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.

Oxidative stress gene expression, DNA methylation, and gut microbiota interaction trigger Crohn's disease: a multi-omics Mendelian randomization study.

BACKGROUND: Oxidative stress (OS) is a key pathophysiological mechanism in Crohn's disease (CD). OS-related genes can be affected by environmental factors, intestinal inflammation, gut microbiota, and epigenetic changes. However, the role of OS as a potential CD etiological factor or triggering factor is unknown, as differentially expressed OS genes in CD can be either a cause or a subsequent change of intestinal inflammation. Herein, we used a multi-omics summary data-based Mendelian randomization (SMR) approach to identify putative causal effects and underlying mechanisms of OS genes in CD. METHODS: OS-related genes were extracted from the GeneCards database. Intestinal transcriptome datasets were collected from the Gene Expression Omnibus (GEO) database and meta-analyzed to identify differentially expressed genes (DEGs) related to OS in CD. Integration analyses of the largest CD genome-wide association study (GWAS) summaries with expression quantitative trait loci (eQTLs) and DNA methylation QTLs (mQTLs) from the blood were performed using SMR methods to prioritize putative blood OS genes and their regulatory elements associated with CD risk. Up-to-date intestinal eQTLs and fecal microbial QTLs (mbQTLs) were integrated to uncover potential interactions between host OS gene expression and gut microbiota through SMR and colocalization analysis. Two additional Mendelian randomization (MR) methods were used as sensitivity analyses. Putative results were validated in an independent multi-omics cohort from the First Affiliated Hospital of Sun Yat-sen University (FAH-SYS). RESULTS: A meta-analysis from six datasets identified 438 OS-related DEGs enriched in intestinal enterocytes in CD from 817 OS-related genes. Five genes from blood tissue were prioritized as candidate CD-causal genes using three-step SMR methods: BAD, SHC1, STAT3, MUC1, and GPX3. Furthermore, SMR analysis also identified five putative intestinal genes, three of which were involved in gene-microbiota interactions through colocalization analysis: MUC1, CD40, and PRKAB1. Validation results showed that 88.79% of DEGs were replicated in the FAH-SYS cohort. Associations between pairs of MUC1-Bacillus aciditolerans and PRKAB1-Escherichia coli in the FAH-SYS cohort were consistent with eQTL-mbQTL colocalization. CONCLUSIONS: This multi-omics integration study highlighted that OS genes causal to CD are regulated by DNA methylation and host-microbiota interactions. This provides evidence for future targeted functional research aimed at developing suitable therapeutic interventions and disease prevention.

Association between the Systemic Immune-Inflammation Index and Prostate Cancer.

The systemic immune-inflammation index (SII) is a novel and integrated marker that has not been studied with prostate cancer. We aimed to ascertain the association between SII levels and prostate cancer. We utilized data from the 1999-2010 cycles of the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression analyses were conducted to evaluate the relationship between SII and prostate cancer. Additionally, subgroup analyses stratified by age, BMI, history of hypertension and diabetes were performed. A total of 8,020 participants were included in our analysis. After full adjustment, SII was associated with a 7% increased risk of prostate cancer (OR 1.07, 95% CI 0.99-1.15, p = 0.094). We further categorized SII values into three segments and found that individuals in the highest SII group had a 33% increased risk of prostate cancer than those in the tertile 1 group (OR 1.33; 95% CI 1.01-1.81; p = 0.044; P for trend = 0.046). In addition, a higher SII level was associated with a 137% increased risk of prostate cancer in the diabetes subgroup (OR 2.37; 95% CI 1.08-5.21; p = 0.031). The current study suggested that SII was positively associated with increased risks of prostate cancer. The SII might be an easily accessible indicator for identifying prostate cancer.

Comparative efficacy and safety of different minimal invasive pyeloplasty in treating patients with ureteropelvic junction obstruction: a network meta-analysis.

