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Organophosphate esters (OPEs) impact health in many ways. Since its relationship with urinary incontinence remains unknown, we aimed to explore their associations in the US general population. We combined the results of urine specimens test and self-reported urinary incontinence conditions from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 among 2666 participants and then conducted linear regression and logistic regression to analyse associations between log2-transformed OPE concentrations and urinary incontinence. We found that 0.92% of men and 15.74% of women complained of mixed urinary incontinence (MUI). The concentrations of diphenyl phosphate (DPHP) were significantly correlated to MUI among women when treated as a continuous variable (adjusted odds ratio (OR) = 1.15; 95% confidence interval (CI), 1.01–1.31; p = 0.0369) and as a categorical variable (adjusted OR = 1.24; 95% CI, 1.03–1.49; p for trend = 0.0245), whereas no positive correlation was found in males. There were no significant associations between the other three OPEs: bis(2-chloroethyl) phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and dibutyl phosphate (DBUP). The association of DPHP with an increased prevalence OR of MUI in women is a public health concern; future prospective studies are needed to explore its potential mechanism. Supplementary Information The online version contains supplementary material available at 10.1007/s11356-021-14153-5.

The purpose of this study was to evaluate the association between dietary inflammatory index (DII) and urinary incontinence (UI) among a representative sample of the US women. We performed a cross-sectional analysis of women younger than 65 years using the 1999 to 2016 NHANES (National Health and Nutrition Examination Survey) populations. DII were calculated based on baseline dietary intake using 24-h dietary recalls. UI was determined and categorized by self-reported questions. Multivariable logistic regression models were used to assess the association between DII and UI. Stratified linear regression models were applied to test for interaction in prespecified subgroup of interest. A total of 13,441 women age between 20 and 65 years were included in the final analysis. Of these participants 3230 (24.03%) complained of urgency UI, 5276 (39.25%) complained of stress UI and 2028 (15.09%) complained of mixed UI. On multivariate analysis, analysis with DII categorized as quartiles revealed significantly increase odds of urgency UI in the most pro-inflammatory quartile compared to the most anti-inflammatory quartile (OR 1.24, 95% CI 1.07–1.44, P = 0.004 for trend) in full adjustment model. Similar results were observed in SUI (OR 1.14, 95% CI 1.00–1.30, P = 0.021 for trend) and MUI (OR 1.20, 95% CI 1.02−1.43, P = 0.022 for trend). More pro-inflammatory diets, as presented by higher DII scores are associated with an increased likelihood of UI in American women younger than 65 years. Further studies are needed to explore the possible physiological mechanism and evaluate the potential therapeutic implications.

Objective:We evaluate the association between the Dietary Inflammatory Index (DII) and kidney stones.Design:We performed a cross-sectional analysis using data from National Health and Nutrition Examination Survey (NHANES). Dietary intake information was assessed using first 24-h dietary recall interviews, and the Kidney Conditions were presented by a questionnaire. The primary outcome was to investigate the association between DII and incidence of kidney stones, and the secondary outcome was to assess the association between DII and nephrolithiasis recurrence.Setting:The NHANES, 2007–2016.Participants:The study included 25 984 NHANES participants, whose data on DII and kidney stones were available, of whom 2439 reported a history of kidney stones.Results:For the primary outcome, after fully multivariate adjustment, DII score is positively associated with the risk of kidney stones (OR = 1·07; 95 % CI 1·04, 1·10). Then, compared Q4 with Q1, a significant 38 % increased likelihood of nephrolithiasis was observed. (OR = 1·38; 95 % CI 1·19, 1·60). For the secondary outcome, the multivariate regression analysis showed that DII score is positively correlated with nephrolithiasis recurrence (OR = 1·07; 95 % CI 1·00, 1·15). The results noted that higher DII scores (Q3 and Q4) are positively associated with a significant 48 % and 61 % increased risk of nephrolithiasis recurrence compared with the reference after fully multivariate adjustment (OR = 1·48; 95 % CI 1·07, 2·05; OR = 1·61; 95 % CI 1·12, 2·31).Conclusions:Our findings revealed that increased intake of pro-inflammatory diet, as a higher DII score, is correlated with increased odds of kidney stones incidence and recurrence.

Inflammation is crucial in the pathogenesis of lower urinary tract symptoms (LUTS) in men. Diet modulates inflammation. Therefore, diet could be a modifiable factor in male LUTS prevention and treatment. We aimed to investigate the association between dietary inflammatory potential and male LUTS. We used two cycles of National Health and Nutrition Examination Survey (NHANES) with self-report LUTS data. We calculated the dietary inflammatory index (DII) based on a 24 h diet recall and evaluated male LUTS. Clinical LUTS was defined as two or more coexisting symptoms. We used univariate and multivariate logistic regression models, the smooth curve fitting to analyze the relationship between clinical LUTS and the DII score. Subgroup analyses were conducted. We observed a positive non-linear relationship between clinical LUTS and DII. We found that when DII was higher than the inflection point 2.39, a 1-unit increase in DII was associated with 26.1% higher adjusted odds of clinical LUTS. Subgroup analyses showed that the DII score was only positively correlated with clinical LUTS risk in non-drinkers, smokers, and non-obese people (DII >2.39). Inflammation might be the key mechanism bridging dietary consumption to male LUTS. Excessive pro-inflammatory food intake (DII >2.39) warrants special vigilance, especially for non-drinkers, smokers, and non-obese men.

