Impact of habitual intake of glucosamine, fresh fruit, and tea on the risk of urolithiasis: A two-sample Mendelian randomization study.

Dietary patterns have a significant impact on the occurrence of urolithiasis. This study aimed to investigate the causal relationships between the consumption of glucosamine, fresh fruits, and tea, and the predisposition to urinary stones using a Mendelian randomization (MR) approach. Genetic proxies for these dietary factors were obtained from the UK Biobank, while the summary data for urolithiasis genome-wide association analyses were sourced from the FinnGen consortium. Five MR methodologies, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, and simple mode, were employed in the analysis. To validate the findings, sensitivity evaluations such as the MR-PRESSO disruption test and Cochran Q test for heterogeneity were performed. The IVW method showed that glucosamine consumption had a strong inverse association with urolithiasis risk (Odds Ratio [OR] = 0.006, 95% Confidence Interval [CI] 0.0001-0.287, P = .009), surpassing the associations of fresh fruits (OR = 0.464, 95% CI 0.219-0.983, P = .045) and tea (OR = 0.550, 95% CI 0.345-0.878, P = .012). These findings were consistent when verified using alternative MR techniques, and the sensitivity analyses further supported their credibility. The results of this MR analysis demonstrate that regular consumption of glucosamine, fresh fruits, and tea is inversely correlated with the risk of developing urolithiasis.

Triangular prismatic JJ stent does not cause more discomfort than tubular ones: a randomised controlled trial comparison.

OBJECTIVE: To compare the stent-related symptoms (SRS) of three commonly used, readily accessible ureteric JJ stents after uncomplicated flexible ureteroscopic lithotripsy (FURL), in a prospective randomised controlled single-blind parallel-group study, in order to see whether structural difference might influence SRS. PATIENTS AND METHODS: Patients undergoing FURL were randomised into three groups: the Cook Group received conventional 6 F Cook Universa Soft JJ stents as control, the Kang Yi Bo (KYB) Group received 6 F KYB anti-reflux JJ stents, and the Urovision Group received 7 F Urovision Visiostar ESWL JJ stents. The ureteric stent symptom questionnaire (USSQ) was administered at 1 week, 4 weeks (before stent removal), and 5 weeks (one week after stent removal as baseline evaluation) after stent insertion. Both raw and baseline-adjusted USSQ domain subscores at 1 week and 4 weeks were compared. RESULTS: A total of 146 patients were included in the analysis. The KYB Group showed significantly lower P6&7 subscore yet higher urinary symptoms score 1 week and 4 weeks after stents insertion than both Cook and Urovision, whilst the Urovision Group achieved similar scores in most domains with Cook. CONCLUSIONS: Although the KYB anti-reflux JJ stent might prevent vesicoureteral reflux, it induces significantly stronger urinary symptoms, both at 1 week or 4 weeks after stent insertion, with or without baseline correction. Despite the unique triangular prismatic shape, the Urovision Visiostar stent does not cause heavier urinary symptoms or pain compared to the conventional cylinder shape counterparts.

Omnidirectional (Flexible) Ureteral Access Sheath: Safety, Efficacy, and Initial Experience Report.

Background: Recently a novel omnidirectional (OD) ureteral access sheath (UAS) has been developed. By retrospectively reviewing and comparing the flexible ureteroscopic lithotripsy (FURL) cases in our institution with either a conventional Cook UAS or an OD UAS in the past year, we shared our experience of the safety, efficacy, and relevant issues on the usage of OD UAS. Materials and Methods: The medical history and surgery details of 199 patients with kidney stones or ureterojunctional stones who underwent FURL in Xinhua Hospital, including 61 Cook UAS and 138 OD UAS, were reviewed and compared. The maximal deflection angle was measured by steering four different types of ureteroscopes to bend the OD UAS in different states. Result: The deflection angle of OD UAS was ∼110° to 130° free load, and 90° to 130° when loaded with different instruments. The stone burden and position were similar in two groups. Given a similar prestent ratio and operation time, the OD UAS group achieved a higher single-session stone-free rate (SFR) (63.9% vs 94.2%, p < 0.0001) at 1-month follow-up evaluated by a CT scan. Conclusion: OD UAS is a novel device with high safety and efficacy. The unique flexible design allows it to bend with the ureteroscope and enter renal calices and be set close to the stone. Combined with the suction port, OD UAS contributes greatly to dealing with large-burden kidney stones, shortens operation time, and improves single-session SFR.

