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Chronic kidney disease is characterized by interstitial fibrosis and proliferation of scar-secreting myofibroblasts, ultimately leading to end-stage renal disease. The hedgehog (Hh) pathway transcriptional effectors GLI1 and GLI2 are expressed in myofibroblast progenitors; however, the role of these effectors during fibrogenesis is poorly understood. Here, we demonstrated that GLI2, but not GLI1, drives myofibroblast cell-cycle progression in cultured mesenchymal stem cell-like progenitors. In animals exposed to unilateral ureteral obstruction, Hh pathway suppression by expression of the GLI3 repressor in GLI1+ myofibroblast progenitors limited kidney fibrosis. Myofibroblast-specific deletion of Gli2, but not Gli1, also limited kidney fibrosis, and induction of myofibroblast-specific cell-cycle arrest mediated this inhibition. Pharmacologic targeting of this pathway with darinaparsin, an arsenical in clinical trials, reduced fibrosis through reduction of GLI2 protein levels and subsequent cell-cycle arrest in myofibroblasts. GLI2 overexpression rescued the cell-cycle effect of darinaparsin in vitro. While darinaparsin ameliorated fibrosis in WT and Gli1-KO mice, it was not effective in conditional Gli2-KO mice, supporting GLI2 as a direct darinaparsin target. The GLI inhibitor GANT61 also reduced fibrosis in mice. Finally, GLI1 and GLI2 were upregulated in the kidneys of patients with high-grade fibrosis. Together, these data indicate that GLI inhibition has potential as a therapeutic strategy to limit myofibroblast proliferation in kidney fibrosis.

IntroductionNon-muscle-invasive bladder cancer (NMIBC) is a biologically heterogeneous disease and is one of the most expensive malignancies to treat on a per patient basis. In part, this high cost is attributed to the need for long-term surveillance. We sought to perform an economic analysis of surveillance strategies to elucidate cumulative costs for the management of NMIBC.MethodsA Markov model was constructed to determine the average 5-year costs for the surveillance of patients with NMIBC. Patients were stratified into low, intermediate, and high-risk groups based on the EORTC risk calculator to determine recurrence and progression rates according to each category. The index patient was a compliant 65-year-old male. A total of four health states were utilized in the Markov model: no evidence of disease, recurrence, progression and cystectomy, and death.ResultsCumulative costs of care over a 5-year period were $52,125 for low-risk, $146,250 for intermediate-risk, and $366,143 for high-risk NMIBC. The primary driver of cost was progression to muscle-invasive disease requiring definitive therapy, contributing to 81% and 92% of overall cost for intermediate- and high-risk disease. Although low-risk tumors have a high likelihood of 5-year recurrence, the overall cost contribution of recurrence was 8%, whereas disease progression accounted for 71%.ConclusionAlthough protracted surveillance cystoscopy contributes to the expenditures associated with NMIBC, progression increases the overall cost of care across all three patient risk groups and most notably for intermediate- and high-risk disease patients.

Improving early cancer detection has the potential to substantially reduce cancer-related mortality. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP–seq) is a highly sensitive assay capable of detecting early-stage tumors. We report accurate classification of patients across all stages of renal cell carcinoma (RCC) in plasma (area under the receiver operating characteristic (AUROC) curve of 0.99) and demonstrate the validity of this assay to identify patients with RCC using urine cell-free DNA (cfDNA; AUROC of 0.86). A cell-free DNA-methylation sequencing assay accurately identifies renal cell carcinoma using plasma and urine samples.

Background Patient preferences are assumed to impact healthcare resource utilization, especially treatment options. There is limited data exploring this phenomenon. We sought to identify factors associated with patients transferring care for prostatectomy, from military to civilian facilities, and the receipt of minimally invasive radical prostatectomy (MIRP). Methods Retrospective review of 2006-2010 TRICARE data identified men diagnosed with prostate cancer (ICD-9 185) receiving open radical prostatectomy (ORP; ICD-9: 60.5) or MIRP (ICD-9 60.5 + 54.21/17.42). Patients diagnosed at military facilities but underwent surgery at civilian facilities were defined as “transferring care”. Logistic regression models identified predictors of transferring care for patients diagnosed at military facilities. A secondary analysis identified the predictors of MIRP receipt at civilian facilities. Results Of 1420 patients, 247 (17.4%) transferred care. These patients were more likely to undergo MIRP (OR = 7.83, p  < 0.01), and get diagnosed at low-volume military facilities (OR = 6.10, p  < 0.01). Our secondary analysis demonstrated that transferring care was strongly associated with undergoing MIRP (OR = 1.51, p  = 0.04). Conclusions Patient preferences induced a demand for greater utilization of MIRP and civilian facilities. Further work exploring factors driving these preferences and interventions tailoring them, based on evidence and cost considerations, is required.

