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.

Transperineal anastomotic posterior urethroplasty with bulbocavernosus flap and fibrin sealant in the complicated posterior urethral stricture reconstruction: a retrospective cohort study.

BACKGROUND: Management of complicated posterior urethral stricture is challenging. Modified transperineal anastomotic urethroplasty (TAU) with bulbocavernosus flap interposition and human fibrin sealant provides another treatment option. The authors aimed to evaluate whether this technique could improve the success rate in the complicated posterior urethral stricture reconstruction in this study. MATERIALS AND METHODS: Between 2016 and 2019, 48 patients underwent either conventional or modified TAU. The criteria for success included both the absence of clinical symptoms and no need for further surgical intervention during follow-up. RESULTS: Twelve patients underwent the modified TAU (group A) using bulbocavernosus flap interposition and human fibrin sealant. Thirty-six patients underwent the traditional end-to-end anastomotic urethroplasty (group B). Follow-up was 24.3-57.2 months. The patients in group A had a higher surgery success rate compared to the patients in group B (91.7 vs. 63.9%, P =0.067), with a quasi-significant result. Besides, no postoperative complications were observed in group A, while two individuals in group B had urinary incontinence, but the difference was not significant (0 vs. 5.6%, P =0.404). CONCLUSION: Based on the preliminary results, modified TAU with bulbocavernosus flap interposition and human fibrin sealant is a safe and feasible technique for complicated posterior urethral stricture reconstruction.

Is antibiotic prophylaxis generally safe and effective in surgical and nonsurgical scenarios? Evidence from an umbrella review of randomized controlled trials.

BACKGROUND: The authors aimed to comprehensively evaluate the efficacy and safety of antibiotic prophylaxis through surgical and nonsurgical scenarios and assess the strength of evidence. MATERIALS AND METHODS: The authors performed an umbrella review of meta-analyses of randomized controlled trials (RCTs). An evidence map was created to summarize the absolute benefits of antibiotic prophylaxis in each scenario and certainty of evidence. RESULTS: Seventy-five meta-analyses proved eligible with 725 RCTs and 78 clinical scenarios in surgical and medical prophylaxis. Of 119 health outcomes, 67 (56.3%) showed statistically significant benefits, 34 of which were supported by convincing or highly suggestive evidence from RCTs. For surgeries, antibiotic prophylaxis may minimize infection occurrences in most surgeries except Mohs surgery, simple hand surgery, herniorrhaphy surgery, hepatectomy, thyroid surgery, rhinoplasty, stented distal hypospadias repair, midurethral sling placement, endoscopic sinus surgery, and transurethral resection of bladder tumors with only low to very low certainty evidence. For nonsurgery invasive procedures, only low to very low certainty evidence showed benefits of antibiotic prophylaxis for cystoscopy, postoperative urinary catheterization, and urodynamic study. For medical prophylaxis, antibiotic prophylaxis showed greater benefits in nonemergency scenarios, in which patients were mainly with weakened immune systems, or at risk of recurrent chronic infections. Antibiotics prophylaxis may increase antibiotic resistance or other adverse events in most scenarios and reached significance in cystoscopy, afebrile neutropenia following chemotherapy and hematopoietic stem cell transplantation. CONCLUSIONS: Antibiotic prophylaxis in surgical and nonsurgical scenarios is generally effective and seems independent of surgical cleanliness and urgency of diseases. Its safety is not well determined due to lack of available data. Nevertheless, the low quality of current evidence limits the external validity of these findings, necessitating clinicians to judiciously assess indications, balancing low infection rates with antibiotic-related side effects.

Do Obesity-Related Traits Affect Prostate Cancer Risk through Serum Testosterone? A Mendelian Randomization Study.