LRRK2 aggravates kidney injury through promoting MFN2 degradation and abnormal mitochondrial integrity.

Mitochondrial dysfunction is one of the key features of acute kidney injury (AKI) and associated fibrosis. Leucine-rich repeat kinase 2 (LRRK2) is highly expressed in kidneys and regulates mitochondrial homeostasis. How it functions in AKI is unclear. Herein we reported that LRRK2 was dramatically downregulated in AKI kidneys. Lrrk2-/- mice exhibited less severity of AKI when compared to wild-type counterparts with less mitochondrial fragmentation and decreased reactive oxygen species (ROS) production in proximal renal tubular cells (PTCs) due to mitofusin 2 (MFN2) accumulation. Overexpression of LRRK2 in human PTC cell lines promoted LRRK2-MKK4/JNK-dependent phosphorylation of MFN2Ser27 and subsequently ubiquitination-mediated MFN2 degradation, which in turn exaggerated mitochondrial damage upon ischemia/reperfusion (I/R) mimicry treatment. Lrrk2 deficiency also alleviated AKI-to-chronic kidney disease (CKD) transition with less fibrosis. In vivo pretreatment of LRRK2 inhibitors attenuated the severity of AKI as well as CKD, potentiating LRRK2 as a novel target to alleviate AKI and fibrosis.

Nephron sparing surgery for a patient with a complicated solitary functioning kidney and a giant pT3 renal cell carcinoma: A case report.

A solitary functioning kidney (SFK) with renal cell carcinoma (RCC) is an imperative indication for nephron-sparing surgery (NSS). Nevertheless, a giant pT3 RCC mass (maximum diameter >20 cm) on the functioning side of a patient with SFK is extremely rare. However, whether NSS is more beneficial than radical nephrectomy (RN) in such patients is controversial. Here, we present the case of a 71-year-old female patient with a 20 cm*16 cm RCC mass in the SFK, who initially presented with hematuria and acute urinary tract obstructive anuria caused by renal calculi. The patient underwent NSS treatment after our evaluation, and the 26-month follow-up revealed that her renal function recovered to the state before the tumor formation. In addition, no relapse or metastasis was detected.

Peripheral tuberculin purified protein derivative specific T cell immunoreactivity dynamics in non-muscle invasive bladder cancer patients receiving bacillus Calmette-Guerin instillation treatment.

Intravesical bacillus Calmette-Guerin (BCG) instillation is recommended as an adjuvant therapy for intermediate-risk and high-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBt) with nearly 70% reoccurrence. In the present study, we investigated the dynamics of peripheral purified protein derivative (PPD)-specific immune responses along the treatment. Intravesical BCG instillation caused a significant increase in peripheral PPD-specific IFN-γ release of NMIBC patients, when compared to those receiving chemo-drug instillation. Through a follow-up study, we detected rapid increase in PPD-specific IFN-γ, IL-2, and IL-17A producing CD4+ and CD8+ T cells in the induction phase. Interestingly, the frequencies of PPD-specific IFN-γ and IL-2 producing CD4+ and CD8+ T cells decreased dramatically after induction treatment and were restored after BCG re-instillation, whereas IL-17A-producing T cells remained at the maintenance phase. However, we only observed that the percentages of peripheral CD8+ T cells were significantly higher in BCG responder patients than those in BCG refractory patients at the baseline with the potential of predicting the recurrence. A more dramatic increase in PPD-specific IFN-γ and IL-2 producing CD4+ and CD8+ T cells after one and two dose BCG instillations was observed in refractory NMIBC patients. Therefore, regional BCG instillation induced transient peripheral PPD-specific T cell responses, which could be restored through repetitive BCG instillation. Higher proportions of peripheral CD8+ T cells at baseline were associated with better responses to BCG instillation for the prevention of recurrence of bladder cancer.

