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Background: Erectile dysfunction (ED) often affects men with type 2 diabetes mellitus (T2DM) due to microvascular damage. However, medical interventions are not always appropriate. Aim: This scoping review aimed to answer the following question: What evidence is available about the effects of non-medical and non-invasive healthcare interventions to improve ED in men with T2DM? Method: Potential studies were collected from the Cumulative Index to Nursing and Allied Health Literature via EBSCO, Embase via Ovid, MEDLINE via Ovid, Web of Science, PubMed, ProQuest, and PsycINFO via Ovid. Findings: From 2,611 identified titles, 17 studies, including 11 interventional and 6 observational studies, were included. Four main alternatives to medical interventions were identified from the included studies. Amongst these, four studies recommended patient education on lifestyle modification, twelve studies encouraged dietary changes and physical activities, two studies emphasized the use of vacuum erectile device, and three studies suggested the application of low-intensity extracorporeal shockwave therapy by healthcare professionals. Discussion: Dietary modification and physical activities were promoted as effective interventions to help maintaining the erectile function in men with T2DM. Several methods of patient education were identified as the approach to facilitate lifestyle modification in men with T2DM-associated ED. The positive outcomes of this review support early ED screening to help preventing T2DM complications such as ED in men. Further, T2DM management is a shared responsibility between the men and healthcare professionals. Despite the success of Vacuum Erectile Device and Low-intensity Extracorporeal Shockwave Therapy in regaining erectile function, further research is needed in this area based on the recommendations of the American Urological Association. Moreover, the health and quality of life of men with T2DM must be improved.

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Introduction: Phosphodiesterase type 5-inhibitors (PDE5is) are the first-line treatment for patients with diabetes mellitus-induced erectile dysfunction (DMED), however, some patients are non-responser to PDE5is. We performed a perspective, randomized, comparative study to explore the efficacy of low intensity extracorporeal shock wave treatment (Li-ESWT) combined with vacuum erectile device (VED) in the treatment of DMED patients who were unresponsive to PDE5is. Methods: One hundred and five eligible patients were randomly divided into three groups: group A (VED), group B (Li-ESWT) and group C (VED plus Li-ESWT). Follow-up was conducted at 4 weeks, 8 weeks and 12 weeks after the end of treatment. The erectile function was estimated by the international index of erectile function-erectile function domain (IIEF-EF), erection hardness score (EHS), sexual encounter profile questions 2 and 3 (SEP2 and SEP3) and global assessment question 1 and 2 (GAQ1 and GAQ2) before and after treatment. The changes of five points in IIEF-EF were calculated as the minimal clinical important difference (MCID), which was considered as the main index of efficacy. Results: The MCID was achieved in 14.7%, 14.7% and 17.6% patients in group A at the follow up on 4 weeks, 8 weeks and 12 weeks, respectively (36.4%, 39.4% and 36.4% in group B; 36.4%, 51.5%, and 66.7% in group C). There were significant differences in the percentage of MCID cases between group A and group C at the follow up on 12 weeks (P<0.001), as well as that between group B and group C (P=0.014). Additionally, comparison in MCID within group C showed that there were significant differences between 4 weeks and 12 weeks follow-up (P=0.014). Conclusion: Our findings indicated the combined therapy Li-ESWT and VED was more beneficial to shift turn PDE5is non-responders to responders for moderate patients with DMED than VED or Li-ESWT monotherapy. Moreover, this study provided evidence that patients with DMED who failed after taking oral PDE5is could attempt to opt for an alternative physicotherapy (Li-ESWT or VED) prior to more invasive alternatives.

