A meta-regression evaluating the effectiveness and prognostic factors of oral phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction

The effectiveness of phosphodiesterase type 5 inhibitors (PDE5-Is) for erectile dysfunction (ED) varies considerably among trials, but available studies investigating the factors that affect the effectiveness are few and findings are not consistent. A systematic search was performed in PubMed, Cochrane Library, and EMBASE to identify randomized controlled trials comparing PDE5-Is with placebo for the treatment of ED. The methodological quality of included studies was assessed by the Cochrane Collaboration''s tool for assessing risk of bias. The associations between prespecified study-level factors and effectiveness were tested by a random effects meta-regression model. This study included 93 trials with 26 139 patients. When all PDE5-Is were grouped together, Caucasian ethnicity was associated with 15.636% (95% confidence interval [CI]: 0.858% to 32.579%) increase in risk ratio (RR) for Global Assessment Questionnaire question-1 (GAQ-1), and 1.473 (95% CI: 0.406 to 2.338) score increase in mean difference (MD) for posttreatment International Index of Erectile Function-Erectile Function domain score (IIEF-EF), compared to Asian ethnicity. A one-score increase in baseline IIEF-EF was associated with −5.635% (95% CI: −9.120% to −2.017%) reduction in RR for GAQ-1, and −0.229 (95% CI: −0.425 to −0.042) score decrease in MD for posttreatment IIEF-EF. In conclusion, PDE5-Is are more effective in Caucasians than Asians, and in patients with more severe ED.     

Positive association between preoperative lymphocyte-to-monocyte ratio and risk of the status of positive surgical margins by prostate cancer: results in 497 consecutive patients treated only by radical prostatectomy

BackgroundPositive surgical margins (PSM) is one of the most important factors affecting the prognosis of prostate cancer (PCa) patients after radical prostatectomy (RP). Although some studies have found the preoperative systematic inflammation-based scores the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) can predict the incidence and prognosis of PCa, few studies have explored the predictive value of preoperative systematic inflammation-based scores on the PSMs for PCa patients after RP.MethodsFrom June 2014 to September 2020 a total of 497 patients underwent RP at our institution. Blood samples from all patients were collected within one week before surgery. Preoperative clinical characteristics including age, body mass index (BMI), prostate-specific antigen (PSA), and biopsy Gleason sum (BGS) were assessed. Postoperatively pathological specimens were assessed for pathological Gleason sum (PGS), pathological stage, and margin status.ResultsIn the multivariable analysis including preoperative variables, PSA and LMR were the independent predictive factors for PSM (OR: 2.817; 95% CI, 1.836–4.320, P<0.001; OR: 1.124; 95% CI, 1.018–1.240, P=0.021. Considering pre-, intra-, and postoperative variables, BGS, perineural invasion, seminal vesicle invasion (SVI), pathologic Gleason sum (PGS) combined, were associated with increased risk of PSM in the univariable analysis (P<0.001 for all variables). However, in the multivariable analysis, perineural invasion (OR: 2.672; 95% CI, 1.649–4.330; P<0.001), PGS (OR: 2.52; 95% CI, 1.556–4.082; P<0.001) were independent predictive factors for the incidence of PSM. Finally, LMR was shown to be an independent predictive factor (OR: 0.881; 95% CI, 0.779–0.996; P=0.043) for apical PSMs, with increasing LMR predicting the lower incidence of apex location. And we also found that LMR was an independent factor that predicts multifocal positive margins (OR: 1.179; 95% CI, 1.023–1.358; P=0.023).ConclusionsPreoperative LMR could be used as an independent predictor to predict the incidence of PSMs after RP. And Considering pre-, intra-, and postoperative variables, we also found that preoperative LMR could predict the occurrence of apical and multifocal PSMs.     

