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Lars Lund,1,2 Harry Nisen,3 Petrus Järvinen,3 Magnus Fovaeus,4 Eirikur Gudmundson,5 Bjarne Kromann-Andersen,6 Börje Ljungberg,7 Frode Nilsen,8 Pernilla Sundqvist,9 Peter E Clark,10 Christian Beisland11,12 1Department of Urology, Odense University Hospital, 2Clinical Institute, Southern University of Denmark, Odense, Denmark; 3Department of Urology, Helsinki University Hospital, Helsinki, Finland; 4Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden; 5Department of Urology, Landspitali University Hospital, Reykjavik, Iceland; 6Department of Urology, Herlev University Hospital, Copenhagen, Denmark; 7Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden; 8Department of Urology, Akershus University Hospital, Lörenskog, Norway; 9Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 10Department of Urology, Atrium Health, Charlotte, NC, USA; 11Department of Urology, Haukeland University Hospital, 12Department of Clinical Medicine, University of Bergen, Bergen, Norway Purpose: To examine the variation in venous thromboembolism prophylactic treatment (VTEP) among renal cancer patients undergoing surgery.Materials and methods: An Internet-based questionnaire on renal tumor management before and after surgery was mailed to all Nordic departments of urology. The questions focused on the use of VTEP and were subdivided into different surgical modalities.Results: Questionnaires were mailed to 91 institutions (response rate 53%). None of the centers used VTEP before surgery, unless the patient had a vena caval tumor thrombus. Overall, the VTEP utilized during hospitalization for patients undergoing renal surgery included early mobilization (45%), compression stockings (52%) and low-molecular-weight heparin (89%). In patients undergoing open radical Nx, 80% of institutions used VTEP during their hospitalization (23% compression stockings and 94% low-molecular-weight heparin). After leaving the hospital, the proportion and type of VTEP received varied considerably across institutions. The most common interval, used in 60% of the institutions, was for a period of 4 weeks. The restriction to the Nordic countries was a limitation and, therefore, may not reflect the practice patterns elsewhere. It is a survey study and, therefore, cannot measure the behaviors of those institutions that did not participate.Conclusion: We found variation in the type and duration of VTEP use for each type of local intervention for renal cancer. These widely disparate variations in care strongly argue for the establishment of national and international guidelines regarding VTEP in renal surgery. Keywords: venous-thrombotic-embolic prophylaxis kidney cancer, surgery, nephrectomy, mortality, complication, minimally invasive methods, thrombosis prophylaxis

Over the last two decades, in an effort to engage youth in polar science, the Students On Ice (SOI; https://studentsonice.com/) project has become a platform for youth to partake in scientific expeditions around the globe. Among the various activities offered, youth are able to join cruises in the North Atlantic or Arctic, and drop sealed glass bottles into the ocean. Of the thousands that have been deployed, 5% of bottles have been recovered and reported back to SOI with details on when and where they were found. Here, we compare the observational bottle data with virtual particle trajectories from a high resolution regional ocean model. Although modelling results indicate a higher likelihood of bottles reaching the shores of the western Atlantic, the majority of recovered bottles were found on the eastern side of the Atlantic. We attribute this disparity to differences in population density in Canada and Europe, biasing the recovery rates. Despite this bias, we find that changes in recovery locations over time are consistent with changes in the main ocean currents associated with the contraction and expansion of the North Atlantic Subpolar Gyre, as simulated in our ocean model. In 2007, a large number of bottles were found in Norway, coinciding with a contracted North Atlantic Subpolar Gyre during 2004-2008. While between 2012-2016, the majority of bottles were recovered on the British Isles, during a time of gyre expansion. These results underline the importance of large scale oceanic cycles for tracking marine debris and pollution, and show how even simple data collection methods, such as drift bottles, can provide clues to the changes in the large scale ocean circulation.

Abstract Numerical model studies have shown that the lateral buoyancy transports from eddies restratify the convection region in the Labrador Sea. However, restratification by vertical motion during and after convection has been underestimated. Here we use a model with 1°/60° resolution which can resolve mesoscale and submesoscale motions, and find that negative feedback that includes the generation of vertical eddy buoyancy flux (VEBF) committed to restratify the mixed layer. In winter, VEBF compensates for nearly half of the surface buoyancy loss and is as important as the lateral buoyancy fluxes in the eddy‐rich region, which results in restraining the development of deep convection. During this period, the surge of VEBF was due to seasonally enhanced frontogenesis, mixed layer instability and the interaction between strong surface winds and eddies on a 10‐day timescale. Therefore, well parameterizing VEBF is important in improving the representation of the deep convection in coarse‐grid climate models.

The Vera C. Rubin Observatory is preparing to execute the most ambitious astronomical survey ever attempted, the Legacy Survey of Space and Time (LSST). Currently the final phase of construction is under way in the Chilean Andes, with the Observatory’s ten-year science mission scheduled to begin in 2025. Rubin’s 8.4-meter telescope will nightly scan the southern hemisphere collecting imagery in the wavelength range 320–1050 nm covering the entire observable sky every 4 nights using a 3.2 gigapixel camera, the largest imaging device ever built for astronomy. Automated detection and classification of celestial objects will be performed by sophisticated algorithms on high-resolution images to progressively produce an astronomical catalog eventually composed of 20 billion galaxies and 17 billion stars and their associated physical properties.In this article we present an overview of the system currently being constructed to perform data distribution as well as the annual campaigns which reprocess the entire image dataset collected since the beginning of the survey. These processing campaigns will utilize computing and storage resources provided by three Rubin data facilities (one in the US and two in Europe). Each year a Data Release will be produced and disseminated to science collaborations for use in studies comprising four main science pillars: probing dark matter and dark energy, taking inventory of solar system objects, exploring the transient optical sky and mapping the Milky Way.Also presented is the method by which we leverage some of the common tools and best practices used for management of large-scale distributed data processing projects in the high energy physics and astronomy communities. We also demonstrate how these tools and practices are utilized within the Rubin project in order to overcome the specific challenges faced by the Observatory.

