Investigating the causal associations between metabolic biomarkers and the risk of kidney cancer.

Metabolic reprogramming plays an important role in kidney cancer. We aim to investigate the causal effect of 249 metabolic biomarkers on kidney cancer from population-based data. This study extracts data from previous genome wide association studies with large sample size. The primary endpoint is random-effect inverse variance weighted (IVW). After completing 249 times of two-sample Mendelian randomization analysis, those significant metabolites are included for further sensitivity analysis. According to a strict Bonferrion-corrected level (P < 2e-04), we only find two metabolites that are causally associated with renal cancer. They are lactate (OR:3.25, 95% CI: 1.84-5.76, P = 5.08e-05) and phospholipids to total lipids ratio in large LDL (low density lipoprotein) (OR: 0.63, 95% CI: 0.50-0.80, P = 1.39e-04). The results are stable through all the sensitivity analysis. The results emphasize the central role of lactate in kidney tumorigenesis and provide novel insights into possible mechanism how phospholipids could affect kidney tumorigenesis.

Genetic susceptibility of urolithiasis: comprehensive results from genome-wide analysis.

BACKGROUND: The pathogenesis of urolithiasis is multi-factorial and genetic factors have been shown to play a significant role in the development of urolithiasis. We tried to apply genome-wide Mendelian randomization (MR) analysis and figure out reliable gene susceptibility of urolithiasis from the largest samples to date in two independent genome-wide association studies (GWAS) database of European ancestry. METHODS: We extracted summary statistics of expression quantitative trait locus (eQTL) from eQTLGen consortium. Urolithiasis phenotype information was obtained from both FinnGen Biobank and UK Biobank. Multiple two-sample MR analysis with a Bonferroni-corrected P threshold (P < 2.5e-06) was conducted. The primary endpoint was the causal effect calculated by random-effect inverse variance weighted (IVW) method. Sensitivity analysis, volcano plots, scatter plots, and regional plots were also performed and visualized. RESULTS: After multiple MR tests between 19942 eQTLs and urolithiasis phenotype from both cohorts, 30 common eQTLs with consistent effect size direction were found to be causally associated with urolithiasis risk. Finally only one gene (LMAN2) was simultaneously identified among all top significant eQTLs from both FinnGen Biobank (beta = 0.6758, se = 0.0327, P = 6.775e-95) and UK Biobank (beta = 0.0044, se = 0.0009, P = 2.417e-06). We also found that LMAN2 was with the largest beta effect size on urolithiasis phenotype from the two cohorts. CONCLUSION: We for the first time implemented genome-wide MR analysis to investigate the genetic susceptibility of urolithiasis in general population of European ancestry. Our results provided novel insights into common genetic variants of urinary stone disease, which was of great help to subsequent researches.

SGLT2 inhibition and three urological cancers: Up-to-date results.

OBJECTIVE: To identify the causal role of sodium-glucose cotransporter 2 (SGLT2) inhibition on three urological cancers. METHODS: Six single nucleotide polymorphisms associated with the expression level of SLC5A2, a proxy for SGLT2 inhibition, from a recent publication were extracted. Three common urological cancers, including bladder cancer, prostate cancer and kidney cancer, were analysed. The main cohort of bladder cancer was derived from UK Biobank (1279 cases and 372,016 controls). The prostate cancer cohort was from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (79,148 cases and 61,106 controls). The kidney cancer phenotype was from the UK Biobank cohort of 463,010 individuals (1114 cases and 461,896 controls). Primary and sensitivity analysis were performed to validate the results. In vitro analysis was also incorporated to validate the Mendelian randomisation results. RESULTS: In primary analysis, SGLT2 inhibition was associated with reduced risk of bladder cancer (OR: 0.98, 95% CI: 0.97-0.99) per unit lowering of HbA1c level. A protective association was also observed for prostate cancer with odds ratio = 0.31 (95% CI = 0.21-0.47). However, we did not discover a causal relationship between SGLT2 inhibition and kidney cancer (OR: 1.00, 95% CI: 0.99-1.00). Sensitivity analysis and in vitro validation did not support the causal role of SGLT2 inhibition in increasing cancer risk. CONCLUSIONS: We did not find any evidence that SGLT2 inhibition could increase the risk of the three cancers. Even in some analysis, SGLT2 inhibition tended to show protective effects on the three urological cancers.