Impact of pathological response after preoperative transcatheter arterial chemoembolization (TACE) on incidences of microvascular invasion and early tumor recurrence in hepatocellular carcinoma: a multicenter propensity score matching analysis

BackgroundTo study the influence of pathological responses (PR) after transcatheter arterial chemoembolization (TACE) on incidences of microvascular invasion (MVI) and early recurrence in hepatocellular carcinoma (HCC) patients.MethodsBetween 2013 to 2015, consecutive HCC patients who underwent liver resection with “curative” intent at three hospitals were enrolled in this study. Patients with different areas of PR after preoperative TACE were compared with those without preoperative TACE on the incidences of MVI, early recurrence rates and patterns of recurrence before and after propensity score matching (PSM).ResultsOf 1,970 patients, 737 patients who received preoperative TACE were divided into three groups according to the areas of PR: ≥90% (n=226), 60–90% (n=447), and <60% (n=64). PR ≥90% was an independent protective factor of incidences of MVI [odds ratio (OR), 0.144; 95% confidence interval (CI), 0.082–0.245, P<0.001) and early recurrence (HR, 0.742; 95% CI, 0.561–0.963, P=0.032); while PR<60% was an independent risk factor of incidences of MVI (OR, 6.076; 95% CI, 3.004–11.728, P<0.001) and early recurrence (HR, 1.428; 95% CI, 1.095–1.929; P=0.009). Furthermore, patients with PR <60% were significantly more likely to develop multiple intrahepatic recurrences involving multiple hepatic segments when compared with patients without preoperative TACE.ConclusionsThis study indicated the area of PR after TACE was closely associated with the incidences of MVI and early tumor recurrence. Patients with PR <60% were at significantly higher risks of having more MVI, early and multiple tumor recurrences     

A systematic review and meta-analysis of neostigmine for urinary retention after surgeries

BackgroundThe aim of this research is to analyze the efficacy of neostigmine in the treatment of postoperative urinary retention (POUR).MethodsIn this research, we screened multiple databases including PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure (CNKI). After a systematic search process, data extraction was conducted. Review Manager 5.2 was adopted for meta-analysis, sensitivity analysis, and bias analysis.ResultsAfter searching for articles, 20 eligible trials including 1,850 patients after surgery were extracted. Our results suggested that the neostigmine group had a higher effective rate for urinary retention than the Chinese traditional and physical therapy group (OR =7.47, 95% CI: 4.10–13.59, overall effect P<0.001). Further subgroup analysis showed that neostigmine acupoint injection was better than neostigmine intramuscular injection. Time to first voiding in the neostigmine acupoint injection group was shorter than that in the neostigmine intramuscular injection group (MD =–81.92, 95% CI: –130.13 to –33.70, overall P<0.001, I²=99% with random effects model). Furthermore, neostigmine acupoint injection improved urine excretion (MD =243.40, 95% CI: 201.62–285.18, overall P<0.0001) and reduced the residual urine volume (MD =–41.31, 95% CI: –58.05 to –24.58, overall P<0.001, I²=75% with random effects model). The results of the sensitivity analysis and publication bias showed that this research was robust and had little publication bias.DiscussionOur meta-analysis results suggest that neostigmine can effectively improve the symptoms of POUR and neostigmine acupoint injection may achieve a better therapeutic effect.     

Liver resection versus liver transplantation for hepatocellular carcinoma within Milan criteria: a meta-analysis of 18,421 patients

BackgroundOutcomes after liver resection (LR) and liver transplantation (LT) for hepatocellular carcinoma (HCC) are heterogenous and may vary by region, over time periods and disease burden. We aimed to compare overall survival (OS) and disease-free survival (DFS) between LT versus LR for HCC within the Milan criteria.MethodsTwo authors independently searched Medline and Embase databases for studies comparing survival after LT and LR for patients with HCC meeting the Milan criteria. Meta-analyses and metaregression were conducted using random-effects models.ResultsWe screened 2,278 studies and included 35 studies with 18,421 patients. LR was associated with poorer OS [hazard ratio (HR) =1.44; 95% confidence interval (CI): 1.14–1.81; P<0.01] and DFS (HR =2.71; 95% CI: 2.23–3.28; P<0.01) compared to LT, with similar findings among intention-to-treat (ITT) studies. In uninodular disease, OS in LR was comparable to LT (P=0.13) but DFS remained poorer (HR =2.95; 95% CI: 2.30–3.79; P<0.01). By region, LR had poorer OS versus LT in North America and Europe (P≤0.01), but not Asia (P=0.25). LR had inferior survival versus LT in studies completed before 2010 (P=0.01), but not after 2010 (P=0.12). Cohorts that underwent enhanced surveillance had comparable OS after LT and LR (P=0.33), but cohorts undergoing usual surveillance had worse OS after LR (HR =1.95; 95% CI: 1.24–3.07; P<0.01).ConclusionsMortality after LR for HCC is nearly 50% higher compared to LT. Survival between LR and LT were similar in uninodular disease. The risk of recurrence after LR is threefold that of LT.     