OBJECTIVE: In recent years, the minimally invasive surgical treatment methods of ureteropelvic junctional obstruction (UPJO) have been diverse, but its approach and choice of surgical method are controversial. This network meta-analysis (NMA) aimed to compare the safety and effectiveness of minimally invasive surgeries for UPJO, which included robotic or laparoscopic pyeloplasty, via the retroperitoneal or transperitoneal approach. METHODS: We searched relevant RCTs in PubMed, Embase, Web of Science, the Cochrane Library, and CNKI. To assess the results of operative time, complications and success rate, pairwise, and NMA were carried out. The models for analyses were performed by Revman 5.3, Addis V1.16.8 and R software. RESULTS: A total of 6 RCTs were included in this study involving four types of surgeries: transperitoneal laparoscopic pyeloplasty (T-LP), retroperitoneal laparoscopic pyeloplasty (R-LP), robot-assisted transperitoneal pyeloplasty (T-RALP), and robot-assisted retroperitoneal pyeloplasty (R-RALP). This study consisted of 381 patients overall. T-RALP had a quicker operational duration (SMD = 1.67, 95% CI 0.27-3.07, P = 0.02) than T-LP. According to the NMA's consistency model, T-RALP improved the surgical success rate more than T-LP (RR = 6303.19, CI 1.28 to 1.47 × 1011). Ranking probabilities indicated that RALP could be the better option than LP and retroperitoneal approach was comparable to transperitoneal approach. All procedures had high surgical success rates and few complications. CONCLUSION: Outcomes for four surgical approaches used in the UPJO were comparable, with T-RALP being the most recommended approach. Selection between the transperitoneal and retroperitoneal approaches primarily depended on the surgeon's preference. Higher quality evidence is needed to further enhance the result.

Association between body mass index, trunk and total body fat percentage with urinary incontinence in adult US population.

INTRODUCTION AND HYPOTHESIS: To assess the association of body mass index (BMI), trunk and total body fat percentage with the prevalence and severity of urinary incontinence (UI) stratified by gender among a US adult population. METHODS: A representative cross-sectional survey of participants aged ≥ 20 years was conducted using the data from the 2011-2018 National Health and Nutrition Examination Survey. Multivariate logistic and linear regression models were used to explore the association among the three obesity measures above with the prevalence and severity of UI. RESULTS: A total of 6964 individuals (4168 males and 2796 females) enrolled for the final analysis. Among males, the weighted prevalence of UI was 7.8%, with 1.3% stress urinary incontinence, 5.8% urge urinary incontinence and 0.7% mixed urinary incontinence. For females, the weighted prevalence of UI was 54.2%, with 31.9% stress urinary incontinence, 7.0% urge urinary incontinence and 15.6% mixed urinary incontinence. Multivariate logistic regression revealed increased BMI and trunk fat percentage significantly increased odds of UI (BMI: OR = 1.05 [per 1 kg/m2], 95% CI: 1.03-1.07, P < 0.001; trunk fat percentage: OR = 1.15 [per 5% increase in trunk fat percentage], 95% CI: 1.06-1.25, P = 0.002) in females. Similar trends were observed in the severity of UI (BMI: ß = 0.07, 95% CI: 0.05-0.09, P < 0.001; trunk fat percentage: ß = 0.18, 95% CI: 0.10-0.26, P < 0.001) by a multivariate linear regression. In males, no significant association was observed (BMI: OR = 0.99 [per 1 kg/m2], 95% CI: 0.97-1.02, P = 0.663; trunk fat percentage: OR = 0.95 [per 5% increase in trunk fat percentage], 95% CI: 0.84-1.08, P = 0.430; total fat percentage: OR = 0.94 [per 5% increase in total fat percentage], 95% CI: 0.80-1.10, P = 0.424). CONCLUSIONS: An increased BMI and trunk fat percentage are significantly associated with higher prevalence and severity of UI in females.

The association of dietary intake of riboflavin and thiamine with kidney stone: a cross-sectional survey of NHANES 2007-2018.

BACKGROUND: Kidney stone disease (KSD) is a common condition that affects 10% population in the United States (US). The relationship between thiamine and riboflavin intake and KSD has not been well-studied. We aimed to investigate the prevalence of KSD and the association between dietary thiamine and riboflavin intake with KSD in the US population. METHODS: This large-scale, cross-sectional study included subjects from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. KSD and dietary intake were collected from questionnaires and 24-hour recall interviews. Logistic regression and sensitivity analyses were performed to investigate the association. RESULTS: This study included 26,786 adult participants with a mean age of 50.12 ± 17.61 years old. The prevalence of KSD was 9.62%. After adjusting for all potential covariates, we found that higher riboflavin intake was negatively related to KSD compared with dietary intake of riboflavin < 2 mg/day in the fully-adjusted model (OR = 0.541, 95% CI = 0.368 to 0.795, P = 0.002). After stratifying by gender and age, we found that the impact of riboflavin on KSD still existed in all age subgroups (P < 0.05) but only in males (P = 0.001). No such associations were found between dietary intake of thiamine and KSD in any of the subgroups. CONCLUSIONS: Our study suggested that a high intake of riboflavin is independently inversely associated with kidney stones, especially in male population. No association was found between dietary intake of thiamine and KSD. Further studies are needed to confirm our results and explore the causal relationships.

