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.     

Effect of phosphodiesterase type 5 inhibitors on prostate cancer risk and biochemical recurrence after prostate cancer treatment: A systematic review and meta‐analysis

Recent studies have examined the impact of phosphodiesterase type 5 inhibitors (PDE5‐Is) use on the risk of prostate cancer, and biochemical recurrence (BCR) in prostate cancer patients, but the results were inconsistent. A meta‐analysis was conducted to assess the associations with all published studies. Databases (PubMed, Web of Science and MEDLINE) were retrieved to identify relevant studies which explored the impact of PDE5‐Is use on the risk of prostate cancer, and BCR in prostate cancer patients. The summary results along with 95% confidence intervals (CIs) were calculated. Nine articles were eligible for the inclusion criteria. The pooled analysis showed that PDE5‐Is use was not related to the increased risk of prostate cancer (odds ratio (OR), 0.71; 95% CI, 0.40–1.29). Moreover, PDE5‐Is use was not linked to BCR risk in prostate cancer patients with erectile dysfunction (ED) following radical prostatectomy or radiation therapy (relative risk (RR), 1.09; 95% CI, 0.89–1.34). The heterogeneity test suggested moderate heterogeneity across studies. PDE5‐Is use does not influence the risk of prostate cancer, and BCR in prostate cancer patients. More well‐designed studies are warranted to confirm the findings of our analyses.     

Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials

The meta-analysis was performed to assess the efficacy and safety of daily oral L-arginine and phosphodiesterase type 5 inhibitors (PDE5Is) alone or combination in treating patients with erectile dysfunction (ED). We performed a search of randomised controlled trials in the following databases: PubMed, EMBASE and Cochrane Library databases. Four articles including 373 patients were studied. Erectile functions were significantly improved in three therapy groups compared with baseline. Patients who received the combination of L-arginine and PDE5Is showed significant improvement compared to those treated with L-arginine and PDE5Is alone, as assessed by sexual function index (p <0.00001 and p =0.005, respectively) and total testosterone (p <0.00001 and p =0.0007, respectively). Furthermore, patients who treated with PDE5Is alone exhibited the better efficacy than those treated with L-arginine alone in respects of sexual function index (p <0.00001) and total testosterone (p =0.0001). However, the combination of L-arginine and PDE5Is had no obvious difference relative to PDE5Is alone in terms of various adverse events (AEs). Conclusively, compared with monotherapy, the combination of L-arginine and PDE5Is showed a greater improvement of sexual function and total testosterone, and did not significantly increase the AEs. Besides, PDE5Is alone revealed a better effect than those treated with L-arginine alone for patients with ED.     

Efficacy of type-5 phosphodiesterase inhibitors in the drug treatment of premature ejaculation: a systematic review

This review examines the role of nitric oxide (NO) as a neurotransmitter involved in the central and peripheral control of ejaculation, the methods of phosphodiesterase type 5 inhibitor (PDE5I) drug treatment studies for premature ejaculation (PE), the adherence of methods to the contemporary consensus of ideal PE drug trial design, the impact of methods on treatment outcomes and the role of PDE5Is in the treatment of PE. NO/cGMP transduction is involved in both the central and peripheral control of emission, but evidence for a direct central or peripheral effect of PDE5Is on ejaculation is speculative. Thirteen of the 14 studies reviewed failed to fulfil the evidence-based medicine criteria for ideal PE drug trial design. Limitations of the studies include inadequately defined study populations, the lack of a double-blind placebo-controlled study design, and the absence of consistent objective physiological measures or sensitive, validated outcome assessment instruments as study endpoints. The broad range of intravaginal ejaculatory latency time (IELT) fold-increases reported with PDE5Is, on-demand selective serotonin re-uptake inhibitor (SSRI) drugs, and combined PDE5I/on-demand SSRIs is testament to the unreliability of data and conclusions from methodologically flawed studies. The one study that fulfilled the evidence-based medicine criteria of an ideal clinical trial design reported that treatment with sildenafil failed to significantly increase baseline IELT, supporting our conclusion that there is no convincing evidence to support any role for PDE5Is in the treatment of men with lifelong PE and normal erectile function. However, there is limited evidence to support a potential role for PDE5Is alone or combined with daily or on-demand SSRIs in the treatment of acquired PE in men with comorbid erectile dysfunction. Further controlled studies adhering to the contemporary consensus of ideal clinical trial design are required to clarify the role of PDE5Is in this subgroup of men with acquired PE.     

