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.

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.

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.

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.

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.

Association between marijuana use and kidney stone: a cross-sectional study of NHANES 2009 to 2018.

Objective: The purpose of this investigation is to determine whether regular marijuana use is related to history of kidney stones in the US population. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. Kidney stone and marijuana use data were collected from self-report questionnaires. Multivariate logistic regression and multiple sensitivity analyses were applied to examine the relationship between marijuana usage and kidney stones. Results: There are approximately 26.04% of the US population have admitted to using marijuana in their lifetime. Compared with none regular users, those with a higher frequency of marijuana use were more males, more non-Hispanic races, lower than high school education, overweight, no recreational activity, without diabetes mellitus, and more coronary heart disease. After adjusting for potential confounders, multivariate regression analysis demonstrated that marijuana use was inversely correlated to kidney stones in males (Odds ratio [OR] = 0.72, 95% Confidence interval [CI] = 0.54-0.97). One to seven times/week regular consumption of marijuana was associated with kidney stones in males (OR = 0.62, 95% CI = 0.43-0.89). Sensitivity analyses validated the robustness of our outcomes. Conclusion: Our findings revealed that regular marijuana male users were inversely associated with kidney stones. Marijuana use one to six times/week was inversely related to the risk of kidney stones in males. Further studies are required to explore the dose and type associations of marijuana with kidney stones.

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 urinary phthalate metabolites and nephrolithiasis in adults: A cross-sectional analysis with NHANES 2007-2018.

Nephrolithiasis is highly prevalent and brings health and economic burdens to patients. The augmentation of nephrolithiasis may be associated with exposure to phthalate metabolites. However, few studies investigated the effect of various phthalates exposure on nephrolithiasis. We analyzed data from 7139 participants aged 20 years or above from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Serum calcium level-stratified univariate and multivariate linear regression analyses were performed to explore the relationship between urinary phthalate metabolites and nephrolithiasis. As a result, the prevalence of nephrolithiasis was approximately 9.96%. After adjusting for confounding factors, associations were found between serum calcium concentration with monoethyl phthalate (P = 0.012) and mono-isobutyl phthalate (P = 0.003) compared with tertile 1 (T1). In adjusted analysis, nephrolithiasis was positively associated with middle and high tertiles of mono benzyl phthalate (P < 0.05) compare with low tertile group. Furthermore, high-level exposure to mono-isobutyl phthalate had a similar positive association with nephrolithiasis (P = 0.028). Our findings provide evidence that exposure to certain phthalate metabolites (i.e. MiBP and MBzP) may be associated with a high risk of nephrolithiasis depending on serum calcium level.

Gut Microbiome-Generated Phenylacetylglutamine from Dietary Protein is Associated with Crohn's Disease and Exacerbates Colitis in Mouse Model Possibly via Platelet Activation.

OBJECTIVES: Our aims were to better understand the interplay of diet and gut microbiota in Crohn's disease [CD], taking advantage of a new-onset treatment-naïve CD cohort. We focus on phenylacetylglutamine [PAGln], a diet-derived meta-organismal prothrombotic metabolite. DESIGN: We collected faecal and serum samples from a CD cohort [n = 136] and healthy controls [n = 126] prior to treatment, and quantified serum PAGln using LC-MS/MS. Diet was assessed using food-frequency questionnaires. Mice [C57BL/6] were fed high/low-protein diets and administered dextran sodium sulphate [DSS] to examine plasma PAGly, thrombosis potential, and colitis severity. PAGly or saline was administered to DSS-induced colitis mice, and colitis severity and colonic tissue gene expression were examined. P-selectin and CD40L expression were determined in human platelet-rich plasma [n = 5-6] after exposure to platelet agonists following PAGln priming. Bioinformatic analysis and bacterial culturing identified the main contributor of PAGln in CD. RESULTS: PAGln, a meta-organismal prothrombotic metabolite, is associated with CD. Administration of PAGly exacerbated colitis in a mouse model and upregulated coagulation-related biological processes. Antiplatelet medicine, dipyridamole, attenuated PAGly-enhanced colitis susceptibility. PAGln enhanced platelet activation and CD40L expression in platelet-rich plasma ex vivo. Further study revealed that high dietary protein intake and increased abundance of phenylacetic acid [PAA]-producing Proteobacteria mediated by phenylpyruvate decarboxylase act in concert to cause the elevated PAGln levels in CD patients. CONCLUSION: Taken together, ppdc-carrying Proteobacteria-generated PAGln from dietary protein is associated with CD and exacerbates colitis possibly via platelet-induced coagulation and inflammation These results suggest that PAGln is a potential early diagnostic marker and therapeutic target of CD.

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.

A Novel Serum Metabolomic Panel for the Diagnosis of Crohn's Disease.