The Effect of Preoperative Tamsulosin on Ureteral Navigation, Operation, and Safety: A Systematic Review and Meta-Analysis.

INTRODUCTION: Urolithiasis is one of the most common diseases in the world, and at present, ureteroscopy (URS) is the first choice for its treatment. Although the effect is good, there is a risk of insertion failure of ureteroscope. Tamsulosin, as an α-receptor blocker, has the function of relaxing ureteral muscles, and can help stones to be discharged from ureteral orifice. In this study, we aimed to determine the effect of preoperative tamsulosin on ureteral navigation, operation, and safety. METHODS: This study was conducted and reported according to the meta-analysis extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The PubMed and Embase databases were searched for studies. Data were extracted according to the PRISMA principles. We collected and combined randomized controlled trial and researches in reviews of preoperative tamsulosin to explore the effect of preoperative tamsulosin on ureteral navigation, operation, and safety. A data synthesis was performed using RevMan 5.4.1 software (Cochrane). Heterogeneity was mainly evaluated with I2 tests. Key metrics include: success rate of ureteral navigation, time of URS, stone-free rate, and postoperative symptoms. RESULT: We summarized and analyzed 6 studies. We noted a statistically significant improvement in the success rate of ureteral navigation (Mantel-Haenszel [M-H], odds ratio [OR]: 3.78, 95% confidence interval [CI]: [2.34, 6.12], p < 0.01) and stone-free rate (M-H, OR: 2.25, 95% CI: [1.16, 4.36], p = 0.02) with tamsulosin preoperatively. At the same time, we also observed that postoperative fever (M-H, OR: 0.37, 95% CI: [0.16, 0.89], p = 0.03) and postoperative analgesia (M-H, OR: 0.21, 95% CI: [0.05, 0.92], p = 0.04) were also reduced because of preoperative tamsulosin. CONCLUSION: Preoperative tamsulosin can not only increase the one-time success rate of ureteral navigation and the stone-free rate of URS but also reduce the incidence of postoperative adverse symptoms such as postoperative fever and postoperative pain.

Higher genetically predicted low-density lipoprotein levels increase the renal cancer risk independent of triglycerides and high-density lipoprotein levels: A Mendelian randomization study.

The causation between lipids and renal cancer remains inconclusive. Our purpose is to explore the causal relationships between the three primary lipid metabolism-related substances, namely triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) with the risk of renal cancer using Mendelian randomization (MR) methods. Genetic instruments for lipids were acquired from the UK Biobank. Outcome data were from the FinnGen study (1397 renal cancer cases and 204 070). Single-variable MR (SVMR) and multi-variable MR (MVMR) analyses were conducted with TwoSampleMR package based on R 4.0.3. The random-effect inverse-variance weighted (IVW), MR-Egger, weighted-median method, and weighted mode were the four main computing methods. We found that per 1 SD elevated LDL level was causally associated with renal cancer occurrence based on SVMR (OR, 1.31, 95% CI: 1.05-1.64, P = .016). Similar significant associations were found in other methods. However, the results of SVMR did not support significant associations between TG, and HDL with renal cancer risk in all methods. The association between LDL and renal cancer was still significant in MVMR analysis (OR for IVW method: 1.22 per 1 SD higher trait (SD, 95% CI: 1.11-1.34, P < .001; OR for MR-Egger: 1.22 per 1 SD higher trait, 95% CI: 1.01-1.47, P = .042) when taking TG and HDL into consideration. Our study supported that elevated serum LDL levels is causally associated with an increased risk of renal cancer independent of TG and HDL.

Prediction of the occurrence of calcium oxalate kidney stones based on clinical and gut microbiota characteristics.

