The effect of combination treatment with low-intensity shockwave therapy and daily tadalafil on severe erectile dysfunction: a double-blind, randomized, sham-controlled clinical trial.

BACKGROUND: Patients with severe erectile dysfunction (ED) remain the most challenging group in terms of available noninvasive treatment modalities. AIM: The study sought to assess the role of combination therapy with low-intensity shockwave therapy (LiST) and daily tadalafil 5 mg in a highly select group of patients with severe vasculogenic ED through a double-blind, randomized trial. METHODS: Forty-eight sexually active men were randomly assigned to 12 sessions of LiST 3 times weekly and tadalafil 5 mg once daily (n = 34) or sham therapy and tadalafil (n = 17) for 4 weeks. Patients were assessed at 1 and 3 months after completion of treatment. OUTCOMES: Improvement of erectile function was evaluated through the International Index of Erectile Function-Erectile Function domain (IIEF-EF) or 6-item IIEF and the Sexual Encounter Profile (SEP) diary. The primary outcome was the difference between the groups in the IIEF-EF at 3 months after completion of treatment. Secondary outcomes comprised (1) the difference between the groups in the IIEF-EF at 1 month after completion of treatment, (2) the difference between the groups in the "yes" responses to question 3 of the SEP diary at 1 and 3 months, and (3) the treatment-related adverse events. The number of patients attaining a minimal clinically important difference in the IIEF-EF (improvement of at least 7 points) was also assessed. RESULTS: After treatment, the absolute scores in the IIEF-EF were higher in patients receiving LiST and tadalafil vs sham therapy and tadalafil both at the 1-month (12.1 ± 2.4 vs 10.2 ± 1.7; P = .002) and at the 3-month (12.9 ± 2.1 vs 10.8 ± 1.8; P < .001) evaluation. Between the 2 groups, the proportion of "yes" responses to question 3 of the SEP diary was not statistically significant, whereas the number of patients attaining a minimal clinically important difference in the IIEF-EF was statistically significant only at the 3-month evaluation. No adverse events occurred. CLINICAL IMPLICATIONS: Application of LiST in patients with severe vasculogenic ED receiving daily dose tadalafil may further improve erectile function compared with tadalafil as a stand-alone treatment on the short term. STRENGTHS AND LIMITATIONS: Although we provided the first study in the field, severe vasculogenic ED was defined based on medical history and clinical examination and not based on penile ultrasound measures. CONCLUSION: The combination of 12 sessions LiST 3 times weekly and daily tadalafil for 4 weeks led to a 2-point difference in the IIEF-EF compared with sham therapy and daily tadalafil among patients with severe vasculogenic ED after 1 and 3 months from completion of treatment.

Efficacy and Safety of Platelet-Rich Plasma Injections for the Treatment of Female Sexual Dysfunction and Stress Urinary Incontinence: A Systematic Review.

Introduction: There is no clear evidence in the literature that platelet-rich plasma (PRP) injections improve female sexual dysfunction (FSD) and female stress urinary incontinence (SUI). Objectives: A systematic review was performed to study the efficacy and safety of PRP injections in women with the above pathologies, as well as to explore the optimal dosing, frequency and area of injections, and duration of treatment. Methods: A systematic search on PubMed, Embase and the Cochrane Library database was performed, as well as sources of grey literature from the date of database or source creation to January 2023. After title/abstract and full-text screening, clinical studies on humans evaluating the efficacy of PRP in gynecological disorders using standardized tools were included. Risk of bias was undertaken with RoB-2 for randomized-controlled trials (RCT) and the Newcastle-Ottawa Scale (NOS) for observational studies. Results: Four prospective and one retrospective study explored FSD, while six prospective and one RCT evaluated female SUI. A total of 327 women with a mean age of 51 ± 12 years were included. For FSD, PRP significantly improved the Female Sexual Function Index (FSFI), the Vaginal Health Index (VHI) and the Female Sexual Distress score (FSDS). For SUI, PRP led to a significant improvement in the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and the Urogenital Distress Inventory (UDI-6). The identified RCT reported a significantly higher mean score of ICIQ-SF (p < 0.05) and UDI-6 (p < 0.01) in the midurethral sling group compared to the PRP injections group. Regarding the risk of bias, the RCT was characterized by high risk, whereas the observational studies were of moderate risk. The protocol for PRP injections for FSD is the injection of 2 mL of PRP into the distal anterior vaginal wall once a month for 3 months. For female SUI, 5-6 mL of PRP should be injected into the periurethral area once a month for 3 months. Conclusions: Despite the promising initial results of PRP injections, the level of current evidence is low due to methodological issues in the available studies. It becomes clear that there is an emerging need for high-quality research examining PRP injections for the treatment of FSD and female SUI.

