Mirabegron Add-On Tamsulosin for Men with Overactive Bladder Symptoms: A Pooled Analysis of Four Randomized Controlled Trials.

INTRODUCTION: Overactive bladder symptoms (OABSs) affect patients' quality of life (QOL) worldwide. This pooled analysis compared the efficacy and safety of mirabegron add-on tamsulosin with those of tamsulosin add-on placebo in OABS treatment. METHODS: PubMed, Embase, MEDLINE, and the Cochrane Controlled Trial Register databases were searched for randomized controlled trials (RCTs) examining the efficacy of mirabegron add-on therapy to tamsulosin in the treatment of OABS. Moreover, references from the selected studies were screened. Review Manager 5.4 was used to analyze data. RESULTS: Four RCTs involving 1,397 patients with OABS were selected. Of the total, 697 patients receiving mirabegron add-on tamsulosin constituted the experimental group, and 700 patients receiving tamsulosin add-on placebo constituted the control group. The efficacy endpoints were as follows: mean number of micturition per day (mean difference [MD] = -0.26, 95% confidence interval [CI] = -0.41 to -0.10, p = 0.0001), urgency episodes per day (MD = -0.67, 95% CI = -1.02 to -0.32, p = 0.0002), urgency urinary incontinence (UUI) episodes per day (MD = -0.42, 95% CI = -0.66 to -0.19, p = 0.0005), mean volume voided/micturition (MD = 10.84, 95% CI = 4.97-16.71, p = 0.0003), total International Prostate Symptom Score (IPSS) (MD = -2.01, 95% CI = -4.02 to -0.01, p = 0.05), and IPSS QOL index (MD = -0.65, 95% CI = -0.94 to -0.35, p < 0.0001). Mirabegron therapy, an add-on therapy to tamsulosin, was effective in treating patients with OABS. Moreover, mirabegron might reduce the total IPSS (MD = -2.01, 95% CI = -4.02 to -0.01, p = 0.05). The safety endpoint, treatment-emergent adverse events (odds ratio = 0.94, 95% CI = 0.78-1.13, p = 0.49), suggested that although mirabegron was well-tolerated, it possibly increased the post-void residual urine volume (MD = 10.28, 95% CI = 1.82-18.75, p = 0.02). CONCLUSION: Combination therapy using mirabegron and tamsulosin may be effective in treating patients with non-neurogenic OABS in terms of UUI episodes, total IPSS, and IPSS QOL index. However, its effectiveness must be verified by analyzing additional factors for OABS through further RCTs.

Bioinformatics analysis based on immune-autophagy-related lncRNAs combined with immune infiltration in bladder cancer.

BACKGROUND: To construct a prognostic model based on immune-autophagy-related long noncoding RNA (IArlncRNAs), mainly to predict the overall survival rate (OS) of bladder cancer patients and investigate its possible mechanisms. METHODS: Transcriptome and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. We identified the IArlncRNA by co-expression analysis, differential expression analysis, and Venn analysis. Then, we identified the independent prognostic IArlncRNAs by univariate Cox regression, LASSO regression, and multivariate Cox regression analysis. Moreover, we constructed the prognostic model based on the independent prognostic IArlncRNAs and clinical features. The proportion of 22 immune cell subtypes was analyzed by the CIBERSORT algorithm. Besides, we identified the differential proportion of 22 immune cell subtypes between the high- and low-risk groups. In addition, we identified the correlation between immune-infiltrating cells (screened by univariate Cox regression and multivariate Cox regression analysis) and IArlncRNAs by Pearson correlation analysis. Finally, we estimated the half-maximal inhibitory concentration (IC50) of chemotherapeutic drugs in patients with bladder cancer based on the pRRophetic algorithm. RESULTS: Four IArlncRNAs were identified as independent prognostic factors, including AL136084.3, AC006270.1, Z84484.1, and AL513218.1. The OS of patients in the high-risk group was significantly worse compared to the low-risk group. The nomogram showed an excellent predictive effect with the C-index of 0.64. The calibration chart showed a good actual vs. predicted probability. B cells naïve, T cells CD8, T cells CD4 memory resting, T cells follicular helper, macrophages M1, dendritic resting and activated cells had higher infiltrations in the low-risk group and lower infiltration of macrophages M2. The fraction of macrophages M2 was positively associated with AL136084.3. The fraction of T cells CD8 was positively associated with Z84484.1. The fraction of M + macrophages M0 was negatively associated with Z84484.1. Further, we identified the differential IC50 of 24 chemotherapeutic drugs between the high- and low-risk groups. CONCLUSIONS: The prognostic model based on 4 IArlncRNAs showed an excellent predictive effect. Furthermore, we reasonably speculated that IArlncRNAs are directly or indirectly involved in the immune regulation of the tumor microenvironment (TME), as well as autophagy.

The efficacy and safety of abiraterone acetate in patients with high-risk prostate cancer: a meta-analysis based on six randomized control trials.