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INTRODUCTION: Vacuum erectile device (VED) therapy is commonly used for penile rehabilitation after radical prostatectomy, however, the underlying mechanism of this effect is not fully understood. AIM: To evaluate the presence of label-retaining cells (LRCs), cells with long-term retention of 5-ethynyl-2-deoxyuridine (EdU) labeling and recognized as adult stem cells or progenitor-like cells, in cavernous tissue after VED treatment using a BCNC rat model. METHODS: Postnatal pups (1 day old) of Sprague Dawley (SD) rats were intraperitoneally injected with EdU (50 ug/g, BID for 3 days) and BCNC surgery was conducted at 6 weeks old (designated as natal-labeled rats). Adult SD rats underwent BCNC surgery and EdU injection (50 ug/g, once) after surgery (designated as adult-labeled rats). One week after surgery, both natal- and adult-labeled rats received daily VED treatment for 4 weeks. Intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured for all rats and then the penile tissue was harvested. The ratio of ICP/MAP was calculated to represent erectile function. Penile tissue was examined by immunofluorescence staining to detect EdU positive cells. MAIN OUTCOME MEASURES: The ratio of Intracavernous pressure (ICP) /MAP and the percentage of EdU positive cells were measured. RESULTS: The erectile function was impaired after BCNC and partially restored after VED treatment in both natal- and adult-labeled rats (P < .05). There was no difference in the percentage of EdU positive cells in natal-labeled rat cavernous tissue in BCNC group compared with VED group. Among the adult-labeled rats, the percentage of EdU positive cells increased in BCNC group (P < .05) but didn't change significantly after VED treatment (P = .35). CONCLUSION: LRCs may play a limited role in the restoration of erectile dysfunction through VED treatment after BCNC. Yang B, Luse D, Cao Y, et al. The Role of Long Term Label-Retaining Cells in the Treatment of Erectile Dysfunction by Vacuum Erectile Device. Sex Med 2021;9:100442.

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BACKGROUND: Vacuum erectile device (VED) therapy has been widely used in penile rehabilitation after radical prostatectomy; however, there is no consensus on the best regimen. OBJECTIVES: To explore an optimal VED therapy regimen in bilateral cavernous nerve crush (BCNC) rat model. MATERIALS AND METHODS: Adult male rats were used to measure the effects of different durations (1-30 min) of VED treatment on penile length, penile blood gas analysis, and adverse effects. Forty-eight adult male rats were randomly divided into Sham, BCNC, and VED treatment groups (2-3-2-3 min, 4-3-3 min, 5-5 min, and 10 min). Penile length, erectile function, and side effects were detected after VED treatment. Histopathological staining and Western blotting were performed to explore the cellular and molecular changes. RESULTS: Prolongation of the duration of VED treatment significantly decreased the penile oxygen saturation, partial oxygen pressure, and arterial blood ratio (P < 0.05). Compared with the BCNC group, all VED treatment regimens partially reversed BCNC-induced penile shortening and erectile dysfunction (P < 0.0001), with the 4-3-3-min and 5-5-min treatment groups exhibiting more significant improvement than the 10-min and 2-3-2-3-min treatment groups (P < 0.0001). The mechanism may be related to the up-regulation of the smooth muscle cell/collagen ratio, endothelial nitric oxide synthase, and α-smooth muscle actin (all P < 0.0001); and the down-regulation of hypoxia-inducible factor-1α, transforming growth factor-ß1, and apoptosis (all P < 0.0001). The incidence of adverse effects in the 2-3-2-3-min treatment group was the highest. DISCUSSION: The commonly used VED therapy regimens maintained erectile function and penile length of BCNC rat by relieving hypoxia and fibrosis, and no further benefits were observed with increased treatment frequency or prolonged treatment duration. CONCLUSION: Two consecutive 5-min treatments with a short interval is the optimal VED therapy regimen for penile rehabilitation in BCNC rat model.