Development and validation of a novel immunotype for prediction of overall survival in patients with clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor. The purpose of the present study was to establish a novel immunotype for different immune infiltration and overall survival (OS) of patients with ccRCC. Methods: Based on the Cancer Genome Atlas Project (TCGA) database (discovery set), a novel immunotype was established using ssGSEA methods. The databases of Fudan University Shanghai Cancer Center (FUSCC) and Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine (XHH) served as an external validation set. GSEA was carried out to identify the immunotype associated signal transduction pathways. Results: A total of 652 ccRCC patients were included in our study. We constructed a novel immunotype of ccRCC to classify patients into three groups: high-immunity, moderate-immunity, and low-immunity. The high-immunity and moderate-immunity groups had higher ImmuneScores, ESTIMATEScores, StromalScores, and lower tumor purity than that of the low-immunity group in both sets. Additionally, the patients from the high-immunity and moderate-immunity groups had longer survival than patients from low-immunity group in both discovery set and validation set (HR = 2.54, 95% CI: 1.56-4.13, p < 0.01; HR = 2.75, 95% CI: 1.24-6.11, p = 0.01). Conclusion: In summary, we defined a novel immunotype of ccRCC. The immune types could be used as a clinical predictive tool to identify ccRCC patients with different survival. In addition, the immune-related biological signaling pathway also brought new insights on the mechanism of ccRCC.

Perioperative anemia predicts kidney injury after partial nephrectomy.

PURPOSE: Partial nephrectomy (PN) induced kidney injury is still a challenging clinical matter that has not been completely conquered. This study aimed to explore the influences of perioperative anemia on renal function after PN. MATERIALS AND METHODS: A total of 114 patients undergoing PN were retrospectively studied. Serum creatinine was tested preoperatively and 24 hours and 3 days after PN to evaluate the occurrence of acute kidney injury (AKI). Perioperative anemia was evaluated on the basis of the hemoglobin (Hb) value at 24 hours and 3 days postoperation. Patients were then followed up for the development of chronic kidney disease (CKD). Associations between perioperative anemia and postoperative AKI and CKD were determined. RESULTS: The cumulative incidence of perioperative anemia was 33.33% in the study. A total of 32.46% of patients suffered from postoperative AKI, and 16.67% of patients progressed to CKD. The incidences of AKI and CKD in perioperative anemia patients were dramatically exceeded in those without anemia. Further statistical analyses indicated that perioperative anemia was a relevant factor for postoperative kidney injury, presenting the highest odds ratio of 31.272 for postoperative AKI and 17.179 for postoperative CKD. Receiver operating characteristic curve analysis showed that ΔHb=(preoperative Hb)-(postoperative Hb nadir) was a meaningful predictor of postoperative kidney injury, with an area under the curve of 0.784 for predicting postoperative AKI and 0.805 for postoperative CKD. CONCLUSIONS: Perioperative anemia can predict kidney injury after PN, and ΔHb shows a meaningful predictive value for postoperative AKI and CKD.

Tumor-associated macrophages promote migration and invasion via modulating IL-6/STAT3 signaling in renal cell carcinoma.

Tumor-associated macrophages (TAMs) promote tumor cell growth and metastasis in various human cancers. However, the role of TAMs in renal cell carcinoma (RCC) is rarely investigated. Herein, we observed that the infiltration of TAMs was obviously elevated in RCC tumor tissues, high infiltration of TAMs was closely associated with tumor progression and poor prognosis in RCC patients. In vitro assays further indicated that the conditioned medium of TAMs (TAMs CM) facilitated migration, invasion, and epithelial-mesenchymal transition (EMT) in RCC cells. Moreover, we found that IL-6 was involved in the functions of TAMs in RCC; IL-6 neutralizing antibody (IL-6NA) partly abolished the effect of TAMs on RCC cells. In addition, we demonstrated that TAMs might exert their roles by activating STAT3 signaling in RCC, and IL-6 was responsible for TAMs-induced STAT3 signaling activation. In conclusion, our results revealed that high infiltration of TAMs may promote RCC cells migration, invasion, and EMT via modulating IL-6/STAT3 signaling, further suggesting a potential of novel treatment strategies targeting TAMs or IL-6 for metastatic RCC.