OBJECTIVE: This study aimed to investigate whether testosterone mediates or confounds the effect of obesity-related traits on prostate cancer (PCa) using Mendelian randomization (MR) analysis. MATERIALS AND METHODS: Data of obesity-related traits (body mass index [BMI], waist-to-hip ratio [WHR], and waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) were obtained from up to 806,834 people of European ancestry; data of testosterone (bioavailable testosterone [BT], total testosterone [TT], and sex hormone-binding globulin [SHBG]) were extracted from up to 194,453 participants in the UK Biobank; and the summary-level data of PCa (79,194 cases and 61,112 controls) were obtained from the PRACTICAL consortium. RESULT: The results supported the causal relationship between higher BMI and a reduced risk of PCa (OR = 0.91, 95% confidence interval [CI]: 0.86-0.96). Furthermore, increased BT levels were associated with an elevated risk of PCa (OR = 1.15, 95% CI: 1.06-1.24). Importantly, our analysis revealed a unidirectional causal effect-higher BMI was linked to lower BT levels (beta = -0.27, 95% CI: -0.3--0.24), but not the other way around. This suggests that BT may mediate the effect of BMI on PCa rather than confound it. Our multivariable MR results further demonstrated that considering BT as a mediator led to the weakening of BMI's effect on PCa risk (OR = 0.97, 95% CI: 0.90-1.05), while the impact of BT on PCa remained unchanged when accounting for BMI. Moreover, we identified a significant indirect effect of BMI on PCa risk (OR = 0.96, 95% CI: 0.94-0.98). CONCLUSION: Our study provided genetic evidence that serum BT can mediate the effect of BMI on the risk of PCa, indicating the possible mechanism by which obesity reduces PCa risk.

Vitamin E and Multiple Health Outcomes: An Umbrella Review of Meta-Analyses.

The relationship between vitamin E intake or circulating α-tocopherol and various health outcomes is still debatable and uncertain. We conducted an umbrella review to identify the relationships between vitamin E intake or circulating tocopherol and health outcomes by merging and recalculating earlier meta-analyses. The connections that were found to be statistically significant were then classified into different evidence levels based on p values, between-study heterogeneity, prediction intervals, and small study effects. We finally included 32 eligible meta-analyses with four vitamin E sources and 64 unique health outcomes. Only the association between circulating α-tocopherol and wheeze or asthma in children was substantiated by consistent evidence. Suggestive evidence was suggested for seven results on endothelial function (supplemental vitamin E): serum C-reactive protein (CRP) concentrations (supplemental vitamin E), cervical cancer (dietary vitamin E), esophageal cancer (dietary vitamin E), cervical intraepithelial neoplasia (CIN, dietary vitamin E), pancreatic cancer (total vitamin E intake), and colorectal cancer (circulating α-tocopherol levels); all of these showed a protective effect consistent with the vitamin E source. In conclusion, our work has indicated that vitamin E is protective for several particular health outcomes. Further prospective studies are required when other factors that may contribute to bias are considered.

Comparison of the efficacy and safety of holmium laser with the Moses technology and regular mode for stone treatment: a systematic review and meta-analysis.

BACKGROUND: As a new pulse modality of holmium laser in retrograde intrarenal stone surgery, the MOSES technique can reduce the possibility of stone drifting and help to powder kidney stones in vitro and in animal experiments. However, there remains controversy about whether the MOSES mode needs to be used instead of the regular mode in clinical practice. This meta-review was conducted to evaluate the clinical efficacy and safety of MOSES technology for stone disease. METHODS: PubMed, Embase, Web of Science, Cochrane Library, and CNKI were searched for relevant studies until September 2022, with 1 RCT and 6 nonrandomized studies included. We pulled data on adverse events, success rates and operative time to analyze based on the random effect model. RESULTS: We found that using MOSES mode could shorten the operative time (standard mean difference [SMD] - 0.43; 95% confidence interval [CI] - 0.79 to - 0.08; P = 0.016) than regular mode especially in a small sample study or in the Asian area. When the number of women is smaller than the number of men, the reduction of the duration was also significant. Stone-free rates of the two modes had no difference (relative risk [RR] 1.06; 95% CI 0.99-1.12; P = 0.30), and there was no publication bias. In terms of safety, no significant difference in complications was detected between the two approaches (RR 0.85; 95% CI 0.48-1.53; P = 0.81) without significant heterogeneity. CONCLUSION: MOSES mode holmium laser was superior to the regular mode laser in terms of procedure time. There was no large disparity in stone-free rates or complications between the two modes. However, our conclusions should be confirmed in prospective studies with high evidence.

