Project description:The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single-cell RNA sequencing of human corpus cavernosum, adenosine deaminase (ADA) and adenosine receptors knock-out mice (ADA-/-, A1-/-, A2a-/-, A2b-/-, and A3-/-), and primary corpus cavernosum smooth muscle cells are used to determine receptor subtypes responsible for adenosine-induced erection. Three rat models are established to characterize refractory erectile dysfunction (ED): age-related ED, bilateral cavernous nerve crush related ED (BCNC), and diabetes mellitus-induced ED. In single-cell RNA sequencing data, the corpus cavernosum of ED patients show a decrease in adenosine A1, A2a and A2b receptors. In vivo, A2b receptor knock-out abolishes adenosine-induced erection but not that of A1, A2a, or A3 receptor. Under hypoxic conditions in vitro, activating the A2b receptor increases HIF-1α and decreases PDE5 expression. In refractory ED models, activating the A2b receptor with Bay 60-6583 improves erectile function and down-regulates HIF-1α and TGF-β. Administering Dipyridamole (40 mg Kg-1) to BCNC rats improve penile adenosine levels and erectile function. Our study reveals that the A2b receptor mediates adenosine-induced penile erection. Activating the A2b receptor promotes penile rehabilitation of refractory ED by alleviating hypoxia and fibrosis.
Project description:BackgroundsConsidering the natural course of cavernous nerve recovery after robot-assisted laparoscopic prostatectomy (RALP), early intervention of low intensity extracorporeal shock wave therapy (LIESWT) would be more effective for enhancing overall recovery of sexual function (SF). Our objective of this study is to analyze longitudinally the alterations of SF in patients after RALP, with a focus on the effect of early and delayed intervention with LIESWT.MethodsA total of 5 and 11 patients underwent early and delayed intervention with LIESWT, respectively. SF was assessed with the Expanded Prostate Cancer Index Composite (EPIC). The same surgeon performed RALP on 178 patients, and these patients were assigned to the non-LIESWT group to establish a control group. The SF score of EPIC was investigated longitudinally before RALP and 3, 6, 9, and 12 months after RALP.ResultsOur results show that penile rehabilitation with LIESWT immediately before urethral catheter removal improved SF scores. In the baseline, the SF score was significantly higher in the early LIESWT group (P=0.0001). The SF score was significantly lower at postoperative 6 months (early 19.2, delayed 17.9, and non-LIESWT 8.1; P=0.0171), 9 months (20.9, 25.8, and 10.2; P=0.0188), and 12 months (28.0, 21.3, and 9.5; P=0.0051) in the non-LIESWT group. We regret that there was no significant difference in the recovery of SF between the early and delayed protocol with LIESWT at all points. In keeping with our results, LIESWT demonstrated the potential to be efficacious in treatment options for severe post-radical prostatectomy (RP) erectile dysfunction (ED) as it may indirectly support its promotion of nerve regeneration in severe ED due to RP.ConclusionsThis is the first study in which LIESWT has been shown to deliver a clinical benefit on its early or delayed intervention to patients after RALP to penile rehabilitation in terms of restoring SF. Our preliminary results suggest that LIESWT could be used as a treatment option in penile rehabilitation.
Project description:ObjectiveTo investigate the rate of erectile dysfunction (ED) after pelvic ring fracture (PRF).DesignSystematic review and meta-analysis.MethodsA systematic literature search of the Cochrane, EMBASE, MEDLINE, Scopus and Web of Science Library databases was conducted in January 2020. Included were original studies performed on humans assessing ED after PRF according to the 5-item International Index of Erectile Function (IIEF-5) questionnaire and fracture classification following Young and Burgess, Tile or Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association. Furthermore, interventional cohort studies assessing the effect of penile rehabilitation therapy with phosphodiesterase-5-inhibitors (PDE-5-I) on IIEF-5 scores compared before and after treatment were included. Results were presented as forest plots of proportions of patients with ED after PRF or mean changes on IIEF-5 questionnaires before and after penile rehabilitation. Studies not included in the quantitative analysis were narratively summarised. Risk of bias assessment was conducted using the revised tool for the Quality Assessment on Diagnostic Accuracy Studies.ResultsThe systematic literature search retrieved 617 articles. Seven articles were included in the qualitative analysis and the meta-analysis. Pooled proportions revealed 37% of patients with ED after suffering any form of PRF (result on probability scale pr=0.37, 95% CI: 0.26 to 0.50). Patients after 3 months of penile rehabilitation therapy reported a higher IIEF-5 score than before (change score=6.5 points, 95% CI: 2.54 to 10.46, p value=0.0013).ConclusionDespite some heterogeneity and limited high-quality research, this study concludes that patients suffering from any type of PRF have an increased risk of developing ED. Oral intake of PDE-5-I for the purpose of penile rehabilitation therapy increases IIEF-5 scores and may relevantly influence quality-of-life in these patients.Prospero registration numberCRD42020169699.