Combination therapy with selective serotonin reuptake inhibitors and phosphodiesterase‐5 inhibitors in the treatment of premature ejaculation

We aimed to evaluate the effectiveness of paroxetine and tadalafil combination in the treatment of premature ejaculation (PE). A total of 150 primary (lifelong)PE patients were randomly distributed into three groups of 50 patients each. Group 1 received 20 mg paroxetine every day for 1 month, Group 2 received 20 mg tadalafil on demand 2 h before intercourse, and Group 3 received paroxetine and tadalafil on demand 2 h before intercourse. Intravaginal ejaculatory latency times (IELT) scores were evaluated at baseline, at the end of the first month of therapy and 1 month after discontinuation of the treatment, while International Index of Erectile Function (IIEF) questionnaire scores were evaluated both prior to and after the treatment. At the end of the first month of therapy, IELT scores were compared with the basal values and statistically significant changes were detected (60.6 ± 30.2–117.3 ± 67.3, 68.5 ± 21.4–110.2 ± 37.3, 71.56 ± 40.23–175.2 ± 60.2)(P < 0.01). IELT scores after discontinuation of treatment were found to be close to the baseline IELT scores (P > 0.05). IIEF scores were evaluated both prior to and after the treatment, and no statistically significant difference was detected (P > 0.05). It is concluded that utilisation of selective serotonin reuptake inhibitors (SSRI) and phosphodiesterase‐5 inhibitors (PDE5i) combination before intercourse seems to provide significantly longer ejaculatory latency times as compared with SSRI alone for a long time in patients with PE.     

Resection with primary anastomosis vs nonrestorative resection for perforated diverticulitis with peritonitis: a systematic review and meta‐analysis

Aim

It is still controversial whether the optimal operation for perforated diverticulitis with peritonitis is primary anastomosis (PRA) or nonrestorative resection (NRR). The aim of this systematic review and meta‐analysis was to evaluate mortality and morbidity rates following emergency resection for perforated diverticulitis with peritonitis and ostomy reversal, as well as ostomy nonreversal rates.

Method

The Pubmed, EMBASE, Cochrane Library, MEDLINE via Ovid, CINAHL and Web of Science databases were systematically searched. Mortality was the primary end‐point. A subgroup meta‐analysis of randomized controlled trials was performed in addition to a meta‐analysis of all eligible studies. Odds ratios (ORs) and mean difference (MD) were calculated for dichotomous and continuous outcomes, respectively.

Results

Seventeen studies, including three randomized controlled trials (RCTs), involving 1016 patients (392 PRA vs 624 NRR) were included. Overall, mortality was significantly lower in patients with PRA compared with patients with NRR [OR (95% CI) = 0.38 (0.24, 0.60), P < 0.0001]. Organ/space surgical site infection (SSI) [OR (95% CI) = 0.25 (0.10, 0.63), P = 0.003], reoperation [OR (95% CI) = 0.48 (0.25, 0.91), P = 0.02] and ostomy nonreversal rates [OR (95% CI) = 0.27 (0.09, 0.84), P = 0.02] were significantly decreased in PRA. In the RCTs, the mortality rate did not differ [OR (95% CI) = 0.46 (0.15, 1.38), P = 0.17]. The mean operating time for PRA was significantly longer than for NRR [MD (95% CI) = 19.96 (7.40, 32.52), P = 0.002]. Organ/space SSI [OR (95% CI) = 0.28 (0.09, 0.82), P = 0.02] was lower after PRA. Ostomy nonreversal rates were lower after PRA. The difference was not statistically significant [OR (95% CI) = 0.26 (0.06, 1.11), P = 0.07]. However, it was clinically significant [number needed to treat/harm (95% CI) = 5 (3.1, 8.9)].

Conclusion

This meta‐analysis found that organ/space SSI rates as well as ostomy nonreversal rates were decreased in PRA at the cost of prolonging the operating time.     