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.

Development of a novel predictive model for a successful stone removal after flexible ureteroscopic lithotripsy based on ipsilateral renal function: a single-centre, retrospective cohort study in China.

OBJECTIVES: The aims of this study were to investigate the effect of preoperative ipsilateral renal function on the success of kidney stone removal with flexible ureteroscopic lithotripsy and to develop a predictive model based on the results. DESIGN: Retrospective cohort study. SETTING: Data from the 2001-2012 period were collected from the electronic records of West China Hospital, Sichuan University. PARTICIPANTS: 576 patients who underwent flexible ureteroscopic lithotripsy were included in the study. PRIMARY OUTCOME: Stone-free rate (SFR) after the procedures. RESULTS: In patients with suspected impaired kidney function, the overall SFR was 70.1%. Stone volume (OR 1.46; 95% CI 1.18 to 1.80), lower calyx stones (OR 1.80; 95% CI 1.22 to 2.65), age (OR 1.02; 95% CI 1.00 to 1.04), body mass index (OR 1.10; 95% CI 1.04 to 1.17) and estimated glomerular filtration rate of the affected kidney (OR 0.95; 95% CI 0.94 to 0.97) were identified as independent predictors of SFR. Lasso regression selected the same five predictors as those identified by univariate and multivariate logistic regression analyses, thus verifying our model. The mean area under the curve, based on 1000 iterations and 10-fold validation, was 0.715 (95% CI 0.714 to 0.716). The Hodges-Lehmann test and calibration curve analysis revealed no significant mismatch between the prediction model and the retrospective cohort. CONCLUSION: Ipsilateral renal function may be a novel independent risk factor for kidney stone removal with flexible ureteroscopic lithotripsy. A novel nomogram for predicting SFR that uses stone volume, lower calyx stones, age, body mass index and estimated glomerular filtration rate was developed, but remains to be externally validated.

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.

Does combined lithotripter show superior stone-success rate than ultrasonic or pneumatic device alone during percutaneous nephrolithotrotomy? A meta-analysis.

OBJECTIVES: To compare the stone clearance rate and stone-success rate among lithotripter with ultrasonic lithotripter alone, pneumatic lithotripter alone and combined mechanisms. METHODS: Up till 2021 May, we conducted a literature search among several widely used database around the world, including Pubmed, Embase (Ovid Version), Medline (Ovid Version) and Cochrane Central Register of Controlled Trials. Only English literature was considered. Pediatric patients were excluded. Reviews and protocols without any published data were excluded. Conference abstracts and articles with unrelated contents were also excluded. RESULTS: Fifteen articles were included in our final meta-analysis, with 9 RCTs and 6 cohort studies. In Lithoclast combined with ultrasonic device vs pneumatic device subgroup, overall stone-success rate yielded insignificant difference. As for subgroup of Shock Pulse vs pneumatic device, pooled analysis yielded a higher 1-month stone-success rate for Shock Pulse (RR = 1.10, 95% CI: 1.01-1.19). In Lithoclast combined with ultrasonic device vs ultrasonic device subgroup and Cyberwand vs ultrasonic device subgroup, both overall stone-success rate did not differ from one another. We found Lithoclast with ultrasonic device was more efficient in stone clearance rate than pneumatic device (mean difference = 8.23, 95% CI: 4.99-11.47). The same situation was applied to the comparison between Lithoclast with ultrasonic device and ultrasonic device (mean difference = 13.02, 95% CI: 4.57-21.46). CONCLUSIONS: Combined lithotripter was more efficient in clearing stones than pneumatic or ultrasonic device alone. However, when it came to stone-success rate, no obvious superiority was seen in combined one.