Urine Macrophages Polarization Predicts Renal Function Recovery after Nephron-Sparing Surgery in Patients with Renal Cell Carcinoma.

INTRODUCTION: This study was conducted to investigate the underlying associations between urine macrophages polarization and renal function recovery after nephron-sparing surgery (NSS) in patients with renal cell carcinoma (RCC) and to explore the potential application values of urine macrophages polarization in predicting the severity of renal ischemia/reperfusion injury (RIRI). METHODS: Sixty-two patients with unilateral RCC who underwent NSS in our departments were prospectively recorded and followed up for long-term renal function to assess the onset of acute kidney injury (AKI) and chronic kidney disease (CKD). Urine samples of patients were collected 72 h after surgery for analyzing pro-inflammatory (classically activated/M1) and pro-reparative (alternatively activated/M2) macrophages polarization by flow cytometry. The detailed correlations between urine macrophages polarization and renal function recovery after NSS were explored by statistical analyses. RESULTS: The cumulative incidence of postoperative AKI was 27.4% (17/62), and 47.0% (8/17) of those eventually developed to CKD during the follow-up. The mean urine M1/M2 ratio was 10.54 ± 8.13 in the AKI group and 3.93 ± 3.10 in the non-AKI group, presenting a significant statistical difference (p < 0.0001). Meanwhile, the urine M1/M2 ratio presented amazing potential in predicting postoperative CKD as well, with a mean ratio of 12.54 ± 9.41 in the CKD group and 4.28 ± 3.21 in the non-CKD group (p < 0.0001). Though univariate analysis implied that urine M1/M2 ratio was a relevant factor of both postoperative AKI and CKD in NSS surgical patients, multivariate analysis did not show satisfying predicting potential in postoperative CKD, mainly due to the very limited candidates enrolled in this study. CONCLUSION: Urine macrophages polarization could predict renal function recovery after NSS in patients with RCC. The urine M1/M2 ratio might a potential biomarker of RIRI but needs to be further verified in clinical settings.

Ischemic Preconditioning Alleviates Mouse Renal Ischemia/Reperfusion Injury by Enhancing Autophagy Activity of Proximal Tubular Cells.

Objectives: Ischemia/reperfusion injury (IRI) is one of the most vital pathogenesis leading to kidney injury but lacks effective prevention and treatment strategies. This study was conducted to investigate the influences of ischemic preconditioning (IPC) on the pathological process of mouse renal IRI (RIRI) and to figure out the role of autophagy of proximal tubular cells (PTCs) in this process. Methods: C57BL/6J mice were randomized to three groups, i.e., sham-operated group, ischemia/reperfusion (I/R) group, and IPC + I/R group. Meanwhile, 3-methyladenine, an autophagy inhibitor, was administered when further verification was needed. Histological and functional severity of kidney injury, the autophagy and apoptosis activity of PTCs, as well as the characterization of the immune cell infiltration landscape in kidney tissues were investigated. Furthermore, HK-2 cells and primary cultured PTC were cultured to set up the hypoxic preconditioning and hypoxia/reoxygenation model for in vitro simulation and verification, and a microarray dataset derived from the Gene Expression Omnibus database was analyzed to explore the transcriptome profiles after IPC. Results: IPC could significantly attenuate I/R-induced kidney injury functionally and histologically both in the acute and recovery phase of RIRI by enhancing the autophagy activity of PTCs. Cell autophagy could regulate the release of monocyte chemoattractant protein-1, and sequentially decrease macrophages infiltration in kidney tissues in the acute phase of RIRI, thus mediating the reno-protective effect. Conclusions: IPC could attenuate mouse RIRI-induced kidney injury. IPC-mediated activation of autophagy of PTCs plays a vital role in affording protection in RIRI-induced kidney injury.