Objective: African American men die from prostate cancer at higher rates than do White men, a health disparity that may result from differences in knowledge and beliefs about prostate cancer and screening. Studies conflict on whether race or socioeconomic status affects knowledge of prostate cancer and screening. This study compared education, race, and screening status to determine how each factor shapes men's knowledge of prostate cancer and screening.Methods: In-depth interviews were conducted with 65 African American and White men, aged 40-64 years, with diverse educational backgrounds.Results: Education, not race or screening status, was associated with knowledge about the prostate gland, prostate cancer symptoms and screening tests, and fear of prostate cancer. The exception was knowledge about the prostate-specific antigen blood test, which was associated with education and screening status.Conclusion: This study suggests that education may be associated with prostate cancer and screening knowledge. Interventions should focus on all men with low education to correct their misconceptions about prostate cancer and to engage them in shared decision-making about screening. [ABSTRACT FROM AUTHOR]

Use of an effective anesthetic strategy can eliminate most of the pain and discomfort associated with this procedure, enabling urologists to perform extensive prostate biopsies in the office setting. [ABSTRACT FROM AUTHOR]

While boys who offend have been a dominant majority and primary concern of the juvenile court since its earliest days, the population of delinquent girls has increased in recent years at a far higher rate in the U.S. The special challenges presented by females, however, continue to be generally overlooked by the justice system. Moreover, while a few specialized programs now serve these girls, the field tends to view young female offenders as a homogeneous group; what distinguishes particular female subpopulations and the characteristics associated with different criminal trajectories have gone largely unexplored. Employing data from the state of Missouri, this study examines girls who offend, identifying models that predict subsequent violent behavior that include indicators such as parental substance abuse and incarceration, and offender substance abuse, mental health, and school behavior. Special attention is given to the effects of child maltreatment, which we find significantly, but weakly correlated with violent behavior. The authors conclude by considering the possibility that maltreatment may be correlated with other criminogenic factors, and by discussing the implications of findings for future research and practice, especially services that take into account the trauma experienced by young women who come to the attention of state authorities.

Abstract Background Recent syphilis outbreaks in the UK have raised serious concerns about the sexual health of the population. Moreover, syphilis appears more likely to facilitate HIV transmission than any other sexually transmitted infection (STI). Methods The sexual and other risk behaviour of a sample of HIV positive and negative gay men with and without syphilis was subjected to a detrended correspondence analysis (DCA). Results A DCA plot was used to illustrate similarity of individuals in terms of their behaviours, regardless of their infection status. The majority of those with syphilis (78%; 18/23) fell into a high-risk group with more partners, and use of anonymous sex venues and drugs during sex. However, 16% of uninfected controls (8/49) and 62% of HIV positive individuals without syphilis (8/13) also fell into this high-risk group. Conclusions Using a statistical technique that is novel for this type of investigation, we demonstrate behavioural overlaps between syphilis-infected individuals in an ongoing UK outbreak and uninfected HIV positive and negative controls. Given the high-risk behaviour of a significant proportion of uninfected individuals, ongoing transmission of syphilis and HIV in this population seems likely.

Background: In the United States (US), Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) disproportionately impacts Asian Americans (AA) and Native Hawaiians and other Pacific Islanders (NHPI) who have no access to screening. EBV-based screening trials in Asia have detected most cases at early stages. We sought to identify a US target population for NPC screening and hypothesized that once-lifetime screening could be cost-effective., Methods: We obtained NPC incidence data from the SEER Asian and Pacific Islander datasets. We estimated the number needed to screen, mortality reduction, and resource utilization using a validated model and performance data from trials. Six evaluated strategies incorporated serology, nasopharyngeal swab PCR, and endoscopy or MRI., Results: Intermediate-incidence and high-incidence populations accounted for 10.7% of US person-years yet 42.7% of cases. Anti-BNLF2b screening with selective endoscopy was the preferred strategy. In high-incidence populations, the median NNS to detect one case was 1,992, with a median of 7.12 NPC deaths averted per 100,000 screened. Screening met the willingness-to-pay threshold in all five high-incidence populations (median ICER/GDP 0.82) and among men in intermediate-incidence populations., Conclusions: Nearly half of NPC in the US arises among the 10% with AA or NHPI ethnicity. A suitable target population for US screening trials would be men and women age 35-65 of Chinese, Sāmoan, or Southeast Asian ethnicity, or men age 35-60 of Guamanian/Chamorro, Filipino, or Native Hawaiian ethnicity. Once-lifetime anti-BNLF2b screening could be cost-effective., Impact: These data may aid the design of US screening trials. Targeted NPC screening might mitigate health disparities.

Introduction: The effect of individual non-narcotic analgesics in cystectomy enhanced recovery after surgery (ERAS) is unknown. Additionally, many non-narcotic medications are associated with side effects pertinent to the cystectomy population. To better understand the actual use and utility of these medications, we sought to characterize the association between non-narcotic medications and milligram morphine equivalent (MME) narcotic score during the postoperative inpatient stay., Methods: We reviewed 260 consecutive ERAS cystectomy patients. The MME impact of non-narcotic compliance and cumulative dose of medication received was evaluated separately with general linear models. We also assessed relationship of non-narcotic compliance to patient reported pain score, length of stay (LOS), and time to return of bowel function (ROBF) and performed manual review of postoperative documentation to identify reasons for medication noncompliance., Results: Compliance with postoperative acetaminophen, gabapentin, and ketorolac was low. There was an inverse relationship between ketorolac dose and MME on postoperative day 1 (-0.026 MME/mg; P = 0.004) and postoperative day 2 (-0.33 MME/mg; P < 0.001). Compliance with ketorolac was associated with lower MME on postoperative day 1 (26.1 MME v. 33.6 MME; P = 0.023). There were no such associations identified with gabapentin or acetaminophen. Gabapentin compliance was associated with earlier ROBF (3.7 days v. 4.3 days; P = 0.006). Ketorolac compliance was associated with lower pain score on POD1 (3.25 VAS v. 4.07 VAS; P = 0.019) and POD2 (3.05 VAS v. 3.85 VAS; P = 0.040) There was no association between medication compliance and LOS. The most common reasons identified for non-compliance with gabapentin and ketorolac were renal function concerns (38% and 40% respectively), bleeding concerns with ketorolac (20%) and concerns for neurologic adverse effect with gabapentin (16%)., Conclusion: Compliance with non-narcotic medications in our ERAS cystectomy protocol was poor. There was a modest association with ketorolac and postoperative MME but no association with gabapentin or acetaminophen. Further study will clarify the role of these medications for cystectomy patients. Component specific analysis of protocolized care is valuable and may alter care pathways., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Benign prostatic hyperplasia (BPH) may decrease patient quality of life and often leads to acute urinary retention and surgical intervention. While effective treatments are available, many BPH patients do not respond or develop resistance to treatment. To understand molecular determinants of clinical symptom persistence after initiating BPH treatment, we investigated gene expression profiles before and after treatments in the prostate transitional zone of 108 participants in the Medical Therapy of Prostatic Symptoms (MTOPS) Trial. Unsupervised clustering revealed molecular subgroups characterized by expression changes in a large set of genes associated with resistance to finasteride, a 5α-reductase inhibitor. Pathway analyses within this gene cluster found finasteride administration induced changes in fatty acid metabolism, amino acid metabolism, immune response, steroid hormone metabolism, and kinase activity within the transitional zone. We found that patients without this transcriptional response were highly likely to develop clinical progression, which is expected in 13.2% of finasteride-treated patients. Importantly, a patient's transcriptional response to finasteride was associated with their pre-treatment kinase expression. Further, we identified novel expression signatures of finasteride resistance among the transcriptionally responded patients. These patients showed different gene expression profiles at baseline and increased prostate transitional zone volume compared to the patients who responded to the treatment. Our work suggests molecular mechanisms of clinical resistance to finasteride treatment that could be potentially helpful for personalized BPH treatment as well as new drug development to increase patient drug response., (© 2024. The Author(s).)