The effect of standard percutaneous nephrolithotomy, miniaturized percutaneous nephrolithotomy and retrograde intrarenal surgery on biomarkers of renal injury: a randomized clinical trial.

Background: Observational studies on the association of endourological procedures with renal parenchymal damage are lacking. This randomized trial examined the effect of standard percutaneous nephrolithotomy (sPCNL) in comparison with miniaturized-PCNL (mini-PCNL) and retrograde intrarenal surgery (RIRS) for nephrolithiasis treatment on novel biomarkers of renal injury. Methods: Seventy-five patients were randomized in a 1:1:1 ratio to receive sPCNL, mini-PCNL and RIRS for nephrolithiasis. The ratios of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) normalized for urinary creatinine (Cr) were calculated from urine samples collected at baseline (2-h preoperatively) and at 2-, 6-, 24- and 48-h postoperatively. Two-way mixed analysis of variance (ANOVA) for repeated measurements was used to evaluate the effects of type of procedure and time on studied biomarkers. Results: Between baseline and 2-h postoperatively, no significant differences were observed in NGAL/Cr changes between sPCNL [median (interquartile range) 9.46 (4.82-14.9)], mini-PCNL [12.78 (1.69-25.24)] and RIRS [6.42 (2.61-23.90)] (P = .902). Similarly, no between-group differences were observed for KIM-1/Cr (P = .853) and IL-18 (P = .980) at 2 h, and all biomarkers at any time-point postoperatively. Within-groups, significant increases from baseline were noted for NGAL/Cr (sPCNL, P < .001; mini-PCNL, P < .001; RIRS, P = .001), KIM-1/Cr and IL-18/Cr at 2 h; progressively lower increases from baseline were noted in all groups for KIM-1/Cr and IL-18/Cr at 6-, 24- and 48-h postoperatively. As such, a significant effect of time but not of type of procedure was evidenced with two-way mixed ANOVA. No significant between-group differences were observed in acute kidney injury incidence and complications. Conclusions: The endourological procedures under study are associated with similar patterns of early tubular injury, detected by novel biomarkers, which is largely reduced within 48 h and no changes in glomerular function.

Platelet-rich plasma for the treatment of erectile dysfunction: a systematic review of preclinical and clinical studies.

INTRODUCTION: There has been tremendous growth in regenerative medicine during the last decade. For erectile dysfunction (ED), after the inclusion of low-intensity shockwave therapy as a treatment modality for ED management by the European Association of Urology sexual health guidelines, intracavernosal injection of platelet-rich plasma (PRP) has gained popularity between urologists and patients as a novel ED therapeutic modality with initial promising results. However, limited clinical data exist regarding efficacy and safety in patients with ED. Furthermore, despite numerous preclinical studies in other tissues and organs, the mechanism of action for restoring erectile function remains undetermined. OBJECTIVES: This systematic review aims to present the current status of preclinical and clinical evidence regarding the use of PRP as treatment option for ED. METHODS: A systematic literature search was conducted using PubMed, Cochrane, and ScienceDirect databases, until February 2023 for studies exploring the effect of PRP on ED. RESULTS: We identified 517 articles, 23 of which were included in this review. These were 7 preclinical (of which 1 was a comparative trial and 6 were placebo-controlled randomized controlled trials) and 16 clinical studies (of which 1 was a comparative trial, 5 were randomized trials, and 2 were placebo-controlled randomized controlled trials). Preclinical data support the regenerative role of PRP in erectile tissue, in accordance with existing evidence in other tissues. Randomized clinical studies, as well as the first 2 available randomized, placebo-controlled clinical trials, showed promising efficacy and a lack of any adverse events. CONCLUSION: As PRP for ED is widely used worldwide, there is an urgent need for high-quality studies with long-term follow-up. Standardization of research protocols, especially on the quality of PRP preparation, is also needed.

Synchronous bilateral testicular cancer with discordant histopathology occurring in a 20-year-old patient: A case report and review of the literature.

