RESUMEN

Background and Objective: Even if treatment with stem cells has been shown to be safe and effective in many patients with stress urinary incontinence (SUI), there is still room for improvement using other regenerative medicine alternatives. Since the beneficial effects of stem cells are probably mediated by secretion of factors rather than by the cells themselves there is a good rationale for further exploring the therapeutic effects of the secretome and/or its components. However, homing factors such as stromal derived growth factor 1 (SDF-1; CXCL12), stimulation of stem cell growth and stem cell mobilization in vivo using low intensity shock wave therapy (Li-ESWT) or regenerative electrical stimulation (RES), are also promising approaches. Methods: A literature search was performed based on PubMed, Scopus and Google Scholar. The search criteria included original basic science articles, systematic reviews and randomized control trials. All studies were published between 2000 and 2023. Selected, peer-reviewed studies were further analyzed to identify those of relevance. Keywords searched included: "female stress incontinence", "homing factors", "CXCL12", "secretome", "low intensity shockwave therapy" and "regenerative electrical stimulation". The peer-reviewed publications on the key word subjects that contained a novel addition to the existing body of literature were included. Key Content and Findings: There is evidence from studies on non-human primates (NHPs) with experimental urinary sphincter injury that CXCL12 can restore sphincter structure and function. Studies with homing factors in human patients with SUI are still to be performed. A large number of clinical studies on the use of secretome or secretome products from mesenchymal stem cells (MSCs) on indications other than human SUI are already available. However, controlled clinical trials on patients with SUI, have to the best of our knowledge, not yet been performed. Also, RES has not been studied in patients with SUI. In contrast, there is clinical evidence that Li-ESWT may improve female SUI. Conclusions: Treatment with homing factors, MSC secretome/secretome components, Li-ESWT and RES are promising frontiers in the treatment of human SUI caused by sphincter damage.

RESUMEN

PURPOSE: To investigate a therapeutic protocol for erectile dysfunction (ED) based on the combination of low-intensity extracorporeal shock wave therapy (Li-ESWT), tadalafil, and L-arginine. MATERIALS AND METHODS: Recruited patients completed the International Index of Erectile Function erectile function domain (IIEF-EF) and the Erection Hardness Score (EHS) questionnaires at baseline and were randomly assigned in two groups: A (treatment group) and B (control group). Men in both groups received six weekly applications of Li-ESWT. Group A was prescribed adjuvant oral therapy with tadalafil 5 mg and L-arginine 2,500 mg. Follow-up visits were scheduled 1, 6, and 12 months after the last Li-ESWT application. At each follow-up visit, the IIEF-EF and EHS questionnaires were administered again. The main outcome measures were the changes from baseline to every follow-up visit in IIEF-EF and EHS scores. RESULTS: The mean IIEF-EF score in group A was 16.0±4.0, 24.8±3.4, 23.3±4.6, and 21.6±5.5 at baseline, 1, 6, and 12 months of follow-up, respectively, whereas in group B the mean IIEF-EF score was 16.5±4.1, 22.7±4.2, 21.5±4.5, and 19.5±4.9, respectively. We reported an increase in the mean EHS score in group A from 2.07±0.72 at baseline to 3.39±0.59, 3.17±0.67, and 2.98±0.72 at 1, 6, and 12 months, respectively, and in group B from 2.12±0.80 at baseline to 3.07±0.78 and 2.95±0.76 at 1 and 6 months, respectively. CONCLUSIONS: Adjuvant daily therapy with L-arginine 2,500 mg and tadalafil 5 mg was safe and effective in increasing the efficacy and the duration of benefits of Li-ESWT.