Are adrenergic α1- antagonists beneficial for the access of retrograde ureteral access sheath or semi-rigid ureteroscope access? A systematic review and meta-analysis.

Introduction: To evaluate the clinical benefit of preoperative adrenergic α1-antagonist therapy in the management of upper urinary calculi. Materials and methods: Publications were searched for The Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE until 1 March 2022 that related to the adrenergic α1- antagonist intake as adjunctive therapy before retrograde surgery. Dichotomous data were reported with risk ratios (RR) with 95% confidence intervals (CIs) and the continuous data were reported with mean difference (MD) with 95% CIs. Results: There were nine studies with 867 patients included in this meta-analysis. Preoperative adrenergic α1- antagonists could significantly elevate the compared with the placebo. Higher successful access rate to the stone was found in patients who received preoperative adrenergic α1- antagonists than those who received the placebo (RR 1.24; 95% CI 1.17-1.33). Besides, the application of preoperative adrenergic α1- antagonists can also elevate 4th-week stone-free rate (RR 1.20; 95% CI 1.12-1.28), decrease postoperative analgesia (RR 0.30;95% CI 0.20-0.46) and result in a lower risk of overall complications (RR 0.38; 95% CI 0.24-0.61). Conclusion: Preoperative adjunctive adrenergic α1- antagonist therapy is effective and safe in the management of retrograde surgery with a higher successful access rate and lower risk of severe complications.

Causal Associations Between Educational Attainment and 14 Urological and Reproductive Health Outcomes: A Mendelian Randomization Study.

Background: The impact of educational attainment (EA) on multiple urological and reproductive health outcomes has been explored in observational studies. Here we used Mendelian randomization (MR) to investigate whether EA has causal effects on 14 urological and reproductive health outcomes. Methods: We obtained summary statistics for EA and 14 urological and reproductive health outcomes from genome-wide association studies (GWAS). MR analyses were applied to explore the potential causal association between EA and them. Inverse variance weighted was the primary analytical method. Results: Genetically predicted one standard deviation (SD) increase in EA was causally associated with a higher risk of prostate cancer [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.05-1.25, P = 0.003] and a reduced risk of kidney stone (OR 0.73, 95% CI 0.62-0.87, P < 0.001) and cystitis (OR 0.76, 95% CI 0.67-0.86, P < 0.001) after Bonferroni correction. EA was also suggestively correlated with a lower risk of prostatitis (OR 0.76, 95% CI 0.59-0.98, P = 0.037) and incontinence (OR 0.64, 95% CI 0.47-0.87, P = 0.004). For the bioavailable testosterone levels and infertility, sex-specific associations were observed, with genetically determined increased EA being related to higher levels of testosterone in men (ß 0.07, 95% CI 0.04-0.10, P < 0.001), lower levels of testosterone in women (ß -0.13, 95% CI-0.16 to-0.11, P < 0.001), and a lower risk of infertility in women (OR 0.74, 95% CI 0.64-0.86, P < 0.001) but was not related to male infertility (OR 0.79, 95% CI 0.52-1.20, P = 0.269) after Bonferroni correction. For bladder cancer, kidney cancer, testicular cancer, benign prostatic hyperplasia, and erectile dysfunction, no causal effects were observed. Conclusions: EA plays a vital role in urological diseases, especially in non-oncological outcomes and reproductive health. These findings should be verified in further studies when GWAS data are sufficient.

Short-Chain Fatty Acids Reduced Renal Calcium Oxalate Stones by Regulating the Expression of Intestinal Oxalate Transporter SLC26A6.