INTRODUCTION: Bilateral testicular tumors are very rare, accounting for 1%-5% of all testicular germ-cell tumors (TGCTs). The vast majority of primary bilateral TGCTs are metachronous, with synchronous tumors comprising approximately 0.5%-1% of all cases. Those occurring synchronously share mostly the same histological pattern, predominantly seminoma, with synchronous bilateral TGCTs (SBTGCTs) with discordant subtypes being extremely rare. CASE PRESENTATION: We present the case of a 20-year-old male complaining of a palpable painless right testicular mass incidentally noticed during sexual intercourse. Ultrasonography (US) and magnetic resonance imaging (MRI) of the scrotum demonstrated bilateral testicular lesions, while staging with contrast-enhanced computed tomography (CT) exhibited normal findings. Right radical orchiectomy and left testis-sparing surgery (TSS) with concomitant onco-testicular sperm extraction (onco-TESE) were initially performed. Histology of the right testis revealed a mixed germ-cell tumor, consisting of seminoma and embryonal carcinoma, while that from the left testis disclosed embryonal carcinoma and intratubular germ-cell neoplasia unclassified (IGCNU) infiltrating the surgical margins. Hence, left orchiectomy was subsequently scheduled with histology unveiling IGCNU in the greatest part of the remaining testicular parenchyma. Following adjuvant chemotherapy, with bleomycin, etoposide, and cisplatin (BEP), the patient received testosterone replacement therapy and remained free of recurrence at an 18-month follow-up. CONCLUSION: This case highlights both the rarity of a bilateral testicular tumor's synchronous appearance and its extremely infrequent discordant histopathology. A comprehensive review of the major series of SBTGCTs with discordant histology cited in the literature is additionally presented.

The Effect of Low-Intensity Shock Wave Therapy on Moderate Erectile Dysfunction: A Double-Blind, Randomized, Sham-Controlled Clinical Trial.

PURPOSE: We conducted the first double-blind, randomized, sham-controlled trial evaluating the efficacy and safety of low-intensity shock wave therapy (LiST) exclusively in patients with moderate erectile dysfunction. MATERIALS AND METHODS: Seventy patients were randomized to 12 sessions of LiST (35) or sham therapy (35) twice weekly. Patients were evaluated at 1 and 3 months after completion of treatment. The proportion of participants attaining minimal clinically important difference (MCID) in the International Index of Erectile Function-Erectile Function (IIEF-EF) and the effect of LiST on erectile function, as well as on safety, were the study outcomes. RESULTS: At 3 months, MCID was attained by 27 (79%) patients in the LiST group compared to 0 patients in the sham group. The risk difference between the 2 groups was 79% (95% confidence interval [CI]: 66-93, p <0.001) and the baseline-adjusted mean between-group-difference in the IIEF-EF was 4.4 points (95% CI: 3.4-5.4, p <0.001). At 1 month, MCID was attained by 20 (59%) patients in the LiST group compared to 1 (2.9%) patient in the sham group. The risk difference between the 2 groups was 56% (95% CI: 38-73, p <0.001) and the baseline-adjusted mean between-group-difference in the IIEF-EF was 3.9 points (95% CI: 2.7-5.2, p <0.001). CONCLUSIONS: Twelve sessions of LiST twice weekly for 6 weeks with a treatment protocol of 5,000 impulses, 0.096 mJ/mm2 energy flux density and 5 Hz frequency are highly effective in patients with moderate erectile dysfunction. Still, further long-term randomized studies are warranted to corroborate our findings.

The Effect of Combination Treatment With Low-Intensity Shockwave Therapy and Tadalafil on Mild and Mild-To-Moderate Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Combination of different first-line treatments for erectile dysfunction (ED) has emerged as a promising therapeutic approach. AIM: To conduct the first double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of combination therapy with low-intensity shockwave therapy (LiST) and tadalafil vs LiST and placebo in patients with mild or mild-to-moderate vasculogenic ED. METHODS: Fifty sexually active patients fulfilling the eligibility criteria were randomly assigned to 6 sessions of LiST twice weekly for 3 weeks and tadalafil (n = 25) or placebo (n = 25) once daily for 4 weeks. Patients were evaluated at 1, 3, and 6 months after completion of the treatment protocol. OUTCOMES: The primary outcome was the mean change from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) domain between the 2 groups at 3 months after treatment. Erectile function was also assessed at 1 and 6 months. The number of patients attaining a minimal clinically important difference (MCID) in the IIEF-EF, as well as the safety of combination therapy were evaluated. RESULTS: Adjusting for the baseline values, IIEF-EF improved by 0.8 points more (95% confidence interval [CI] = -0.2 to 1.9, P = .12) at 1 month, 1 point more (95% CI = 0.1-1.9, P = .02) at 3 months and 1.7 points more (95% CI = 0.8-2.7, P < .001) at 6 months in patients treated with combination therapy compared to monotherapy. The number of patients attaining a MCID in the IIEF-EF between the 2 groups improved significantly only at the 3-month evaluation. No adverse events were reported during the whole study period. CLINICAL IMPLICATIONS: Combination of LiST twice weekly for 3 weeks and tadalafil 5 mg once daily for 4 weeks may further ameliorate mild or mild-to-moderate vasculogenic ED compared to LiST monotherapy. STRENGTHS & LIMITATIONS: We conducted the first randomized trial exploring the role of LiST and tadalafil in the management of ED. Conversely, our study lacks external validity due to its single-center design. CONCLUSION: The addition of daily low-dose tadalafil during application of LiST may further improve erectile function compared to application of LiST as a standalone treatment in patients with mild or mild-to-moderate vasculogenic ED. Still, further high-quality studies are warranted to corroborate our findings. Mykoniatis I, Pyrgidis N, Zilotis F, et al. The Effect of Combination Treatment With Low-Intensity Shockwave Therapy and Tadalafil on Mild and Mild-To-Moderate Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Sex Med 2022;19:106-115.