18F-DCFPyL PET/CT in Newly Diagnosed Prostate Cancer: Diagnostic Value of Intraprostatic PSMA Uptake in Risk Classification of Prostate Cancer.

PURPOSE: 18F-DCFPyL prostate-specific membrane antigen (PSMA) PET/CT is commonly applied to locate lesions of prostate cancer (PCa), but its diagnostic function of quantitative parameters is ignored. Our study evaluates the parameters of intraprostatic PSMA uptake in patients newly diagnosed with PCa and explores their predictive value in risk classification, which is similar to D'Amico criteria. MATERIALS AND METHODS: We quantified the maximal standardized uptake value (SUVmax), mean SUV (SUVmean), total lesion (TL)-PSMA, prostate/muscle (P/M) ratio of the primary tumor, and PSMA-derived tumor volume (PSMA-TV) from 62 patients with histologically proven PCa. Patients newly diagnosed with PCa were allocated into risk groups (at low, intermediate, and high risk, respectively) in accordance with D'Amico criteria. Afterwards, the five parameters mentioned above among three different risk groups were compared, and their predictive values in the risk classification of PCa were explored. RESULTS: Significantly decreased levels of SUVmax, SUVmean, TL-PSMA, and P/M ratio were observed in the risk groups of low or intermediate or both, compared with the high-risk group. However, only the P/M ratio significantly elevated in patients with intermediate risk [mean ± SD (median): 46.58 ± 9.74 (45.27), P = 0.042] or high risk [98.95 ± 38.83 (97.52), P < 0.001], compared with low-risk patients [12.33 ± 5.93 (9.81)]. When P/M ratio was used to distinguish between low-risk and intermediate-risk patients, its c-statistics was 0.660. On the other hand, when distinguishing between intermediate-risk and high-risk groups, the c-statistics of P/M ratio was 0.667. Finally, when P/M ratio was used to distinguish between low-risk and high-risk patients, the c-statistics was 0.969. P/M ratio had a positive correlation with prostate-specific antigen in all enrolled PCa patients. CONCLUSION: The quantitative parameters of 18F-DCFPyL PET/CT, including SUVmax, SUVmean, and P/M ratio, might assist in distinguishing low-risk or intermediate-risk groups from the high-risk group. Of these parameters, P/M ratio appears to be the better promising parameter for risk classification of prostate cancer than SUVmax.

The combination therapy of Everolimus and anti-PD-1 improves the antitumor effect by regulating CD8+ T cells in bladder cancer.

This study aimed to investigate the efficacy of Everolimus (EVE) in combination with immune checkpoint inhibitors (ICIs) in bladder cancer treatment and the underlying mechanisms. In vitro, MB49 cells were exposed to gradient concentrations (0 nM-100 nM) of EVE for 48 h, to investigate the cell viability and cell proliferative potential. In vivo, we applied a subcutaneous tumor mouse model of bladder cancer and the mice were treated with EVE monotherapy (different doses) or in combination with anti-programmed cell death protein 1 (PD-1) agents to study the impacts on tumor growth and explore the immune mechanism. The influences of treatments on peripheral immune profiles and tumor immune microenvironment were also discussed. EVE could inhibit the growth of MB49 cells in vitro. Though high-dose EVE monotherapy could induce tumor regression in vivo, it also contributed to immunosuppression. High-dose EVE inhibited the expression of PD-L1 by inhibiting Th1 cytokine secretion, while combined therapy with PD-1 inhibitors showed no extra profit. Low-dose EVE in combination with PD-1 inhibitors could effectively suppress tumor growth by increasing periphery CD8+ T cell frequency and GZMB+ CD8+ T cell frequency in the tumor microenvironment. High-dose EVE monotherapy induced tumor regression, but with immunosuppression to some content. Combination therapy with low-dose EVE and PD-1 inhibitor could effectively inhibit the growth of bladder tumors by enhancing the antitumor immunity of CD8+ T cells in both periphery and tumor microenvironment.