PURPOSE: To predict the occurrence of calcium oxalate kidney stones based on clinical and gut microbiota characteristics. METHODS: Gut microbiota and clinical data from 180 subjects (120 for training set and 60 for validation) attending the West China Hospital (WCH) were collected between June 2018 and January 2021. Based on the gut microbiota and clinical data from 120 subjects (66 non-kidney stone individuals and 54 kidney stone patients), we evaluated eight machine learning methods to predict the occurrence of calcium oxalate kidney stones. RESULTS: With fivefold cross-validation, the random forest method produced the best area under the curve (AUC) of 0.94. We further applied random forest to an independent validation dataset with 60 samples (34 non-kidney stone individuals and 26 kidney stone patients), which yielded an AUC of 0.88. CONCLUSION: Our results demonstrated that clinical data combined with gut microbiota characteristics may help predict the occurrence of kidney stones.

A bibliometric analysis of top-cited journal articles in interstitial cystitis and bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: To identify and compare the top-cited articles from all indexed journals and urology-nephrology and obstetrics-gynecology journals in the Institute for Scientific Information Web of Science's Citation Index Expanded on interstitial cystitis and bladder pain syndrome (IC/BPS). METHODS: Cross-sectional bibliometric analysis of top-cited articles in Web of ScienceTM (WoS) from 1900-2022. The articles were retrieved by the MeSH terms from NCBI. The characteristics of top 100 cited articles from all indexed journals and specialized journals were evaluated. RESULTS: A total of 5547 articles were collected from 1115 journals, in which 3225 articles were from 141 urological and gynecological specialized journals. The USA and the UK were the top two origins for articles on interstitial cystitis. The articles from non-specialized journals were more frequently cited than those from specialized journals (median [IQR], 221.5 [189.8-313.5] vs 131.0 [126.0-142.8], P < 0.0001). The citation number per year showed similar results (median [IQR], 239.9 [194.5-311.8] vs 132.0 [126.7-140.5], P < 0.0001). There were many more open-access articles in non-specialized than specialized journals (P = 0.0018). CONCLUSIONS: The current study initially queried the articles published on WoS on IC/BPS by the number of citations to identify the differences between two journal categories. The characteristics and trends of research were analyzed by citations to provide insights into the current research status and future direction.

The relationship between gut microbiota and short chain fatty acids in the renal calcium oxalate stones disease.

The relationship of gut microbiota and calcium oxalate stone has been limited investigated, especially with no study of gut microbiota and short chain fatty acids (SCFAs) in nephrolithiasis. We provided Sprague Dawley rats of renal calcium oxalate stones with antibiotics and examined the renal crystals deposition. We also performed a case-control study by analyzing 16S rRNA microbial profiling, shotgun metagenomics and SCFAs in 153 fecal samples from non-kidney stone (NS) controls, patients with occasional renal calcium oxalate stones (OS) and patients with recurrent stones (RS). Antibiotics reduced bacterial load in feces and could promote the formation of renal calcium crystals in model rats. In addition, both OS and RS patients exhibited higher fecal microbial diversity than NS controls. Several SCFAs-producing gut bacteria, as well as metabolic pathways associated with SCFAs production, were considerably lower in the gut microbiota among the kidney stone patients compared with the NS controls. Representation of genes involved in oxalate degradation showed no significance difference among groups. However, fecal acetic acid concentration was the highest in RS patients with high level of urinary oxalate, which was positively correlated with genes involvement in oxalate synthesis. Administration of SCFAs reduced renal crystals. These results shed new light on bacteria and SCFAs, which may promote the development of treatment strategy in nephrolithiasis.

A novel nomogram for the delayed transperineal anastomotic urethroplasty based on relative position between the proximal urethra and the pubic ramus in pelvic fracture injury patients: a retrospective analysis.

PURPOSE: Many reconstructive urologists have observed that higher urethra injuries lead to potentially less successful repairs. This article introduces a novel prognostic factor for pelvic fracture caused urethral injury (PFUI) to predict stricture recurrence after delayed transperineal anastomotic urethroplasty (TAU) patients with PFUI based on urethra injury locations. MATERIALS AND METHODS: Patients who underwent suprapubic cystostomy tube placement and delayed TAU for PFUI by a single surgeon between 2009 and 2018 were screened. A total of 151 patients completed the follow-up. The relative location between the proximal urethra and the pubic ramus (PUE-PR), a novel stricture length classification method based on the anatomical landmark, was divided into a lower, middle, and upper group reflected by urethrogram. The nomogram was developed based on significant coefficients identified by multivariable Cox regression. RESULTS: Based on the relative position between the proximal urethra end and the pubic ramus (PUE-PR), 47 (31%), 66 (44%), and 38 (25%) patients were assigned to the lower, middle, and upper group, respectively. A total of 33 patients (22%) patients had a recurrence. The median (IQR) follow-up was 49 months (28-75). Smoking, endoscopic treatment history, and PUE-PR were identified as independent risk factors for stricture recurrence. The nomogram showed good discrimination with a C-index of 76.67%. The decision curve analysis (DCA) indicated that the model could bring more clinical net benefit when a threshold probability is larger than 8%. CONCLUSIONS: PUE-PR is a new prognostic factor for PFUI to predict stricture recurrence after TAU. A novel nomogram incorporating PUE-PR could be applied to facilitate the prediction of stricture recurrence after delayed TAU for PFUI.