The Effect of Phosphodiesterase-type 5 Inhibitors on Erectile Function: An Overview of Systematic Reviews.

Background: Multiple systematic reviews explore the effect of phosphodiesterase type 5 (PDE5) inhibitors on erectile dysfunction (ED), with each study addressing specific outcomes. However, physicians and policymakers require a holistic approach of this topic. Objective: To summarize the current evidence regarding the efficacy and safety of PDE5 inhibitors for the management of ED through an overview of systematic reviews. Methods: Studies were identified by searching PubMed, Web of Science, Cochrane Library and Scopus databases, as well as sources of grey literature until June 12, 2021 (PROSPERO: CRD42020216754). We considered systematic reviews, meta-analyses or network meta-analyses of randomized trials that provided outcomes about the efficacy and safety of any approved PDE5 inhibitor (avanafil, sildenafil, tadalafil and vardenafil). We constructed forest plots for meta-analytic effects regarding the change in erectile function, adverse events and dropouts after administration of PDE5 inhibitors in the general population and in specific patient groups. Results: We included 23 studies with 154,796 participants and a total of 258 meta-analytic effects. Sildenafil 25 mg [Weighted Mean Difference (WMD): 13.08, 95% Confidence Interval (CI): 10.1-16.06] seemed to be statistically superior to all interventions in improving erectile function compared to placebo, but studies with low-dose sildenafil are lacking. Moreover, comparing among different PDE5 inhibitors, sildenafil 50 mg or sildenafil 100 mg were considered the most effective compounds in the general population. The latter derived, however, predominantly from indirect comparisons among different PDE5 inhibitors. Still, sildenafil 100 mg was associated with more treatment-related adverse events and dropouts. Interestingly, low-dose daily tadalafil may be more effective than high-dose on-demand tadalafil (WMD: 1.24, 95% CI: 0.03-2.44). Furthermore, testosterone and PDE5 inhibitors in patients with ED and hypogonadism seem to further improve symptoms, while the addition of a-blockers in patients with urinary symptoms treated with PDE5 inhibitors does not provide additional benefits (WMD: -0.8, 95% CI: -1.65-0.06). Conclusion: Although the efficacy and safety of PDE5 inhibitors, compared to placebo, is well-documented, the existing evidence comparing different PDE5 inhibitors is low. Therefore, high-quality, head-to-head, trials comparing different PDE5 inhibitors are necessary to determine their ideal dosage and formulation based on their safety and efficacy profile. Systematic Review Registration: PROSPERO, identifier [CRD42020216754].

Effect of phosphodiesterase-type 5 inhibitors on erectile function: an overview of systematic reviews and meta-analyses.

INTRODUCTION: Phosphodiesterase-type 5 inhibitors (PDE5i) are the recommended first-line treatment for erectile dysfunction. Previous systematic reviews and meta-analyses suggest that they are a safe and effective option in many patient groups. Similarly, PDE5i may be effective as part of combination therapy in non-responders to PDE5i. We will generate an overview of systematic reviews, meta-analyses and network meta-analyses aiming to summarise the available knowledge regarding the efficacy and safety of PDE5i in the general population and in multiple subgroups of patients. METHODS AND ANALYSIS: This overview was designed in accordance with the PRIO-harms and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and its protocol was registered at PROSPERO. We will systematically search PubMed, Web of Science, Cochrane Library and Scopus databases from inception to November 2020 without any language restrictions. We will include systematic reviews or meta-analyses: (1) comparing the efficacy and safety of any dose of PDE5i with each other, with placebo or with other effective treatments for the management of erectile function; (2) exploring the use of any PDE5i alone or in combination with other treatment modalities in the general male population or in specific subgroups and (3) conducted with systematic procedures. Our overview will employ the AMSTAR 2 tool to evaluate the quality of the included studies and the Grading of Recommendations Assessment, Development and Evaluation approach to assess the strength of evidence for all outcomes. We will construct forest plots of risk estimates with the corresponding CI for all outcomes. ETHICS AND DISSEMINATION: In this overview, we will undertake an extensive literature search in an attempt to evaluate the potential benefits and risks of treatment with one PDE5i versus another or versus placebo and provide recommendations for clinicians and policy-makers. No ethical approval is required. PROSPERO REGISTRATION NUMBER: CRD42020216754.