Novel Ferroptosis-Related Multigene Prognostic Models for Patients with Bladder Cancer.

OBJECTIVE: Bladder cancer contributes to a serious disease burden in clinical settings. The characteristics and prognosis of patients with muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC) are distinctly different. The study aims to figure out the respective role of ferroptosis in MIBC and NMIBC and to construct ferroptosis-related gene signatures that could predict patients' prognoses. METHODS: A total of 608 MIBC and 414 NMIBC RNA-seq transcriptome data with intact clinical and follow-up information were downloaded from The Cancer Genome Atlas (TCGA), ArrayExpress, and Gene expression omnibus (GEO) database. Ferroptosis-related multigene prognostic models were constructed and externally validated, respectively, in MIBC and NMIBC. Further functional enrichment analyses were also performed to explicate the underlying mechanisms and the differences between the two bladder cancer subtypes. RESULTS: In MIBC, a 7-gene signature for prognostic prediction was constructed. Patients were then divided into high-risk and low-risk groups according to the risk scores calculated by the 7-gene prognostic model. Patients in the high-risk group presented an impaired OS when compared with patients in the low-risk group both in the training cohort and validation cohort. Further functional analyses revealed distinctly different immune statuses between the two risk-stratification groups, speculating that exhausted immune cell function was a cause of the worst OS in the high-risk group. In NMIBC, 6 ferroptosis-related genes were identified that were significantly correlated with recurrence-free survival (RFS). Similarly, a 6-gene prognostic model was constructed and verified as an independent prognostic predictor for RFS. Functional analyses revealed significant differences in the expressions of nuclear division genes between the high-risk group and low-risk group. CONCLUSION: Two novel ferroptosis-related multigene prognostic models for, respectively, predicting OS in MIBC and RFS in NMIBC were identified in this study, which indicated ferroptosis played vital roles in the oncogenesis and development of MIBC and NMIBC.

Partial inhibition of activin receptor-like kinase 4 alleviates bladder fibrosis caused by bladder outlet obstruction.

The bladder undergoes profound structural alterations after bladder outlet obstruction (BOO), characterized by hypertrophy of the bladder wall and accumulation of extracellular matrix (ECM). Transforming growth factor-ß (TGF-ß) has been found to promote fibrosis of the bladder induced by partial bladder outlet obstruction (pBOO). Activin receptor-like kinase 4 (ALK4) is a downstream receptor of the TGF-ß superfamily. However, the role of the ALK4-Smad2/3 pathway in the pathogenesis of bladder fibrosis caused by pBOO remains unknown. This study focused on learning the role of ALK4 in the process of bladder fibrosis caused by pBOO. The pBOO mice models showed that ALK4 expression was found to upregulate in the wild-type bladder 6 weeks after pBOO compared to control group. Then, mice with heterozygous knockout of the ALK4 gene (ALK4+/-) were generated. Histological analysis and Western blot (WB) results showed significant suppression of collagen expression in the bladders of ALK4+/- mice after pBOO compared with WT mice. WB also showed that ALK4+/- mice demonstrated significant suppression of phosphorylated Smad2/3 (p-Smad2/3) expression in the bladder 6 weeks after pBOO but not of phosphorylated extracellular signal-regulated kinase, c-Jun N-terminal kinase or protein 38 (p-ERK, p-JNK, p-P38) expression. This effect might have occurred through partial inactivation of the Smad2/3 signaling pathway. In vitro, ALK4 overexpression promoted collagen production in cultured BSMCs and activated the Smad2/3 signaling pathway. Taken together, our results demonstrated that ALK4 insufficiency alleviated bladder fibrosis in a mouse model of pBOO partly by suppressing Smad2/3 activity.

Correlation of prostatic morphological parameters and clinical progression in aging Chinese men with benign prostatic hyperplasia: Results from a cross-sectional study.