Systematic review and meta-analysis on laparoscopic cystectomy in bladder cancer

BackgroundThis study aimed to systematically evaluate the efficacy of laparoscopic radical cystectomy (LRC) surgical therapy in patients with bladder cancer (BC), and to provide evidence for the clinical treatment of BC.MethodsThe Embase, Ovid, PubMed, Medline, Springer, and Web of Sciences database were searched to screen articles with clinical controlled trials on LRC treatment of BC. The Cochrane Handbook 5.0.2 software and Review Manager 5.3 software were adopted to evaluate the risk of bias and to perform a meta-analysis of the included articles in this study.ResultsA total of 12 articles were obtained, including 1,283 research cases. The meta-analysis results showed that relative to the control group (Ctrl), the observation group (Observ group) had significantly lower intraoperative blood loss (IBL) after LRC [mean difference (MD) =−458.75; 95% confidential interval (CI): −505.75 to −411.76; Z=19.13; P<0.00001], blood transfusion rate (BTR) (odds ratio =0.36; 95% CI: 0.13–0.94; Z=2.08; and P=0.04), use of analgesics (MD =−24.53; 95% CI: −39.04 to −10.01; Z=3.31; and P=0.0009), and incidence of postoperative complications (Risk ratio =0.58; 95% CI: 0.39–0.85; Z=2.77; and P=0.006). However, and the length of hospital stay could not be shortened (MD =–2.43; 95% CI: –4.83 to –0.02; Z=1.98; and P=0.05).DiscussionLRC treatment of BC could effectively reduce the amount of IBS, and lower the intraoperative BTR, use of analgesics, and incidence of postoperative complications. Therefore, it could be used in the clinical surgical treatment of BC patients.     

Extreme body mass index is associated with poor survival outcomes after radical cystectomy: a retrospective cohort study in a Chinese population

BackgroundBody mass index (BMI) has been evidenced to be a significant prognostic factor in multiple cancers. This retrospective study aimed to investigate the association between BMI and survival outcomes after radical cystectomy (RC) in patients with bladder cancer (BCa).MethodsClinical and pathological parameters of patients who were diagnosed with BCa and received RC between 2010 and 2018 were collected. The associations between BMI at surgery and clinicopathological features were examined. The prognostic value of BCa for overall survival (OS) and cancer-specific survival (CSS) was examined using the Kaplan-Meier method and Cox regression models.ResultsAmong the 217 patients enrolled in this study, 13 (6.0%), 121 (55.8%), 60 (27.6%), and 23 (10.6%) had a BMI value of <18.5 kg/m² (underweight), 18.5–23.9 kg/m² (normal), 24–27.9 kg/m² (overweight), and ≥28 kg/m² (obese), respectively. Underweight and obese patients tended to have poorer survival after RC than normal and overweight patients (P<0.05). Multivariable Cox regression revealed that extreme BMI was an independent predictor of both OS (BMI <18.5 vs. 18.5–27.9 kg/m², OR =2.675, 95% CI: 1.131–6.327, P=0.025; BMI ≥28 vs. 18.5–27.9 kg/m², OR =3.693, 95% CI: 1.589–8.583, P=0.002) and CSS (BMI <18.5 vs. 18.5–27.9 kg/m², OR =3.012, 95% CI: 1.180–7.687, P=0.021; BMI ≥28 vs. 18.5–27.9 kg/m², OR =3.801, 95% CI: 1.526–9.469, P=0.004), along with tumor stage and urinary diversion type.ConclusionsBeing underweight or obese is associated with a poor prognosis in patients with BCa undergoing RC. For patients who are preparing to undergo RC for BCa, controlling the BMI index through diet or exercise before surgery may contribute to the surgical curative effect and an improved prognosis.     