Objective: Studies have showed that different follow-up starting points might potentially impact the comparison between primary (PMIBC) and secondary muscle-invasive bladder cancer (SMIBC), but the only previous meta-analysis did not differentiate the follow-up starting points of included studies. With more trials published, we aim to update the meta-analysis comparing PMIBC and SMIBC. Methods: PubMed, Embase, Cochrane Library and ClinicalTrial.gov. systematically searched. Literatures comparing the survival outcomes of PMIBC and SMIBC were selected. Outcomes of cancer-specific mortality (CSM), overall mortality (OM) and recurrence-free survival (RFS) were pooled and grouped based on the starting point of follow-up (after initial diagnosis or radical cystectomy (RC)). Newcastle-Ottawa Scale (NOS) and funnel plot were employed to assess the study quality and publication bias, respectively. Results: A total of 17 high-quality studies were selected, with 5558 patients aged from 59.8 to 72.7 (mean value) involved. The male-to-female ratio was roughly 4:1 (4390/1124). SMIBC had lower risk of CSM after initial diagnosis (HR 0.81, 95%CI 0.67-0.98, P=0.03, I2=70%), but higher risk of CSM after RC (HR 1.45, 95%CI 1.27-1.65, P

This study used National Health and Nutrition Examination Surveys data from 1999 to 2006 to investigate the association between dietary inflammatory potential, represented by dietary inflammatory index (DII) scores, and the risk of sarcopenia in U.S. adults. A total of 25,781 participants were included in the study. The DII scores were calculated based on dietary information collected from 24-hour recalls. Men and women were classified as sarcopenic if appendicular lean mass (ALM) adjusted for BMI (ALMBMI) was

Background Patients with metastatic prostate cancer (mPCa) have a very low 5-year survival rate. How to choose proper treatment of mPCa remains controversial. Method Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015), we performed analyses of cancer-specific mortality (CSM) and overall mortality (OM) in the comparisons of local treatment (LT) versus no local treatment (NLT) and radical prostatectomy (RP) versus radiation therapy (RT). To balance the characteristics between 2 treatment groups, propensity score matching was performed. Considering the selection bias, we additionally used an instrument variate (IVA) to calculate the unmeasured confounders. Result Multivariate regression showed that patients receiving LT had the lower risks of OM and CSM after adjustment of covariates (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.35-0.44 and HR 0.39, 95% CI 0.34-0.45). In the IVA-adjusted model, LT showed more survival benefits compared with NLT, with HR of 0.57 (95% CI 0.50-0.65) and cancer-specific HR of 0.59 (95% CI 0.51-0.68), respectively. For those receiving LT, adjusted multivariate regression indicated that RP is superior to RT (HR 0.60; 95% CI 0.43-0.83 for OM and HR 0.61; 95% CI 0.42-0.91 for CSM). The IVA-adjusted model also showed that RP presented with potentially better survival outcome compared with RT, although the effect was not statistically significant (HR 0.63; 95% CI 0.26-1.54 for OM and HR 0.47; 95% CI 0.16-1.35 for CSM). Conclusion Among patients with metastatic prostate cancer, LT might bring better survival benefits in decreasing CSM and all-cause mortality compared with NLT. For those receiving LT, RP showed better survival outcomes than RT.

Immunotherapy has been a milestone for muscle-invasive bladder cancer (MIBC), but only a small portion of patients can benefit from it. Therefore, it is crucial to develop a robust individualized immune-related signature of MIBC to identify patients potentially benefiting from immunotherapy. The current study identified patients from the Cancer Genome Atlas (TCGA) and immune genes from the ImmPort database, and used improved data analytical methods to build up a 45 immune-related gene pair signature, which could classify patients into high-risk and low-risk groups. The signature was then independently validated by a Gene Expression Omnibus (GEO) dataset and IMvigor210 data. The subsequent analysis confirmed the worse survival outcomes of the high-risk group in both training (p < 0.001) and validation cohorts (p = 0.018). A signature-based risk score was proven to be an independent risk factor of overall survival (p < 0.001) and could predict superior clinical net benefit compared to other clinical factors. The CIBERSORT algorithm revealed the low-risk group had increased CD8+ T cells plus memory-activated CD4+ T-cell infiltration. The low-risk group also had higher expression of PDCD1 (PD-1), CD40, and CD27, and lower expression of CD276 (B7-H3) and PDCD1LG2 (PD-L2). Importantly, IMvigor210 data indicated that the low-risk group had higher percentage of “inflamed” phenotype plus less “desert” phenotype, and the survival outcomes were significantly better for low-risk patients after immunotherapy (p = 0.014). In conclusion, we proposed a novel and promising prognostic immune-related gene pair (IRGP) signature of MIBC, which could provide us a panoramic view of the tumor immune microenvironment of MIBC and independently identify MIBC patients who might benefit from immunotherapy.