OBJECTIVES: Our study aimed to investigate the correlation of prostatic morphological parameters and benign prostatic hyperplasia (BPH) clinical progression in aging Chinese men. METHODS: In this retrospective study, a total of 1038 patients were reviewed. Prostatic morphology was measured by transrectal ultrasound (TRUS). Detailed medical history of all candidates was recorded and analyzed after being classified by specific prostatic measurements. Univariate and multivariate logistic regression analyses were used to estimate the correlation between variables. RESULTS: The cumulative incidence of BPH clinical progression was 63.68% (661/1038) in the study population. Prostate volume (PV), transitional zone volume (TZV), transitional zone index (TZI), and intravesical prostatic protrusion (IPP) were all positively associated with BPH progression (all p < .001). Patients with a PV > 60 ml, TZV > 15 ml, TZI > 0.5, or IPP > 5 mm had a significantly higher possibility of overall BPH clinical progression (adjusted odds ratio (OR): 2.485, 1.678, 1.886, and 1.924, respectively; 95% confidence interval (CI): 1.559-3.960, 1.131-2.489, 1.379-2.579, and 1.357-2.728, correspondingly). CONCLUSION: Prostatic morphological parameters are significantly associated with BPH clinical progression. Patients with larger prostatic morphological parameters are more easily prone to clinical progress. As a result, reasonable managements should be timely considered for those patients before clinical progression occurs.

Serum interleukin 6 and acute urinary retention in elderly men with benign prostatic hyperplasia in China: a cross-sectional study.

BACKGROUND: While acute urinary retention (AUR) is a severe complication of benign prostatic hyperplasia (BPH), it can also indicate the progression of this common disease in aging men. This study aimed at exploring the possible relationship between serum interleukin 6 (sIL-6) and AUR in BPH patients. METHODS: A cross-sectional study was conducted based on 256 elderly men with BPH in China. The association between the sIL-6 level and the occurrence of AUR was evaluated by univariate and multivariable logistic regressions. The receiver operating characteristic (ROC) curve was utilized to determine the discriminant validity of the sIL-6 level and the optimal cut-off value. RESULTS: The concentration of sIL-6 was significantly elevated in the AUR group (P<0.001). A positive correlation was observed between the sIL-6 level and AUR in BPH patients [odds ratio (OR) =1.365, 95% confidence interval (CI): 1.174-1.586, P<0.001]. Based on the ROC curve analysis for sIL-6, the optimal cut-off point of 4.475 pg/mL was set to identify the occurrence of AUR in these patients [area under the curve (AUC) =0.7596, 95% CI: 0.6976-0.8216, P<0.001]. A high sIL-6 level (≥4.475 pg/mL) had a significantly stronger correlation with AUR (OR =9.666, 95% CI: 4.347-21.491, P<0.001). CONCLUSIONS: There was a positive correlation between the sIL-6 level and the occurrence of AUR in elderly Chinese patients with BPH. This study provides potential strategies for the screening of BPH individuals with a possible risk of AUR, which may contribute to the early implementation of effective interventions to improve the quality of life and prognosis. Long-term prospective studies are still required to further illustrate the causal relationship.

Preoperative hydronephrosis predicts adverse pathological features and postoperative survival in patients with high-grade upper tract urothelial carcinoma

ABSTRACT Purpose: Epidemiological studies reported conflicting results about preoperative hydronephrosis in upper tract urothelial carcinoma (UTUC). This study aimed to investigate the association between preoperative hydronephrosis and pathologic features and oncologic outcomes in patients with UTUC treated by radical nephroureterectomy (RNU). Materials and Methods: This was a retrospective, single-center cohort study of 377 patients treated by RNU without perioperative chemotherapy between January 2001 and December 2014. Logistic regression, Cox regression, and survival analyses were performed. Results: Among the 226 patients with high-grade UTUC, 132 (58%) had preoperative hydronephrosis. Multivariable logistic regression revealed that hydronephrosis was independently associated with advanced pT stage (P=0.017) and lymph node or lymphovascular invasion (P=0.002). Median follow-up was 36 months (interquartile range: 20-48 months). The 3- and 5-year overall survival (OS) rates in patients with hydronephrosis were significantly lower than in those without hydronephrosis (both P <0.001). The 3- and 5-year cancer-specific survival (CSS) rates in patients with hydronephrosis were significantly lower than in those without hydronephrosis (both P=0.001). Hydronephrosis was independently associated with OS and CSS (P=0.001 and P=0.004, respectively). Among the 151 patients with low-grade UTUC, hydronephrosis was not associated with pathologic features and postoperative survival. Conclusions: Preoperative hydronephrosis was significantly associated with adverse pathologic features and postoperative survival in patients with high-grade UTUC.