Renal calcium oxalate (CaOx) stone is a common urologic disease with a high prevalence and recurrence rate. However, short-chain fatty acids (SCFAs) are less often reported in the prevention of urolithiasis. This study aimed to explore the effect of SCFAs on the renal CaOx stone formation and the underlying mechanisms. Ethylene glycol was used to induce renal CaOx crystals in rats. SCFAs (acetate, propionate, or butyrate) were added as supplements to the drinking water with or without antibiotics. Because intestinal oxalate transporters SLC26A6 and SLC26A3 regulate the excretion and absorption of oxalate in the intestine, we injected adeno-associated virus 9 (AAV9)-SLC26A6-shRNA (short hairpin RNA) and AAV9-SLC26A3 into the tail vein of rats to suppress SLC26A6 and overexpress SLC26A3 expression in the intestine, respectively, to explore the role of SLC26A3 and SLC26A6 (SLC26A3/6) in the reduction of renal CaOx crystals induced by SCFAs. Results showed that SCFAs reduced renal CaOx crystals and urinary oxalate levels but, however, increased the abundance of SCFA-producing bacteria and cecum SCFA levels. SCFA supplements still reduced renal crystals and urinary oxalate after gut microbiota depletion. Propionate and butyrate downregulated intestinal oxalate transporter SLC26A3 expression, while acetate and propionate upregulated SLC26A6 expression, both in vivo and in vitro. AAV9-SLC26A3 exerted a protective effect against renal crystals, while AAV9-SLC26A6-shRNA contributed to the renal crystal formation even though the SCFAs were supplemented. In conclusion, SCFAs could reduce urinary oxalate and renal CaOx stones through the oxalate transporter SLC26A6 in the intestine. SCFAs may be new supplements for preventing the formation of renal CaOx stones. IMPORTANCE Some studies found that the relative abundances of short-chain-fatty-acid (SCFA)-producing bacteria were lower in the gut microbiota of renal stone patients than healthy controls. Our previous study demonstrated that SCFAs could reduce the formation of renal calcium oxalate (CaOx) stones, but the mechanism is still unknown. In this study, we found that SCFAs (acetate, propionate, and butyrate) reduced the formation of renal calcium oxalate (CaOx) crystals and the level of urinary oxalate. Depleting gut microbiota increased the amount of renal crystals in model rats, and SCFA supplements reduced renal crystals and urinary oxalate after gut microbiota depletion. Intestinal oxalate transporter SLC26A6 was a direct target of SCFAs. Our findings suggested that SCFAs could reduce urinary oxalate and renal CaOx stones through the oxalate transporter SLC26A6 in the intestine. SCFAs may be new supplements for preventing the formation of renal CaOx stones.

Lymph Node Dissections for T3T4 Stage Penile Cancer Patients Without Preoperatively Detectable Lymph Node Metastasis Bring More Survival Benefits: A Propensity Matching Analysis.

BACKGROUND AND AIMS: The current guidelines for the treatment of penile cancer patients with clinically non-invasive normal inguinal lymph nodes are still broad, so the purpose of this study is to determine which patients are suitable for lymph node dissection (LND). METHODS: Histologically confirmed penile cancer patients (primary site labeled as C60.9-Penis) from 2004 to 2016 in the Surveillance, Epidemiology, and Results database were included in this analysis. Univariate and multivariate Cox regression analyses were applied to determine an overall estimate of LND on overall survival and cancer-specific survival. A 1:1 propensity matching analysis (PSM) was applied to enroll balanced baseline cohort, and further Kaplan-Meier (KM) survival analysis was used to get more reliable results. RESULTS: Out of 4,458 histologically confirmed penile cancer patients with complete follow-up information, 1,052 patients were finally enrolled in this analysis. Age, pathological grade, T stage, and LND were identified as significant predictors for overall survival (OS) in the univariate Cox analysis. In the multivariate Cox regression, age, pathological grade, T stage, and LND were found significant. The same results were also found in the univariate and multivariate Cox regression analyses for cancer-specific survival (CSS). After the successful PSM, further KM analysis revealed that LND could bring significant OS and CSS benefits for T3T4 patients without lymph node metastasis. CONCLUSION: Lymph node dissection may bring survival benefits for penile cancer patients without preoperatively detectable lymph node metastasis, especially for T3T4 stage patients. Further randomized control trial is needed.

