and reliable alternative to intracavernous injection for penile dynamic duplex ultrasonography?

No study has yet been done to evaluate topical alprostadil as a less invasive alternative vasoactive agent for Penile Dynamic Duplex Ultrasonography (PDDU) in the diagnosis of erectile dysfunction. The main aim of our study was to evaluate the usability and reliability of topical alprostadil for PDDU compared with standard intracavernous injection. A further objective was to determine the patients' preference between these two different approaches. During session A, patients received injection while during session B, they received topical alprostadil. Each patient underwent both sessions, 1 week apart from the other. A total of 80 patients were enrolled. After 20 min from drug administration, no significant difference was found between the two procedures in terms of peak systolic velocity and end-diastolic velocity, while Erection Hardness Score was significantly higher with injection. Patients reported less pain/discomfort during the procedure in case of topical alprostadil use and an overall preference towards this examination modality. Topical alprostadil could represent a usable and reliable alternative to intracavernous injection for PDDU, with less discomfort and greater preference by patients.

A Review of Current and Emerging Therapeutic Options for Erectile Dysfunction.

Contemporary treatment algorithms for erectile dysfunction (ED) involve the use of medical therapies such as phosphodiesterase type 5 (PDE5) inhibitors and intracavernosal injection therapy of vasoactive agents, as well as vacuum erection devices and penile prosthesis implants in medically refractory cases. However, the current therapeutic options only address the symptoms of ED and not the underlying pathogenesis that results in ED. Newer and novel ED therapies aspire to reverse ED conditions by preventing cavernosal fibrosis, promoting endothelial revascularization and modulating various neuro-hormonal pathways. Regenerative therapeutic strategies such as low-intensity shock wave, gene and cellular-based therapies, and penile transplants are designed to improve penile hemodynamics and revitalize the cavernosal smooth muscle to mitigate and/or reverse underlying ED. This state-of-art article evaluates current and emerging therapeutic options for ED.

Pharmacodynamics of the agents used for the treatment of erectile dysfunction.

INTRODUCTION: Erectile dysfunction (ED) is one of the most common complaints encountered by the practicing urologist, particularly when treating older men. The last 20 years have represented a pivotal time in the treatment of ED. Areas covered: Several pharmacologic agents have been approved by regulatory agencies, including phosphodiesterase type 5 (PDE5) inhibitors, intraurethral suppositories, and vasoactive injectable agents. This review will focus on the pharmacodynamic properties of these agents and the clinical consequences of those properties. Expert opinion: The decision on which agent to use should be individualized and based on the patient's goals and likelihood of success with the chosen treatment. The selection is also often driven by side-effect profiles that can be minimized by understanding the interplay between the individual patient and the medication. A thorough knowledge of the metabolism and pharmacologic properties of the available therapies will aid the urologist in selecting an individualized treatment plan for each patient.