The Long-Term Agroecosystem Research Network (LTAR), through its Common Experiment (CE) framework, contrasts prevailing and alternative agricultural practices for efficacy and sustainability within the indicator domains of environment, productivity, economics, and society. Invasive species, wildfire, and climate change are principal threats to Great Basin agroecosystems. Prescribed grazing may be an effective tool for restoring lands degraded by these disturbances. At the Great Basin (GB) LTAR site headquartered in Boise, ID, our contribution to the CE contrasts a prevailing (PRV), cattle grazing practice of fixed moderate stocking and duration with an alternative (ALT), prescribed grazing practice called high-intensity low-frequency (HILF) grazing where stocking and duration are tailored to suppress invasive annual grass competition with native or desirable plant species and thus promote recovery of rangelands degraded by annual grass invasion and recurrent wildfire. Preliminary results indicate cheatgrass density and fuel height have been reduced in ALT-treated paddocks compared to PRV paddocks. Since its inception in 2014, our GB CE has been a research co-production effort among ranchers, public land managers, and researchers. Future directions for this research will center on expanding the experiment to multiple study areas to better address the scope of the annual grass/wildfire problem. We expect this research will lead to effective and sustainable grazing practices for restoring >41 million hectares of degraded rangelands in the Great Basin and other areas of the western United States., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Introduction: Previous literature suggests socioeconomic status and racial disparities impact management decisions for patients with small renal masses. We aim to build upon these findings and examine how these modalities impact patient adherence to their management plan., Methods: This retrospective study analyzed our Kidney Tumor Program database (n = 1476) containing patients from 2000 to 2020. Socioeconomic status was estimated using 2 modalities: Area Deprivation Index and household income. Patients were then evaluated for differences in adherence, nonadherence, and loss to follow-up. Adherent patients completed all recommended appointments within 6 months of their initial follow-up. Nonadherent patients did not complete all recommended appointments within 6 months of their originally scheduled follow-up but eventually did. Patients lost to follow-up were recommended to follow up but never did., Results: Patient adherence was not significantly different across sex or primary treatment method but differed with respect to race/ethnicity. Black patients were significantly more likely to be nonadherent ( P = .021) and lost to follow-up ( P = .008). After adjusting for race/ethnicity, Area Deprivation Index and income bracket were significantly associated with adherence and loss to follow-up. Patients with a high socioeconomic status had significantly higher rates of adherence (ADI, quartile [Q] 1 vs Q4, P = .038; income, >$120,000 vs $30,000-$59,999, P < .003) and decreased loss to follow-up (ADI, Q1 vs Q4, P = .03; income, >$120,000 vs $30,000-$59,999, P = .002)., Conclusions: Our results demonstrate that Black race and low socioeconomic status are associated with decreased adherence and increased loss to follow-up. Possible strategies to target these disparities include financial assistance programming, social determinants of health screening, and nurse navigator programs.

Introduction: Men with advanced germ cell tumors (GCT) treated with chemotherapy are at high risk of venous thromboembolism (VTE). Predictors of VTE may identify patients who would benefit from prophylactic anticoagulation., Patients and Methods: Men with advanced GCT (Stage IS, II, III) treated with chemotherapy were identified at 2 centers. High genomic risk was defined from a 5 single nucleotide polymorphism (SNP) germline panel. Logistic regression was used to evaluate the impact of genomic risk on VTE within 6 months of chemotherapy initiation. Orthogonal Projection to Latent Structures Discriminant Analysis (OPLS-DA) was used to build models to predict VTE based on clinical variables and an 86 SNP panel., Results: This 123-patient cohort experienced a VTE rate of 26% with an incidence of high genomic risk of 21%. Men with high genomic risk did not have a significantly higher VTE rate (31%, 8/26) than men with low genomic risk (25%, 24/97), unadjusted OR 1.4 (95% CI 0.5-3.5, P = .54). Incorporation of clinical variables (Khorana score, N3 status and elevated LDH) resulted in adjusted OR 2.1 (95% CI 0.7-6.5, P = .18). A combined model using clinical variables and 86 SNPs performed similarly (AUC 0.77) compared to clinical variables alone (AUC 0.72)., Conclusions: A previously established 5-SNP panel was not associated with VTE among patients with GCT receiving chemotherapy. However, multivariable models based on clinical variables alone warrant further validation to inform prophylactic anticoagulation strategies., Competing Interests: Disclosure LCB declares the following relationships: Consulting with Seattle Genetics and Pfizer. MR, MM, NS, JS, WS, RP, BN, TA, CL, WL, NH, AH, MH, and PEC report no conflicts of interest pertaining to this project. JP declares the following relationships: Research funding from Bristol Myer Squibb. EFB declares the following relationships: Stock/ownership with Exelixis, Becton Dickson, Gilead Sciences, Medtronic; Honoraria from Exelixis, Janssen Oncology, Novartis, Pfizer, Merck, Consulting for Johnson & Johnson; Speakers Bureau for AstraZenica and Exelixis, Research funding from Pfizer and Astellas Pharma., (Copyright © 2024. Published by Elsevier Inc.)