Introduction: We aimed to develop an easy-to-use individual survival prognostication tool based on competing risk analyses to predict the risk of 5-year cancer-specific death after radical prostatectomy for patients with prostate cancer (PCa).Methods: We obtained the data from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2016). The main variables obtained included age at diagnosis, marital status, race, pathological extension, regional lymphonode status, prostate specific antigen level, pathological Gleason Score. In order to reveal the independent prognostic factors. The cumulative incidence function was used as the univariable competing risk analyses and The Fine and Gray's proportional subdistribution hazard approach was used as the multivariable competing risk analyses. With these factors, a nomogram and risk stratification based on the nomogram was established. Concordance index (C-index) and calibration curves were used for validation.Results: A total of 95,812 patients were included and divided into training cohort (n = 67,072) and validation cohort (n = 28,740). Seven independent prognostic factors including age, race, marital status, pathological extension, regional lymphonode status, PSA level, and pathological GS were used to construct the nomogram. In the training cohort, the C-index was 0.828 (%95CI, 0.812–0.844), and the C-index was 0.838 (%95CI, 0.813–0.863) in the validation cohort. The results of the cumulative incidence function showed that the discrimination of risk stratification based on nomogram is better than that of the risk stratification system based on D'Amico risk stratification.Conclusions: We successfully developed the first competing risk nomogram to predict the risk of cancer-specific death after surgery for patients with PCa. It has the potential to help clinicians improve post-operative management of patients.

Previous studies have revealed lymph node density (LND) to be an independent prognostic factor in cancer. However, data from 20 years ago failed to demonstrate the prognostic value of LND in node-positive renal-cell carcinoma (RCC). This study was undertaken to comprehensively investigate the prognostic value of LND in node-positive RCC.Within the Surveillance, Epidemiology and End Results database, we accessed data on patients diagnosed with histologically confirmed node-positive RCC from 2004 to 2014. The cubic spline smoothing technique and Cox regression were used to evaluate the correlation between LND and cancer-specific mortality (CSM). The X-Tile program was used to identify the optimal cut point of LND in node-positive RCC. Robustness of the results in various subgroups was also explored. Univariable and multivariable analyses were performed to determine predictors of CSM. Sensitivity analyses were performed.A total of 1750 node-positive RCCs were identified. We found a nonlinear positive correlation between the likelihood of CSM and LND. X-Tile analysis identified best cut point of LND as 35% with a maximum chi-square of 18.58. Every 10% increase in LND increased CSM by 5% (hazard ratio = 1.05; 95% confidence interval, 1.02-1.07; P .0001), and LND ≥ 35% was associated with 41% increase in CSM (hazard ratio = 1.41; 95% confidence interval, 1.20-1.65; P .0001) in fully adjusted Cox regression. Results of sensitivity analyses were consistent with those of the primary analysis.LND is an independent prognostic factor in node-positive RCC and should be incorporated into the cancer staging system.

Objective: Administration of drugs targeting anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) is often associated with serious immune-related adverse events (irAEs). Here, we performed a comprehensive analysis of organ-specific irAEs and treatment-related hematologic abnormalities and musculoskeletal disorders resulting from anti-CTLA-4 treatment. Materials and methods: PubMed, the Cochrane library, Web of Science, and ClinicalTrials.gov were searched for studies between January 1990 and March 2018 reporting AEs associated with anti-CTLA-4 therapies. Results: A total of 11 clinical trials with 7,088 patients were included; of these, data were accessible for 10 on ClinicalTrials.gov. Compared with control therapies (placebo, chemotherapy, radiation therapy, or vaccine), anti-CTLA-4 therapies (ipilimumab and tremelimumab) were associated with an increased risk of serious irAEs, predominantly dermatologic (rash: odds ratio [OR] 3.39, P

Background Lipid profiles are believed to play an important role in the tumorigenesis and progression of prostate cancer (PCa), but research combining those data is lacking. Therefore, this meta-analysis aims to assess the prognostic role of lipid profiles after RP. Method We systematically searched PubMed, Embase, and Cochrane Library Central Register of Controlled Trials for articles evaluating association between lipid profiles and prognosis after RP. Odds ratio (OR) and hazard ratio (HR) of lipid profiles for advanced pathological tumor features and biochemical recurrence (BCR) were extracted and pooled OR and HR were calculated. Newcastle-Ottawa scale was used for study quality assessment and funnel plot was used for evaluating publication bias. Results Twelve articles involving 11,108 patients were eventually selected. We found low HDL was associated with more frequent occurrence of pathological T stage (pT) ≥ T3 (pooled OR = 1.29, 95% CI 1.07–1.56) and Gleason score (GS) ≥8 (pooled OR = 1.32, 95% CI 1.02–1.72) after RP. Hypertriglyceridemia was also linked with higher risk of pT ≥ T3 (pooled OR = 1.20, 95% CI 1.01–1.42) and positive surgical margin (PSM) (pooled OR = 1.36, 95% CI 1.11–1.65). However, no significant association was observed between BCR and abnormal lipid profile levels. Conclusion Low HDL level was associated with more common occurrence of pT ≥ T3 and GS ≥8, and elevated triglycerides level was linked higher risk of pT ≥ T3 and PSM, but none of the lipid subfractions was correlated with biochemical recurrence after RP. Electronic supplementary material The online version of this article (10.1186/s12944-019-1068-6) contains supplementary material, which is available to authorized users.