Platelet-Rich Plasma (PRP) Improves Erectile Function: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Animal studies postulate that platelet-rich plasma (PRP) injections improve key elements of the pathophysiologic mechanisms leading to erectile dysfunction (ED). AIM: To conduct the first double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of PRP injections in patients with mild and moderate ED. METHODS: Sixty sexually active patients with mild and moderate ED were randomly assigned to two sessions, with a one-month difference, of 10 mL PRP (n = 30) or placebo (n = 30) intracavernosal injections. An FDA-approved separation system was used. Patients were evaluated at 1, 3 and 6 months after completion of the treatment protocol. A per-protocol analysis was applied. All participants withheld any ED treatment during the trial. OUTCOMES: The achievement of minimal clinically important difference (MCID) in the International Index of Erectile Function - Erectile Domain (IIEF-EF) from baseline to 6 months after final treatment. Erectile function at all time points, as well as safety of PRP injections, were also evaluated. RESULTS: At 6 months, a MCID was achieved by 20/29 (69%) patients in the PRP group compared to 7/26 (27%) in the placebo group. The risk difference between the two groups was 42% (95%CI: 18-66), P < 0.001 and the baseline-adjusted mean between-group-difference in the IIEF-EF score was 3.9 points (95%CI: 1.8-5.9). Similarly, a statistically significant difference of both the number of participants attaining a MCID and the IIEF-EF score was also observed at the 1- and 3-month evaluation between the two groups. Accordingly, patients receiving PRP were more satisfied with the treatment. No adverse events were observed during the study period. CLINICAL IMPLICATIONS: Intracavernosal PRP injection therapy used as outlined in this trial appears to be a safe and effective short-term treatment for the management of mild to moderate ED. STRENGTHS & LIMITATIONS: We conducted the first clinical trial exploring the role of PRP in the management of ED. Conversely, our findings lack external validity due to single-center design. Furthermore, our results cannot be extrapolated to other PRP separation systems. CONCLUSIONS: PRP intracavernosal injections may be a promising addition to the urologist's armamentarium for the management of ED. Still, further high-quality studies are warranted to corroborate our findings. Evangelos P, Mykoniatis I, Pyrgidis N, et al. Platelet-Rich Plasma (PRP) Improves Erectile Function: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Sex Med 2021;18:926-935.

Comparing two different low-intensity shockwave therapy frequency protocols for nonbacterial chronic prostatitis/chronic pelvic pain syndrome: A two-arm, parallel-group randomized controlled trial.

BACKGROUND: Despite encouraging results, the optimal low-intensity shockwave therapy (LiST) protocol in patients with chronic prostatitis/chronic pelvic pain syndrome (CPPS) remains unknown. We conducted a two-arm, parallel-group, randomized controlled trial aiming to compare the efficacy and safety of six LiST sessions applied once or twice weekly. METHODS: Fifty patients with CP/CPPS type IIIb were randomly assigned to six LiST sessions once (Group A, n = 25) or twice weekly (Group B, n = 25). Both groups followed the same treatment protocol in terms of LiST application, impulses (5000/session), energy flux density (0.096 mJ/mm2 ) and frequency (5 Hz). Subsequently, all participants were evaluated at 1 and 3 months after completion of LiST protocol. RESULTS: At the follow-up evaluations, LiST significantly improved the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) total, pain and quality of life scores, as well as the International Index of Erectile Function-Erectile Domain (IIEF-ED) in both groups (p < .001 for all measures). Comparing between the two groups, no significant differences were demonstrated in the NIH-CPSI total, pain, urinary and quality of life scores, as well as in the International Prostate Symptom Score, IIEF-ED, and LiST-induced pain at both follow-up evaluations. Accordingly, no adverse events and no dropouts were observed in both groups. CONCLUSION: Six sessions of LiST applied once weekly for 6 weeks or twice weekly for 3 weeks seem to be equally safe and effective in patients with CP/CPPS. Nevertheless, further studies are necessary, since LiST gradually gains its place for the management of CP/CPPS.