Asunto(s)

RESUMEN

Energy-based therapies are novel treatments for erectile dysfunction that are thought to work by stimulation of tissue vasodilation, neoangiogenesis, and so forth. Low-intensity extracorporeal shock wave therapy (Li-ESWT) is the energy-based therapy with the most robust evidence basis demonstrating efficacy and safety. Among this evidence, randomized controlled trials (RCTs) evaluating Li-ESWT have largely been focused on responders to phosphodiesterase-5 inhibitors. Many of these RCTs have limitations including short follow-up durations, inconsistent protocols, and small sample sizes. Until more diverse patient populations are studied and these limitations are addressed, the use of Li-ESWT should remain limited to IRB-approved clinical research trials.

Asunto(s)

RESUMEN

INTRODUCTION: Erectile dysfunction (ED) affects a significant portion of the United States population and causes negative psychological burdens that affects men and their partner's quality of life and satisfaction. Extracorporeal shock therapy (ESWT) utilizing focused ESWT and radial ESWT in Low-intensity shock wave therapy has been used to treat ED with some success. Wharton's Jelly (WJ) is a biologic substance with large amounts of stem cells, growth factors, cytokines and extracellular components. The use of combined focused and radial ESWT (DualStim therapy) with injected WJ have potential uses in ED that may have advantages over current treatments. MATERIALS: A randomized, single-blinded, controlled clinical trial will be conducted to evaluate the efficacy and safety of DualStim therapy and intracavernosal injection of WJ in moderate to severe ED. A total of 60 patients with moderate to severe ED will be enrolled and treated with DualStim therapy with intracavernosal injection of WJ or saline for a period of 7 weeks. The International Index of Erectile Function - Erectile Function score will be used to gauge the treatment related changes in relation to the subject's baseline. The scores will be recorded at baseline and compared to follow-ups 1,3 and 6 months post-treatment. Any adverse events or severe adverse events will be recorded in the corresponding case report forms. Sexual Encounter Profile, as well as the Global Assessment Questionnaire and the Erection Hardness Score will be used to determine the sexual activity improvement from baseline leading to optimal penetration at follow-ups 1,3 and 6 months post-treatment. DISCUSSION: This clinical trial is one of the first studies to determine the immediate and short-term efficacy of DualStim therapy, with and without intracavernosal injection of formulated umbilical cord-derived WJ to improve and/or restore erectile function in patients with moderate to severe ED. This study will also provide insight into the safety and efficacy of WJ. We anticipate clinically significant improvement in patients suffering from moderate and severe ED treated with DualStim therapy with WJ compared to their baseline and DualStim with saline.

RESUMEN

INTRODUCTION: Current non-invasive treatments for erectile dysfunction (ED) include oral medications, intracavernosal injections, and vacuum-assisted devices. Though these therapies work well for many, a subset of patients have contraindications or are unsatisfied with these options. Restorative therapies for ED are a new frontier of treatments focused on regenerating diseased tissue and providing a potential "cure" for ED. AIM: The aim of this position statement is to examine existing clinical trial data for restorative therapies and identify elements that require further research before widespread adoption. METHODS: A literature review was performed to identify all clinical trials performed with regenerative therapy for ED. This includes treatments such as stem cell therapy (SCT), platelet rich plasma (PRP), and restorative related technologies like low-intensity shockwave therapy (LiSWT). MAIN OUTCOME MEASURES: Most clinical trials in restorative therapies were assessed for safety, feasibility, or efficacy. This included recording adverse events, changes in sexual function and erectile function questionnaires, and diagnostics measures. RESULTS: To date there is an absence of robust clinical data supporting the efficacy of restorative therapies regarding ED, though technologies such as LiSWT have established relative safety. CONCLUSIONS: Restorative therapies are a promising technology that represents a new frontier of treatment geared towards reversing disease pathology rather than just treating symptoms. However, current published clinical studies are limited. Future work needs to be adequately powered, multi-center, randomized, sham/placebo-controlled trials in well-characterized patient populations to ensure safety and demonstrate efficacy. Until these studies are done, restorative therapies should be reserved for clinical trials and not offered in routine clinical practice. Liu JL, Chu KY, Gabrielson AT, et al. Restorative Therapies for Erectile Dysfunction: Position Statement From the Sexual Medicine Society of North America (SMSNA). J Sex Med 2021;9:100343.