Project description:To review the evidence of clinical efficacy of low-intensity extracorporeal shock wave therapy (Li-ESWT) for the treatment of erectile dysfunction (ED). A search on PubMed using Medical Subject Headings terms [((low intensity extracorporeal shockwave therapy) OR (Li-ESWT)) AND (erectile dysfunction)] was conducted in August 2022, to obtain studies on the use of Li-ESWT for the treatment of ED. Its success rate in terms of International Index of Erectile Function-5 (IIEF-5) score and Erection Hardness Score (EHS) improvement was recorded and analysed. A total of 139 articles were reviewed. Overall, 52 studies were included in the final review. 17 studies were on vasculogenic ED, 5 on post pelvic surgery ED, 4 specifically on ED in diabetic patients, 24 on non-specified origin ED and 2 on mixed pathophysiological origin ED. The mean age of patients was 55.87±7.91 (standard deviation) years and the duration of ED was 4.36±2.08 years. The mean IIEF-5 score went from 12.04±2.67 at baseline to 16.12±5.72, 16.30±3.26 and 16.85±1.63 respectively at 3, 6 and 12 months. The mean EHS went from 2.00±0.46 at baseline to 2.58±0.60, 2.75±0.46 and 2.87±0.16 respectively at 3, 6 and 12 months. Li-ESWT may be a safe and efficacy option for the treatment and cure of ED. Further studies are needed to assess which patients are more suitable for this procedure and which Li-ESWT protocol can lead to the best outcomes.
Project description:The present umbrella review of five systematic reviews and meta-analyses was conducted to investigate the effectiveness of Low-Intensity Extracorporeal Shock Wave Therapy (Li-ESWT) in the treatment of vascular origin Erectile Dysfunction (ED). A search was carried out in the databases of Pubmed, Scopus, Medline, Scielo and Embase. Participants were divided into two groups: an experimental group receiving Li-ESWT and a control group receiving simulated shock waves. The main variable of this study is ED, measured using the International Index of Erectile Function-Erectile Function (IIEF-EF) and the Erection Hardness Score (EHS) scale. The results showed a statistically significant increase in the mean IIEF-EF score in the experimental group. Overall, four out of five articles reported an increase in the EHS score in the Li-ESWT group compared to the placebo. Concerning the treatment parameters, better outcomes were observed with an energy density of 0.09 mJ/mm2 and the application of 1500-2000 pulses. Additionally, a follow-up of 6-12 months resulted in greater improvement in ED compared to 3 months, although more studies investigating follow-ups beyond 12 months are needed. Obtaining conclusive and clear results is challenging; however, everything indicates that Li-ESWT is an innovative therapeutic alternative for vascular-origin ED due to its low risk and improvement in erectile function.
Project description:Patients complaining of short penile length pose a challenge in urology practice. Those men who present seeking penile lengthening surgery usually overestimate 'normal' penile length, and may in often cases relate their penile length with the degree of masculinity and self-esteem. Penile prosthetic devices are the gold standard treatment of erectile dysfunction (ED) after failure of conservative options. Penile shortening is the most prevalent long-term complaint after successful inflatable penile prosthesis (IPP) placement. This has a significant impact on patient's overall satisfaction and quality of life. Using PubMed, we performed a thorough literature review of the current procedures of preservation or enhancement of penile length as well as reported perioperative protocols in patients undergoing penile prosthesis (PP) insertion. Keywords used were "penile lengthening", "penile enhancement", "penile girth", "inflatable penile prosthesis" and "glans augmentation". Several surgical techniques can be offered in the setting of penile shortening concurrently with PP insertion, e.g., sub-coronal approach of PP placement, sliding technique, modified sliding technique (MoST), multiple-slide technique (MuST), and tunica mesh expansion procedure (TMEP). Adjuvant techniques can also improve subjective penile length include, ventral phalloplasty, suprapubic lipectomy, suspensory ligament release and use of expanding penile implants. Preoperative protocols including use of a vacuum erectile device, traction therapy also seem to improve postoperative outcomes, minimizing postoperative pain, and encouraging the early device use. Currently, there is no consensus among experts on a particular lengthening procedure or when they can be performed to optimize outcomes. Furthermore, it is imperative to set proper expectations before surgery, with extensive patient and partner counseling. When used in the properly selected patient, penile lengthening procedures show promising results with minimal complication rates.