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BACKGROUND: Penile traction therapy with the use of a traction device (TD) or vacuum erectile device (VED) has been studied as local modalities for Peyronie's disease (PD). AIM: To identify changes of penile curvature, erectile function, and possible cellular and molecular mechanisms between the TD and VED in a rat model of PD. METHODS: Peyronie's plaque was induced in 30 adult male rats. Then, rats were randomly divided into control (PD without treatment), VED, and TD groups. In the VED group, vacuum pressure was applied to the cylinder to induce penile engorgement inside the cylinder for 1 minute. The penis was allowed to deflate completely for another 1 minute. This was repeated for five cycles (inflate and deflate). In the TD group, the rat penis was straightened by a suspended tension gauge at the same tension by clamping the prepuce. This was performed three times per day at 20 minutes per session, with 5-minute intervals between sessions. The entire treatment duration was 4 weeks. OUTCOMES: Penile curvature, intracavernosal pressure, and mean arterial pressure were measured. Immunohistochemistry for α-smooth muscle actin, transforming growth factor-ß1 and mothers against decapentaplegic homolog 2/3 were performed. RESULTS: The TD and VED groups had less penile curvature compared with the control group (15.3 ± 5.3° for TD, 28.4 ± 6.8° for VED, 38.6 ± 10.5° for control; P < .001 for TD vs control, P < .05 for VED vs control). The TD group also had less penile curvature compared with the VED group (P < .05). The VED group had a higher ratio of intracavernosal pressure to mean arterial pressure compared with the two other groups (0.56 ± 0.10 for VED, 0.38 ± 0.06 for TD, 0.32 ± 0.07 for control; P < .001). The immunohistochemistry results showed the VED group had more preserved α-smooth muscle actin with less transforming growth factor-ß1 and mothers against decapentaplegic homolog 2/3 than the TD and control groups in the corpus cavernosa. CLINICAL TRANSLATION: Various benefits can be observed with the TD and VED for the treatment of PD. STRENGTHS AND LIMITATIONS: This study explored the mechanism and benefits of TD and VED therapies for the treatment of PD. The rat model might not represent the human condition. CONCLUSION: Penile traction therapy with the TD or VED is beneficial to decrease penile curvature in animal models of PD. The underlying mechanism could be related to antiapoptosis, antifibrosis, and smooth muscle preservation. Lin H, Liu C, Wang R. Effect of Penile Traction and Vacuum Erectile Device for Peyronie's Disease in an Animal Model. J Sex Med 2017;14:1270-1276.

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OBJECTIVE: To review contemporary knowledge concerning the innovative trends and perspectives in the treatment of erectile dysfunction (ED). METHODS: Medline was reviewed for English-language journal articles between January 2000 and March 2016, using the terms 'erectile dysfunction treatments', 'new trends' and 'perspectives'. In all, 114 original articles and 16 review articles were found to be relevant. Of the 76 cited papers that met the inclusion criteria, 51 papers had level of evidence of 1a-2b, whilst 25 had level of evidence of 3-4. Criteria included all pertinent review articles, randomised controlled trials with tight methodological design, cohort studies, and retrospective analyses. We also manually reviewed references from selected articles. RESULTS: Several interesting studies have addressed novel phosphodiesterase type 5 inhibitors (PDE5Is), orodispersible tablets, their recent chronic use, and combination with other agents. A few controlled studies have addressed herbal medicine as a sole or additional treatment for ED. Experimental studies and exciting review papers have addressed stem cells as novel players in the field of ED treatment. Other recent articles have revised the current status of low-intensity extracorporeal shockwave therapy in the field of ED. A few articles without long-term data have addressed new technologies that included: external penile support devices, penile vibrators, tissue engineering, nanotechnology, and endovascular tools for ED treatment. CONCLUSIONS: The current treatment of ED is still far from ideal. We expect to see new drugs and technologies that may revolutionise ED treatment, especially in complex cases.

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Generally, hypoxia is a normal physiological condition in the flaccid penis, which is interrupted by regular nocturnal erections in men with normal erectile function. [1] Lack of spontaneous and nocturnal erections after radical prostatectomy due to neuropraxia results in persistent hypoxia of cavernosal tissue, which leads to apoptosis and degeneration of cavernosal smooth muscle fibers. Therefore, overcoming hypoxia is believed to play a crucial role during neuropraxia. The use of a vacuum erectile device (VED) in penile rehabilitation is reportedly effective and may prevent loss of penile length. The corporal blood after VED use is increased and consists of both arterial and venous blood, as revealed by color Doppler sonography and blood gas analysis. A similar phenomenon was observed in negative pressure wound therapy (NPWT). However, NPWT employs a lower negative pressure than VED, and a hypoperfused zone, which increases in response to negative pressure adjacent to the wound edge, was observed. Nonetheless, questions regarding ideal subatmospheric pressure levels, modes of action, and therapeutic duration of VED remain unanswered. Moreover, it remains unclear whether a hypoperfused zone or PO 2 gradient appears in the penis during VED therapy. To optimize a clinical VED protocol in penile rehabilitation, further research on the mechanism of VED, especially real-time PO 2 measurements in different parts of the penis, should be performed.