Sexual Dysfunction in Women With End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: In women with end-stage renal disease (ESRD), female sexual dysfunction (SD) remains underestimated. AIM: To explore the prevalence, correlates, diagnostic approach and treatment modalities of sexual symptoms in females with ESRD. METHODS: We performed a systematic review and meta-analysis to estimate both the prevalence of SD and the pooled Female Sexual Function Index (FSFI) scores in ESRD females. Similarly, for studies reporting the FSFI score before and after renal transplantation (RT), we estimated the effect of RT on sexual function. Further assessment of heterogeneity was conducted via subgroup and sensitivity analyses, cumulative meta-analysis and univariate meta-regression of important correlates. Records were identified through searching PubMed, Cochrane Library and Scopus databases as well as sources of grey literature until November 2020 (PROSPERO ID: CRD42020215178). OUTCOMES: We included 47 studies with 61 patient group entries and 3490 ESRD female individuals (median age: 45.2 years, ΙQR: 40.4-50.6). RESULTS: The SD prevalence in all females with ESRD was 74% (95%CI: 67%-80%, I2 = 92%) and the FSFI total score 16.1 points (95%CI: 14.3-17.8, I2 = 98%). The female SD prevalence was 63% (95%CI: 43%-81%, I2 = 92%) in renal transplant recipients, 80% (95%CI: 72%-87%, I2 = 91%) in hemodialysis patients and 67% (95%CI: 46%-84%, I2 = 90%) in peritoneal dialysis patients. The total FSFI score improved by 7.5 points (95%CI: 3.9-11.1, I2 = 92%) after RT. Older age and menopause were associated with higher SD prevalence. CLINICAL TRANSLATION: Female SD is highly prevalent in all ESRD women, but renal transplant recipients reported improved sexual function. STRENGTHS & LIMITATIONS: We provide the first study about SD in females and assessed the role of RT on sexual function. Contrary, none of the included studies evaluated the concomitant presence of distress with SD. The levels of heterogeneity were substantially high for all outcomes and we could not adjust for further correlates, which might have affected our measures. CONCLUSIONS: Sexual symptoms negatively affect the quality of life and warrants appropriate clinical attention, as they are an underdetermined and undertreated clinical entity in females with ESRD. Studies on treatment modalities of female SD in patients with ESRD are mandatory, as currently no relevant studies or clinical recommendations exist. Pyrgidis N, Mykoniatis I, Tishukov M, et al. Sexual Dysfunction in Women With End-Stage Renal Disease: A Systematic Review and Meta-Analysis. Sex Med Rev 2021;18:936-945.

The Effect of Low-Intensity Extracorporeal Shockwave Treatment on the Urinary Bladder in an Experimental Diabetic Rat Model.

PURPOSE: Preclinical data increasingly support an impact of low-intensity extracorporeal shockwave therapy (Li-ESWT) on the bladder. We investigated the molecular effects of Li-ESWT on the bladder of a streptozotocin-induced diabetic rat model. METHODS: Fifteen 8-week-old male Wistar rats were randomized into 3 groups: a control group (n=5), a group of diabetic rats without treatment (diabetes mellitus [DM], n=5) and a group of diabetic rats treated with Li-ESWT (DM-ESWT, n=5). A single intraperitoneal dose of streptozotocin (60 mg/kg) was used to induce diabetes. Twenty days after diabetes induction, each rat in the DM-ESWT group received 300 shockwaves with an energy flux density of 0.09 mJ/mm2. Sessions were repeated 3 times/week for 2 weeks, followed by a 2-week washout period. Total RNA from bladder tissue was extracted, cDNA was synthesized, and quantitative real-time polymerase chain reaction was performed to analyze the expression pattern of transient receptor potential vanilloid 1 (Trpv1), interleukin-1ß (Il1b), and the muscarinic receptors M1, M2, and M3 (Chrm1, Chrm2, and Chrm3). RESULTS: The expression of Trpv1, Il1b, and Chrm2 genes was significantly different between the 3 groups (P=0.002, P<0.0001, and P=0.011, respectively; 1-way analysis of variance). In the DM group, the expression of all genes was higher than in the control group, but statistical significance was observed only for Trpv1 and Il1b (P=0.002 and P<0.0001, respectively). Li-ESWT significantly reduced the expression of Il1b and Chrm2 (P=0.001 and P=0.011, respectively), whereas a nonsignificant tendency for reduced expression was noted for Trpv1 (P=0.069). CONCLUSION: The induction of diabetes was associated with increased expression of genes related to mechanosensation, inflammation/ischemia, and contraction in the rat bladder. Li-ESWT reduced the expression of IL1b, Chrm2, and to a lesser extent Trpv1 toward the control levels, suggesting the therapeutic potential of this treatment modality for diabetic cystopathy.