Avanafil for male erectile dysfunction： a systematic review and meta-analysis

Avanafil, a potent new selective phosphodiesterase type 5 （PDE5） inhibitor, has been developed for the treatment of erectile dysfunction （ED）. We carried out a systematic review and meta-analysis to assess the efficacy and safety of this drug for the treatment of ED. A literature review was performed to identify all published randomized, double-blind, placebo-controlled trials of avanafil for the treatment of ED. The search included the following databases： MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Four publications, involving a total of 1381 patients, were used in the analysis, including four randomized controlled trials （RCTs） that compared avanafU with a placebo. Among the co-primary efficacy end points indicating that avanafil 100 mg was more effective than a placebo were successful vaginal penetration （SEP2） （the odds ratio （OR） =5.06, 95% confidence interval （CI） =3.29-7.78, P〈 0.00001） and successful intercourse （SEP3） （OR = 3.99, 95% CI = 2.80-5.67, P 〈 0.00001）. Men randomized to receive avanafil were less likely than those receiving the placebo to drop out due to an adverse event （AE） （OR = 1.48, 95% CI = 0.54-4.08, P = 0.44）. Specific AEs with avanafil included headache and flushing, which were significantly less likely to occur with placebo. This meta-analysis indicates that avanafil 100 or 200 mg is an effective and well-tolerated treatment for ED. Compared with avanafil 100 mg, patients who take avanafil 200 mg are more likely to experience headaches.     

Prognostic effect of preoperative serum albumin to globulin ratio in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma

BackgroundAccurate identification of ideal candidates for cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is an unmet need. We tested the association between preoperative value of systemic albumin to globulin ratio (AGR) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.MethodsmRCC patients treated with CN were included. The overall population was therefore divided into two AGR groups using cut-off of 1.43 (low, <1.43 vs. high, ≥1.43). Univariable and multivariable Cox regression analyses tested the association between AGR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel’s concordance index (C-index). The clinical value of the AGR was evaluated with decision curve analysis (DCA).ResultsAmong 613 mRCC patients, 159 (26%) patients had an AGR <1.43. Median follow-up was 31 (IQR: 16–58) months. On univariable analysis, low preoperative serum AGR was significantly associated with both OS (HR: 1.55, 95% CI: 1.26–1.89, P<0.001) and CSS (HR: 1.55, 95% CI: 1.27–1.90, P<0.001). On multivariable analysis, AGR <1.43 was associated with worse OS (HR: 1.51, 95% CI: 1.23–1.85, P<0.001) and CSS (HR: 1.52, 95% CI: 1.24–1.86, P<0.001). The addition of AGR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index=0.640 vs. C-index=0.629). On DCA, the inclusion of AGR marginally improved the net benefit of the prognostic model. Low AGR remained independently associated with OS and CSS in the IMDC intermediate risk group (HR: 1.52, 95% CI: 1.16–1.99, P=0.002).ConclusionsIn our study, low AGR before CN was associated with worse OS and CSS, particularly in intermediate risk patients.     

Systematic review and meta-analysis on phosphodiesterase 5 inhibitors and α-adrenoceptor antagonists used alone or combined for treatment of LUTS due to BPH

The aim of this systematic review is to determine the comparative effectiveness and safety of phosphodiesterase 5 inhibitors (PDE5-Is) and α-blockers used alone or combined for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). An electronic search of PubMed, Cochrane Library and Embase up to January 2014 was performed to identify randomized controlled trials comparing the efficacy and safety of PDE5-Is and α-blockers for treatment of lower urinary tract symptoms due to benign prostatic hyperplasia, which assessed IPSS score, maximum flow rate, postvoided residual urine, quality of life and Erectile Function (IIEF) score as outcomes. Data were analyzed by fixed or random effect models using Cochrane Collaboration review manager software. A total of 12 studies were included. Our novel data demonstrated that there was a trend that α-blockers were more efficacious than PDE5-Is on decreasing IPSS score and increasing maximum flow rate. α-blockers were significantly more effective than PDE5-Is on reduction of postvoided residual urine with a mean difference of 3.67 (95% CI 1.56 to 5.77, P = 0.0006) and PDE5-Is showed greater effect than α-blockers on increasing IIEF score with a mean difference of 9.82 (95% CI 3.80 to 15.85, P = 0.001). In conclusion, our novel data demonstrated that PDE5-Is plus ABs ranked the highest on the improvement of LUTS/BPH. PDE5-Is monotherapy was also effective in this kind of disorder except less reduction of PVR than ABs. In addition, both combined- or mono-therapy were safe.     