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OBJECTIVE: To evaluate the efficacy and safety of combination therapy of sildenafil plus vacuum erection devices in men with type 2 diabetes mellitus with moderate to severe erectile dysfunction who are dissatisfied with the results of using sildenafil alone. METHODS: The study included 66 diabetes mellitus patients presenting erectile dysfunction for at least 6 months and dissatisfied with the use of 100 mg sildenafil monotherapy. The patients were randomized in two groups. Those in group A (n = 33) were instructed to use a vacuum erection device only, whereas those in group B (n = 33) were treated with combination therapy, including sildenafil 100 mg and a vacuum erection device. Erectile function was evaluated subjectively using the International Index of Erectile Function, Sexual Encounter Profile questionnaire questions 2 and 3 at visit 1 (baseline; study entry), visit 2 (4 weeks after baseline), and visit 3 (12 weeks after baseline; study end). RESULTS: There were no significant differences in average patient age, duration of diabetes, duration of erectile dysfunction, baseline International Index of Erectile Function scores, hypertension, blood testosterone, smoking and alcohol consumption between two groups. Mean International Index of Erectile Function scores were significantly higher for group B at the 1-month (14.86 ± 2.17 vs 12.41 ± 2.63; P < 0.0001) and 3-months (17.53 ± 2.95 vs 14.29 ± 2.81; P < 0.0001) visits. Men in group B had better successful penetration (73.3% vs 46.6%) and successful intercourse (70% vs 46.6%) at 3 months compared with group A. CONCLUSION: Combined use of sildenafil and vacuum erection device therapy significantly enhances erectile function, and it is well tolerated by diabetes mellitus patients not responding to first-line sildenafil alone.

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New discoveries and technological advances in medicine are rapid. The role of technology in the treatment of erectile dysfunction (ED) will be widened and more options will be available in the years to come. These erectile technologies include external penile support devices, penile vibrators, low intensity extracorporeal shockwave, tissue engineering, nanotechnology and endovascular technology. Even for matured treatment modalities for ED, such as vacuum erectile devices and penile implants, there is new scientific information and novel technology available to improve their usage and to stimulate new ideas. We anticipate that erectile technologies may revolutionize ED treatment and in the very near future ED may become a curable condition.

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INTRODUCTION: Radical prostatectomy (RP) is a standard surgical treatment for clinically localized prostate cancer. Erectile dysfunction (ED) and penile shrinkage are common complications. Vacuum Erectile Device (VED) therapy uses negative pressure to distend the corporal sinusoids and to increase blood inflow into the penis. It is the second most commonly used method for penile rehabilitation after RP. However, the underlying mechanisms are still unclear. This paper is designed to review the scientific evidences of VED therapy after RP and discuss the possible mechanisms. METHODS: We reviewed published papers of post-prostatectomy penile rehabilitation using VED. We analyzed the scientific evidences of VED therapy and discussed the possible underlying mechanisms. RESULTS: There are existing clinical evidences for VED therapy to improve ED and preserve penile size. Emerging basic scientific evidence is available and further study is still needed to understand the mechanisms at the molecular level. CONCLUSIONS: Current clinical evidences support the safety, tolerability, effectiveness and benefits of early VED therapy after RP. The available basic scientific evidences demonstrate that VED therapy for penile rehabilitation is achieved by increasing arterial inflow, anti-apoptotic, anti-fibrotic and anti-hypoxia mechanisms.