Project description:Several methods of treatment of erectile dysfunction (ED) are offered with low energy shock-wave therapy (LESWT) gaining increasing attention. Reports have documented that LESWT stimulates tissue neovascularization, proliferation and differentiation of endothelial cells, and production of nitric oxide - all can improve the condition of erectile tissue. However, the overall and sexual condition of men deteriorates with age which is linked with a constant decrease in testosterone concentration. A higher risk of sexual health disorders and reduced physical fitness correlates with a testosterone concentration of <12 nmol/L. Such patients may require testosterone replacement therapy. We conducted a target literature review to investigate whether testosterone concentration is taken into account in studies on the use of LESWT in the treatment of ED. We found that most studies did not provide any information on testosterone status. Only 8 of 25 studies examined showed values of testosterone concentrations. Only one of these analyses checked the relationship between the efficacy of LESWT and testosterone concentration. As a result, meta-analyses published to date may not show the full value of LESWT in the treatment of ED. We conclude that in the light of the significant role testosterone plays in the process of an erection and the mechanism of LESWT action, it can be recommended to examine testosterone concentration and to diagnose hypogonadism during the qualification of patients to studies on LESWT efficacy. Moreover, the effectiveness of LESWT in relation to the current testosterone concentration should also be further investigated.
Project description:Penile echo-color Doppler ultrasound (PCDU) is the gold standard for the diagnosis of arterial erectile dysfunction (ED). Its reliability in patients with anxiety was questioned, due to false-positive results. To assess the penile hemodynamic response to intracavernous injection (ICI) of alprostadil in patients with anxiety-related ED. Patients with non-organic ED and a 5-item International Index of Erectile Function (IIEF-5) score ranging between 5 and 7 were enrolled. They were asked to compile the 7-item Generalized Anxiety Disorder (GAD-7) questionnaire to assess the degree of anxiety and were divided according to the GAD-7 score in Group 1 with minimal level of anxiety (n = 20), Group 2 with mild anxiety (n = 20), Group 3 with moderate anxiety (n = 20), and Group 4 with severe anxiety (n = 20). Peak systolic velocity (PSV) and the end-diastolic velocity (EDV) were sampled in all patients, through PCDU in the flaccid state, and 5, 10, 15, and 20 min after ICI of alprostadil at the standard dose of 10 μg. In penile flaccidity, the patients showed a mean PSV of 8.0 ± 4.0 cm/s. The degree of anxiety was found to significantly influence both PSV and EDV at all assessed time-points. Particularly, it was negatively associated with the PSV at time 5 (r = -0.9, p < 0.01), 10 (r = -0.9, p < 0.01), 15 (r = -0.9, p < 0.01), and 20 (r = -0.7, p < 0.01) minutes, and positively with the EDV at time 5 (r = 0.7, p < 0.01), 10 (r = 0.6, p < 0.01), 15 (r = 0.5, p < 0.01), and 20 (r = 0.3, p < 0.01) minutes. Although all patients showed a mean dynamic PSV > 25 cm/s (which excluded an arterial ED according to the current guidelines), a peculiar hemodynamic pattern was found in patients with severe anxiety. In these patients, normal PSV values were reached only after 20 min from ICI, suggesting a "late-responder" profile. If further studies confirm the existence of a distinct hemodynamic profile in patients with severe anxiety, sampling the PSV and the EDV values could be proposed, for detecting patients with severe anxiety-related ED. Dynamic PCDU could be considered an accurate diagnostic test in patients with non-organic ED, since zero false-positive results were found in the present study. PSV in the flaccid state is not able to discriminate between arterial- or non-organic ED.