Catheters for intermittent catheterization: a systematic review and network meta-analysis.

STUDY DESIGN: Systematic review and network meta-analysis. OBJECTIVES: Intermittent catheterization (IC) is considered the standard treatment for neuro-urological patients who are unable to empty their bladders. The present study aimed to conduct a systematic evaluation and network meta-analysis of all available types of intermittent catheters, and determine which one is best suited for clinical use. METHODS: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases to identify relevant studies. Only randomized clinical trials (RCTs) were included. Five types of catheters were identified based on the included studies. A Bayesian network meta-analysis was then performed. The surface under the cumulative ranking (SUCRA) curve was used to determine the best catheter for each outcome. RESULTS: A total of 25 RCTs, involving 1233 participants, were included. The pooled odds ratios of symptomatic UTI were lower for two ready-to-use single-use catheters (gel-lubricated non-coated catheter, OR: 0.30, 95% CI 0.095-0.86; pre-activated hydrophilic-coated catheter, OR: 0.41, 95% CI 0.19-0.83) as compared to single-use non-coated catheter. In terms of patient satisfaction, the SUCRA results showed that the pre-activated hydrophilic-coated catheter may the preferred option (SUCRA = 82.8%). However, there were no significant differences in all outcome measures between traditional single-use non-coated catheters and clean non-coated catheters. CONCLUSION: Ready-to-use single-use catheters are associated with lower rates of UTI compared to traditional catheters. Patients may be most satisfied with the pre-activated one. For traditional single-use non-coated catheters and clean non-coated catheters, there is still no convincing evidence as to which is better. Thus, more well-designed trials are needed.

Participation in Virtual Urology Conferences During the COVID-19 Pandemic: Cross-sectional Survey Study.

BACKGROUND: Due to the influence of the COVID-19 pandemic, conventional face-to-face academic conferences have been restricted, and many of these conferences have moved onto the internet. OBJECTIVE: The aim of this study was to investigate the virtual conferences in the field of urology during the COVID-19 pandemic and provide suggestions for better organization of such conferences. METHODS: A cross-sectional survey was conducted from May 30 to June 15, 2020, in China. Our team designed a 23-item questionnaire to investigate the conferences attended by urologists during the COVID-19 pandemic. SPSS 22.0 (IBM Corporation) was applied to analyze the data collected. RESULTS: A total of 330 Chinese urologists participated in our survey, and the response rate was 89.7% (330/368). Among the participants, 40.9% (135/330) were associate chief physicians. The proportion of participants who took part in conventional face-to-face academic conferences decreased from 92.7% (306/330) before the COVID-19 pandemic to 22.1% (73/330) during the pandemic (P<.001). In contrast, the proportion of urologists who took part in virtual conferences increased from 69.4% (229/330) to 90% (297/330) (P<.001). Most urologists (70.7%, 210/297) chose to participate in the virtual conferences at home and thought that a meeting length of 1-2 hours was most appropriate. Among the urologists, 73.7% (219/297) reported that their participation in the virtual conferences went smoothly, while the remaining respondents reported that they had experienced lags in video and audio streaming during the virtual conferences. When comparing conventional face-to-face conferences with virtual conferences, 70.7% (210/297) of the respondents thought that both conference formats were acceptable, while 17.9% (53/297) preferred virtual conferences and 11.5% (34/297) preferred conventional face-to-face meetings. CONCLUSIONS: Virtual conferences are increasing in popularity during the COVID-19 pandemic; however, many aspects of these conferences could be improved for better organization.

Association between Sitting Time and Urinary Incontinence in the US population: Data from the National Health and Nutrition Examination Survey (NHANES) 2007 to 2018.