Serum vitamin D levels and erectile dysfunction: A systematic review and meta‐analysis

Suboptimal levels of serum vitamin D levels have been implied to be associated with cardiovascular diseases and endothelial dysfunction, conditions closely associated with erectile dysfunction (ED). The present systematic review and meta‐analysis was performed to evaluate the vitamin D levels in subjects with ED compared to controls and the 5‐item version of the international index of erectile function (IIEF‐5) score in subjects with vitamin D deficiency compared to those without vitamin D deficiency in order to elucidate the role of vitamin D in the pathogenesis of ED. Studies evaluating the possible association between vitamin D levels and ED were initially screened and thus included following electronic literature search of database Cochrane Library, PUBMED, EMBASE and MEDLINE. Essential article information including outcome measures was extracted from the qualified studies by two independent authors, and STATA 12.0 software was used conducted the meta‐analysis. Subgroup analyses were conducted by vitamin D detection methods and sample size. The standard mean difference (SMD) as well as the 95% confidence intervals (95% CIs) was applied to estimate the outcome measures. A total of seven articles were included in our meta‐analysis with a total of 4,132 subjects. Pooled estimate was in favour of increased vitamin D levels in subjects without ED with a SMD of 3.027 ng/ml, 95%CI 2.290–3.314, p = 0.000. However, subgroup analysis showed an opposite trend, after one study with a sample size over 1,000 that could possibly influence the weight balance was excluded, with a SMD of 0.267, 95%CI ?0.052 to 0.585, p = 0.101. We also identified about 0.320 higher in IIEF‐5 score (95%CI = 0.146–0.494, p = 0.000) in subjects without vitamin D deficiency versus with vitamin D deficiency. Nevertheless, subgroup analysis based on vitamin D detection methods obtained differential results (radioimmunoassay subgroup, SMD(95%CI) = 0.573 (0.275–0.870), p = 0.000; immunoassay subgroup, SMD(95%CI) = 0.189 (?0.025 to 0.404), p = 0.084). In conclusion, results from the present meta‐analysis did not provide a strong relationship between vitamin D and the risk of ED. However, the results should be interpreted with caution and more high quality studies are warranted.     

Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis

Previous studies have reported inconsistent findings regarding the association between the use of selective serotonin reuptake inhibitors (SSRIs) and the risk of fracture. We identified relevant studies by searching three electronic databases (MEDLINE, EMBASE, and the Cochrane Library) from their inception to October 20, 2010. Two evaluators independently extracted data. Because of heterogeneity, we used random‐effects meta‐analysis to obtain pooled estimates of effect. We identified 12 studies: seven case‐control studies and five cohort studies. A meta‐analysis of these 12 observational studies showed that the overall risk of fracture was higher among people using SSRIs (adjusted odds ratio [OR] = 1.69, 95% confidence interval [CI] 1.51–1.90, I² = 89.9%). Subgroup analysis by adjusted number of key risk factors for osteoporotic fracture showed a greater increased fracture risk in those adjusted for fewer than four variables (adjusted OR = 1.83, 95% CI 1.57–2.13, I² = 88.0%) than those adjusted for four or more variables (adjusted OR = 1.38, 95% CI 1.27–1.49, I² = 46.1%). The pooled ORs anatomical site of fracture in the hip/femur, spine, and wrist/forearm were 2.06 (95% CI 1.84–2.30, I² = 62.3%), 1.34 (95% CI 1.13–1.59, I² = 48.5%), and 1.51 (95% CI 1.26–1.82, I² = 76.6%), respectively. Subgroup analysis by exposure duration revealed that the strength of the association decreased with a longer window of SSRI administration before the index date. The risk of fracture was greater within 6 weeks before the index date (adjusted OR = 3.83, 95% CI 1.96–7.49, I² = 41.5%) than 6 weeks or more (adjusted OR = 1.60, 95% CI 0.93–2.76, I² = 63.1%). Fracture risk associated with SSRI use may have a significant clinical impact. Clinicians should carefully consider bone mineral density screening before prescribing SSRIs and proper management for high‐risk populations. © 2012 American Society for Bone and Mineral Research.     