Background For localized prostate cancer (PCa), radical prostatectomy (RP) and radiotherapy (RT) are two standard interventions to decrease PCa mortality. Contemporary studies contained the elderly people; analyses focusing on patients over 75 years of age were still lacking. Method In the Surveillance Epidemiology and End Results (SEER) database (2004‐2015), people over 75 years of age with cT2 stage were selected in our research. Multivariable Cox proportional hazard models were used to analyze cancer‐specific mortality (CSM) and overall mortality (OM) after adjustment. The propensity score matching was performed to assume the randomization. An instrument variate (IVA) was used to calculate the unmeasured confounders. Results Radical prostatectomy is superior to RT in OM and CSM after adjustment for covariates (HR = 0.54, 95% CI = 0.47‐0.62, P

Background: Long non-coding RNAs (lncRNAs) have been documented to be associated with genomic instability. Genomic instability-associated lncRNAs of prostate cancer (PCa) and their critical clinical implications remain to be understood. Method: A signature ( GILncSig ) was derived by genomic instability-associated lncRNAs to classify PCa patients into high-risk and low-risk group. The association of GILncSig and biochemical recurrence (BCR) is validated across three different datasets. The mutation burden and critical gene expression were compared between two risk groups. Findings: GILncSig separated patients into high-risk (n=121) group and low-risk (n=121) group in the train set. Patients with high GILncSig score suffered from more frequent BCR than those with low GILncSig score. The results were further validated in the test, the whole TCGA cohort, and different subgroups stratified by age and Gleason score (GS). High GILncSig risk score was significantly associated with high mutation burden and the low PTEN and CDK12 expression in PCa. The predictive performance of our BCR model outperformed other existing BCR models of PCa. The GILncSig could also predict BCR in the subgroup of patients with TP53 mutation or wild type. Interpretation: This study may provide a vital method to evaluate the impact of lncRNAs in genomic instability and new insights into the epigenetic mechanism of BCR. Funding: This work was supported by the National key research and development program of China (Grant No. 2017YFC0908003), National Natural Science Foundation of China (Grant No.81902578, 81974098, 8197032158), China Postdoctoral Science Foundation (2017M612971), Post-doctoral Science Research Foundation of Sichuan University (2020SCU12041). Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: Due to the public availability of data in the TCGA database, there was no need to provide ethical consent.

There is a significant heterogeneity in the immunotherapeutic responsiveness of each muscle-invasive bladder cancer (MIBC) patient. In our research, we aimed to identify a novel classification of MIBC based on immunogenomic profiling that may facilitate the reasonable stratification of prognosis and response to immunotherapy. The single-sample gene-set enrichment analysis (ssGSEA) was used to analyze the RNA-seq data of 29 important immune signatures from TCGA. Unsupervised hierarchical clustering was performed to identify an immunogenomic classification of MIBC. Then, we assessed the features of the classification in prognosis, immune infiltration, tumor-infiltration lymphocytes, HLA genes, and PD-L1 expression level. A total of 399 MIBC samples were included and three subtypes named Immunity_High, Immunity_Medium, and Immunity_Low were identified. The Immunity_High had a significant advantage in overall survival over the Immunity_Medium and Immunity_Low (p = 0.046 and p = 0.024). From Immunity_Low to Immunity_High, immune cell infiltration and stromal content showed an upward trend (p < 0.001). Meanwhile, Immunity_High was associated with a significantly higher proportion of TILs including dendritic cells resting, macrophages M1, mast cells resting, T cells CD4 memory activated, and T cells CD8+. And the expression levels of all HLA genes and PD-L1 of Immunity_High were the highest, consistent (p < 0.001). Two hundred ninety eight MIBC patients treated with immunotherapy from the IMvigor210 were included to form an independent validation cohort to verify the robustness of immunogenomic classification and the ability to predict the response to immunotherapy. This classification had potential clinical implications for predicting prognosis and immunotherapeutic responsiveness of MIBC patients.