Association of 5-alpha-reductase inhibitor and prostate cancer incidence and mortality: a meta-analysis

Background5-Alpha-reductase inhibitors (5-ARIs) have been suggested as potential chemopreventive agents for prostate cancer (PCa). This study was conducted to evaluate the effect of 5-ARIs on the incidence and mortality of PCa.MethodsThe PubMed, Embase and Cochrane Library databases were searched comprehensively from database inception to October 2019. The clinical outcomes included the incidence of overall PCa, high-grade (Gleason8-10) PCa, metastatic PCa, overall survival (OS), and cancer-specific survival (CSS).ResultsOverall, 23 studies were included in the present study, representing 11 cohort studies, 5 case-control studies, and 8 randomized controlled trials. The use of 5-ARIs was associated with a decreased risk of overall PCa [relative risk (RR) =0.77; 95% CI: 0.67–0.88; P<0.001] and increased risk of Gleason 8–10 PCa (RR=1.19; 95% CI: 1.01–1.40; P=0.036). In terms of metastatic PCa, there were no significant between-group differences (RR=1.23; 95% CI: 0.69–2.18; P=0.487). Furthermore, we found that prediagnostic 5-ARI usage was not associated with an increased risk of overall or prostate cancer mortality, with HRs of 1.00 (95% CI: 0.92–1.08; P=0.938) and 0.98 (95% CI: 0.80–1.21; P=0.881), respectively.ConclusionsIn conclusion, while male 5-ARI users were associated with a decreased risk of overall prostate cancer and increased risk of high-grade prostate cancer (Gleason 8–10), they were not associated with an increased risk of overall or prostate cancer mortality. 5-ARIs should be recommended carefully for use as chemopreventive agents.     

Coronavirus-associated kidney outcomes in COVID-19, SARS,and MERS: a meta-analysis and systematic review

ObjectivesA meta-analysis and systematic review was conducted on kidney-related outcomes of three recent pandemics: SARS, MERS, and COVID-19, which were associated with potentially fatal acute respiratory distress syndrome (ARDS).MethodsA search of all published studies until 16 June 2020 was performed. The incidence/prevalence and mortality risk of acute and chronic renal events were evaluated, virus prevalence, and mortality in preexisting hemodialysis patients was investigated.ResultsA total of 58 eligible studies involving 13452 hospitalized patients with three types of coronavirus infection were included. The reported incidence of new-onset acute kidney injury (AKI) was 12.5% (95% CI: 7.6%–18.3%). AKI significantly increased the mortality risk (OR = 5.75, 95% CI 3.75–8.77, p < 0.00001) in patients with coronavirus infection. The overall rate of urgent-start kidney replacement therapy (urgent-start KRT) use was 8.9% (95% CI: 5.0%–13.8%) and those who received urgent-start KRT had a higher risk of mortality (OR = 3.43, 95% CI 2.02–5.85, p < 0.00001). Patients with known chronic kidney disease (CKD) had a higher mortality than those without CKD (OR = 1.97, 95% CI 1.56–2.49, p < 0.00001). The incidence of coronavirus infection was 7.7% (95% CI: 4.9%–11.1%) in prevalent hemodialysis patients with an overall mortality rate of 26.2% (95% CI: 20.6%–32.6%).ConclusionsPrimary kidney involvement is common with coronavirus infection and is associated with significantly increased mortality. The recognition of AKI, CKD, and urgent-start KRT as major risk factors for mortality in coronavirus-infected patients are important steps in reducing future mortality and long-term morbidity in hospitalized patients with coronavirus infection.     

Comparative Effectiveness and Safety of Oral Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction: A Systematic Review and Network Meta-analysis

Context

Phosphodiesterase type 5 inhibitors (PDE5-Is) are currently the first-line therapy for erectile dysfunction (ED), but available studies investigating the comparative effects of different PDE5-Is are limited.

Objective

To compare the efficacy and safety of different classes of oral PDE5-Is for ED.

Evidence acquisition

A systematic search was performed in PubMed, Cochrane Library, and Embase to identify randomized controlled trials that compared different PDE5-Is or PDE5-Is with a placebo for ED. The methodological quality of included studies was appraised with the Cochrane Collaboration bias appraisal tool, and the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation system.