Conversion to mammalian target of rapamycin inhibitors increases risk of de novo donor‐specific antibodies

In kidney transplantation, conversion to mammalian target of rapamycin (mTOR) inhibitors may avoid calcineurin inhibitor (CNI) nephrotoxicity, but its impact on post‐transplant allo‐immunization remains largely unexplored. This retrospective cohort study analyzed the emergence of donor‐specific antibodies (DSA) in kidney transplant recipients relative to their immunosuppressive therapy. Among 270 recipients without pretransplant immunization who were screened regularly for de novo DSA, 56 were converted to mTOR inhibitors after CNI withdrawal. DSA emergence was increased in patients who were converted to mTOR inhibitors (HR 2.4; 95% CI 1.06–5.41, P = 0.036). DSA were mainly directed against donor HLA‐DQB1 antigens. The presence of one or two DQ mismatches was a major risk factor for DQ DSA (HR 5.32; 95% CI 1.58–17.89 and HR 10.43; 95% CI 2.29–47.56, respectively; P < 0.01). Rejection episodes were more likely in patients converted to mTOR inhibitors, but this difference did not reach significance (16% vs. 7.9%, P = 0.185). Concerning graft function, no significant change was observed one year after conversion (P = 0.31). In conclusion, conversion to mTOR inhibitors may increase the risk of developing class II DSA, especially in the presence of DQ mismatches: this strategy may favor chronic antibody‐mediated rejection and thus reduce graft survival.     

Association between CRT(D)/ICD and renal insufficiency: A systematic review and meta‐analysis

Cardiac resynchronization therapy with or without a defibrillator (CRT(D)) and implantable cardioverter defibrillator (ICD) may reduce the risk of arrhythmia or heart failure‐specific mortality and improves the prognosis of patients with chronic kidney disease (CKD) or dialysis. The aim of this study was to perform a meta‐analysis investigating the relationship between CRT(D)/ICD and renal insufficiency. Cochrane Library, Web of Science, Embase, and Pubmed were systematically searched from inception to 29 October 2019. We included studies that report all‐cause mortality of patients with renal insufficiency who received CRT(D)/ICD therapy. Twenty‐six studies (n = 119,263) were included, exploring the relationship between CRT(D)/ICD and renal insufficiency from two aspects: (1) Compared with ICD‐only, CRT(D) was associated with lower risk of all‐cause mortality in CKD patients (odds ratios (OR) = 0.67; 95% confidence interval (CI), 0.60 to 0.75). For non‐primary prevention (secondary prevention or both), the analysis revealed a lower risk of all‐cause mortality in the ICD group than in the no‐ICD group (OR = 0.47; 95% CI, 0.40 to 0.55). (2) CKD increased all‐cause mortality in comparison with control group (OR = 2.12; 95% CI, 1.85 to 2.44), and so did dialysis (OR = 2.53; 95% CI, 2.34 to 2.73). Furthermore, compared with CKD3 (eGFR: 30‐59 ml/min/1.73 m²), CKD4/5 (eGFR <30 ml/min/1.73 m²) was observed to have a significantly higher risk of all‐cause mortality (OR = 2.70; 95% CI, 1.93 to 3.80). This review shows a clear association between CRT(D)/ICD and renal insufficiency in the aspect of all‐cause mortality, and may provide a reference for the clinical application of CRT(D)/ICD.     

CAG‐repeat polymorphisms in the polymerase γ gene and male infertility: a meta‐analysis

CAG‐repeat in the polymerase γ (POLG) gene encoding polymerase γ for mitochondria is important to spermatogenesis. Compared with a few researchers who raised alteration of CAG‐repeat‐affected male reproductive ability, others did not find the association between CAG‐repeat polymorphisms and male infertility. Therefore, a comprehensive meta‐analysis is necessary to determine the association; 13 case–control studies were screened out using keywords search. From these studies, characteristics were extracted for conducting meta‐analysis. Odds ratio (OR) and 95% confidence interval (CI) were used to describe the results; the results indicated that CAG‐repeat allele was not a risk factor to male infertility (pooled OR = 1.03, 95% CI: 0.79–1.34, P = 0.828). Four different genetic comparisons also demonstrated a negative result: heterozygote comparison (not 10/10 versus 10/10. Pooled OR = 0.99, 95% CI: 0.77–1.27, P = 0.948), homozygote comparison (not 10/not 10 versus 10/10. Pooled OR = 1.08, 95% CI: 0.56–2.06, P = 0.816), the recessive genetic comparison (not 10/not 10 versus not 10/10 + 10/10. Pooled OR = 1.07, 95% CI: 0.58–1.95, P = 0.829) and the dominant genetic comparison (not 10/not 10 + not 10/10 versus 10/10. Pooled OR = 0.97, 95% CI: 0.72–1.29, P = 0.804); based on current researches, this meta‐analysis demonstrated no apparent association between POLG‐CAG‐repeat and male infertility. Similarly, CAG‐repeat was not a sensitive site to male infertility.     