Predictors of trimodality therapy in patients with muscle-invasive bladder cancer and effect on survival

Background Due to its unique advantages over radical cystectomy (RC), trimodality therapy (TMT) is increasingly being utilized by patients diagnosed with muscle-invasive bladder cancer (MIBC) who are not suitable for or refuse RC. However, achieving a satisfactory oncological outcome with TMT requires strict patient selection criteria, and the comparative oncological outcomes of TMT versus RC remain controversial. Methods Patients diagnosed with non-metastatic MIBC who underwent TMT or RC were identified from the SEER database during 2004–2015. Before one-to-one propensity score matching (PSM), logistic regression was utilized to identify predictors of TMT. After matching, K-M curves were generated to estimate cancer-specific survival (CSS) and overall survival (OS) with log-rank to test the significance. Finally, we conducted univariate and multivariate Cox analyses to identify independent prognostic factors for CSS and OS. Results The RC and TMT groups included 5812 and 1260 patients, respectively, and the TMT patients were significantly older than the RC patients. Patients with advanced age, separated, divorced, or widowed (SDW) or unmarried marital status (married as reference), and larger tumor size (< 40 mm as reference) were more likely to be treated with TMT. After PSM, TMT was found to be associated with worse CSS and OS, and it was identified as an independent risk factor for both CSS and OS. Conclusion MIBC patients may not be carefully evaluated prior to TMT, and some non-ideal candidates underwent TMT. TMT resulted in worse CSS and OS in the contemporary era, but these results may be biased. Strict TMT candidate criteria and TMT treatment modality should be required (AU)

Predictors of trimodality therapy in patients with muscle-invasive bladder cancer and effect on survival.

BACKGROUND: Due to its unique advantages over radical cystectomy (RC), trimodality therapy (TMT) is increasingly being utilized by patients diagnosed with muscle-invasive bladder cancer (MIBC) who are not suitable for or refuse RC. However, achieving a satisfactory oncological outcome with TMT requires strict patient selection criteria, and the comparative oncological outcomes of TMT versus RC remain controversial. METHODS: Patients diagnosed with non-metastatic MIBC who underwent TMT or RC were identified from the SEER database during 2004-2015. Before one-to-one propensity score matching (PSM), logistic regression was utilized to identify predictors of TMT. After matching, K-M curves were generated to estimate cancer-specific survival (CSS) and overall survival (OS) with log-rank to test the significance. Finally, we conducted univariate and multivariate Cox analyses to identify independent prognostic factors for CSS and OS. RESULTS: The RC and TMT groups included 5812 and 1260 patients, respectively, and the TMT patients were significantly older than the RC patients. Patients with advanced age, separated, divorced, or widowed (SDW) or unmarried marital status (married as reference), and larger tumor size (< 40 mm as reference) were more likely to be treated with TMT. After PSM, TMT was found to be associated with worse CSS and OS, and it was identified as an independent risk factor for both CSS and OS. CONCLUSION: MIBC patients may not be carefully evaluated prior to TMT, and some non-ideal candidates underwent TMT. TMT resulted in worse CSS and OS in the contemporary era, but these results may be biased. Strict TMT candidate criteria and TMT treatment modality should be required.

The association between the metabolic score for insulin resistance (METS-IR) index and urinary incontinence in the United States: results from the National Health and Nutrition Examination Survey (NHANES) 2001-2018.