Short Chain Fatty Acids Prevent Glyoxylate-Induced Calcium Oxalate Stones by GPR43-Dependent Immunomodulatory Mechanism.

Calcium oxalate (CaOx) stones are the most common type of kidney stones and are associated with high recurrence, short chain fatty acids (SCFAs), and inflammation. However, it remains uncertain whether SCFAs affect the formation of CaOx stones through immunomodulation. We first performed mass cytometry (CyTOF) and RNA sequencing on kidney immune cells with glyoxylate-induced CaOx crystals (to elucidate the landscape of the associated immune cell population) and explored the role of SCFAs in renal CaOx stone formation through immunomodulation. We identified 29 distinct immune cell subtypes in kidneys with CaOx crystals, where CX3CR1+CD24- macrophages significantly decreased and GR1+ neutrophils significantly increased. In accordance with the CyTOF data, RNA sequencing showed that most genes involved were related to monocytes and neutrophils. SCFAs reduced kidney CaOx crystals by increasing the frequency of CX3CR1+CD24- macrophages and decreasing GR1+ neutrophil infiltration in kidneys with CaOx crystals, which was dependent on the gut microbiota. GPR43 knockdown by transduction with adeno-associated virus inhibited the alleviation of crystal formation and immunomodulatory effects in the kidney, due to SCFAs. Moreover, CX3CR1+CD24- macrophages regulated GR1+ neutrophils via GPR43. Our results demonstrated a unique trilateral relationship among SCFAs, immune cells, and the kidneys during CaOx formation. These findings suggest that future immunotherapies may be used to prevent kidney stones using SCFAs.

Coffee Consumption and Prostate Cancer Risk: Results from National Health and Nutrition Examination Survey 1999-2010 and Mendelian Randomization Analyses.

The aim of this study was to examine the association between coffee and prostate cancer. Firstly, we conducted an observational study using data from National Health and Nutrition Examination Survey (NHANES) 1999-2010. Coffee intake was derived from 24 h dietary recalls. Weighted multivariable-adjusted logistic regression was applied to evaluate the association. Then, we performed Mendelian randomization (MR) to explore the possible causal effect of coffee on prostate cancer risk. Primary and secondary genetic instruments were obtained from genome-wide association studies among 375,833 and 91,462 individuals separately. Prostate cancer summary statistics were extracted from Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome (PRACTICAL) (79,194 cases and 61,112 controls) and FinnGen project (4754 cases and 63,465 controls). Inverse variance weighted (IVW) was the primary analytical method. Through selection, we enrolled 8336 individuals (weighted number = 58,796,070) for our observational study in NHANES. Results suggested that there was no association between coffee and prostate cancer. MR analyses with primary genetic instruments also did not support a causal association between coffee intake and prostate cancer risk, whether using summary data from PRACTICAL (IVW: OR 1.001, 95% CI 0.997-1.005) or FinnGen (IVW: OR 1.005, 95% CI 0.998-1.012). Similar results were observed when using secondary genetic instruments. Therefore, our study did not support a causal association between coffee intake and prostate cancer risk. Further studies with a larger sample size are needed to examine if an association exists by different coffee bean types, roasting procedures, and brewing methods.

Changes of renal function after retrograde intrarenal surgery using flexible ureteroscope in renal stone patients.