At present, focal laser ablation (FLA) as a new PCa local treatment has attracted attention. We aim at comparing the survival outcomes between radiotherapy (RT) and FLA to reveal whether FLA can be used as an alternative to RT for patients with low and intermediate-risk localized PCa.We conducted analyses with data from the SEER database (2004–2015). Propensity score matching and instrumental variate (IV) were used to reduce the influence of bias and unmeasured confounders maximally.In the adjusted multivariate regression, FLA had lower overall survival (OS) benefits (HR = 1.49; 95%CI: 1.18–1.87; p

Background: Papillary renal carcinoma (PRCC) is one of the important subtypes of kidney cancer, with a high degree of heterogeneity. At present, there is still a lack of robust and accurate biomarkers for the diagnosis, prognosis and treatment selection of PRCC. Considering the important role of tumor immunity in PRCC, we aim to construct a signature based on immune-related gene pairs (IRGPs) to estimate the prognostic of patients with PRCC.Methods: We obtained gene expression profiling and clinical information of patients with PRCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), which were divided into discovery and validation cohorts, respectively. The immune-related genes in the samples were used to construct gene pairs, and the immune-related genes pairs (IRGPs) with robust impact for overall survival (OS) were screened out to construct the signature by univariate analysis, multivariate Cox analysis, and least absolute shrinkage and selection operator (Lasso) analysis. Then we verified the prognostic role of the signature, and assessed the relationship between this signature with tumor immune infiltration and functional pathways.Results: A total of 315 patients were included in our study, and divided to discovery (n=287) and validation (n=28) cohorts. Finally, we selected 14 IRGPs with a panel of 22 unique genes to construct the prognostic signature. According to the signature, we stratified patients into high-risk group and low-risk group. In both discovery and validation cohorts, the results of Kaplan-Meier analysis showed that there were significant differences in OS between the two groups (p+ T cells, Tregs, and T follicular cell helper were significantly higher in the high-risk group. Functional analysis showed that multiple immune-related signaling pathways were enriched in the high-risk group.Conclusions: We successfully established an individualized prognostic immune-related gene pairs signature, which can accurately and independently predict the OS of patients with PRCC.

Background: Immunotherapy has become an essential suppressing tumor treatment with wide prospects, particular in advanced bladder cancer. However, the relationship between immune cell mixture and cancer cell phenotype is still unclear. Methods: To select specific immune genes forming subtype indicating disparate prognosis, we used BC transcriptomic profiles from six published datasets. Except for unsupervised clustering based on different expression of genes, we additionally performed binomial logistic regression, focusing on mRNA level of single sample. Results: Unsupervised clustering showed 4 clusters captured the best segmentation. After validation with survival data and simplification using binomial logistic regression, we found the poor prognosis cluster (cluster B&D) had specific immune related characteristics in tumor microenvironment. Bonding with clinical data, more proportion of risk factors were assigned into worse prognosis subtype. And immune cell infiltration, nucleotide polymorphism (SNP) and copy number variation (CNV) all showed difference between clusters. Through phenotypical analysis, we found metabolism and proliferation phenotypes associated with the immune clusters and mutually exclusive in BC, of which proliferation contributed to worse outcomes. Conclusion: With this novel clustering criterion based on immune related genes, we provide a better understanding of immune microenvironment, as the same time highlight a correlation between tumor phenotype and immune contexture. Funding Statement: This work was supported by the National key research and development program of China (Grant No. SQ2017YFC0908003), National Natural Science Foundation of China (Grant No.81702536, 81770756), the Sichuan Science and Technology Program (2017HH0063), China Postdoctoral Science Foundation (2017M612971), Post-Doctor Research Project, West China Hospital, Sichuan University (2018HXBH085), National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (Z2018C01). Declaration of Interests: The authors have declared that no competing interest exists.

Supplemental Digital Content is available in the text, Background: Previous evidence directly evaluating the efficacy and safety of abiraterone and enzalutamide treatment for castration-resistant prostate cancer (CRPC) is limited. We aim to include more randomized controlled trials (RCTs) to comprehensively assess the efficacy and safety of abiraterone and enzalutamide treatment. Methods: PubMed, Embase, and ClinicalTrial.gov were systematically searched. Pooled hazard ratios (HRs) were calculated using Stata 12.0 software. The comparison of the prostate-specific antigen (PSA) response rate and adverse events (AEs) between the treatment and control groups were performed using RevMan 5.3 software. Results: Eight eligible RCTs with 6,490 patients were selected. Pooled HRs were 0.72 for overall survival, 0.45 for radiographic progression-free survival (rPFS), and 0.36 for PSA PFS. abiraterone and enzalutamide could significantly increase the PSA response rate OR = 8.67, 95%CI 4.42–17.04) and any AE occurrence (OR = 1.98, 95%CI 1.46–2.68). The treatment group had more occurrence of fatigue (OR = 1.34, 95%CI 1.20–1.49), back pain (OR = 1.15, 95%CI 1.01–1.15), hot flush (OR = 1.76, 95%CI 1.50–2.06), diarrhea (OR=1.22, 95%CI 1.07–2.40) and arthralgia (OR = 1.34, 95%CI 1.16–1.54). Particularly, AEs of special interest including any grade hypertension (OR = 2.06, 95%CI 1.71–2.47), hypokalemia (OR = 1.80, 95%CI 1.42–2.30) and fluid retention or edema (OR = 1.38, 95%CI 1.17–1.63) also occurred less in the control group. Moreover, a higher incidence of high-grade hypertension (OR = 2.60, 95%CI 1.79–3.79) and extremity pain (OR = 4.46, 95%CI 2.81–7.07) was observed in the treatment group. Conclusion: The survival benefits of abiraterone and enzalutamide for CRPC were evident and promising, while the risk of AE occurrence was also acceptably higher in the treatment group than in the placebo group.