Knowledge of how grazing cattle utilize heterogeneous landscapes in Mediterranean silvopastoral areas is scarce. Global positioning systems (GPS) to track animals, together with geographic information systems (GIS), can relate animal distribution to landscape features. With the aim to develop a general spatial model that provides accurate prediction of cattle resource selection patterns within a Mediterranean mountainous silvopastoral area, free-roaming Sarda cows were fitted with GPS collars to track their spatial behaviors. Resource selection function models (RSF) were developed to estimate the probability of resource use as a function of environmental variables. A set of over 500 candidate RSF models, composed of up to five environmental predictor variables, were fitted to data. To identify a final model providing a robust prediction of cattle resource selection pattern across the different seasons, the 10 best models (ranked on the basis of the AIC score) were fitted to seasonal data. Prediction performance of the models was evaluated with a Spearman correlation analysis using the GPS position data sets previously reserved for model validation. The final model emphasized that watering point, elevation, and distance to fences were important factors affecting cattle resource-selection patterns. The prediction performances (as Spearman rank correlation scores) of the final model, when fitted to each season, ranged between 0.7 and 0.94. The cows were more likely to select areas lower in elevation and farther from the watering point in winter than in summer (693 ± 1 m and 847 ± 13 m vs. 707 ± 1 m and 635 ± 21 m, respectively), and in spring opted for the areas furthest from the water (963 ± 12). Although caution should be exercised in generalizing to other silvopastoral areas, the satisfactory Spearman correlations scores from the final RSF model applied to different seasons indicate resource selection function is a powerful predictive model. The relative importance of the individual predictors within the model varied among the different seasons, demonstrating the RSF model's ability to interpret changes in animal behavior at different times of the year. The RSF model has proven to be a useful tool to interpret the spatial behaviors of cows grazing in Mediterranean silvopastoral areas and could therefore be helpful in managing and preserving ecosystem services of these areas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MB declared a shared parent affiliation with the author PC to the handling editor at the time of review., (Copyright © 2024 Acciaro, Pittarello, Decandia, Sitzia, Giovanetti, Lombardi and Clark.)

Introduction: Patient education is an essential element of the treatment pathway. Augmented reality (AR), with disease simulations and three-dimensional visuals, offers a developing approach to patient education. We aim to determine whether this tool can increase patient understanding of their disease and post-visit satisfaction in comparison to current standard of care (SOC) educational practices in a randomized control study., Methods: Our single-site study consisted of 100 patients with initial diagnoses of kidney masses or stones randomly enrolled in the AR or SOC arm. In the AR arm, a physician used AR software on a tablet to educate the patient. SOC patients were educated through traditional discussion, imaging, and hand-drawn illustrations. Participants completed pre- and post-physician encounter surveys adapted from the Press Ganey ® patient questionnaire to assess understanding and satisfaction. Their responses were evaluated in the Readability Studio ® and analyzed to quantify rates of improvement in self-reported understanding and satisfaction scores., Results: There was no significant difference in participant education level ( P = 0.828) or visit length (27.6 vs. 25.0 min, P = 0.065) between cohorts. Our data indicate that the rate of change in pre- to post-visit self-reported understanding was similar in each arm ( P ≥ 0.106 for all responses). The AR arm, however, had significantly higher patient satisfaction scores concerning the educational effectiveness and understanding of images used during the consultation ( P < 0.05)., Conclusions: While AR did not significantly increase self-reported patient understanding of their disease compared to SOC, this study suggests AR as a potential avenue to increase patient satisfaction with educational tools used during consultations., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Urology.)