BACKGROUND: A distinctive metabolic phenotype provides the opportunity to discover noninvasive biomarkers for the diagnosis of Crohn's disease (CD) and for differentiating it from other intestinal inflammatory diseases. The study sought to identify new biomarkers for CD diagnosis. METHODS: Serum metabolites from 68 newly diagnosed and treatment-naïve patients with CD and 56 healthy control (HC) subjects were profiled using targeted liquid chromatography-mass spectrometry. Five metabolic biomarkers were identified to distinguish patients with CD from the HC subjects and validated in a separate cohort consisting of 110 patients with CD and 90 HC subjects using a combination of univariate analysis, orthogonal partial least-squares discriminant analysis, and receiver-operating characteristic curve analysis. Differences in the 5 metabolites were evaluated among patients with CD and patients with ulcerative colitis (n = 62), intestinal tuberculosis (n = 48), and Behçet's disease (n = 31). RESULTS: Among the 185 quantified metabolites, a panel of 5 (pyruvate, phenylacetylglutamine, isolithocholic acid, taurodeoxycholic acid, and glycolithocholic acid) were found to distinguish patients with CD with high accuracy from HC subjects, with an area under the curve of 0.861 (P < .001). The performance of the model in assessing clinical disease activity was comparable to that of the present biomarkers: C-reactive protein and erythrocyte sedimentation rate. The 5 metabolites were significantly different among the patients and were valuable in the differentiation between CD and other chronic intestinal inflammatory diseases. CONCLUSIONS: The combination of 5 serum metabolite biomarkers for the diagnosis of CD has the potential to provide an accurate, noninvasive, and inexpensive alternative to conventional tests and might be valuable for the differentiation from other diagnostically challenging intestinal inflammatory diseases.

Serum metabolomic analysis was performed on patients with Crohn's disease and healthy control subjects, which discovered 5 metabolites as a novel serum metabolomic panel. These metabolites were further validated in a second patient cohort and a third differentiation cohort. The data showed that these metabolites were valuable in diagnosis of Crohn's disease and for differentiating it from other intestinal inflammatory diseases.

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.

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.

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.

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.

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.

The effect of COVID-19 vaccines on sperm parameters: a systematic review and meta-analysis.

Published data were gathered for a meta-analysis to determine the difference in sperm parameters before and after administration of different types of coronavirus disease 2019 (COVID-19) vaccines, because the reproductive toxicity of COVID-19 vaccines has not yet been evaluated in clinical trials and COVID-19 has been associated with decreases in sperm quality. The preferred procedures for systematic reviews and meta-analyses were followed in the conduct and reporting of this study. The average sperm parameters of all sperm donors' multiple sperm donations were compared before and after receiving various COVID-19 vaccinations. Semen volume, total sperm motility, total sperm count, morphological change, and sperm concentration were the primary outcome measures. We compiled and analyzed the results of six studies on total sperm motility, six studies on semen volume, six studies on sperm concentration, two studies on morphological change, and two studies on total sperm count. Parameter comparisons with patients who had and had not been vaccinated were only reported in one of the included studies. When different types of COVID-19 vaccine injections were compared, no discernible differences in parameters were observed. According to the available data, the parameters of semen are unaffected by inactivated or messenger RNA (mRNA) COVID-19 vaccinations. To support these findings, additional prospectively designed research is required.

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 between heavy metal exposure and erectile dysfunction in the United States.

Literature regarding the impacts of heavy metal exposure on erectile dysfunction (ED) is scarce. We aimed to evaluate the correlation between 10 urinary metals and ED in a large, nationally representative adult male sample. The dataset was extracted from the National Health and Nutrition Examination Survey (NHANES) during the period of 2001-2002 and 2003-2004. Weighted proportions and multivariable logistic regression analysis adjusted for confounding variables were utilized to determine the relationship between metal exposure and ED. Weighted quantile sum (WQS) regression was utilized to evaluate the impact of a mixture of urinary metals on ED. A total of 1328 participants were included in our study. In multivariable logistic regression analysis, cobalt (Co) and antimony (Sb) were positively associated with ED (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.10-1.73, P = 0.020; and OR: 1.41, 95% CI: 1.12-1.77, P = 0.018, respectively) after full adjustment. Men in tertile 4 for Co (OR: 1.49, 95% CI: 1.02-2.41, P for trend = 0.012) and Sb (OR: 1.53, 95% CI: 1.08-2.40, P for trend = 0.041) had significantly higher odds of ED than those in tertile 1. Furthermore, the WQS index was significantly linked with increased odds of ED after full adjustment (OR: 1.31, 95% CI: 1.04-1.72, P < 0.05). Our study expanded on previous literature indicating the possible role of heavy metal exposure in the etiology of ED. The evaluation of heavy metal exposure should be included in the risk assessment of ED.