Quantitative super-resolution microscopy reveals promoting mitochondrial interconnectivity protects against AKI.

Background: The root of many kidney diseases in humans can be traced to alterations or damage to subcellular organelles. Mitochondrial fragmentation, endoplasmic reticulum (ER) stress, and lysosomal inhibition, among others, ultimately contribute to kidney injury and are the target of therapeutics in development. Although recent technological advancements allow for the understanding of disease states at the cellular level, investigating changes in subcellular organelles from kidney tissue remains challenging. Methods: Using structured illumination microscopy, we imaged mitochondria and other organelles from paraffin sections of mouse tissue and human kidney biopsy specimens. The resulting images were 3D rendered to quantify mitochondrial size, content, and morphology. Results were compared with those from transmission electron microscopy and segmentation. Results: Super-resolution imaging reveals kidney tubular epithelial cell mitochondria in rodent and human kidney tissue form large, interconnected networks under basal conditions, which are fragmented with injury. This approach can be expanded to other organelles and cellular structures including autophagosomes, ER, brush border, and cell morphology. We find that, during unilateral ischemia, mitochondrial fragmentation occurs in most tubule cells, and they remain fragmented for >96 hours. Promoting mitochondrial fusion with the fusion promotor M1 preserves mitochondrial morphology and interconnectivity and protects against cisplatin-induced kidney injury. Conclusions: We provide, for the first time, a nonbiased, semiautomated approach for quantification of the 3D morphology of mitochondria in kidney tissue. Maintaining mitochondrial interconnectivity and morphology protects against kidney injury. Super-resolution imaging has the potential to both drive discovery of novel pathobiologic mechanisms in kidney tissue and broaden the diagnoses that can be made on human biopsy specimens.

Preoperative hydronephrosis predicts adverse pathological features and postoperative survival in patients with high-grade upper tract urothelial carcinoma.

PURPOSE: Epidemiological studies reported conflicting results about preoperative hydronephrosis in upper tract urothelial carcinoma (UTUC). This study aimed to investigate the association between preoperative hydronephrosis and pathologic features and oncologic outcomes in patients with UTUC treated by radical nephroureterectomy (RNU). MATERIALS AND METHODS: This was a retrospective, single-center cohort study of 377 patients treated by RNU without perioperative chemotherapy between January 2001 and December 2014. Logistic regression, Cox regression, and survival analyses were performed. RESULTS: Among the 226 patients with high-grade UTUC, 132 (58%) had preoperative hydronephrosis. Multivariable logistic regression revealed that hydronephrosis was independently associated with advanced pT stage (P=0.017) and lymph node or lymphovascular invasion (P=0.002). Median follow-up was 36 months (interquartile range: 20-48 months). The 3- and 5-year overall survival (OS) rates in patients with hydronephrosis were significantly lower than in those without hydronephrosis (both P <0.001). The 3- and 5-year cancer-specific survival (CSS) rates in patients with hydronephrosis were significantly lower than in those without hydronephrosis (both P=0.001). Hydronephrosis was independently associated with OS and CSS (P=0.001 and P=0.004, respectively). Among the 151 patients with low-grade UTUC, hydronephrosis was not associated with pathologic features and postoperative survival. CONCLUSIONS: Preoperative hydronephrosis was significantly associated with adverse pathologic features and postoperative survival in patients with high-grade UTUC.