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objectives: To increase the population-level understanding of upper tract imaging evaluation during risk-based hematuria assessment. Using a national, privately-insured cohort, we evaluated the rates of imaging and the diagnostic yield of each imaging modality. We hypothesized that the rate of upper tract disease would be low and that the benefit of computed tomography over renal ultrasound would be limited., Methods: We identified patients with an incident diagnosis of microscopic or gross hematuria between 2010 and 2015 within the MarketScan database. Multivariable logistic regression was used to predict the adjusted likelihood of any upper tract finding, with a subset analysis limited to malignant outcomes., Results: We identified 466,710 patients; 150,880 (32.3%) received ultrasound, 219,449 (47.0%) received computed tomography, and 96,381 (20.7%) received other imaging. Ultrasound detected 1,469 findings among 150,880 patients (1%); computed tomography detected 3,764 findings among 219,449 patients (1.7%); other imaging detected 2,612 findings among 96,381 patients (2.7%) (P < 0.0001). When adjusted for comorbidities, increased age, male sex, increased Elixhauser index, gross hematuria, and CT or other imaging were associated with upper tract findings, in the overall and subset analysis (all p < 0.0001)., Conclusions: The diagnostic yield of imaging is higher than expected; however, the detection rate remained low. As supported by updated clinical practice guidelines, clinicians should pursue risk-based imaging strategies during hematuria evaluation, although these data may support increased utilization of ultrasound at the initial evaluation., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interests to report related to the study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Opioid use, misuse, and diversion is of paramount concern in the United States. Radical cystectomy is typically managed with some component of opioid pain control. We evaluated persistent opioid and benzodiazepine use after radical cystectomy and assessed the impact of their preoperative use on this outcome. We also explored associations between preoperative use and perioperative outcomes., Methods and Materials: We used prospectively maintained data from our enhanced recovery after surgery (ERAS) cystectomy database and the Prescription Reporting with Immediate Medication Utilization Mapping (PRIMUM) database to identify controlled substance prescriptions for radical cystectomy patients. We separated patients by frequency of preoperative opioid and/or benzodiazepine prescriptions (0, 1, 2+) and used these cohorts to explore persistent use (prescription 3-12 months after surgery) alongside perioperative outcomes., Results: Our cohort included 257 patients undergoing cystectomy at a single institution from 2017 to 2021. Preoperative opioid and benzodiazepine prescriptions were documented for 120 (46.7%) and 26 (10.1%) patients, respectively. Persistent opioid use was observed in 20 (14.6%) of opioid-naive patients (no prescriptions in 9 months prior to surgery) while 13 (19.7%) patients with 1 preoperative prescription and 28 (51.9%) patients with 2 or more preoperative prescriptions demonstrated persistent use. New persistent benzodiazepine use occurred in 6 (2.6%) patients. Overall persistent benzodiazepine use was present in 11 (4.3%) patients. In a multivariable model, preoperative opioid and benzodiazepine prescriptions were associated with persistent opioid use (P < 0.001; P = 0.027 respectively). No association was identified between preoperative opioid or benzodiazepine usage and perioperative outcomes including length of stay, return of bowel function, inpatient opioid usage, inpatient or discharge complications, readmissions, or emergency department visits. Inpatient pain scores were noted to be higher in patients with ≥ 2 preoperative opioid prescriptions (P = 0.037)., Conclusions: Persistent opioid use was present in 23.7% of patients, with a new persistent use rate of 14.6%. Benzodiazepine use was less frequent than opioids, with a small number demonstrating new persistent use. Preoperative opioid and benzodiazepine use is associated with persistent opioid use postoperatively. Preoperative opioid and benzodiazepine use did not affect perioperative outcomes in our cohort., Competing Interests: Declaration of Competing Interest The authors have no relevent disclosures or competing interests. Previously presented as a poster at the Southeastern Section of the American Urological Association Annual Meeting in March 2022., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Novel regimens targeting immune checkpoints and the cMET or HER2 pathways are under investigation in metastatic urothelial carcinoma (mUC) though co-expression of these molecular targets has not been defined. We sought to characterize the protein co-expression rates of PD-L1, cMET and HER2 in primary and metastatic mUC lesions and agreement rates in paired biopsies., Materials and Methods: We assessed PD-L1, cMET and HER2 protein expression by immunohistochemistry (IHC) in archival mUC samples identified from an institutional database (n = 143). Correlation of expression between primary and metastatic biopsies was performed in patients with available paired biopsies (n = 79). Protein expression levels by predefined thresholds were measured, and Cohen's kappa statistics (κ) were utilized to assess the agreement in expression between paired primary and metastatic samples., Results: In primary tumors (n = 85), high expression of PD-L1, cMET, and HER2 was observed in 14.1%, 34.1%, and 12.9%, respectively. In metastatic samples (n = 143), high expression of PD-L1, cMET and HER2 was detected in 9.8%, 41.3%, and 9.8%, respectively. Expression agreement rates between paired specimens (n = 79) were PD-L1: 79.7% (κ = 0.09), cMET: 69.6% (κ = 0.35), HER2: 84.8% (κ = 0.17). High PD-L1/cMET co-expression was observed in only 5.1% (n = 4) of primary and 4.9% (n = 7) of metastatic specimens. High co-expression of PD-L1/HER2 occurred in 3.8% (n = 3) of primary samples and no metastatic samples. The overall co-expression agreement between paired samples was 55.7% (κ = 0.22) for PD-L1/cMET and 67.1% (κ = 0.06) for PD-L1/HER2, but agreement for high co-expression between paired samples was very low (2.5% for PD-L1/cMET and 0% for PD-L1/HER2)., Conclusions: Tumor co-expression of high cMET or HER2 and PD-L1 is low in this cohort. Agreement of high co-expression between primary and metastatic sites is rare. Biomarker-based strategies used in selection of patients for contemporary trials testing combinations of immune checkpoint inhibitors with either cMET or HER2-targeted agents should account for discordant biomarker expression between primary and metastatic sites., Competing Interests: Declaration of Competing Interest The authors have declared no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To prevent avoidable treatment and make more informed care decisions about small renal masses, the use of renal mass biopsies has increased since the early 2000s. In April 2017, Atrium Health Carolinas Medical Center began requiring biopsies before all percutaneous thermal ablation procedures for renal masses. We aim to determine the effect of this preablation biopsy mandate on small renal mass treatment decisions., Materials and Methods: Our study is a retrospective analysis of a prospectively managed database designed to track patients with small renal masses presented at the Kidney Tumor Program from 2000-2020. We separated patients into 2 cohorts (pre- and postmandate) based on the initial encounter date, excluding those from April 2017-April 2018 to allow for implementation of the mandate. We also excluded patients with masses >4 cm., Results: Overall, we found no significant difference between the pre- and postmandate cohorts, with race as an exception. Implementation of the mandate coincided with an increase in biopsies for both ablation and nonablation treatment pathways ( P < .001, P = .01). Renal mass biopsy rates increased in all socioeconomic groups except the lowest quartile. Additionally, Black/Hispanic patients had the highest biopsy rate. We found significant changes in treatment decisions between our cohorts: surgery decreased 24% ( P < .001), active surveillance increased 28% ( P < .001), and patients with no follow-up decreased 8% ( P = .03)., Conclusions: Our data indicate that a preablation renal mass biopsy mandate is associated with the wider use of biopsies for all small renal mass patients, fewer surgical interventions, and an increase in active surveillance.

Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility., Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry., Design, Setting, and Participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry., Outcome Measurements and Statistical Analysis: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness., Results and Limitations: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10 -4 )., Conclusions: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry., Patient Summary: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: The purpose of this guideline is to provide a useful reference on the effective evidence-based diagnoses and management of non-metastatic upper tract urothelial carcinoma (UTUC)., Materials/methods: The Pacific Northwest Evidence-based Practice Center of Oregon Health & Science University (OHSU) team conducted searches in Ovid MEDLINE (1946 to March 3rd, 2022), Cochrane Central Register of Controlled Trials (through January 2022), and Cochrane Database of Systematic Reviews (through January 2022). The searches were updated August 2022. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (Table 1).[Table: see text]Results:This Guideline provides updated, evidence-based recommendations regarding diagnosis and management of non-metastatic UTUC including risk stratification, surveillance and survivorship. Treatments discussed include kidney sparing management, surgical management, lymph node dissection (LND), neoadjuvant/adjuvant chemotherapy and immunotherapy., Conclusion: This standardized guideline seeks to improve clinicians' ability to evaluate and treat patients with UTUC based on available evidence. Future studies will be essential to further support these statements for improving patient care. Updates will occur as the knowledge regarding disease biology, clinical behavior and new therapeutic options develop.