Combining immune checkpoint inhibitors has shown its efficacy compared to monotherapy in advanced malignancies. We conducted this meta-analysis to provide latest evidence on the objective response rate (ORR) and incidence of treatment-related high-grade adverse events (AEs) during nivolumab and ipilimumab combination treatment and further explore from different drug dose level. PubMed and the 2019 American Society of Clinical Oncology (ASCO) annual meeting abstracts were searched for qualified clinical trials up to June 2019. Of the 23 clinical trials (13 from publications and 11 from ASCO abstracts) included, 2,114 and 2,674 patients were eligible for efficacy and safety analysis, respectively. Pooled analysis suggested that the overall ORR was achieved in 34.5% [95% confidence interval (CI), 29.1–40.4%] of patients. There was no significant difference between nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks (N3I1-Q3W) and nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (N1I3-Q3W) arms in ORR [30.8% vs 41%; odds ratio (OR), 0.72; 95% CI, 0.39–1.30; P = 0.275]. Grade 3–4 AEs related to combination therapy occurred in 39.9% (95% CI, 33.5–46.7%) of patients; the most commonly reported grade 3–4 treatment-related AEs were diarrhea (5.28%), colitis (3.96%) and increased alanine aminotransferase (3.51%). Incidence of grade 3–4 AEs were significant lower in N3I1-Q3W arm than in N1I3-Q3W arm (31.3% vs 55.9%; OR 0.52; 95% CI, 0.32–0.87; P = 0.012). Treatment-related death was rare and occurred in 2.0% (95% CI, 1.5–2.7%) of patients. Our comprehensive study provides more precise data on the incidence of treatment-related high-grade AEs and ORR among patients receiving nivolumab and ipilimumab combination regimens. Patients on the N3I1-Q3W arm had comparable ORR and significantly occurred less grade 3–4 AEs than patients on the N1I3-Q3W arm. Our finding is of great importance in assisting clinical trial design and clinical medication choice.

The continuous intake of antithrombotic drugs during holmium laser enucleation of the prostate (HoLEP) remains nonconsensual. We aim to pool those controversial evidence and provide practical guidance of oral antithrombotics on HoLEP for benign prostate hyperplasia (BPH). PubMed, Embase and CENTRAL database were systematically searched up to June 2019 for trials on patients with and without oral antithrombotics undergoing HoLEP. Number of events and mean value with standard deviation were, respectively, extracted for dichotomous and continuous parameters. Subgroup analyses of anticoagulation and antiplatelet were also performed. All statistical analyses were conducted with Review Manager v.5.3 software. Newcastle–Ottawa Scale (NOS) was used to assess the quality of selected trials. Nine studies with 5528 patients were eventually selected, and patients included were generally older than 65 years. It revealed that the non-antithrombotic group had a lower rate of blood transfusion (OR 0.21, 95% CI 0.10–0.45, P

Background: Previous evidence directly evaluating the efficacy and safety of the treatment for castration-resistant prostate cancer (CRPC) by androgen receptor (AR) signaling-axis inhibitors was limited by the quantity of randomized controlled trials (RCT) and biased by non-RCTs. We aim to comprehensively assess the efficacy and safety of abiraterone and enzalutamide using only RCTs. Patients and methods: We systematically searched Pubmed, Embase, MEDLINE and ClinicalTrial.gov for RCTs providing data of treatment outcomes by AR inhibitors (abiraterone and enzalutamide). Pooled hazard ratios (HR) with 95%CI for survival benefits were calculated using STATA 12.0. Comparison of prostate-specific antigen (PSA) response rate, aggregated adverse event (AE) statistics, any grade AE, high-grade AE (grade ≥3), AE of special interest between the treatment and control groups were performed by RevMan 5.3 and STATA 12.0. Results: Eight eligible RCTs with 6296 patients were selected. Pooled HR were 0.72 for overall survival, 0.45 for radiographic progression-free survival and 0.36 for PSA PFS. AR inhibitors could significantly increase the rate of PSA response (OR=8.67, 95%CI 4.42-17.04) and AE occurrence (OR=1.98, 95%CI 1.46-2.68). The treatment group had a higher occurrence of any-grade fatigue (OR=1.34, 95%CI 1.20-1.49), back pain (OR=1.15, 95%CI 1.01-1.15), hot flush (OR=1.76, 95%CI 1.50-2.06), diarrhea (OR=1.22, 95%CI 1.07-2.40) and arthralgia (OR=1.34, 95%CI 1.16-1.54). Particularly, the outcomes for AEs of special interest including any grade hypertension (OR=2.06, 95%CI 1.71-2.47), hypokalemia (OR=1.80, 95%CI 1.42-2.30) and fluid retention or edema (OR=1.38, 95%CI 1.17-1.63) also favored the control group. In terms of high-grade AEs, a higher occurrence of hypertension (OR=2.60, 95%CI 1.79-3.79) and pain in extremity (OR=4.46, 95%CI 2.81-7.07) was observed in the treatment group. There was no significant difference regarding other AEs analyzed in this study. Conclusion: The survival benefits by AR inhibitors for CRPC were evident and promising at the cost of acceptably higher risk of AEs occurrence.

