The American Urological Association (AUA) provides guidance on primary prevention for nephrolithiasis; however, patient compliance is often poor. The role of healthy literacy in the primary prevention of nephrolithiasis is not well understood. Understanding kidney stone formers’ perceptions and knowledge of primary prevention is critical to evaluating their health literacy. This study aimed to assess these perceptions and explore how they relate to counseling intensity and quality of life among patients with nephrolithiasis. A cross-sectional web-based survey was administered to a random sample of adult volunteers. Disease specific information was queried for stone formers and all participants were asked a series of questions based on the AUA Metabolic Stone Management Guidelines (2016) regarding primary prevention. Receipt of dietary counseling was categorized by comprehensiveness. Patient quality of life was assessed using the Wisconsin Stone Quality of Life questionnaire (WisQOL). Multivariable linear regression was used to identify predictors of stone-specific health literacy. Of the 2482 participants, 429 (17

Introduction and Objective:Totally tubeless percutaneous nephrolithotomy (PCNL) has been demonstrated to be feasible and safe, particularly for mini-PCNL. Having an objective test to guide patient selection could improve confidence in this practice and facilitate broader adoption. The purpose of this study was to evaluate the utility of an intraoperative methylene blue test to determine candidacy for totally tubeless PCNL. Methods:Adult patients undergoing PCNL at four institutions were included in this study. Patients with prior reconstructive surgery, chronic pain, or requiring ureteral dilation were excluded. After stone clearance, 10 mL methylene blue (MB) dye was injected into the percutaneous access tract. A positive test ("pass") was defined as visualization of blue dye in the bladder catheter within two minutes of injection. In some standard PCNL cases, totally tubeless management was simulated by placement of a capped nephrostomy tube. Post-operative complications within 7 days were evaluated as the primary outcome. Results:The intraoperative MB test was performed in 91 PCNL cases: 60 mini-PCNLs (16 Fr access) and 31 standard PCNLs (24+ Fr access). Mini-PCNL cases were more likely to pass the MB test compared to standard PCNL cases (75% vs 38.7%, p = 0.001). Of the 45 mini-PCNL subjects who passed, 40 were left totally tubeless, resulting in two minor complications (urinary retention, obstructing ureteral stone fragment). In the standard PCNL cohort, 12 passed the MB test. Five were left totally tubeless and 3 simulated totally tubeless management with capped nephrostomy tubes; one subject had a transient postoperative creatinine elevation, and one required uncapping for steinstrasse. There were no other obstructive or infectious complications, and no surgical reintervention was required. Conclusions:An intraoperative methylene blue test is a simple test with high positive-predictive value to determine candidacy for totally tubeless PCNL in real time for both mini and standard PCNLs.

Randall's plaques have been long thought to be precursors for kidney stone formation, but how their presence impacts future stone recurrence is not known. The aim of this study was to determine whether patients with endoscopically visible plaques were more likely to have subsequent stone events compared to those without. The presence of Randall's plaque in adult patients was prospectively assessed during endoscopic cases as part of the Registry for Stones of the Kidney and Ureter (ReSKU). In each case, the visible Randall's plaque burden was scored by the attending surgeon as "none," "minimal," or "many." Data regarding stone composition, 24-hour urine tests, and subsequent stone events on follow up were collected. Stone events were defined as patient-reported stone passage or any primary operation for kidney stones; second-look or staged operations were not counted as separate stone events. We identified 673 subjects with a Randall's plaque assessment, of which 78 had "none," 306 had "minimal," and 289 had "many." Despite having no significant differences in initial stone burden, subjects with visible Randall's plaque ("minimal" or "many") had a higher relative risk of stone recurrences after surgery compared to those without (RRR 1.711 (1.121-2.611), p = 0.01). Interestingly, no significant differences in 24-hour urine analytes were observed. Subjects with visible plaque were more likely to have calcium-based stones (84% vs. 58%, p < 0.001). The presence of endoscopically visible Randall's plaque is associated with an increased risk of stone recurrence independent of urine composition.

Benign prostatic hyperplasia (BPH) is characterized by excessive cell proliferation and inflammation and affects most aging men. The development of new therapies for BPH requires a deeper understanding of the underlying pathophysiology and cellular components of BPH. Single-cell RNA-sequencing was performed on prostate tissue from 15 patients undergoing holmium laser enucleation of the prostate for treatment of BPH. Clustering and differential expression analysis on aligned single-cell RNA-seq data was performed to annotate all cell types. 16,234 cells were analyzed and specific stromal, epithelial, and immune subgroups were found to be strongly associated with inflammation. A rare luminal subgroup was identified and pseudotime analysis indicated this luminal subgroup might give rise to other luminal cells. Using a gene set derived from epithelial stem cells, we found that this luminal subgroup had a significantly higher stem cell signature score than all other epithelial subgroups, suggesting this subgroup is a luminal precursor state. Ligand-receptor interactions between stromal, epithelial, and immune cells were explored with CellPhoneDB. Significant interactions involving MIF, a pro-inflammatory cytokine that promotes epithelial cell growth and inflammatory response in the prostate, were identified between the progenitor-like luminal subgroup and both fibroblasts and macrophages. Our single-cell profiling of BPH provides a roadmap for investigating inflammation-linked cell subgroups and highlights a progenitor-like luminal subgroup interacting with other cell groups via MIF that may contribute to the inflammation and cell proliferation phenotype associated with BPH.