BACKGROUND: The association between insulin resistance and urinary incontinence (UI) has not been investigated widely. The purpose of this study is to assess the relationship between a novel indicator for assessing insulin resistance the metabolic score for insulin resistance (METS-IR) index and urinary incontinence (UI). METHODS: This study utilized data from National Health and Nutrition Examination Survey (NHANES) 2001-2018. Weighted multivariable logistic regression models were conducted to explore the association of METS-IR index with three types of UI [stress UI (SUI), urgency UI (UUI), and mixed UI (MUI)]. Smooth curve fitting was utilized to investigate the linear relationship. Subgroup analysis was used to examine the stability of the connection between METS-IR index and UI in different stratifications. RESULTS: A total of 17,474 participants were included in this study, of whom 23.76% had SUI, 20.05% had UUI, and 9.59% had MUI. METS-IR index was positively associated with three types of UI with full adjustment [SUI: odds ratio (OR) = 1.023, 95% confidence interval (CI) 1.019-1.027; UUI: OR = 1.015, 95% CI 1.011-1.019; MUI: OR = 1.020, 95% CI 1.016-1.025, all p < 0.001]. After transferring METS-IR index into a categorical variable by quartiles, the positive connection between METS-IR index and UI was still observed in the highest METS-IR group compared to the lowest METS-IR interval (SUI: OR = 2.266, 95% CI 1.947-2.637, p < 0.001; UUI: OR = 1.534, 95% CI 1.344-1.750, p < 0.001; MUI: OR = 2.044, 95% CI 1.707-2.448, p < 0.001). The analysis of smooth curves fitting showed that METS-IR index was positively linearly related to three types of UI. Moreover, the association between METS-IR index and SUI was more significant in females compared to males (p for interaction < 0.05). CONCLUSION: An elevated METS-IR index was related to increased risks of three types of UI (SUI, UUI, and MUI) in the United States population. METS-IR index was more significantly connected to SUI in females than males. The association between insulin resistance and UI needs to be explored with more studies.

Identification of circRNA-miRNA-mRNA network as biomarkers for interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a long-lasting and incapacitating disease, and the exact factors that affect its onset and advancement are still uncertain. Thus, the main aim was to explore new biomarkers and possible therapeutic targets for IC/BPS. Next-generation high-throughput sequencing experiments were performed on bladder tissues. Based on the interactions between circRNA and miRNA, as well as miRNA and mRNA, candidates were selected to build a network of circRNA-miRNA-mRNA. The STRING database and Cytoscape software were utilized to build a protein-protein interaction (PPI) network to pinpoint the hub genes associated with IC/BPS. The expression levels of circRNA and miRNA in the network were confirmed through quantitative polymerase chain reaction. Western blot was applied to confirm the stability of the lipopolysaccharide-induced IC/BPS model, and the effect of overexpression of circ.5863 by lentivirus on inflammation. Ten circRNA-miRNA interactions involving three circRNAs and six miRNAs were identified, and IFIT3 and RSAD2 were identified as hub genes in the resulting PPI network with 19 nodes. Circ.5863 showed a statistically significant decrease in the constructed model, which is consistent with the sequencing results, and overexpression via lentiviral transfection of circ.5863 was found to alleviate inflammation damage. In this study, a circRNA-miRNA-mRNA network was successfully constructed, and IFIT3 and RSAD2 were identified as hub genes. Our findings suggest that circ.5863 can mitigate inflammation damage in IC/BPS. The identified marker genes may serve as valuable targets for future research aimed at developing diagnostic tools and more effective therapies for IC/BPS.

Sex differences in renal cell carcinoma: a single-cell analysis reveals exhausted CD8+ T-cells highly infiltrated in males.

BACKGROUND: Although sex bias has been reported in the development and progression of renal cell carcinoma (RCC), the underlying mechanisms remain enigmatic. Here, we investigated the sex differences in the tumor microenvironment (TME) of RCC and explored a promising combination drug regimen to enhance the efficacy of immunotherapy. METHODS: Single-cell RNA sequencing (scRNA-seq) data from four published datasets were analyzed to investigate the sex differences in RCC patients, and tumor tissues were collected to validate the sex differences using multiplex immunofluorescence (MxIF) and flow cytometry (FCM). The function of the androgen-androgen receptor axis in sex differences was explored in vivo and in vitro experiments. RESULTS: Our analysis of scRNA-seq data from 220,156 cells, as well as MxIF and FCM assays, revealed that CD8+ T-cells infiltrated highly in the TME of male RCC, but were mostly in an exhausted and dysfunctional state. In vitro and in vivo experiments indicated that the dysfunction and exhaustion of CD8+ T-cells in male TME were induced by androgen. Clinically, higher serum androgen was significantly associated with a worse prognosis in male RCC patients receiving immunotherapy. Androgen receptor inhibitors could activate tumor-infiltrating CD8+ T-cells and enhance the efficacy of immunotherapy of RCC in vivo. CONCLUSIONS: Our study delineated the difference in TME between male and female patients with RCC, and demonstrated that the androgen-androgen receptor axis plays an important role in immunosuppression in male RCC. Our findings suggest that androgen receptor inhibitors in combination with immunotherapy may be a promising treatment option for male RCC patients.