Evidence synthesis

A total of 118 trials (31 195 individuals) were included. There was no major difference in the results between the traditional meta-analysis and the network meta-analysis. Network meta-analysis demonstrated that PDE5-Is were superior to placebo to improve erectile function. Compared with tadalafil (relative risk [RR]: 0.61; 95% confidence interval [CI], 0.33–0.90) and vardenafil (RR: 0.63; 95% CI, 0.35–0.92), avanafil was less effective on Global Assessment Questionnaire question 1. Tadalafil was more effective than vardenafil (mean difference [MD]: 1.49; 95% CI, 0.50–2.50) and udenafil (MD: −1.84; 95% CI, −3.31 to −0.33) as measured by the erectile function domain of the International Index of Erectile Function. For all efficacy outcomes, the absolute effects and the rank tests indicated that tadalafil and vardenafil were the most effective agents. After adjusting for dosage, the conclusion remained the same. Safety analysis showed there was no major difference among different agents.

Conclusions

In recommended doses, oral PDE5-Is are more effective than placebo for ED, and tadalafil seems to be the most effective agent, followed by vardenafil. PDE5-Is are generally safe and well tolerated, and there is no major difference on the safety profile.     

Predictive factors for postoperative renal function after off-clamp,non-renorrhaphy partial nephrectomy

BackgroundThere is limited information on perioperative renal function during off-clamp, non-renorrhaphy open partial nephrectomy. Therefore, this retrospective study aimed to identify predictive factors of perioperative decline in renal function after off-clamp, non-renorrhaphy open partial nephrectomy.MethodsClinical records of 138 patients with renal tumors who underwent off-clamp, non-renorrhaphy open partial nephrectomy at our institution were reviewed. Off-clamp, non-renorrhaphy partial nephrectomy was performed using a soft coagulation system. Perioperative estimated glomerular filtration rate (eGFR) preservation was calculated, and predictors were identified using multivariate regression analysis at 5 days, 1 month, and 3 months after surgery.ResultsThe median operation time was 122 minutes, and the median volume of estimated blood loss was 155 mL. The mean eGFR preservation at 5 days, 1 month, and 3 months after surgery was 95.3%, 91.0%, and 90.7%, respectively. Estimated blood loss was an independent predictor of perioperative decline in eGFR 5 days after surgery [odds ratio (OR): 0.97; 95% confidence interval (CI): 0.96, 0.98; P<0.001]. Preoperative eGFR and estimated blood loss were independent predictors of perioperative decline in eGFR 1 month after surgery (OR: 0.86; 95% CI: 0.77, 0.95; P=0.007 and OR: 0.98; 95% CI: 0.97, 0.99; P<0.001, respectively). Age, preoperative eGFR, and estimated blood loss were independent predictors of perioperative decline in eGFR 3 months after surgery (OR: 0.64; 95% CI: 0.54, 0.81; P<0.001, OR: 0.72; 95% CI: 0.61, 0.85; P<0.001; and OR: 0.98; 95% CI: 0.97, 0.99; P=0.004, respectively).ConclusionsEstimated blood loss during surgery was a predictor of perioperative decline in eGFR within 3 months after off-clamp, non-renorrhaphy open partial nephrectomy. Age was a predictor of perioperative decline in eGFR 3 months after surgery.     

Phosphodiesterase type 5 inhibitors in postprostatectomy erectile dysfunction: a critical analysis of the basic science rationale and clinical application

Context

Erectile dysfunction (ED) after radical prostatectomy (RP) has a significant negative impact on a patient's health-related quality of life. Phosphodiesterase type 5 inhibitors (PDE5-Is) have recently been utilized not only as a treatment of ED in this population but also as a preventive strategy in penile rehabilitation programs.

Objective

To elucidate the pathophysiologic mechanisms of post-RP ED, to assess the need for rehabilitation following surgery, and to analyze the basic scientific evidence and clinical applications of PDE5-Is for the prevention and treatment of ED.