Background: Urinary incontinence (UI) is a common health problem that affects the quality of life and health of millions of people in the United States (US). We aimed to investigate the association between sitting time and UI symptoms in the US population. Methods: A cross-sectional survey of participants aged 20 and above from the National Health and Nutrition Examination Survey 2007-2018 was performed. A self-report questionnaire that reported complete data on UI, sitting time and covariates was included. Weighted multivariable logistic and regression models were used to assess the association between sitting time and UI symptoms. Results: A total of 22,916 participants were enrolled. Prolonged sitting time was associated with urgency UI (UUI, odds ratio [OR] = 1.2, 95% confidence interval [CI] = 1.1 to 1.3, p = 0.001). Compared with patients with sitting a time shorter than 7 hours (h), moderate recreational activity modified the association between sitting time and mixed UI in males in the fully adjusted model (OR = 2.5, 95% CI = 1.4 to 4.5, p = 0.002). A sitting time over 7 h was related to mixed UI (MUI, OR = 1.6, 95% CI = 1.1 to 2.2, p = 0.01) in males, and stress UI (SUI, OR = 0.9, 95% CI = 0.8 to 0.98, p = 0.03) in females. However, no significant difference was found among the UI, SUI, and MUI groups in fully adjusted model. Conclusions: A prolonged sitting time (≥7 h) was associated with UUI symptoms in all populations, SUI symptoms in females and MUI symptoms in males compared with sitting time lower than 7 h. Compared with those sit shorter than 7 h, moderate recreational activity may be a modifier between prolonged sitting and MUI symptoms in male participants, which warrants further studies for confirmation.

Risk factors for nephrolithiasis formation: An Umbrella Review.

OBJECTIVE: Nephrolithiasis is prevalent and burdensome worldwide. At present, evidence on the risk factors for nephrolithiasis is unconsolidated and the associations remain uncertain. We systematically evaluate the robustness of the meta-analytic evidence and aid more reliable interpretations of the epidemiological relationships. METHODS: We conducted a comprehensive review of the meta-analyses, screened the included studies with the aid of the AMSTAR 2 evaluation tool, and then used R (4.1.1) software to perform data analysis to evaluate the association between candidate risk factors and kidney stones, and evaluated the credibility of the evidence of the association between risk factors and kidney stones according to the GRADE classification, and finally obtained the strength and effectiveness of the association. RESULTS: We finally included 17 meta-analyses regarding 46 risk factors, 34 of which (73.9%) showed statistically significant association with nephrolithiasis. Among the significant associations, we found that waist circumference, BMI, dietary intake and fructose intake were positively correlated with the occurrence and development of nephrolithiasis. Caffeine, dietary fiber and DASH-diet showed a tendency to reduce kidney stones. Interestingly, calcium supplementation, dietary calcium, and vitamin D, which are widely believed to be responsible for stone formation, made no difference or even reduced the risk of nephrolithiasis. CONCLUSIONS: Our study demonstrates the suggestive causal (central obesity, T2D, gout, dietary sodium, fructose intake and higher temperatures) risk factors of nephrolithiasis. We also demonstrate the suggestive causal (coffee/alcohol/beer intake, dietary calcium and DASH-diet) protective factors of nephrolithiasis. To provide epidemiological basis for the treatment and prevention of nephrolithiasis.

Comparison of safety and efficacy of different positions in percutaneous nephrolithotomy: a network meta-analysis.

OBJECTIVES: Various new positions for percutaneous nephrolithotomy (PCNL) were proposed to reduce the limitations of the traditional position. This study was aimed to evaluate the efficacy and safety of the different PCNL positions. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for relevant randomized controlled trials (RCTs) up to 18 April 2023. The authors collected five common surgical positions used for PCNL: oblique supine position (OSP), supine position (SP), flank position (FP), split-leg oblique supine/flank position (SLP), and prone position (PP). Paired and network meta-analysis were conducted to compare relevant outcomes, including complications, operative time, stone-free rates, hospital stay, and hemoglobin loss among these different positions. RESULTS: The study included 17 RCTs with a total of 1841 patients. The result demonstrated that SLP significantly outperformed in terms of decreasing operation time (FP vs SLP MD- MD-41.65; OSP vs SLP MD 28.97; PP vs SLP MD 34.94), hospital stay, and hemoglobin loss. Ranking probabilities showed SLP had highest stone-free rate. Prone position was more likely to occur complications than others. Based on SMAA model, the benefit-risk analysis suggested the SLP was the optimal position in PCNL. CONCLUSIONS: For PCNL, the split-leg, flank, supine, and OSPs are as secure as the prone position. Further RCTs are necessary to confirm the outstanding safety and efficacy of split-leg position. Besides, the position should be selected regard for the patient's demands, the surgeon's preference and learning curve.