Introduction: The American Cancer Society estimates 79,000 individuals will be diagnosed with kidney cancer in 2022, most of which are initially found as small renal masses (SRMs). Proper management of SRM patients includes careful evaluation of risk factors such as medical comorbidities and renal function. To investigate the importance of these risk factors, we examined their effect on crossover to delayed intervention (DI) and overall survival (OS) in patients undergoing active surveillance (AS) for SRMs., Methods: This is an Institutional Review Board-approved retrospective analysis of AS patients presented at kidney tumor conferences with SRMs between 2007 and 2017. Univariable and multivariable logistic regression analyses were performed to determine how factors including estimated glomerular filtration rate (eGFR), diabetes, and chronic kidney disease are associated with DI and OS., Results: A total of 111 cases were reviewed. In general, AS patients were elderly and had significant comorbidities. On univariate analysis, intervention was more likely to occur in patients with a younger age ( P = 0.01), better kidney function ( P = 0.01), and higher tumor growth rates (GRs) ( P = 0.02). Higher eGFR was associated with better survival ( P = 0.03), while higher tumor GRs ( P = 0.014), greater Charlson Comorbidity Index ( P = 0.01), and larger tumors ( P = 0.01) were associated with worse OS. Of the comorbidities, diabetes was found to be an independent predictor of worse OS ( P = 0.01)., Conclusions: Patient-level factors - such as diabetes and eGFR - are associated with the rate of DI and OS among SRM patients. Consideration of these factors may facilitate better AS protocols and improve patient outcomes for those with SRMs., Competing Interests: Conflicts of interest: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Urology.)

Background: Galectin-1 (Gal-1) and Galectin-3 (Gal-3) are carbohydrate binding proteins with a wide range of biological activity, including regulation of cellular adhesion, proliferation, and apoptosis in solid tumors. Prior small studies have reported that Gal-3 expression is associated with progression of disease in urothelial carcinoma (UC), from non-muscle invasive UC progression to muscle invasive UC. We assessed Gal-1 and Gal-3 protein expression H-score utilizing a tissue microarray (TMA) created from 301 cystectomy specimens., Methods: Immunohistochemistry for Gal-1 and Gal-3 was performed on TMA generated from tumor blocks from chemotherapy naïve cystectomy specimens. The variable of interest, H-score, was defined as the product of the percentage of cells staining positive (0-100) and intensity score (0-3) scored by a single pathologist. Survival end points were analyzed using Kaplan-Meier and Cox Proportional Hazards methods. Clinical data including Charlson Comorbidity Index (CCI), pathologic tumor (T) stage, tumor size, node stage, and surgical margins, were included in multivariable analysis., Results: We found that Gal-1 and Gal-3 expression correlated with intratumoral T stage (median Gal-1 H-score was 0 across non-invasive tissue types and 200 in invasive, P<0.01 and median Gal-3 score was 270 across non-invasive tissue types and 70 in invasive, P<0.01). However, the highest intratumoral H-score per cystectomy core did not independently predict for recurrence-free survival (RFS) (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.65) or OS (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.72) in this cohort. Significant intratumoral heterogeneity was present for both Gal-1 and Gal-3, with an average difference between the highest and lowest H score was 95 for Gal-1 and 109 for Gal-3 for cystectomy specimens with more than one biopsy., Conclusions: Gal-1 and Gal-3 H-score per bladder did not independently predict for RFS or OS. Intra-tumoral Gal-1/Gal-3 heterogeneity complicates the use of Gal-1 and Gal-3 expression as a prognostic biomarker. Future studies should consider the evaluation of serum and urinary galectins as an approach to mitigate tumor heterogeneity., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-494/coif). EFB reports honorarium fees from Exelixis and AstraZeneca, consulting relationship with Johnson and Johnson, and grants from Pfizer and Astellas, and owns stock in Exelixis, Becton Dickinson, Calithera Biosciences, Medtronic, Macrogenics, Arvinas, Autolus. The other authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

Cancers arising from the bladder urothelium often exhibit lineage plasticity with regions of urothelial carcinoma adjacent to or admixed with regions of divergent histomorphology, most commonly squamous differentiation. To define the biologic basis for and clinical significance of this morphologic heterogeneity, here we perform integrated genomic analyses of mixed histology bladder cancers with separable regions of urothelial and squamous differentiation. We find that squamous differentiation is a marker of intratumoral genomic and immunologic heterogeneity in patients with bladder cancer and a biomarker of intrinsic immunotherapy resistance. Phylogenetic analysis confirms that in all cases the urothelial and squamous regions are derived from a common shared precursor. Despite the presence of marked genomic heterogeneity between co-existent urothelial and squamous differentiated regions, no recurrent genomic alteration exclusive to the urothelial or squamous morphologies is identified. Rather, lineage plasticity in bladder cancers with squamous differentiation is associated with loss of expression of FOXA1, GATA3, and PPARG, transcription factors critical for maintenance of urothelial cell identity. Of clinical significance, lineage plasticity and PD-L1 expression is coordinately dysregulated via FOXA1, with patients exhibiting morphologic heterogeneity pre-treatment significantly less likely to respond to immune checkpoint inhibitors., (© 2022. The Author(s).)