Comparison between microsurgical varicocelectomy with and without testicular delivery for treatment of varicocele: A systematic review and meta‐analysis

The present study was conducted to assess the semen parameters, complications and clinical effect of microsurgical varicocelectomy with testicular delivery (TD) for treatment of varicocele. Relevant studies were collected and reviewed systemically from PubMed, Medline, Embase, Web of Science, China National Knowledge Infrastructure databases and the Cochrane Library and a meta‐analysis was performed. Relative ratio (RR), standardised mean difference (SMD) and their 95% confidence intervals (CIs) were adopted to estimate the outcome measures. Eight articles and a total of 1,139 subjects including 487 patients with TD in microsurgical varicocelectomy and 652 patients without TD were enrolled in this meta‐analysis. The pooled RR indicated that microsurgical varicocelectomy with TD increased the incidence of orchiepididymitis (RR = 4.36, 95% CI = 1.12–16.99, p = 0.034) and scrotal oedema (RR = 4.25, 95% CI = 2.40–7.54, p = 0.000) than microsurgical varicocelectomy without TD postoperatively. In conclusion, compared to microsurgical varicocelectomy without TD, TD to further ligate the gubernacular veins in microsurgical varicocelectomy results in a higher incidence of orchiepididymitis and scrotal oedema and take longer operation time. However, TD may not have any beneficial influences on semen parameters, serum testosterone, varicocele occurrence, wound infection and natural conception.     

Circumcision does not have effect on premature ejaculation: A systematic review and meta‐analysis

We attempted to evaluate whether circumcision has an effect on premature ejaculation. We searched three databases: PubMed, EMBASE and Google scholar on 1 May 2016 for eligible studies that referred to male sexual function after circumcision. No language restrictions were imposed. The Cochrane Collaboration's RevMan 5.2 software was employed for data analysis, and the fixed or the random‐effect model was selected depending on the heterogeneity. Twelve studies were included in the meta‐analysis, containing a total of 10019 circumcised and 11570 uncircumcised men. All studies were divided into five subgroups by types of study design to evaluate the effect of circumcision on premature ejaculation (PE). Intravaginal ejaculation latency time (IELT), difficulty of orgasm, erectile dysfunction (ED) and pain during intercourse were also assessed because PE was usually discussed along with these subjects. There were no significant differences in PE (odds ratio [OR], 0.90; 95% confidence interval (CI), 0.72‐1.13; p = .37) and orgasm (OR, 1.04; 95% CI, 0.89‐1.21; p = .65) between circumcised and uncircumcised group. However, IELT (OR, 0.72; 95% CI, 0.60‐0.83; p < .00001), ED (OR, 0.42;95% CI, 0.22‐0.78; p = .40) and pain during intercourse (OR, 0.36; 95% CI, 0.17‐0.76; p = .007) favoured circumcised group. Based on these findings, circumcision does not have effect on PE.     