BACKGROUND: Retrograde intrarenal surgery (RIRS) is widely performed for renal stones. Theoretically, removing renal stones could prevent the deterioration of renal function. However, two studies reported that not all patients would see an increase in renal function after RIRS. The aim of our study was to evaluate the change of renal function of the operative site, and to identify predictors of improvement or deterioration of renal function after RIRS. METHODS: We retrospectively reviewed renal stones patients who received RIRS and single-photon emission computed tomography (SPECT) before and after surgery. Improved renal function was defined as the change of glomerular filtration rate (GFR) >10% postoperatively, and that <-10% was regarded as deteriorated renal function. Logistic and least absolute shrinkage and selection operator regression analyses were used to identify predictors for the improvement or deterioration of renal function, and predictive nomogram models were built. RESULTS: A total of 120 renal stone patients were included. Twenty-one (17.5%), 79 (65.8%) and 20 (16.7%) patients had improved, stable and deteriorated renal function of operative site after surgery, respectively. Lower alkaline phosphatase, lower low-density lipoprotein, lower GFR of the operative site, thicker renal parenchyma, higher serum creatinine, and extracorporeal shock wave lithotripsy (SWL) history were associated with the improved renal function. The predictive accuracy of the model for the improved renal function was 0.800. Additionally, older age, longer flexible ureteroscopic time, thinner renal parenchyma and existence of ureteral stones were risk factors for deteriorated renal function. The predictive accuracy of the model for the deteriorated renal function was 0.725. CONCLUSIONS: The renal function of most renal stone patients did not decrease after RIRS. For patients with potential deterioration of renal function postoperatively, urologists could shorten flexible ureteroscopic time to prevent the occurrence of this outcome.

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.

The association between hepatitis C virus infection and renal cell cancer, prostate cancer, and bladder cancer: a systematic review and meta-analysis.

To update the current evidence on whether hepatitis C virus (HCV) infection represents a possible risk factor for renal cell cancer (RCC), prostate cancer (PCa), and bladder cancer (BC). We searched the literature on Pubmed, Web of Science, and Embases before April 2021. A systematic review and meta-analysis were performed. Finally, we extracted 12 studies based on the eligible criteria. Across 11 studies for HCV and RCC, the incorporated RR was 1.28 (95% CI 1.05-1.55), which meant that participants with HCV infection were associated with higher RCC risk. The pooled RR in hazard ratio (HR) subgroup (HR 1.59, 95% CI 1.22-2.08), cohort studies subgroup (RR 1.47, 95% CI 1.18-1.82), and North America subgroup (RR 1.71, 95% CI 1.40-2.09) detected a stronger association between HCV and RCC risk. Although an inverse association was seen for PCa (RR 0.75, 95% CI 0.54-1.03) across seven studies, it was not statistically significant (P = 0.075). There was no significant association between HCV and BC with an incorporated RR of 0.92 (95% CI, 0.82-1.03) across five studies. Our study demonstrated that HCV infection was significantly associated with increased RCC risk. There appeared to be an inverse association for HCV in PCa risk but not statistically significant. No significant association was found between HCV and BC risk. Prospective, large-scale, and well-designed cohort studies are required to validate the association between HCV and RCC, and to investigate the role of HCV on PCa.

Phosphodiesterase type-5 inhibitors for erectile dysfunction following nerve-sparing radical prostatectomy: A network meta-analysis.

BACKGROUND: To verify which phosphodiesterase type 5 inhibitors (PDE5is) strategy is better for erectile dysfunction (ED) following nerve-sparing radical prostatectomy (NSRP). METHODS: This systematic literature search was conducted in MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials database to identify eligible studies from the startup of these databases to 1 November, 2019. The ED recovery rate was the main outcome. Traditional pair-wise meta-analysis and multivariate random-effects network meta-analysis (NMA) were performed to explore direct and indirect comparisons, respectively. The surface under the cumulative ranking (SUCRA) probabilities was used to evaluate the efficacy of treatments. RESULTS: A total of 14 randomized controlled trials with four kinds of PDE5is were included. Further pooled evidence suggested that PDE5is followed by NSRP had a benefit for penile rehabilitation compared to placebo using traditional pair-wise meta-analyses. Our NMA showed that Avanafil 200 mg on demand might be most likely to be the best treatment option according to the first rank of SUCRA both in NMA (SUCRA 83.5) and sensitivity analysis (SUCRA 90.2). CONCLUSION: Avanafil 200 mg on demand has the highest probability of being the best intervention among PDE5is in treating ED following NSRP. However, more randomized controlled trials are needed to validate this in consideration of the published data regarding Avanafil is relatively small scale.