YAP-mediated mechanotransduction in urinary bladder remodeling: Based on RNA-seq and CUT&Tag.

Yes-associated protein (YAP) is an important transcriptional coactivator binding to transcriptional factors that engage in many downstream gene transcription. Partial bladder outlet obstruction (pBOO) causes a massive burden to patients and finally leads to bladder fibrosis. Several cell types engage in the pBOO pathological process, including urothelial cells, smooth muscle cells, and fibroblasts. To clarify the function of YAP in bladder fibrosis, we performed the RNA-seq and CUT&Tag of the bladder smooth muscle cell to analyze the YAP ablation of human bladder smooth muscle cells (hBdSMCs) and immunoprecipitation of YAP. 141 differentially expressed genes (DEGs) were identified through RNA-seq between YAP-knockdown and nature control. After matching with the results of CUT&Tag, 36 genes were regulated directly by YAP. Then we identified the hub genes in the DEGs, including CDCA5, CENPA, DTL, NCAPH, and NEIL3, that contribute to cell proliferation. Thus, our study provides a regulatory network of YAP in smooth muscle proliferation. The possible effects of YAP on hBdSMC might be a vital target for pBOO-associated bladder fibrosis.

Vitamin D Levels and Risk of Male Factor Infertility: A Mendelian Randomization Study.

PURPOSE: No consensus exists about the causal relationship between vitamin D (VD) and male factor infertility due to heterogeneity and confounding factors even in randomized controlled trials (RCTs). This study aimed to investigate the causal association between 25 hydroxyvitamin D (25OHD) levels and male factor infertility through Mendelian randomization (MR) and provide complementary information for optimization of future RCTs. MATERIALS AND METHODS: Two-sample MR analyses with four steps were performed. Single-nucleotide polymorphisms (SNPs) for VD were extracted from 417,580 Europeans in the UK Biobank, and the summary-level data of male factor infertility (825 cases and 85,722 controls) were extracted from the FinnGen. RESULTS: Totally 99 SNPs robustly associated with the 25OHD were included, and a 1-unit increase in genetically predicted natural-log transformed 25OHD levels was associated with decreased risk of male factor infertility (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.44-0.89; p=0.010), which was consistent in all three sensitivity analyses (MR-Egger, weighted median, and weighted mode methods). The conclusion still stands after removing SNPs which explained more variation in the male factor infertility than the 25OHD (OR, 0.61; 95% CI, 0.42-0.88; p=0.009; n=62), and which were associated with confounders (body mass index, type 2 diabetes, smoking, and coronary artery diseases) of male factor infertility (OR, 0.58; 95% CI, 0.39-0.85; p=0.005; n=55). CONCLUSIONS: VD supplement to increase serum 25OHD levels may be clinically beneficial for male factor infertility in the general population. The well-designed RCTs should be performed in priority to address this question.

Association between the systemic immune-inflammation index and kidney stone: A cross-sectional study of NHANES 2007-2018.

Background: The incidence rate of kidney stones increased over the past decades globally, which brought medical expenditure and social burden. The systemic immune-inflammatory index (SII) was initially identified as a prognosis of multiple diseases. We performed an updated analysis on the impact of SII on kidney stones. Methods: This compensatory cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey 2007-2018. Univariate and multivariate logistic regression analyses were performed to investigate the association between SII and kidney stones. Results: Of the 22220 participants, the mean (SD) age was 49.45 ± 17.36 years old, with a 9.87% incidence rate of kidney stones. A fully adjusted model showed that SII higher than 330 x 109/L was parallel associated with kidney stones (Odds ratio [OR] = 1.282, 95% Confidence interval [CI] = 1.023 to 1.608, P = 0.034) in adults aged 20-50. However, no difference was found in the elderly subgroup. Multiple imputation analyses confirmed the robustness of our results. Conclusions: Our findings suggested SII was positively associated with a high risk of kidney stones in US adults aged less than 50. The outcome compensated for previous studies that still needed more large-scale prospective cohorts for validation.