Adjuvant radiotherapy versus observation following lumpectomy in ductal carcinoma in‐situ: A meta‐analysis of randomized controlled trials

The role of adjuvant radiotherapy (RT) following lumpectomy for ductal carcinoma in‐situ (DCIS) was addressed in four major randomized controlled trials (RCTs) which were conducted two to three decades ago. Initial results of these trials suggested the protective role of RT in reducing the ipsilateral breast recurrences. Long‐term results of all these four trials, based on more than 10‐years follow‐up data, have recently been published. A meta‐analysis of four published RCTs which have addressed the role of adjuvant RT following lumpectomy for DCIS was conducted. Review manager (Cochrane Collaboration's software) version RevMan 5.2 was used for analysis. Evaluated events were ipsilateral breast recurrences (both DCIS and invasive), regional recurrences, contralateral breast events, distant recurrences, and overall mortality. The events were entered as dichotomous variable. The present meta‐analysis included four RCTs and a total of 3680 patients – 1710 received adjuvant RT following lumpectomy while 1970 patients did not receive any adjuvant treatment. Patients who received RT had almost half of risk of ipsilateral breast recurrence (RR = 0.53, 95% CI = 0.45‐0.62) and regional recurrence (RR = 0.54, 95% CI = 0.32‐0.91) compared to those who did not receive adjuvant treatment – there was absolute risk reduction in 15% (95% CI = 12%‐17%) for ipsilateral breast recurrences in adjuvant RT treated patients. There was no significant difference in distant recurrence (RR = 1.06, 95% CI = 0.74‐1.53), contralateral breast events (RR = 1.22, 95% CI = 0.98‐1.52) and overall mortality (RR = 0.93, 95% CI = 0.79‐1.09). Though addition of postoperative RT to lumpectomy does not reduce overall mortality, the present meta‐analysis confirms that it decreases the ipsilateral breast and regional recurrence by almost half.     

Underweight and obesity increase the risk of mortality after lung transplantation: a systematic review and meta‐analysis

Many studies have found an association between abnormal body mass index (BMI) and poor outcomes among lung transplant recipients. We performed a systematic review and meta‐analysis to identify outcomes associated with an abnormal pretransplant BMI after lung transplantation (LTx). The MEDLINE and EMBASE databases were searched from inception to May 2015 with focus on original observational studies with post‐transplant survival data in candidates with abnormal BMI (underweight, overweight, or obese). We performed meta‐analyses examining survival and primary graft dysfunction after LTx. We identified 866 citations; 13 observational cohort studies involving 40 742 participants met our inclusion criteria for systematic review. Seven of the 13 were included in the meta‐analysis. There was a significant risk of mortality after LTx in candidates with underweight and obesity (underweight versus normal, relative risk [RR] 1.36, 95% confidence interval [CI] 1.11–1.66, I² = 0%; obesity vs. normal, RR 1.90, 95% CI 1.45–2.56, I² = 0%; overweight vs. normal, RR 1.36, 95% CI 1.11–1.66, I² = 0). There was also a significant risk of primary graft dysfunction in obese (RR 1.92, 95% CI 1.39–2.65, I² = 0%) and overweight (RR 1.72, 95% CI, 1.32–2.24, I² = 0%) candidates. Lung transplant candidates who are underweight or obese have a higher risk of post‐transplant mortality than recipients with a normal BMI.     

Early intervention with phosphodiesterase‐5 inhibitors after prostate brachytherapy improves subsequent erectile function

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To examine the early use of phosphodiesterase‐5 inhibitor (PDE‐5i; sildenafil citrate) in preventing subsequent erectile dysfunction (ED) after (monotherapy) prostate brachytherapy (PB, an accepted option for Gleason 6 or low‐volume Gleason 7 prostate cancer), as PB is currently being offered more frequently in younger patients, and ED can be a side‐effect often within the first 12 months after treatment.

PATIENTS AND METHODS

We examined a single‐surgeon series of 69 patients who had been treated with PB from 2002 to 2005. All patients had a follow‐up of ≥1 year; prospectively, and patients had baseline, 6‐ and 12‐month assessments using the Sexual Health Inventory for Men (SHIM) and International Index of Erectile Function (IIEF)‐6 scores. The 69 patients were divided into early treatment with PDE‐5i (31) and not treated with PDE‐5i (38), and their SHIM and IIEF‐6 scores were compared at baseline, 6 and 12 months. Daily sildenafil (25–50 mg) was given immediately after PB for 12 months. Overall, for the entire group, the mean prostate‐specific antigen (PSA) level was 6.8 ng/mL; 78% had Gleason 6 cancer and 20% had Gleason 7 (3 + 4) cancer. The mean age in the early PDE‐5i group was 64.8 years, and was 66.0 years in the no‐PDE‐5i group. The mean radiation dose in the early PDE‐5i group was 50.2 Gy, and 43.9 Gy in the other group (P= 0.08).