Evidence acquisition

A systematic review of the literature using Medline, Cancerlit, and the Cochrane Library was conducted for the period between January 1997 and June 2008 using the keywords erectile dysfunction, radical prostatectomy, and phosphodiesterase inhibitors. Efficacy and safety of PDE5-Is in the randomized, placebo-controlled trials are evaluated in this review, and the limitations of the remaining studies are also discussed.

Evidence synthesis

Post-RP ED has many factors. Cavernosal nerve injury induces pro-apoptotic factors (ie, loss of smooth muscle) and pro-fibrotic factors (ie, an increase in collagen) within the corpora cavernosa. Cavernosal changes may also be attributed to poor oxygenation due to hemodynamic changes. Experimental data support the concept of cavernosal damage and suggest a protective role for daily dosage of a PDE5-I; however, similar data have not yet been replicated in humans. Penile rehabilitation programs are common in clinical practice, but there is no definitive evidence to support their use or the best treatment strategy. PDE5-Is are efficacious and safe in young patients with normal preoperative erectile function who have undergone bilateral nerve-sparing radical prostatectomy. On-demand use of a PDE5-I may be at least as efficacious as daily use. PDE5-I use in penile rehabilitation programs is not supported by rigorous level 1 evidence-based medicine.

Conclusions

PDE5-Is are an efficacious and safe treatment for post-RP ED in properly selected patients. The experimental results on the protective role of daily dosages of PDE5-Is, while robust, have not been replicated in humans. With current human data, the role of a PDE5-I alone as a rehabilitation strategy is unclear and deserves further investigation.     

Value of preoperative urine white blood cell and nitrite in predicting postoperative infection following percutaneous nephrolithotomy: a meta-analysis

BackgroundTo evaluate to what degree preoperative urine white blood cell (WBC) and urine nitrite (NIT) values are predictive of postoperative infections following percutaneous nephrolithotomy (PCNL).MethodsA systematic literature search was performed of the PubMed, Embase, Cochrane Library, Wanfang Data, National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (CSTJ or VIP) online databases to identify relevant studies that examined the predictive value of urine WBC or NIT as risk factors for post-PCNL infection, and the search was finished on February 28, 2020. Two independent reviewers screened the relevant studies, extracted necessary data from the eligible case-control studies (CCS), and assessed the quality of included studies through the Newcastle-Ottawa scale (NOS). RevMan 5.3 software and the Stata 16.0 software were used to complete the statistical analysis of data. Results are expressed as odds ratio (OR) with 95% confidence intervals (CIs).ResultsAccording to the statistical analysis of 12 eligible studies involving 6113 patients, positive urine WBC (WBC+: OR =3.86, 95% CI: 3.03–4.91, P<0.001) and positive NIT (NIT⁺: OR =7.81, 95% CI: 5.44–11.21, P<0.001) in preoperative tests were identified as independent risk factors for postoperative infections following PCNL.ConclusionsIn summary, as risk factors for postoperative infections, the presence of preoperative urine WBC+ and NIT+ should be evaluated as part of clinical procedure, in order to reduce infections of PCNL.     

Efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors in treating erectile dysfunction after bilateral nerve‐sparing radical prostatectomy

We carried out a systematic review and meta‐analysis to assess the efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors for treating erectile dysfunction (ED) after bilateral nerve‐sparing radical prostatectomy (BNSRP). A literature review was performed to identify all published randomised double‐blind, placebo‐controlled trials of PDE5 inhibitors for the treatment of ED after BNSRP. The search included the following databases: MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Six publications involving a total of 1678 patients were used in the analysis, including six RCTs that compared PDE5 inhibitors (tadalafil, sildenafil, avanafil and vardenafil) with placebo. Co‐primary efficacy end points: International Index of Erectile Function‐Erectile Function (IIEF‐EF) domain score [the standardised mean difference (SMD) = 4.04, 95% confidence interval (CI) = 2.87–5.22, P < 0.00001]; successful vaginal penetration (SEP2) [the odds ratio (OR) = 14.87, 95%CI = 4.57–48.37, P < 0.00001]; and successful intercourse (SEP3) (OR = 47, 95%CI = 3–13.98, P < 0.00001) indicated that PDE5 inhibitors was more effective than the placebo. Specific adverse events with PDE5 inhibitors included headache (12.08%), dyspepsia (6.76%) and flushing (6.52%), which were significantly less likely to occur with placebo. This meta‐analysis indicates that PDE5 inhibitors to be an effective and well‐tolerated treatment for ED after BNSRP.     