Adrenocorticotropic hormone application lowered aldosterone/cortisol value on dominant side without superior surgical outcomes during adrenal venous sampling.

Adrenal venous sampling (AVS) is thought to be the gold standard for primary aldosteronism (PA) subtype discrimination, during which the application of adrenocorticotropic hormone (ACTH) arouses heated debate. We aimed to identify the effect of ACTH on AVS and surgical outcomes. After propensity score matching (PSM), a total of 220 patients diagnosed with PA and completed AVS were included (110 without ACTH stimulation and 110 with ACTH stimulation). According to AVS results, surgeries were conducted in appropriate patients. ACTH stimulation significantly increased almost all selectivity index (SI) in both left adrenal vein (LAV) and right adrenal vein (RAV). We discovered that aldosterone/cortisol (A/C) value on dominant side significantly reduced after ACTH stimulation, with a reduction in lateralization index (LI) observed. Finally, 39 patients in unstimulated group and 32 patients in stimulated group completed surgery and enough follow-up. The comparison between surgical outcomes with and without ACTH stimulation was analyzed and the difference was not significant (p = .464). In conclusion, ACTH application significantly lowered A/C value instead of the relative aldosterone secretion index (RASI) value on dominant side, which did not yield superior surgical outcomes and might render confusing AVS interpretation.

Which frequency is better for pediatric shock wave lithotripsy? Low intermediate or high: A systematic review and meta-analysis.

Background: To explore the optimal frequency for pediatric extracorporeal shock wave lithotripsy (ESWL) in the treatment of upper urinary stones. Methods: A systematic literature search was undertaken using PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials databases to identify eligible studies published before January 2023. Primary outcomes were perioperative efficacy parameters, including ESWL time, anesthesia time for ESWL sessions, success rates after each session, additional interventions needed, and treatment sessions per patient. Secondary outcomes were postoperative complications and efficiency quotient. Results: Four controlled studies involving 263 pediatric patients were enrolled in our meta-analysis. In the comparison between the low-frequency and intermediate-frequency groups, we observed no significant difference as regards anesthesia time for ESWL session (WMD = -4.98, 95% CI -21.55∼11.58, p = 0.56), success rates after ESWL sessions (first session: OR = 0.02 95%CI -0.12∼0.17, p = 0.74; second session: OR = 1.04 95%CI 0.56∼1.90, p = 0.91; third session: OR = 1.62 95%CI 0.73∼3.60, p = 0.24), treatment sessions needed (WMD = 0.08 95%CI -0.21∼0.36, p = 0.60), additional interventions after ESWL (OR=0.99 95%CI 0.40∼2.47, p = 0.99) and rates of Clavien grade 2 complications (OR = 0.92 95%CI 0.18∼4.69, p = 0.92). However, the intermediate-frequency group may exhibit potential benefits in Clavien grade 1 complications. In the comparison between intermediate-frequency and high-frequency, the eligible studies exhibited higher success rates in the intermediate-frequency group after the first session, the second session and the third session. More sessions may be required in the high-frequency group. With respect to other perioperative, postoperative parameters and major complications, the results were similar. Conclusions: Intermediate-frequency and low-frequency had similar success rates and seemed to be the optimal frequency for pediatric ESWL. Nevertheless, future large-volume, well-designed RCTs are awaited to confirm and update the findings of this analysis. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022333646.

Immunotherapy vs. Chemotherapy in Subsequent Treatment of Malignant Pleural Mesothelioma: Which Is Better?