BACKGROUND: Abiraterone acetate, a CYP17 enzyme inhibitor, can block the synthesis of androgens in the adrenal gland, prostate, and testis. The purpose of this study was to investigate the efficacy and safety of abiraterone acetate in high-risk prostate cancer patients, including metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC). METHODS: A meta-analysis based on 6 randomized controlled trials (RCTs) was undertaken in compliance with the guidelines of systematic reviews and meta-analyses. Databases including PubMed, EMBASE, and Cochrane library were searched for relevant literature through to September 2019. RESULTS: The pooled analysis reported abiraterone acetate showed significant efficacy in high-risk prostate cancer patients, including overall survival (OS) [HR 0.66, 95% confidence interval (CI), 0.61-0.73, P<0.001], the time to prostate-specific antigen (PSA) progression (HR 0.45, 95% CI, 0.34-0.59, P<0.001), progression-free survival (PFS) (according to radiographic evidence) (HR 0.55, 95% CI, 0.45-0.68, P<0.001) and PSA response rate (RR 2.49, 95% CI, 1.47-4.22, P<0.001). A subgroup analysis was carried out due to the significant heterogeneity between the studies. The incidence of arthralgia (RR 1.19), hypokalemia (RR 2.47), cardiac disorder (RR 1.48), and hypertension (RR 1.57) in the abiraterone acetate group was moderately higher than the control group. CONCLUSIONS: The efficacy and safety of abiraterone acetate as an androgen receptor (AR) pathway targeted drug in high-risk prostate cancer patients was confirmed.

The critical role of BAP1 mutation in the prognosis and treatment selection of kidney renal clear cell carcinoma.

BACKGROUND: The BAP1 mutation is commonly found kidney renal clear cell carcinoma (KIRC) and a potential biomarker of individualized therapy. We evaluated the clinical significance of BAP1 mutation in the prognosis and treatment therapies for KIRC. Potential key pathways and related genes associated with these mechanisms were also identified in this investigation. METHODS: We identified the relevant data of patients BAP1 mutated on the cBioPortal and the compounds with significant selectivity to BAP1 mutations on the Genomics of Drug Sensitivity in Cancer (GDSC). And then, we identified the differences in mRNA expression levels of biological function annotation and pathways between mutated and wild type BAP1 patients by GSEA analysis. Furthermore, we screened the differentially expressed genes (DEGs) between BAP1 mutated and wild typed in KIRC patients and performed the GO and KEGG analysis. Finally, we conducted a protein-protein interaction (PPI) network to investigate the interaction between proteins encoded by candidate DEGs. RESULTS: Review of the TCGA data revealed 41 patients (10%) with KIRC displayed the BAP1 mutation. Further analysis led to the identification of 730 DEGs, while 617 genes were shown to be down-regulated, with 113 genes displaying upregulation. GO and KEGG pathway analysis indicated DEGs as enriched in metabolism, drug metabolism-cytochrome P450, and Drug-metabolizing enzymes. Subsequently, the top 10 hub genes, ranked by the degree in the PPI network were identified. Furthermore, our findings verify that the BAP1 mutation was associated with the deterioration of prognosis in patients with KIRC. Additionally, analysis of the GDSC database revealed that KIRC patients with BPP1 mutation are more prone to responding to Linsitinib. CONCLUSIONS: Our investigation identified the main pathways and relevant genes related to the BAP1 mutation in KIRC, which can contribute to the development of targeted treatment strategies for enhanced prognostic predictions of KIRC.

Risk factors for hemorrhage requiring embolization after percutaneous nephrolithotomy: a meta-analysis.

BACKGROUND: The aim of this meta-analysis was to systematically review and identify the risk factors for severe hemorrhage after percutaneous nephrolithotomy (PCNL). METHODS: We searched the PubMed and EMBASE database for literature related to the risk factors of severe hemorrhage after PCNL requiring angiography and embolization through to September 2019. The necessary data for each eligible study were extracted by 2 independent reviewers. The Newcastle-Ottawa Scale (NOS) was used for assessing the methodological quality of the included studies. Statistical analyses were conducted using Comprehensive Meta-Analysis version 2 to identify whether there was a statistical association between risk factors and severe hemorrhage post-PCNL. RESULTS: The results of this meta-analysis showed that urinary tract infection (UTI) (OR =1.98, 95% CI, 1.21-3.26, P=0.007), diabetes mellitus (OR =4.07, 95% CI, 1.83-9.06, P=0.001), staghorn stone (OR =3.49, 95% CI, 1.25-9.76, P=0.017), and multiple tracts (OR =2.09, 95% CI, 1.33-3.28, P=0.001) were independent risk factors for severe hemorrhage post-PCNL, while hypertension (OR =1.18, 95% CI, 0.58-2.42, P=0.65) showed no significant statistical difference. CONCLUSIONS: Urologists should focus on the above identified risk factors for severe hemorrhage post-PCNL, including UTI, diabetes mellitus, staghorn stone, and multiple tracts. More high-quality studies with larger sample sizes are needed to validate these conclusions.