Micro-Ultrasound-Guided vs Multiparametric Magnetic Resonance Imaging-Targeted Biopsy in the Detection of Prostate Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Micro-ultrasound is a novel high resolution ultrasound technology aiming to improve prostate imaging and, consequently, the diagnostic accuracy of ultrasound-guided prostate biopsy. Micro-ultrasound-guided prostate biopsy may present comparable detection rates to the standard of care multiparametric magnetic resonance imaging-targeted prostate biopsy for the diagnosis of clinically significant prostate cancer. We aimed to compare the detection rate of micro-ultrasound vs multiparametric magnetic resonance imaging-targeted prostate biopsy for prostate cancer diagnosis. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of diagnostic accuracy studies comparing micro-ultrasound-guided prostate biopsy to multiparametric magnetic resonance imaging-targeted prostate biopsy as a reference standard test (PROSPERO ID: CRD42020198326). Records were identified by searching in PubMed®, Scopus® and Cochrane Library databases, as well as in potential sources of gray literature until November 30th, 2020. RESULTS: We included 18 studies in the qualitative and 13 in the quantitative synthesis. In the quantitative synthesis, 1,125 participants received micro-ultrasound-guided followed by multiparametric magnetic resonance imaging-targeted and systematic prostate biopsy. Micro-ultrasound and multiparametric magnetic resonance imaging-targeted prostate biopsies displayed similar detection rates across all prostate cancer grades. The pooled detection ratio for International Society of Urological Pathology Grade Group ≥2 prostate cancer was 1.05 (95% CI 0.93-1.19, I2=0%), 1.25 (95% CI 0.95-1.64, I2=0%) for Grade Group ≥3 and 0.94 (95% CI 0.73-1.22, I2=0%) for clinically insignificant (Grade Group 1) prostate cancer. The overall detection ratio for prostate cancer was 0.99 (95% CI 0.89-1.11, I2=0%). CONCLUSIONS: Micro-ultrasound-guided prostate biopsy provides comparable detection rates for prostate cancer diagnosis with the multiparametric magnetic resonance imaging-guided prostate biopsy. Therefore, it could be considered as an attractive alternative to multiparametric magnetic resonance imaging-targeted prostate biopsy. Nevertheless, high quality randomized trials are warranted to corroborate our findings.

Assessment of Combination Therapies vs Monotherapy for Erectile Dysfunction: A Systematic Review and Meta-analysis.

Importance: Combining 2 first-line treatments for erectile dysfunction (ED) or initiating other modalities in addition to a first-line therapy may produce beneficial outcomes. Objective: To assess whether different ED combination therapies were associated with improved outcomes compared with first-line ED monotherapy in various subgroups of patients with ED. Data Sources: Studies were identified through a systematic search in MEDLINE, Cochrane Library, and Scopus from inception of these databases to October 10, 2020. Study Selection: Randomized clinical trials or prospective interventional studies of the outcomes of combination therapy vs recommended monotherapy in men with ED were identified. Only comparative human studies, which evaluated the change from baseline of self-reported erectile function using validated questionnaires, that were published in any language were included. Data Extraction and Synthesis: Data extraction and synthesis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: A meta-analysis was conducted that included randomized clinical trials that compared outcomes of combination therapy with phosphodiesterase type 5 (PDE5) inhibitors plus another agent vs PDE5 inhibitor monotherapy. Separate analyses were performed for the mean International Index of Erectile Function (IIEF) score change from baseline and the number of adverse events (AEs) by different treatment modalities and subgroups of patients. Results: A total of 44 studies included 3853 men with a mean (SD) age of 55.8 (11.9) years. Combination therapy compared with monotherapy was associated with a mean IIEF score improvement of 1.76 points (95% CI, 1.27-2.24; I2 = 77%; 95% PI, -0.56 to 4.08). Adding daily tadalafil, low-intensity shockwave therapy, vacuum erectile device, folic acid, metformin hydrochloride, or angiotensin-converting enzyme inhibitors was associated with a significant IIEF score improvement, but each measure was based on only 1 study. Specifically, the weighted mean difference (WMD) in IIEF score was 1.70 (95% CI, 0.79-2.61) for the addition of daily tadalafil, 3.50 (95% CI, 0.22-6.78) for the addition of low-intensity shockwave therapy, 8.40 (95% CI, 4.90-11.90) for the addition of a vacuum erectile device, 3.46 (95% CI, 2.16-4.76) for the addition of folic acid, 4.90 (95% CI, 2.82-6.98) for the addition of metformin hydrochloride and 2.07 (95% CI, 1.37-2.77) for the addition of angiotensin-converting enzyme inhibitors. The addition of α-blockers to PDE5 inhibitors was not associated with improvement in IIEF score (WMD, 0.80; 95% CI, -0.06 to 1.65; I2 = 72%). Compared with monotherapy, combination therapy was associated with improved IIEF score in patients with hypogonadism (WMD, 1.61; 95% CI, 0.99-2.23; I2 = 0%), monotherapy-resistant ED (WMD, 4.38; 95% CI, 2.37-6.40; I2 = 52%), or prostatectomy-induced ED (WMD, 5.47; 95% CI, 3.11-7.83; I2 = 53%). The treatment-related AEs did not differ between combination therapy and monotherapy (odds ratio, 1.10; 95% CI, 0.66-1.85; I2 = 78%). Despite multiple subgroup and sensitivity analyses, the levels of heterogeneity remained high. Conclusions and Relevance: This study found that combination therapy of PDE5 inhibitors and antioxidants was associated with improved ED without increasing the AEs. Treatment with PDE5 inhibitors and daily tadalafil, shockwaves, or a vacuum device was associated with additional improvement, but this result was based on limited data. These findings suggest that combination therapy is safe, associated with improved outcomes, and should be considered as a first-line therapy for refractory, complex, or difficult-to-treat cases of ED.