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. The classic manifestation of IgAN is episodic hematuria and proteinuria. Nephrotic syndrome (NS) is not very common in IgAN, reported to occur in only 5–10% of IgAN patients. However, the clinical and pathological characteristics and long-term outcomes of patients with NS-IgAN at onset remain unknown. A retrospective study was conducted, enrolling 1165 patients with biopsy-proven IgAN from West China Hospital in 2008–2015. Patients with renal biopsy of minimal change disease with mesangial IgA deposits were excluded. The renal endpoint was defined as 50% decrease in eGFR or progressing into end-stage renal disease (ESRD). A total of 1165 patients were enrolled with average age of 34.58, and 171 (14.7%) patients were presented with NS. Comparing NS and non-NS groups, significance differences were shown in hypertension (HTN), 24-h urine protein, serum albumin, serum creatine, eGFR and uric acid. NS group had severe pathological changes such as endocapillary hypercellularity, tubular atrophy or interstitial fibrosis and crescent, but less segmental glomerulosclerosis or adhesion and global sclerosis. During the average follow-up of 44.27 months, 29.8% (51/171) NS patients and 15.8% (157/994) non-NS patients progressed to the renal endpoint. 5-year renal survival rates were 73.1% and 87.8% (P

Xiaonan Zheng,1,* Shi Qiu,1,2,* Xinyang Liao,1 Xin Han,3 Kun Jin,1 Lu Yang,1 Qiang Wei1 1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Center of Biomedical Big Data, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3West China Medical School, Sichuan University, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work Objective: To evaluate the association between metabolic syndrome (MetS) and the accumulation of its components with prostate cancer (PCa). Patients and methods: Patients undergoing radical prostatectomy were retrospectively included. Patients were grouped by low risk and intermediate-high risk according to International Society of Urological Pathology grade. Multivariable logistic regression and Cox hazard regression model were utilized to assess the association of MetS with overall survival, biochemical recurrence, upgrading, upstaging, and positive surgical margin (PSM) after prostatectomy. Besides, trend test was also performed to evaluate the impact of the accumulation of MetS components on postoperative pathological feature. Results: A total of 1,083 patients were eventually enrolled. With a median follow-up of 40.45 months, 197 patients were diagnosed with MetS. No significant association between MetS and survival outcomes and pathological features was found. However, we did notice that the accumulation of the MetS components could lead to an elevated gradient of the PSM risk in the entire cohort (one component: OR=1.46; two components: OR=1.89; ≥3 components: OR=2.07; P for trend=0.0194) and intermediate-high risk group (one component: OR=1.4; two components: OR=1.85; ≥3 components: OR=2.05; P for trend=0.0127). Conclusion: The accumulation of MetS components could lead to increasing risk of PSM on the entire PCa cohort and patients with intermediate-high risk PCa after prostatectomy, but not for the low-risk patients. Keywords: prostate cancer, PCa, metabolic syndrome, MetS, International Society of Urological Pathology, ISUP, positive surgical margin, PSM

Currently, the standard management for locally advanced prostate cancer (PCa) is still controversial. In our study, we aimed to compare the survival outcomes of radical prostatectomy (RP) versus external beam radiotherapy (EBRT). We conducted analyses with a large cohort of 38,544 patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2016). Propensity score matching, Kaplan-Meier method, and Cox proportional hazard regression were used to reduce the influence of bias and compare the overall survival (OS) and cancer specific survival (CSS). Several different sensitivity analyses including inverse probability of treatment weighting and standardized mortality ratio weighting were used to verify the robustness of the results. Totally, 33,388 men received RP and 5,156 men received EBRT with cT3-4N0M0 PCa were included in this study. According to the Kaplan-Meier curves, RP performed better in both OS and CSS compared with EBRT (P