Comparative effectiveness of medical treatment vs. metabolic surgery for histologically proven non-alcoholic steatohepatitis and fibrosis: a matched network meta-analysis

BackgroundNon-alcoholic steatohepatitis (NASH) comprises a major healthcare problem affecting up to 30% of patients with obesity and the associated risk for cardiovascular and liver-related mortality. Several new drugs for NASH-treatment are currently investigated. No study thus far directly compared surgical and non-surgical therapies for NASH. This network meta-analysis compares for the first time the effectiveness of different therapies for NASH using a novel statistical approach.MethodsThe study was conducted according to the PRISMA guidelines for network meta-analysis. PubMed, CENTRAL and Web of Science were searched without restriction of time or language using a validated search strategy. Studies investigating therapies for NASH in adults with liver biopsies at baseline and after at least 12 months were selected. Patients with liver cirrhosis were excluded. Risk of bias was assessed with ROB-2 and ROBINS-I-tools. A novel method for population-adjusted indirect comparison to include and compare single-arm trials was applied. Main outcomes were NASH-resolution and improvement of fibrosis.ResultsOut of 7,913 studies, twelve randomized non-surgical studies and twelve non-randomized surgical trials were included. NASH-resolution after non-surgical intervention was 29% [95% confidence interval (CI): 23–40%] and 79% (95% CI: 72–88%) after surgery. The network meta-analysis showed that surgery had a higher chance of NASH-resolution than medication [odds ratio (OR) =2.68; 95% CI: 1.44–4.97] while drug treatment was superior to placebo (OR =2.24; 95% CI: 1.55–3.24). Surgery (OR =2.18; 95% CI: 1.34–3.56) and medication (OR =1.79; 95% CI: 1.39–2.31) were equally effective to treat fibrosis compared to placebo without difference between them. The results did not change when only new drugs specifically developed for the treatment of NASH were included.ConclusionsMetabolic surgery has a higher effectiveness for NASH-therapy than medical therapy while both were equally effective regarding improvement of fibrosis. Trials directly comparing surgery with medication must be urgently conducted. Patients with NASH should be informed about surgical treatment options.     

A systematic review and meta-analysis of radical cystectomy in the treatment of muscular invasive bladder cancer (MIBC)

BackgroundA meta-analysis was conducted to evaluate the curative effect of radical cystectomy in the treatment of muscular invasive bladder cancer (MIBC).MethodsChinese and English databases were searched using free combinations of the terms “bladder cancer,” “radical cystectomy,” “muscle invasive bladder cancer,” and “bladder preservation.” Review Manager 5.3 software was used for the meta-analysis.ResultsA total of 12 articles were included in the meta-analysis, most of which had low-bias risk and were of medium and high quality. A funnel chart showed that the circles of some studies were basically symmetrical with the midline, suggesting that the research accuracy was high, the publications were not biased, and the final conclusions were credible. Twelve articles analyzed patients’ 5-year survival rate in randomized controlled trials (RCTs). In these RCTs, the experimental group (expt group) comprised 775 cases and the control group (ctrl group) comprised 766 cases. A heterogeneity test using the fixed-effects model (FEM) showed Chi² =2.19, df =11, I²=0%, P=1.00>0.1, Z =2.57, odds ratio (OR) =1.30, 95% confidence interval (CI): 1.06–1.59, and P=0.01<0.05. 3 articles analyzed patients’ 10-year survival rates in RCTs. These trials comprised a total of 417 patients (209 in the expt group and 208 in the ctrl group). The overall heterogeneity test showed Chi² =0.40, df =2, I²=0%, P=0.82>0.1, Z =1.42, OR =1.32, 95% CI: 0.90–1.94, and P=0.16>0.05. 6 articles analyzed 5-year distant metastasis rates (DMRs) in RCTs. The overall heterogeneity test showed Chi² =1.68, df =5, I²=0%, P=0.89>0.1, Z =1.70, OR =1.28, 95% CI: 0.96–1.71, and P=0.09>0.05).DiscussionOur meta-analysis confirmed that radical cystectomy is effective in the treatment of MIBC and is worthy of clinical promotion.