Objectives The Prostate Imaging Quality (PI-QUAL) score is a new metric to evaluate the diagnostic quality of multiparametric magnetic resonance imaging (MRI) of the prostate. This study assesses the impact of an intervention, namely a prostate MRI quality training lecture, on the participant’s ability to apply PI-QUAL. Methods Sixteen participants (radiologists, urologists, physicists, and computer scientists) of varying experience in reviewing diagnostic prostate MRI all assessed the image quality of ten examinations from different vendors and machines. Then, they attended a dedicated lecture followed by a hands-on workshop on MRI quality assessment using the PI-QUAL score. Five scans assessed by the participants were evaluated in the workshop using the PI-QUAL score for teaching purposes. After the course, the same participants evaluated the image quality of a new set of ten scans applying the PI-QUAL score. Results were assessed using receiver operating characteristic analysis. The reference standard was the PI-QUAL score assessed by one of the developers of PI-QUAL. Results There was a significant improvement in average area under the curve for the evaluation of image quality from baseline (0.59 [95 % confidence intervals: 0.50–0.66]) to post-teaching (0.96 [0.92–0.98]), an improvement of 0.37 [0.21–0.41] ( p < 0.001). Conclusions A teaching course (dedicated lecture + hands-on workshop) on PI-QUAL significantly improved the application of this scoring system to assess the quality of prostate MRI examinations. Key Points • A significant improvement in the application of PI-QUAL for the assessment of prostate MR image quality was observed after an educational intervention. • Appropriate training on image quality can be delivered to those involved in the acquisition and interpretation of prostate MRI. • Further investigation will be needed to understand the impact on improving the acquisition of high-quality diagnostic prostate MR examinations.

PurposeThis study aims to analyze patient demographics, hospital characteristics, and clinical risk factors which predict penile prosthesis removal. We also examine costs of penile prosthesis removal and trends in inflatable versus non-inflatable penile prostheses implantation in the USA from 2003 to 2015.MethodsCross-sectional analysis from Premier Perspective Database was completed using data from 2003 to 2015. We compared the relative proportion of inflatable versus non-inflatable penile prostheses implanted. We separated the prosthesis removal group based on indication for removal—Group 1 (infection), Group 2 (mechanical complication), and Group 3 (all explants). All groups were compared to a control group of patients with penile implants who were never subsequently explanted. Multivariate analysis was performed to analyze patient and hospital factors which predicted removal. Cost comparison was performed between the explant groups.ResultsThere were 5085 penile prostheses implanted with a stable relative proportion of inflatable versus non-inflatable prosthesis over the 13-year study period. There were 3317 explantations. Patient factors associated with prosthesis removal were non-black race, Charlson Comorbidity Index, diabetes, and HIV status. Hospital factors associated with removal included non-teaching status, hospital region, year of removal, and annual surgeon volume. Median hospitalization costs of all explantations were $10,878. Explantations due to infection cost $11,252 versus $8602 for mechanical complications.ConclusionsThis large population-based study demonstrates a stable trend in inflatable versus non-inflatable prosthesis implantation. We also identify patient and hospital factors that predict penile prosthesis removal which has clinical utility for patient risk stratification and counseling.

Pain from renal colic is often severe and incapacitating. Many patients require emergent hospitalization and aggressive analgesia to relieve such discomfort. For many years, the optimal analgesic strategy has been sought to manage such severe pain. One of the mainstays of therapy for acute renal colic is with non-steroidal anti-inflammatory drugs (NSAIDs). This paper reviews the mechanism by which NSAIDs allow pain relief in renal colic, the evidence for their use in this condition, and the use of NSAIDs combined with other agents in renal colic.

We aim to understand how Medicaid expansion under the ACA has affected utilization of surgical services. The State Inpatient Databases were used to compare utilization of a broad array of surgical procedures among nonelderly adults (aged 19–64 years) in a multistate population that experienced ACA-related Medicaid expansion to one that did not. We performed a difference-in-differences (DID) analysis to determine the effect of Medicaid expansion on utilization of surgical services from 2012 to 2014. There were 259,061 cases identified in the Medicaid expansion population and 261,269 in the control population. In the expansion group, there was a smaller decrease in utilization - by a margin of 21.68 cases per 100,000 individuals (p < 0.001). Percent of surgical patients covered by Medicaid increased among the expansion group from 12.00% to 15.48% (DID = 3.93%; p < 0.001). Year one of Medicaid expansion under the ACA was associated with a modest but statistically significant difference in utilization of surgical services as well as an increase in percent of surgery patients covered by Medicaid. •We found a smaller decrease in surgical utilization in a population with Affordable Care Act-related Medicaid expansion compared to one without.•The divergence of trends in this study was driven by increased utilization of discretionary surgery.•We observed an increase in Medicaid coverage among patients undergoing surgery.

To investigate the temporal relationship of hospital charges relative to recorded costs for surgical episodes of care. This retrospective cohort study selected individuals who underwent any of 8 index urologic surgical procedures at 392 unique institutions from January 1, 2005, through December 31, 2015. For each surgical encounter, cost and charge data reported by hospitals were extracted and adjusted to 2016 US dollars. Trend analysis and multivariable logistic regression modeling were used to assess outcomes. The primary outcome was trend in median charge and cost. Secondary outcomes consisted of hospital characteristics associated with membership in the highest quartile of institutional charge-to-cost ratio. Cohort-level median cost per encounter trended down from $6824 in 2005 to $5586 in 2015 (P for trend<.001), and charges increased from $20,210 to $25,773 during the same period (P for trend<.001). Hospitals in the highest quartile of institutional charge-to-cost ratio were more likely to be safety net, nonteaching, urban, lower surgical volume, smaller, and located outside the Midwest (P<.001 for each characteristic). The pricing trends shown herein could indicate some success in cost-containment for surgical episodes of care, although higher hospital charges may be increasingly used to bolster reimbursement from third-party payers and to compensate for escalating costs in other areas.