(1) Background: Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor arising from the pleural surface. For relapsed MPM, there is no accepted standard of- are for subsequent treatment. Thus, we aimed to compare the efficacy of chemotherapy, targeting drugs, and immune-checkpoint inhibitors (ICIs) as subsequent therapy for relapsed MPM. (2) Methods: The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched several acknowledged databases. Primary outcomes were defined as overall median progressive survival (mPFS) and median overall survival (mOS) in different treatment groups. Secondary outcomes were defined as objective response rate (ORR), the proportion of stable disease (SD), and progressive disease (PD). (3) Results: Ultimately, 43 articles were selected for the meta-analysis. According to the results of a pooled analysis of single-arm studies, ICIs showed a slight advantage in mOS, while chemotherapy showed a slight advantage in mPFS (mOS: 11.2 m vs. 10.39 m and mPFS: 4.42 m vs. 5.08 m for ICIs group and chemotherapy group, respectively). We identified only a few studies that directly compared the efficacy of ICIs with that of chemotherapy, and ICIs did not show significant benefits over chemotherapy based on mOS. (4) Conclusions: Based on current evidence, we considered that immunotherapy might not be superior to chemotherapy as a subsequent therapy for relapsed MPM. Although several studies investigated the efficacy of ICIs, targeting drugs, and chemotherapy in relapsed MPM, there was still no standard of care. Further randomized control trials with consistent criteria and outcomes are recommended to guide subsequent therapy in relapsed MPM and identify patients with certain characteristics that might benefit from such subsequent therapy.

Smoking is an independent risk factor for stricture recurrence after the urethroplasty: a systematic review and meta-analysis

ABSTRACT Objective: To clarify the association between smoking and stricture recurrence after urethroplasty. Materials and Methods: Pubmed, Web of Science, Embase, and Cochrane databases were searched with keywords: "urethroplasty," "buccal mucosa graft urethroplasty," "oral mucosa graft urethroplasty," "excision and primary anastomosis urethroplasty," "urethral stricture recurrence" until July 1, 2022. Inclusion and exclusion criteria were based on PICOS principles. The quality of included studies was assessed by Newcastle-Ottawa Scale (N.O.S.) system. Hazard ratio (H.R.), odds ratio (OR), and relative risk (RR) with 95% confidence interval (CI) were extracted or re-calculated from included studies. Meta-analysis was performed with Stata 15.0 based on univariate and multivariate data separately. Sensitivity analysis was performed to test the stability of the meta-analysis. I2 was calculated to evaluate heterogeneity. Publication biases were assessed by Egger's and Begg's tests. Funnel plots of univariate analysis and multivariate analysis were also offered. Results: Twenty one studies with 6791 patients were involved in this meta-analysis. The analysis results of the two stages were consistent. In the univariate meta-analysis stage, 18 studies with 5811 patients were pooled, and the result indicated that smoking might promote stricture recurrence (RR=1.32, P=0.001). Based on the adjusted estimate, 11 studies with 3176 patients were pooled in the multivariate meta-analysis stage, and the result indicated that smoking might promote stricture recurrence (RR=1.35, P=0.049). There was no significant heterogeneity in both the univariate and multivariate stages. Conclusion: Our study demonstrates that smoking may prompt stricture recurrence after the urethroplasty. Quitting smoking may be a good option for patients undergoing urethroplasty surgery.

Antifibrotic Effects of Tetrahedral Framework Nucleic Acids by Inhibiting Macrophage Polarization and Macrophage-Myofibroblast Transition in Bladder Remodeling.

Bladder outlet obstruction (BOO) is a prevalent condition arising from urethral stricture, posterior urethral valves, and benign prostatic hyperplasia. Long-term obstruction can lead to bladder remodeling, which is characterized by inflammatory cell infiltration, detrusor hypertrophy, and fibrosis. Until now, there are no efficacious therapeutic options for BOO-induced remodeling. Tetrahedral framework nucleic acids (tFNAs) are a type of novel 3D DNA nanomaterials that possess excellent antifibrotic effects. Here, to determine the treatment effects of tFNAs on BOO-induced remodeling is aimed. Four single-strand DNAs are self-assembled to form tetrahedral framework DNA nanostructures, and the antifibrotic effects of tFNAs are investigated in an in vivo BOO animal model and an in vitro transforming growth factor beta1 (TGF-ß1)-induced fibrosis model. The results demonstrated that tFNAs could ameliorate BOO-induced bladder fibrosis and dysfunction by inhibiting M2 macrophage polarization and the macrophage-myofibroblast transition (MMT) process. Furthermore, tFNAs regulate M2 polarization and the MMT process by deactivating the signal transducer and activator of transcription (Stat) and TGF-ß1/small mothers against decapentaplegic (Smad) pathways, respectively. This is the first study to reveal that tFNAs might be a promising nanomaterial for the treatment of BOO-induced remodeling.