RESUMEN

Published literature shows low intensity extracorporeal shock wave therapy (LIESWT) and low intensity pulsed ultrasound (LIPUS) therapy to improve erectile function and penile hemodynamic by inducing neovascularisation and promoting tissue regeneration. Key opinion leaders across the Asia Pacific region attended the recent biennial meeting of the Asia Pacific Society for Sexual Medicine in Australia, and presented the current evidence on LIESWT and LIPUS for erectile dysfunction (ED). The clinical findings were internally discussed, and the quality of evidence was graded based on the Oxford Centre for Evidence-Based Medicine recommendations. Existing literature supports the use of LIESWT and LIPUS in men with ED, with many clinical studies reported encouraging results with improved erectile function, good safety profile and short-term durability. However, controversial exists due to sampling heterogeneity, non-standardised treatment protocol and lack of large multiinstitutional studies. There is a need to better define which subgroup of ED population is best-suited, and specific treatment protocol to optimise shock wave energy delivery. More stringent and larger multi-institutional randomised placebo-controlled trials are warranted before clinical adoption of LIESWT and LIPUS as the new standard of care for men with ED.

RESUMEN

INTRODUCTION: Erectile dysfunction is defined as the inability to achieve and maintain an erection to satisfactorily complete intercourse. Treatment depends on the cause and includes phosphodiesterase 5 inhibitor medications, penile pumps, implants, and surgery. Low-intensity shockwave therapy has been shown to be effective and safe for the treatment of erectile dysfunction. OBJECTIVE: We explored the role of low-intensity radial shockwave therapy for erectile dysfunction treatment in a dermatology and/or medical aesthetic practice setting. MATERIALS AND METHODS: A literature review was conducted on radial low-intensity shockwave technology in use for erectile rejuvenation to explore its positioning, safety, efficacy, tolerability, subject satisfaction, and usability in a dermatology and/or medical aesthetic setting. RESULTS: Low-intensity shockwave therapy was shown to be effective in subjects with organic erectile dysfunction, and the treatment effect was maintained for up to 2 years post-treatment. The treatment is reported to be safe and well-tolerated and have little downtime. Many dermatologists use low-intensity shockwave therapy for the treatment of cellulite and other conditions. This type of treatment is now available for erectile dysfunction and seems an attractive and safe option for subjects with organic vascular erectile dysfunction. CONCLUSIONS: Studies and clinical experience suggest that male erectile rejuvenation using low-intensity radial shockwave therapy seems an attractive option. The treatment can be safely, and effectively, delivered by trained staff as part of the total package that is available to men in a dermatology and/or medical aesthetic practice.

Asunto(s)