RESULTS

In the no‐PDE‐5i group, the mean baseline SHIM score of 17.1 decreased rapidly to 9.1 at 6 months (P= 0.01) and stayed at 9.3 at 12 months (P= 0.01). In the early PDE‐5i group, the mean baseline SHIM score of 21.8 decreased slightly to 17.6 at 6 months (P= 0.2), and was maintained at 17.9 at 12 months (P= 0.2). Using the Wilcoxon rank‐sum test, the 6‐ and 12‐month SHIM scores in the two groups (P < 0.001). The IIEF‐6 questionnaire confirmed the SHIM analysis.

CONCLUSIONS

After PB patients had a significant decline in SHIM/IIEF‐6 scores at 6 and 12 months. Our results indicate a 50% decrease in the quality of their erections. This provides an opportunity to initiate early intervention with PDE‐5i or perhaps vacuum constriction devices or intraurethral alprostadil. In this study, the early use of PDE‐5i after PB maintained erectile function at both 6 and 12 months.     

Short‐term outcomes of intra‐aortic balloon pump combined with venoarterial extracorporeal membrane oxygenation: A systematic review and meta‐analysis

The effectiveness of intra‐aortic balloon pump (IABP) combined with venoarterial extracorporeal membrane oxygenation (VA‐ECMO) in patients with cardiogenic shock or cardiac arrest remains controversial. The aim of this systematic review and meta‐analysis was to investigate the short‐term clinical outcomes of IABP combined with VA‐ECMO versus VA‐ECMO alone. We searched PubMed, Embase, and the Cochrane Library for English language articles published from inception to August 18, 2018. Observational studies comparing IABP combined with VA‐ECMO with VA‐ECMO were considered eligible for the current study. Twelve observational studies with 3704 patients were included. In the IABP combined with VA‐ECMO group mortality was 59.7%, compared with 65.8% in the VA‐ECMO alone group. The risk ratio (RR) for this comparison was 0.90 (95% confidence interval [CI], 0.80–1.02; P = 0.107; 59.7% vs. 65.8%). In the one‐way sensitivity analysis for estimating the effect of each study on mortality, omission of each study did not make a significant difference. Furthermore, the proportion of patients weaned from VA‐ECMO was significantly higher in IABP combined VA‐ECMO group than in the VA‐ECMO alone group (RR, 1.28; 95% CI, 1.21–1.35; P < 0.001; 77.9% vs. 61.2%). IABP combined with VA‐ECMO could improve success rate of weaning from VA‐ECMO, but did not reduce in‐hospital mortality in patients with cardiogenic shock or cardiac arrest.     

Meta‐analysis of the association of oestrogen receptor‐beta gene RsaI (G/A) and AluI (A/G) polymorphisms with male infertility

A more precise assessment of association of oestrogen receptor‐beta genes RsaI(G/A) and AluI(A/G) polymorphisms with male infertility from current contradictory results is the aim of this meta‐analysis including five RsaI and six AluI studies respectively. No association was observed between infertility and RsaI or AluI. In the stratified analysis by ethnicity, increased risk was found among Caucasians with GA versus GG (OR = 2.263, 95% CI = 1.073–4.776, I² = 57.1%) and dominant model (OR = 2.117, 95% CI = 1.018–4.403, I² = 49.0%) of RsaI. It was not observed for AluI. In the stratified analysis by infertility subtypes, a reduced risk in GA of AluI was observed among azoospermia or severe oligospermia (GA versus AA: OR = 0.686, 95% CI = 0.498–0.945, I² = 21.2%; recessive model: OR = 1.403, 95% CI = 1.056–1.864, I² = 31.7%), and reduced risk was in recessive model (OR = 0.650, 95% CI = 0.446–0.948, I² = 0.0%) of subtypes, except for azoospermia or severe oligospermia. However, this finding was not observed in RsaI. The meta‐analysis showed GA and GG of AluI are possibly resistant factors for spermatogenesis dysfunction and deteriorated sperm quality.