Does repeat transurethral resection of bladder tumor influence the diagnosis and prognosis of T1 bladder cancer? A systematic review and meta-analysis.

BACKGROUND: To reduce recurrence or progression of tumor, NCCN guidelines recommend repeat transurethral resection of bladder tumors (reTURB) for non-muscle-invasive bladder cancer (NMIBC). The study aims to compare the impact of initial TURB and reTURB on the rate of residual or upstaging tumors and short-term and long-term survival outcomes of T1 bladder cancer (BC). MATERIALS AND METHODS: We searched through several public database, including PubMed, Embase, Ovid Medline and Ovid EBM Reviews - Cochrane Central Register of Controlled Trials. The latest search time was October 2021. RESULTS: In general, 68 articles were involved. Short-term RFS (1-year and 3-year) of reTURB group was better compared with TURB group in T1 patients. The pooled RR were 1.10 (95%CI: 1.01-1.19) and 1.15 (95%CI: 1.03-1.28), respectively. While reTURB did not improve long-term RFS (5-year, 10-year, 15-year) in T1 patients. The pooled RR were 1.12 (95%CI: 0.97-1.30), 1.11 (95%CI: 0.82-1.50) and 1.37 (95%CI: 0.50-3.74), respectively. Analysis of PFS, OS and CSS demonstrated similar outcomes with RFS. We found that about two-thirds of samples contained detrusor. The residual tumor rate in stage T1 was 0.48 (95%CI: 0.42-0.53). While the rate of upstaging in stage T1 was 0.10 (95%CI: 0.07-0.13). CONCLUSIONS: In conclusion, reTURB might provide short-term survival benefits for T1 BC, but it was not the same for long-term outcomes. The residual and upstaging rates of T1 BC in reTURB were around 50% and 10%, respectively. Our study might be conducive to clinically informed consents when patients expressed their concerns about the necessity of reTURB and its impact on diagnosis, treatment and prognosis.

Smoking is an independent risk factor for stricture recurrence after the urethroplasty: a systematic review and meta-analysis.

OBJECTIVE: To clarify the association between smoking and stricture recurrence after urethroplasty. MATERIALS AND METHODS: Pubmed, Web of Science, Embase, and Cochrane databases were searched with keywords: "urethroplasty," "buccal mucosa graft urethroplasty," "oral mucosa graft urethroplasty," "excision and primary anastomosis urethroplasty," "urethral stricture recurrence" until July 1, 2022. Inclusion and exclusion criteria were based on PICOS principles. The quality of included studies was assessed by Newcastle-Ottawa Scale (N.O.S.) system. Hazard ratio (H.R.), odds ratio (OR), and relative risk (RR) with 95% confidence interval (CI) were extracted or re-calculated from included studies. Meta-analysis was performed with Stata 15.0 based on univariate and multivariate data separately. Sensitivity analysis was performed to test the stability of the meta-analysis. I2 was calculated to evaluate heterogeneity. Publication biases were assessed by Egger's and Begg's tests. Funnel plots of univariate analysis and multivariate analysis were also offered. RESULTS: Twenty one studies with 6791 patients were involved in this meta-analysis. The analysis results of the two stages were consistent. In the univariate meta-analysis stage, 18 studies with 5811 patients were pooled, and the result indicated that smoking might promote stricture recurrence (RR=1.32, P=0.001). Based on the adjusted estimate, 11 studies with 3176 patients were pooled in the multivariate meta-analysis stage, and the result indicated that smoking might promote stricture recurrence (RR=1.35, P=0.049). There was no significant heterogeneity in both the univariate and multivariate stages. CONCLUSION: Our study demonstrates that smoking may prompt stricture recurrence after the urethroplasty. Quitting smoking may be a good option for patients undergoing urethroplasty surgery.

Recovery from diabetes mellitus in primary aldosteronism patients after adrenalectomy.