Introduction: We sought to assess the comparative hospital outcomes and costs among a population-based cohort of bladder cancer patients by surgical approach and diversion., Methods: From a privately insured national database, we identified all bladder cancer patients who underwent open or robotic radical cystectomy and ileal conduit or neobladder from 2010 to 2015. The primary outcomes were length of stay, readmissions, and total health care costs at 90 days from surgery. We used multivariable logistic regression and generalized estimating equations to assess for 90-day readmission and health care costs, respectively., Results: Most patients underwent open radical cystectomy with ileal conduit (56.7%; n = 1,680) followed by open radical cystectomy with neobladder (22.7%; n = 672), robotic radical cystectomy with ileal conduit (17.4%; n = 516), and robotic radical cystectomy with neobladder (3.1%; n = 93). On multivariable analysis, patients had higher odds of 90-day readmissions for open radical cystectomy and neobladder (OR: 1.36; P = .002) and robotic radical cystectomy with neobladder (OR 1.60; P = .03) relative to open radical cystectomy with ileal conduit. After adjusting for patient covariates, we also found lower adjusted total 90-day health care costs for open radical cystectomy with ileal conduit ($67,915) and open radical cystectomy with neobladder ($67,371) compared to robotic radical cystectomy with ileal conduit ($70,677) and neobladder ($70,818; P < .05)., Conclusions: In our study, neobladder diversion was associated with higher odds of 90-day readmission, while robotic surgery increased total 90-day health care costs.

Objective: To elucidate regional trends of infectious complications following transrectal ultrasound prostate biopsy (TRUS-PB) from a national, privately-insured database., Matereial and Methods: Using Market Scan, we identified all men who underwent TRUS-PB from 2010 to 2015. Infectious complications (UTI, prostatitis, sepsis) occurring 30 days after the prostate biopsy from emergency room (ER) visits or hospital admissions constituted the primary outcomes. We analyzed unadjusted and adjusted rates of infectious complications from ER visits and hospital admissions per 100 prostate biopsies by state. Multivariable logistic regression analyses were used to identify patient covariates associated with infectious complications., Results: During the study interval, we identified 193,490 patients who underwent TRUS-PB. The mean age was 57.6 years (SD: 5.0). Over time the unadjusted national rates of infectious complications remained similar from 0.4 ER visits per 100 prostate biopsies in 2010 -0.2 in 2015 (P = 0.83), and 1.2 hospital admissions per 100 prostate biopsies in 2010 to 1.1 in 2015 (P= 0.58). Connecticut had the lowest unadjusted infectious complication rate per 100 biopsies at 0.64, whereas West Virginia had the highest at 2.34. Multivariable analysis revealed higher Elixhauser status and patient age were associated with higher odds of infectious complications (P<0.05)., Conclusions: While rates of infectious complications attributable to prostate biopsies remain relatively stable, significant variation exists at the state level regarding this adverse outcome., (Copyright © 2022. Published by Elsevier Inc.)

Introduction and Objective: Enhanced Recovery After Surgery (ERAS) protocols have been increasingly applied to urologic surgeries such as cystectomy and prostatectomy, though research defining protocols and outcomes for renal ERAS programs (RERAS) for nephrectomy remains limited. We aim to assess perioperative outcomes following implementation of our RERAS protocol modified from ERAS society cystectomy guidelines, as well as describe compliance with protocol guidelines., Methods: We performed a retrospective cohort analysis of 400 patients who underwent partial or radical nephrectomy between October 2017 and August 2020. RERAS protocol was initiated September 30, 2018, and patients were categorized into pre- and post-RERAS implementation cohorts based on surgery date. Perioperative outcomes including complications, 30-day readmissions, length of stay, and opioid consumption were compared across pre- and post-RERAS cohorts. Protocol compliance was reported based on adherence to program recommendations., Results: Among 400 patients included in analysis, the pre-RERAS cohort included 133 patients and the post-RERAS cohort included 267 patients. There were no differences in overall complications (P = 0.354) and 30-day readmissions (P = 0.078). Length of stay (P < 0.001) and postoperative opioid consumption (P < 0.001) were significantly reduced post-RERAS. We observed an increase in compliance with RERAS recommendations over time (P< 0.001)., Conclusion: RERAS implementation was associated with decreased length of stay and opioid usage, underscoring the benefits of program adoption in an era of opioid dependence and strained hospital capacity. Successful initiation of a RERAS protocol requires intentional organization and buy in from all providers involved., Competing Interests: Conflict of Interest No disclosures or conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Small cell bladder carcinoma (SCBC) represents a rare histologic variant with a poor prognosis and for which no routine biomarkers exist. Limited reports of genomic sequencing in SCBC have demonstrated a high prevalence of TP53 and RB1 gene mutations, though the prognostic value of these and other gene variants in SCBC remains undefined. In this study, we performed targeted genomic sequencing on a cohort of SCBC patients and correlated genomic findings with clinical outcomes to identify potential novel biomarkers., Materials and Methods: Thirty-one patients with SCBC and available treatment-naïve tumor specimens were identified from an institutional database (23 limited stage [LS], 8 extensive stage [ES]). Small cell carcinoma specimens were microdissected and subjected to tumor next-generation whole-exon sequencing with a 592 gene panel. Kaplan-Meier techniques and Cox proportional hazards models were used to evaluate genomic aberration association with relapse-free survival (RFS) and overall survival (OS) in the limited stage cohort., Results: The most common pathogenic gene variants included ARID1A (48%), TP53 (48%) and RB1 (48%). Mutations in genes with potential therapeutic targets not routinely evaluated in SCBC included BRCA1/2 (16%), POLE (13%), JAK2 (13%), PDGFB (13%) and FGFR3 (3%). Multiple novel biomarker candidates showed trends for improvements in OS in the LS subset including ERCC2 (HR 0.322, P = 0.122) and RB1 (HR 0.481, P = 0.182), while LS patients with TP53 mutations (HR 2.730, P = 0.056), and MCL1 gene amplification (HR 4.183, P = 0.018) suggested inferior OS. Additionally, gene or copy number variants with potential prognostic benefit included UBR5 and DAXX (P = 0.02, [hazard ratios nonestimable due to zero events in biomarker positive groups])., Conclusions: These results support the role for tumor genomic profiling in SCBC and identify multiple potential novel biomarkers and therapeutic targets in this rare disease. Efforts to validate these findings should lead to improved decision-making and treatment outcomes in SCBC., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To examine the performance of Leibovich score versus GRade, Age, Nodes, and Tumor score in predicting disease recurrence in renal cell carcinoma., Methods: In total, 7653 patients diagnosed with renal cell carcinoma from 2010 to 2018 were captured in the nationwide DaRenCa database; 2652 underwent radical or partial nephrectomy and had full datasets regarding the GRade, Age, Nodes, and Tumor score and Leibovich score. Discrimination was assessed with a Cox regression model. The results were evaluated with concordance index analysis., Results: Median follow-up was 40 months (interquartile range 24-56). Recurrence occurred in 17%, and 15% died. A significant proportion of patients (36%) had missing data for the calculation of the Leibovich score. Among 1957 clear cell renal cell carcinoma patients the distribution of GRade, Age, Nodes, and Tumor score of 0, 1, 2, or 3/4 was 21%, 56%, 21% and 1.4%, respectively, and for Leibovich score of low/intermediate/high this was 47%, 36% and 18%, respectively. A similar distribution was seen in 655 non-clear cell patients. Both Leibovich and GRade, Age, Nodes, and Tumor scores performed well in predicting outcomes for the favorable patient risk groups. The Leibovich score was better at predicting recurrence-free survival (concordance index 0.736 versus 0.643), but not overall survival (concordance index 0.657 versus 0.648). Similar results were obtained in non-clear cell renal cell carcinoma., Conclusion: GRade, Age, Nodes, and Tumor and Leibovich scores were validated in clear cell and non-clear cell renal cell carcinoma. Leibovich score outperformed the GRade, Age, Nodes, and Tumor score in predicting recurrence-free survival and should remain the standard approach to risk stratify patients during follow-up when all data are available., (© 2022 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