RESUMEN

BACKGROUND: Erectile dysfunction (ED) caused by pelvic neurovascular injury (PNVI) is often refractory to treatment. In many cases, erectogenic therapy is administered in a delayed fashion. AIM: To evaluate penile hemodynamic effects and histologic changes associated with delayed low-intensity extracorporeal shock wave therapy (Li-ESWT) after PNVI ED in a rat model. We visualized images using immunofluorescence and 3-dimensional imaging of solvent-cleared organs (3DISCO), a novel imaging technique. METHODS: A total of 32 Sprague-Dawley male rats aged 12 weeks were divided equally into 4 groups: sham surgery as normal controls (NC), PNVI controls (PC), PNVI with very-low-energy Li-ESWT (PVL), and PNVI with low-energy Li-ESWT (PL). Bilateral cavernous nerve crush and internal pudendal bundle ligation were performed in the 3 PNVI groups. Li-ESWT was administered twice a week for 4 weeks in the PL and PVL groups starting at 4 weeks after PNVI. OUTCOMES: Intracavernous pressure (ICP) studies (normalized to mean arterial pressure [MAP]) were conducted in all subject animals. After testing, tissue was harvested for immunofluorescence staining and 3DISCO analysis. RESULTS: Mean ICP/MAP was lower in PC animals compared with NC animals (0.37 ± 0.03 vs 0.91 ± 0.03, respectively; P = .001). The ICP/MAP ratio was significantly higher in PVL and PL animals (0.66 ± 0.07 and 0.82 ± 0.05, respectively) compared with PC animals (P = .002 and .001, respectively). Detailed microstructures and trajectories of nerves and vessels were identified with immunofluorescence and 3DISCO. The PC group had lower density of nerves, axons, neuronal nitric oxide synthase-positive nerves, and Schwann cells in the dorsal penis. Animals in the PL group had significantly higher expression of all of these markers compared with PC animals. CLINICAL IMPLICATIONS: Li-EWST may have utility in the management of severe ED related to PNVI from severe pelvic injury or radical pelvic surgeries, even when administered in a delayed fashion. STRENGTH & LIMITATIONS: This study of a severe ED phenotype involved treatment administered in a delayed fashion, which is more consistent with how therapy likely would be delivered in a real-world clinical context. Moreover, because the treatment commenced at 4 weeks after injury, when nerve and tissue atrophy have already occurred, the results imply that Li-ESWT can be used for regenerative therapy. Additional studies on dose optimization and treatment interval are needed to inform the design of human clinical trials. CONCLUSION: Li-ESWT ameliorates the negative functional and histologic effects of severe pelvic neurovascular injury in a rat model system. 3DISCO provides high-resolution images of neuroanatomy and neural regeneration. Wang HS, Ruan Y, Banie L, et al. Delayed Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Impaired Penile Hemodynamics in Rats Subjected to Pelvic Neurovascular Injury. J Sex Med 2019;16:17-26.

Asunto(s)

RESUMEN

The prevalence of erectile dysfunction (ED) is increasing, especially among men over 40 years old, and is positively correlated with age. It is predicted that there will be as many as 300 million ED patients around the world by the year 2025. Recent years has witnessed deeper insights into the pathophysiological mechanisms of ED and significant breakthroughs in its treatment. However, few achievements have been made in the studies of its pathological change at the molecular level and the measures for its management and rehabilitation. Besides, quite a few cases fail to respond to 5-phosphodiesterase inhibitors. Fortunately, low-intensity shock wave therapy (LiSWT), as a novel non-invasive micro-energy therapeutic option, is promising to get repaired the injured corpus cavernosum of the ED patient and provide a new concept for the management of ED. This review introduces the current situation of the diagnosis and treatment of ED and the mechanisms of LiSWT acting on ED in animal experiments and clinical studies.

Asunto(s)

RESUMEN

INTRODUCTION: Current treatment for erectile dysfunction (ED) mostly attempts to improve erectile function with limited impact on altering the underlying pathophysiology of ED. Recent animal experiments have supported the notion that low intensity extracorporeal shockwave therapy (LIESWT) significantly improves penile hemodynamics and might induce structural changes that regenerate penile tissue. Areas covered: This review article provides an overview of the basic mechanics and clinical studies pertaining to LIESWT and its use in the field of ED. We identify several key aspects of LIESWT and compare contemporary LIESWT machines and their clinical outcomes. Expert commentary: There is emerging and strong literature to support the use of LIESWT in men with ED, with many clinical studies reported encouraging results in the use of LIESWT with improved erectile function, good safety records, and short-term durability. However, there is a need to define which subgroup of ED population is best suited and the LIESWT treatment protocol including LIESWT template, modality of shock waves energy, emission frequency, and total energy delivery. More stringent randomised controlled trials are warranted before there is widespread acceptance of this LIESWT technology as the standard of care in ED.