Histologic variant (HV) subtypes of bladder cancer are clinically aggressive tumors that are more resistant to standard therapy compared to conventional urothelial carcinoma (UC). Little is known about the transcriptional programs that account for their biological differences. Here we show using single cell analysis that HVs harbor a tumor cell state characterized by expression of MUC16 (CA125), MUC4 , and KRT24 . This cell state is enriched in metastases, predicted to be highly resistant to chemotherapy, and linked with poor survival. We also find enriched expression of TM4SF1 , a transmembrane protein, in HV tumor cells. Chimeric antigen receptor (CAR) T cells engineered against TM4SF1 protein demonstrated in vitro and in vivo activity against bladder cancer cell lines in a TM4SF1 expression-dependent manner, highlighting its potential as a therapeutic target.

BACKGROUND:Ex-vivo normothermic perfusion (EVNP) with a blood based perfusate has the potential to both assess viability of and repair high-risk organs prior to transplantation. The optimal perfusate is yet to be established. METHODS:We assessed hemodynamic, functional, and metabolic changes of eight paired high-risk human kidneys perfused with either a leukocyte-depleted packed red blood cell (PRBC) or a whole blood (WB) perfusate during a three-hour EVNP. RESULTS:After a mean cold ischemia time (CIT) of 54 hours, all kidneys showed high renal blood flow (RBF) through perfusion. Renal resistance (RR) increased for both groups during the first hour and then decreased to similar terminal values. The kidneys perfused with PRBC had 55 ml/min greater RBF (95% CI of 21 to 89; P=0.004) and higher total urine output (UO) (145 vs 25 ml, P= 0.002) compared to the WB group. Urinary acute kidney biomarkers of NGAL and KIM-1 were also significantly lower (mean differences of 281 and 2.1 ng/ml respectively; P<0.01) in the PRBC perfused kidneys. Compared to PRBC, within group tissue metabolic profiling revealed a similar (23% vs 18%) but a more pronounced alteration involving (branched chain) amino acid and mitochondrial energy metabolism in the WB group. Similarly, lipid profile temporal changes showed WB group were highlighted by elevation of plasma membrane and structure lipids including glycerolipids, sphingolipids, and steroids. The PRBC group had minimal temporal tissue lipid profile changes. CONCLUSIONS:Compared to WB, PRBC perfusion is superior in mitigating post-ischemia damage and facilitating function and metabolic recovery of high-risk kidneys subjected to long CITs during a three-hour EVNP.

Financial toxicity (FT), first reported in oncologic patients and generally defined as harm to patients caused by the cost of treatment, is less well described in non-malignant urology. In chronic conditions related to lower urinary tract symptoms (LUTS), such as BPH, treatment costs may result in a significant substantial burden. The goal of this study was to characterize the association between FT and LUTS. A cross-sectional web-based survey was administered to a random sample of adult men through a national registry of volunteers (ResearchMatch). Disease-specific information, validated symptom scores, and an 11-item measure of LUTS-related financial toxicity were used to characterize participants. Multivariable logistic regression was performed to identify predictors of financial toxicity. A total of 294 respondents with a self-reported history of BPH-associated LUTS were included, 41

On-treatment 24-h urine testing rates are low outside of tertiary care centers. A common criticism is the paucity of evidence demonstrating the optimization of urinary parameters correlates with reduced stone recurrence. Using standard and novel analytic approaches, we sought to evaluate whether improvements in 24-h urine parameters associated with decreased symptomatic stone recurrence. Kidney stone patients who underwent multiple 24-h urine tests and had an initial parameter abnormality were identified from a prospective database. A novel 24-h urine severity score was calculated at both the initial and subsequent tests and used to stratify patients. Negative binomial regression was used to evaluate the impact of analyte changes on stone recurrence. Two hundred patients met inclusion criteria. Low voided volume, hypercalciuria, hyperoxaluria, hypocitraturia and low pH were identified in 56%, 28%, 40%, 49% and 35% respectively. Patients with hypercalciuria and hypocitraturia who consistently normalized these values showed decreased recurrence (p < 0.001). Increasing initial 24-h urine severity scores associated with increased stone recurrence (0.09, 0.18 and 0.31 stone events per year for the lowest, 25-75th and highest quartiles, p < 0.001). On multivariable analysis, severity score improvement or stabilization was associated with reduced risk of recurrence across all quartiles (RRR 0.319 to 0.591, all p < 0.001). Consistent control of 24-h urine parameters was associated with decreased stone recurrence. Not only did novel 24-h urine composite severity scores based on initial 24-h urines independently predict stone recurrence, improvements in this score over time also predicted decreased recurrence.

OBJECTIVES:To identify associations between 24-h urine abnormalities and clinical risk factors for recurrent stone formers. PATIENTS AND METHODS:The Registry for Stones of the Kidney and Ureter was queried for all patients who underwent 24-h urine studies. Patients were categorised by the number of clinical risk factors for recurrent stone disease. Stone recurrence was calculated by stone events per person-year. We utilised a novel method to calculate an overall severity score for 24-h urine parameters. The stone recurrence and 24-h urinary analyte values were then compared using Student's t-tests, chi-square analysis and negative binomial regression. RESULTS:A total of 614 stone patients met our inclusion criteria and were categorised by the number of clinical stone risk factors. On adjusted and unadjusted analysis, an escalating number of clinical risk factors predicted increased stone recurrence risk. However, there were no differences in mean 24-h urine analyte values amongst these groups aside from higher urinary calcium. However, after calculation of a 24-h urine severity score there was a significantly higher mean severity as the number of clinical risk factors increased. This severity score also independently predicted stone recurrence on adjusted negative binomial regression. CONCLUSIONS:Utilising a novel 24-h urine scoring system, we showed that higher-risk stone patients have more severe 24-h urine characteristics, which was not apparent using conventional analysis. Both the severity score and clinical characteristics independently identified those at risk of stone recurrence.