BACKGROUND: The prevalence of diabetes mellitus (DM) was higher in primary aldosteronism (PA) patients. We aimed to evaluate the outcome of DM after adrenalectomy and determine the factors associated with that in PA patients. METHODS: PA patients with DM (PA + DM patients) who received adrenalectomy were recruited into the study. The patients were classified into 3 groups based on their DM conditions after treatment, including "remission", "improved" and "unchanged" groups. Univariate and multivariate logistic regression analysis was conducted to uncover the preoperative factors affecting the outcome of DM after adrenalectomy. RESULTS: A total of 54 PA + DM patients received adrenalectomy. After adrenalectomy, 16.7%, 33.3% and 50.0% of patients were classified into the "remission", "improved" and "unchanged" groups, respectively. The factors negatively associated with remission or improvement from DM after adrenalectomy were longer duration of hypertension (P = 0.029). Higher concentration of urinary magnesium (P = 0.031) and higher 24 h urinary potassium (P = 0.049) were factors negatively associated with the "remission" from DM after adrenalectomy. CONCLUSIONS: Adrenalectomy was beneficial for the remission and improvement from DM in the half of PA patients with DM. Longer duration of hypertension, higher concentration of urinary magnesium and higher 24 h urinary potassium may prevent the remission and improvement from DM after adrenalectomy in PA patients. Examination of urinary electrolyte could be considered in PA patients with DM for predicting the outcome of DM after adrenalectomy.

Do clinical trials affect anxiety, depression, and quality of life in the caregivers of patients with cancer?

Objective: To investigate the effect of clinical trials on anxiety, depression, and the quality of life experienced by the family caregivers (FCs) of cancer patients. Materials and methods: We screened the FCs of patients who were participating in clinical trials and FCs of patients who were not participating in clinical trials [group FCs-GCP (FG) and group FCs-non-GCP (FNG) at Cancer Center of West China Hospital]. We assessed the anxiety, depression, and quality of life of the FCs using the Hospital Anxiety and Depression Scale and SF-12. The demographic characteristics of FCs and patients were analyzed. Results: The prevalences of anxiety and depression showed no significant difference between FG and FNG (46.3 vs. 51.5%, P = 0.604; 36.6 vs. 51.5%, P = 0.131, respectively). Physical Component Scores (PCS) were 48.87 ± 7.67 for FG and 48.01 ± 8.12 for FNG (P = 0.618) while Mental Component Scores (MCS) were 48.92 ± 7.78 and 44.89 ± 11.42, respectively (P = 0.031). The anxiety of FCs was positively associated with patients' advanced disease (HR 4.292 [1.409, 13.072], P = 0.010) and initial treatment (HR 3.105 [1.014, 9.515], P = 0.047). Depression was positively related to advanced disease (HR 3.347 [1.140, 9.832], P = 0.028), and negatively related to patients participating in clinical trials (HR 0.421 [0.180, 0.985], P = 0.046) and the education degree of FCs (HR 0.355 [0.149, 0.843], P = 0.019). MCS was positively associated with patients participating in clinical trials (ß = 5.067, 95% CI [0.817, 9.317], P = 0.020) and negatively associated with advanced disease (ß = -8.055, 95% CI [-19.804, 6.528], P = 0.002). Conclusion: The FCs of the cancer patients who participated in clinical trials showed a comparable worrying situation of anxiety and depression to the FCs of regular cancer patients. This indicates that more concern and attention should be given to this population, and further study on them is warranted.

The association between urinary organophosphate insecticide metabolites and erectile dysfunction in the United States.

Organophosphate (OP) insecticides are the main chemicals used in agriculture for pest elimination, and they have been linked with many diseases. However, there is no literature regarding the impacts of organophosphate insecticide metabolite exposure on erectile dysfunction (ED). We aimed to evaluate the correlation between 4 urinary organophosphate insecticide metabolites and the presence of ED in a representative sample of men aged 20 and older. The dataset including a total of 555 subjects was obtained from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. ED was assessed by a question from a self-report questionnaire. Weighted proportions and multivariable logistic regression analysis were utilized to examine the relationship between organophosphate insecticide metabolite exposure and ED. In multivariable logistic regression analysis, diethylphosphate (DEP) was positively correlated with ED (OR 1.07; 95% CI 1.01-1.14; P = 0.033) after full adjustment. Men in DEP tertile 4 had a significant 33% higher risk of ED than those in tertile 1. Furthermore, in a subgroup analysis, our results showed that higher DEP levels were significantly associated with ED in the young age group (20 ≤ age ≤ 39). Our study revealed a significant association between organophosphate insecticide metabolite exposure and an increased risk of ED. Moreover, the correlations were more evident in the young age group. The evaluation of urinary organophosphate insecticide metabolite exposure should be included in the risk assessment of ED. Further study to investigate the underlying mechanism, such as how long the urinary metabolite is present, whether ED is reversible in this population by lowering DEP concentrations, and how exposure to this metabolite affects erectile tissue, is warranted.