Background: For localized prostate cancer (PCa), radical prostatectomy (RP) and radiotherapy (RT) are two standard interventions to decrease PCa mortality. Contemporary studies contained the elderly people, analyses focusing on patients over 75 years old were still lacking. Method: In the Surveillance Epidemiology and End Results (SEER) database (2004-2015), old people over 75-year-old with cT2 stage were selected in our research. Multivariable Cox proportional hazard models were used to analyze cancer-specific mortality (CSM) and overall mortality (OM) after adjustment. The propensity score matching was performed to assume the randomization. An instrument variate (IVA) was used to calculate the unmeasured confounders. Results: It showed that RP is superior to RT in OM and CSM after adjustment for covariates (hazard ratio [HR] = 0.54, 95% CI = 0.47-0.62, p

Background: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide and up to 40% will develop end-stage renal disease (ESRD) within 20 years. However, predicting which patients will progress to ESRD is difficult. The purpose of this study was to develop a predictive model which could accurately predict whether IgAN patients would progress to ESRD. Methods: Six machine learning algorithms were used to predict whether IgAN patients would progress to ESRD: logistic regression, random forest, support vector machine (SVM), decision tree, artificial neural network (ANN), k nearest neighbors (KNN). Nineteen demographic, clinical, pathologic and treatment parameters were used as input for the prediction models. Results: Random forest is best able to predict progression to ESRD. The model had accuracy of 93.97% and sensitivity and specificity of 80.60% and 95.27%, respectively. Conclusions: Machine learning algorithms can effectively predict which patients with IgA nephropathy will progress to end stage renal disease.

Metabolic syndrome (MetS) has been reported to be associated with adverse outcomes in cancer patients. However, the relationship between MetS and upper tract urothelial carcinoma (UTUC) has yet to be explored.To investigate the prognostic value of MetS in UTUC after radical nephroureterectomy.A total of 644 patients with UTUC after radical nephroureterectomy were identified at West China Hospital from May 2003 to December 2016. MetS was defined as the co-existence of 3 or more of 5 components (obesity, hypertension, elevated fasting glucose, decreased high-density lipoprotein-cholesterol, and hypertriglyceridemia). Logistic and Cox regression analyses were performed to evaluate the associations of MetS with pathological features and survival outcomes. Decision curve analysis and Harrell concordance index were used to determine the clinical utility of the prediction models.Of 644 patients, 157 (24.4%) had MetS. Over a median follow-up of 39 months, 269 (41.8%) experienced disease recurrence, 233 (36.2%) died, and 185 (28.7%) died of UTUC. MetS was independently associated with high-grade disease, advanced pT stage (≥pT3), and lymphovascular invasion (each P0.05). Multivariate Cox regression analysis showed that MetS was an independent factor for decreased cancer-specific survival (hazard ratio [HR]: 1.38, 95% confidence intervals [CI]: 1.01-1.89, P = 0.042) but not for recurrence-free survival (HR: 1.27, 95% CI: 0.97-1.67, P = 0.078), and overall survival (HR: 1.24, 95% CI: 0.95-1.62, P = 0.121). The estimated c-index of the multivariate models for cancer-specific survival was 0.763 compared with 0.769 when MetS added.MetS is a negative prognostic factor in UTUC. Further studies of MetS in UTUC are demanded.

117 Background: To evaluate the association between tertiary Gleason pattern (TGP) 5 and the biochemical recurrence (BCR) in patients with prostate cancer (PCa) of Gleason score (GS) 7 after radical prostatectomy(RP). Methods: This retrospective study collected 387 patients received RP and diagnosed GS 7 (3+4 or 4+3) in the West China Hospital from January 2009 to December 2017.Regardlessly the first Gleason pattern, patients were divide into 2 groups: TGP5 absence and TGP5 presence. Furthermore, we added the primary Gleason pattern to divided patients into 4 groups: GS 3+4, GS 3+4/TGP 5, Gleason 4+3, Gleason 4+3/TGP 5. Cox proportional-hazards models was used to evaluate the association between the status of TGP5 and BCR after adjusting the confounding factors with follow-up time as the underlying time scale. All the analyses were conducted with the use of statistical software packages Rnand EmpowerStats and conducted as two sides and P values less than 0.05 were considered statistical significance. Results: In the results by using Cox proportional-hazards model, regardless the primary Gleason pattern, comparing TGP5 absence (89.7%) and presence (10.3%), the risk of BCR for patients with tertiary Gleason pattern 5 presence was statistically significantly higher than absence (P = 0.02, HR = 2.24, 95%Cl: 1.12-4.49). In terms of the patients with primary Gleason pattern 4, the risk of BCR for patients with Gleason 4+3/TGP5 was statistically significantly higher than Gleason 4+3.(P = 0.02, HR = 2.56, 95%Cl: 1.16-5.67). There was a marked trend that patients with Gleason 3+4/TGP 5 has a higher risk of BCR compared with patients with Gleason 3+4, although there was no statistical difference (P = 0.58, HR = 1.82, 95%Cl: 0.22-14.96). Conclusions: The TGP5 in patients with GS 7 had strong association with the risk of BCR and it was an independent predictor for BCR. This result was more obvious in patients with GS 7 (4+3) in our study. Further researches with larger data size were needed to confirm these funding.