Assessment of single-probe dual-energy lithotripters in percutaneous nephrolithotomy: a systematic review and meta-analysis of preclinical and clinical studies.

PURPOSE: To evaluate the safety and efficacy of single-probe dual-energy (SPDE) lithotripters in patients undergoing percutaneous nephrolithotripsy (PCNL) through a systematic review and meta-analysis. METHODS: We searched PubMed, Cochrane Library, Scopus and Embase databases until July 2022 for any preclinical or clinical studies, exploring the safety and efficacy of different SPDE lithotripters in patients undergoing PCNL. We performed a meta-analysis to compare stone-free rate, bleeding, or other complications and mean operative time between SPDE lithotripters and other lithotripters (PROSPERO: CRD42021285631). RESULTS: We included 16 studies (six preclinical, seven observational and three randomized with 625 participants) in the systematic review and four in the meta-analysis. Preclinical studies suggest that SPDE lithotripters are safe and effective for the management of renal stones. Among clinical studies, four studies assessed Trilogy with no comparative arm, two compared Trilogy or ShockPulse with a dual-probe dual-energy lithotripter, two compared Trilogy with a laser, one compared ShockPulse with a pneumatic lithotripter, and one directly compared Trilogy with ShockPulse. Comparing SPDE lithotripters to other lithotripters, no significant differences were demonstrated in stone free rate (OR 1.13, 95% CI 0.53-2.38, I2 = 0%), postoperative blood transfusion (OR 1.33, 95% CI 0.34-5.19, I2 = 0%), embolization (OR 0.45, 95% CI 0.02-12.06), operative time (WMD: 2.82 min, 95% CI -7.31-12.95, I2 = 78%) and postoperative complications based on the Clavien-Dindo classification. CONCLUSIONS: SPDE lithotripters represent a promising treatment modality for patients requiring PCNL. Despite the initial encouraging findings of preclinical and isolated clinical studies, it seems that Trilogy or ShockPulse provide similar efficiency compared to older generation devices.

Assessment of Conservative Combination Therapies for Active and Stable Peyronie's Disease: A Systematic Review and Meta-analysis.

CONTEXT: In patients with Peyronie's disease (PD), oral, injected, or topical agents provide limited efficacy. In this setting, combination of two or more conservative treatments may improve symptoms further. OBJECTIVE: To explore the effects of available conservative combination therapies for active and stable PD through a systematic review and meta-analysis. EVIDENCE ACQUISITION: We searched multiple databases and sources of gray literature until June 2021. We included randomized or observational comparative studies assessing any conservative combination therapies for PD. We undertook a random-effect meta-analysis when at least two studies employed the same treatment modality (PROSPERO: CRD42021224517). EVIDENCE SYNTHESIS: Overall, 13 studies on active PD and ten on stable PD (1962 participants) were included. Most included studies raised methodological concerns. In patients with active or stable PD, the available evidence is inconclusive to support the use of any combination treatment modality, such as intralesional verapamil injections, antioxidants, and other oral, injected, or topical agents. Based on data availability, we performed a meta-analysis to compare the effect of collagenase Clostridium histolyticum (CCH) plus adjunctive mechanical therapies (penile traction or vacuum pump) versus CCH monotherapy on penile curvature and length in patients with stable PD. CCH and adjunctive mechanical therapies resulted in an additional decrease of 0.3° in penile curvature (95% confidence interval [CI]: -3.97 to 4.49, I2 = 0%) and in an increase of 0.5 cm in penile length (95% CI: -0.32 to 1.4, I2 = 70%) compared with CCH monotherapy. CONCLUSIONS: The available combination treatment modalities, including the addition of adjunctive mechanical therapies to CCH, do not improve symptoms further compared with monotherapy and should not be implemented in patients with active or stable PD. Further high-quality randomized trials combining only recommended treatments are mandatory. PATIENT SUMMARY: Despite the interest in and optimism for combination treatment modalities, the road to an effective conservative therapy for Peyronie's disease still seems long.

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.