Effects of catheter-based renal denervation on renin-aldosterone system, catecholamines, and electrolytes: A systematic review and meta-analysis.

In recent years, catheter-based renal denervation (RDN) has emerged as a promising instrumental therapy for hypertension. The interruption of sympathetic nervous system was regarded as a possible mechanism for RDN regulating blood pressure. While the results reflected by renin-angiotensin-aldosterone system (RAAS), catecholamines and electrolytes remained inconsistent and was never systematically assessed. Pubmed, Embase, and Web of Science were comprehensively searched from inception to September 5, 2021. Studies that evaluated the effects of RDN on RAAS, catecholamines, and electrolytes were identified. Primary outcomes were changes in RAAS hormones after RDN, and secondary outcomes involved changes in plasma norepinephrine, serum, and urinary sodium and potassium. Out of 6391 retrieved studies, 20 studies (two randomized controlled studies and 18 observational studies) involving 771 persons were eventually included. Plasma renin activity had a statistically significant reduction after RDN (0.24 ng/mL/h, 95% CI 0.04 to 0.44, P = .02). While no significant change was found regarding plasma aldosterone (1.53 ng/dL, 95% CI -0.61 to 3.67, P = .16), norepinephrine (0.42 nmol/L, 95% -0.51 to 1.35, P = 0.38), serum sodium and potassium (0.16 mmol/L, 95% CI -0.17 to 0.49, P = .34; -0.02 mmol/L, 95% CI -0.09 to 0.04, P = .48, respectively), and urinary sodium and potassium (3.95 mmol/24 h, 95% CI -29.36 to 37.26, P = .82; 10.22 mmol/24 h, 95% CI -12.11 to 32.54, P = .37, respectively). In conclusion, plasma renin activity significantly decreased after RDN, while no significant change was observed in plasma aldosterone, plasma norepinephrine, and serum and urinary electrolytes.

Superior calyceal access vs. other calyceal access in percutaneous nephrolithotomy: A systematic review and meta-analysis.

Purpose: To evaluate the superior calyceal access's performance and safety in relation to other calyceal access during percutaneous nephrolithotomy (PCNL). Methods: The suggested reporting items for systematic reviews and meta-analysis were used to conduct this meta-analysis (PRISMA). To find pertinent studies for this meta-analysis, we searched PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI). Operation time and hospital stay are two secondary outcomes, whereas failed stone clearance and complication events are the two major outcomes. Utilizing Stata 15.0, RevMan 5.3, and R 4.0.2, relative data were extracted and evaluated. Results: This meta-analysis was based on 16 studies with 8,541 individuals. Pooled results suggested that superior calyceal access could offer fewer failed stone clearance [odds ratio (OR): 0.64, 95% confidence interval (CI), 0.47-0.88, P = 0.006] and lower additional puncture rate (OR: 0.35, 95% CI, 0.24-0.51, P < 0.001) than other calyceal access. No complication difference was found (OR: 1.10, 95% CI, 0.78-1.56, P = 0.57). Superior calyceal access could offer shorter operation time [standard mean difference (SMD): -0.57, 95% CI, -0.98 to -0.15, P = 0.007]. No hospital stay difference was found (SMD: 0.07, 95% CI, -0.09 to 0.22, P = 0.38). Large heterogeneity was detected in stone clearance comparison (I 2 = 71%, P < 0.001) and operation time (I 2 = 97%, P < 0.001). The stone clearance comparison also identified significant publication bias (P = 0.026). These defects weaken the credibility of the results. Conclusion: Superior calyceal access in PCNL may result in a higher stone clearance rate, a lower rate of subsequent punctures, and a faster operation duration with no increase in postoperative complications or hospital stay for kidney stone patients, despite the significant heterogeneity and publication bias. By conducting bigger randomized controlled studies, this discovery still has to be confirmed.