Low-intensity shockwave therapy for the management of chronic prostatitis/chronic pelvic pain syndrome: a systematic review and meta-analysis.

OBJECTIVES: To perform a systematic review and meta-analysis aiming to improve the level of evidence and determine the efficacy and safety of low-intensity shockwave therapy (LiST) in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: We searched PubMed, Cochrane Library and Scopus databases from inception to November 2020 for randomised controlled trials (RCTs) exploring the role of LiST for the management of CP/CPPS. We performed a random-effects meta-analysis of RCTs comparing LiST vs sham therapy on CP/CPPS symptoms at different time-points after treatment. Weighted mean differences (WMDs) with the corresponding confidence intervals (CIs) were estimated. Furthermore, we assessed the strength of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42020208813). RESULTS: We included five sham RCTs and one non-sham RCT. In the meta-analysis of sham RCTs, both the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) pain domain score and the numeric pain rating scale improved significantly after LiST vs sham therapy at the assessment directly after treatment protocol completion (WMD 3.2, 95% CI 0.88-5.52, I2 = 90%; and WMD 1.43, 95% CI 0.85-2.01, I2 = 32%, respectively), at 1 month (WMD 4.4, 95% CI 2.84-5.95, I2 = 68%, and WMD 2.59, 95% CI 1.92-3.27, I2 = 83%, respectively), and at 3 months after last treatment session (WMD 3.61, 95% CI 1.49-5.74, I2 = 90%, and WMD 2.64, 95% CI 2.13-3.16, I2 = 71%, respectively). Similarly, the NIH-CPSI total and quality-of-life domain scores improved significantly after LiST compared to sham therapy for the same time-points. Conversely, the long-term efficacy of LiST, as well as the effect of LiST on lower urinary tract symptoms and erectile function, was clinically insignificant. CONCLUSIONS: LiST is an effective treatment modality for the improvement of pain and quality of life in patients with CP/CPPS. Therefore, it should be recommended as a part of individualised treatment strategies in such patients.

Evaluation of a low-intensity shockwave therapy for chronic prostatitis type IIIb/chronic pelvic pain syndrome: a double-blind randomized sham-controlled clinical trial.

BACKGROUND: Currently, there is no efficacious treatment method for chronic prostatitis type IIIb/chronic pelvic pain syndrome (CP/CPPS). Aim of the study was to investigate and compare the efficacy and safety of low-intensity shockwave therapy (LiST) vs. sham treatment in CP/CPPS patients. METHODS: Patients with CP/CPPS diagnosis were randomized in this prospective, sham-controlled, double-blind study either to the active groups (Group B, C) who received 5000 shockwaves per session with energy flux density 0.1 mJ/mm2 or to the sham group (Group A) who received 5000 shockwaves from a visually identical sham probe. All groups underwent six sessions (once/week). LiST effects on pain, micturition, quality of life (QoL), and erectile function were evaluated at 4, 12, and 24 weeks after treatment. The parameters were investigated using validated questionnaires. Uroflowmetry and post void residual calculation were performed at baseline and at 4- and 12-week FU visit. Prostate mpMRI and PSA measurement were performed at baseline and 12-week FU visit. RESULTS: Overall, 45 men were randomized to the active (n = 30) and sham groups (n = 15). Regarding impact of LiST in National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) total, pain, and QoL subdomains scores a clear and persistent in all FU timepoints improvement was found compared to sham treatment. NIH-CPSI urinary subdomain, International Prostate Symptom Score [IPSS], PSA, and mpMRI-PIRADS scores did not differ between the two groups. The mean difference between the LiST and sham group in the change of the NIH-CPSI pain-domain score (Q1-4) from baseline to 12 weeks after final treatment which was 3.3 (95% CI, 1.8, 4.7). Perineal LiST was easy and safe to perform without anesthesia or any side-effects. CONCLUSIONS: LiST seems to be a safe and effective treatment option for CP/CPPS, considerably improving pain and quality of life. Lack of any side-effects, and the potential for repetition make LiST a promising treatment choice for CP/CPPS patients.