Asunto(s)

RESUMEN

OBJECTIVES: To evaluate the efficacy of low-intensity shock wave therapy and to identify the predictive factors of its efficacy in Japanese patients with erectile dysfunction. METHODS: The present study included 57 patients with erectile dysfunction who satisfied all the following conditions: more than 6-months history of erectile dysfunction, sexual health inventory for men score of ≤ 12 without phosphodiesterase type-5 inhibitor, erection hardness score grade 1 or 2, mean penile circumferential change by erectometer assessing sleep related erection of < 25 mm and non-neurological pathology. Patients were treated by a low-energy shock waves generator (ED1000; Medispec, Gaithersburg, MD, USA). A total of 12 shock wave treatments were applied. Sexual health inventory for men score, erection hardness score with or without phosphodiesterase type-5 inhibitor, and mean penile circumferential change were assessed at baseline, 1, 3 and 6 months after the termination of low-intensity shock wave therapy. RESULTS: Of 57 patients who were assigned for the low-intensity shock wave therapy trial, 56 patients were analyzed. Patients had a median age of 64 years. The sexual health inventory for men and erection hardness score (with and without phosphodiesterase type-5 inhibitor) were significantly increased (P < 0.001) at each time-point. The mean penile circumferential change was also increased from 13.1 to 20.2 mm after low-intensity shock wave therapy (P < 0.001). In the multivariate analysis, age and the number of concomitant comorbidities were statistically significant predictors for the efficacy. CONCLUSIONS: Low-intensity shock wave therapy seems to be an effective physical therapy for erectile dysfunction. Age and comorbidities are negative predictive factors of therapeutic response.

Asunto(s)

RESUMEN

PURPOSE: To evaluate the efficacy, safety and patient satisfaction outcomes following low intensity extracorporeal shock wave therapy (LiESWT) in men with Peyronie's disease (PD) using a standardised protocol. MATERIALS AND METHODS: In this open-label single arm prospective study, patients with PD were enrolled following informed consent. Patient demographics, change in penile curvature and plaque hardness, International Index of Erectile Function (IIEF)-5 score, and overall satisfaction score (on a 5-point scale) were recorded. Treatment template consists of 3000 shock waves to the Peyronie's plaque over 20 minutes, twice weekly for 6 weeks. RESULTS: The majority of patients have PD history longer than 6 months (mean, 12.8 months; range, 6-28 months). Two thirds of patients have received and failed oral medical therapy. There were improvements in penile curvature (more than 15 degrees in 33% of men), plaque hardness (60% of men) and penile pain (4 out of 6 men) following LiESWT. There was a moderate improvement in IIEF-5 score (>5 points reported in 20% of men). No complication was reported and the majority of patients were satisfied (rated 4 out of 5; 70% of men) and would recommend this therapy to others. CONCLUSIONS: In a carefully selected group of men with PD, LiESWT appears to be safe, has moderate efficacy and is associated with high patient satisfaction rate in the short term.

Asunto(s)

RESUMEN

PURPOSE: To evaluate the efficacy, safety and patient satisfaction outcomes following low intensity extracorporeal shock wave therapy (LiESWT) in men with Peyronie's disease (PD) using a standardised protocol. MATERIALS AND METHODS: In this open-label single arm prospective study, patients with PD were enrolled following informed consent. Patient demographics, change in penile curvature and plaque hardness, International Index of Erectile Function (IIEF)-5 score, and overall satisfaction score (on a 5-point scale) were recorded. Treatment template consists of 3000 shock waves to the Peyronie's plaque over 20 minutes, twice weekly for 6 weeks. RESULTS: The majority of patients have PD history longer than 6 months (mean, 12.8 months; range, 6-28 months). Two thirds of patients have received and failed oral medical therapy. There were improvements in penile curvature (more than 15 degrees in 33% of men), plaque hardness (60% of men) and penile pain (4 out of 6 men) following LiESWT. There was a moderate improvement in IIEF-5 score (>5 points reported in 20% of men). No complication was reported and the majority of patients were satisfied (rated 4 out of 5; 70% of men) and would recommend this therapy to others. CONCLUSIONS: In a carefully selected group of men with PD, LiESWT appears to be safe, has moderate efficacy and is associated with high patient satisfaction rate in the short term.

Asunto(s)