Objective: To evaluate whether racial disparities in MRI-Bx usage persisted after correction for socioeconomic, demographic, and clinical factors., Methods: This is a retrospective cohort study of patients who received either MRI-Bx or systematic biopsy (SB) within a single academic medical center between January 2018 - June 2020. For each patient, socioeconomic variables including household income, education, percent below poverty, and unemployment were estimated using 2015 American Community Survey census-tract level data. Chi-square analysis was used to examine differences in clinical and demographic characteristics between the two groups. The Benjamini-Hochberg procedure was used to control false discovery rate (FDR) for multiple testing., Results: Eighteen percent of Black men (53/295) received MRI-Bx while 41% (228/561) of white men received MRI-Bx. Patients coming from highly impoverished areas were less likely to receive MRI-Bx, 25% vs 75%, respectively. In multivariate analysis, race remained significantly different across MRI-Bx and SB groups. Clinical factors including family history, DRE, BMI, and prostate volume were not significantly different between patients receiving MRI-Bx and SB., Conclusion: Black men are less likely to receive MRI-Bx than white men, even after adjusting for clinical and socioeconomic characteristics. Further work is necessary to identify and study methods to increase equity in PCa diagnostic testing., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Biomarkers are needed in muscle-invasive bladder cancer (MIBC). We previously reported that high tumor aurora kinase (AURK) A expression identifies patients with MIBC with poor prognosis. Aberrant p53 expression has also been associated with poor outcomes in MIBC, though to the best of our knowledge, co-expression rates of p53 and aurora kinases have not been previously described in MIBC. As aurora kinase and p53 family members may co-regulate each other, the present study investigated whether tumor p53 or p63 protein expression influenced the prognostic value of AURKA in a pilot study of 50 patients with MIBC treated with curative intent. Immunohistochemistry for AURKA, AURKB, p53 and p63 were performed on archival pre-treatment tumor specimens and correlated with clinical outcomes in patients with MIBC who received neoadjuvant chemotherapy (NAC) prior to cystectomy. Baseline p53 [hazard ratio (HR) 1.46; 95% confidence interval (CI)=0.55-3.9; P=0.448) and p63 (HR 2.02; 95% CI=0.51-8.1; P=0.313) protein expression did not predict for overall survival (OS). Low p53 protein expression did not correlate with high AURKA (φ=0.190) or AURKB (φ=0.075) expression. However, in tumors with low p53 expression (n=17), the presence of either high AURKA or AURKB expression levels predicted an increased risk for relapse (HR 27.1; 95% CI=2.7-270.1; P=0.005) and mortality (HR 14.9; 95% CI=2.3-95.6; P=0.004) compared to tumors with both low AURKA and AURKB levels. The relationship between p63 and AURKA/B expression levels was not tested due to the prevalence (80%) of high p63 expression in the present cohort. In tumors with low AURKA expression, p53 status did not predict for OS (HR 0.62; 95% CI 0.2-3.2; P=0.572). In multivariable analysis, only high baseline AURKA expression predicted for inferior OS (HR 4.9; 95% CI 1.7-14.1; P=0.003). To the best of our knowledge, the present study was the first to report co-expression of p53 and aurora kinase family members in MIBC, and although wild-type p53 may regulate the aurora kinases in preclinical models, the adverse prognostic value of tumor AURKA overexpression was independent from baseline tumor p53 protein expression in the present cohort. AURKA remains an important prognostic biomarker in patients with MIBC and warrants further evaluation in prospective studies to validate whether baseline AURKA can identify patients that are unlikely to benefit from standard of care with NAC., Competing Interests: The authors declare they have no competing interests., (Copyright: © Burgess et al.)

A rare African ancestry-specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.40% in Ghana and 0.31% in Nigeria to 0% in Uganda and South Africa, with a range of frequencies in men with admixed African ancestry from North America and Europe (0-0.26%). HOXB13 X285K was associated with 2.4-fold increased odds of prostate cancer (95% confidence interval [CI] = 1.5-3.9, p = 2 × 10 -4 ), with greater risk observed for more aggressive and advanced disease (Gleason ≥8: odds ratio [OR] = 4.7, 95% CI = 2.3-9.5, p = 2 × 10 -5 ; stage T3/T4: OR = 4.5, 95% CI = 2.0-10.0, p = 2 × 10 -4 ; metastatic disease: OR = 5.1, 95% CI = 1.9-13.7, p = 0.001). We estimated that the allele arose in West Africa 1500-4600 yr ago. Further analysis is needed to understand how the HOXB13 X285K variant impacts the HOXB13 protein and function in the prostate. Understanding who carries this mutation may inform prostate cancer screening in men of West African ancestry. PATIENT SUMMARY: A rare African ancestry-specific germline deletion in HOXB13, found only in men of West African ancestry, was reported to be associated with an increased risk of overall and advanced prostate cancer. Understanding who carries this mutation may help inform screening for prostate cancer in men of West African ancestry., (Copyright © 2022. Published by Elsevier B.V.)