Noninvasive Tests for Bladder Cancer Detection and Surveillance: A Systematic Review of Commercially Available Assays.

BACKGROUND: An important reason for the high health care costs associated with bladder cancer is the need for frequent cystoscopy for detection and surveillance of this disease. Cytologic analysis of voided urine specimens can assist, but is too inaccurate to replace cystoscopy. In an effort to create reliable, objective, noninvasive mechanisms for detecting bladder cancer, a number of urine-based molecular tests have been developed with the ultimate goal of reducing the frequency of cystoscopy. OBJECTIVE: To summarize the performance of urine-based biomarker tests, currently commercially available in the US, as part of the initial workup for hematuria and for bladder cancer surveillance. METHODS: In accordance with PRISMA guidelines we performed a systematic review of the literature on the performance of NMP22, BTA, UroVysion, ImmunoCyt/uCyt, CxBladder, and Bladder EpiCheck. Median sensitivity, specificity, negative (NPV) and positive predictive values (PPV) were calculated for each test based on the included studies. RESULTS: Twenty-eight studies met inclusion criteria for the performance of five urine-based biomarker tests in the setting hematuria workup. Median sensitivity ranged from 65.7% -100% and specificity ranged from 62.5% -93.8%. Median NPV ranged from 94.2% -98.3% and PPV ranged from 29% -58.7%. Fourteen studies met inclusion criteria for the performance of six tests in the setting of bladder cancer surveillance. Median sensitivity ranged from 22.6% -92.0% and specificity from 20.5% -97.9%. Median NPV ranged from 52.9% -96.5% and PPV ranged from 48.1% -75.7%. CONCLUSIONS: Our analysis finds that while these tests may provide some clinical utility, none of the assays have thus far demonstrated objective evidence to supplant the gold diagnostic standard.

Implementation and Validation of a High-fidelity Simulation Model for Surgical Resident Training: Management of Acute Intraoperative Hemorrhage during Robot-assisted Surgery.

OBJECTIVE: To improve our previous simulation-based training module by using sustainable material to mold an anatomically accurate terrain and reproducing major vascular injuries encountered during robot-assisted nephrectomy. METHODS: The simulator was built with a pump, gauge, and valve linked via silicone tubing. Artificial blood was made from cornstarch, water, and red dye, and pumped through 3D-Med artificial vessels with the dimensions of an average renal artery. Silicone was used to emulate the pliability of organic tissue and mold an anatomically accurate terrain. Eight urologic residents participated in the pilot simulation. We employed validated assessment tools including Non-Technical Skills for Surgeons and Objective Structured Assessment of Technical Skills forms to guide debrief sessions moderated by an expert physician after individual performance evaluations. RESULTS: The apparatus demonstrated high reproducibility across all simulation scenarios, enhancing resident problem-solving skills. Residents' pre-simulation surveys revealed significant concern regarding their acute hemorrhage management. Residents' post-simulation survey demonstrated average realism scores increased from 4.375 to 4.75. Residents also felt the simulator enhanced learning, offering valuable practice and knowledge applicable to their surgical specialty. CONCLUSION: The management of acute hemorrhage during robot-assisted surgery remains a space for additional surgical education and training. Our simulation successfully provided a reliable, reproducible training for residents to practice their technical and non-technical skills in managing acute hemorrhage.

The New Urology Match: How Recent Innovations Including Virtual Interviews and Preference Signaling Have Changed Match Outcomes.

OBJECTIVES: To determine how recent changes in the urology match occurring from 2021 to 2023, including virtual interviews (VIs) and preference signals (PS), affected match outcomes. METHODS: The American Urological Association (AUA) match data from 2021 to 2023 was compared to the 15 years prior. This was obtained from the AUA website and a previous study of public AUA match data. Self-reported applicant characteristics and outcomes from the Urology Residency Applicant Spreadsheet 2021-2023 were compared to the four years prior. RESULTS: Between 2021 and 2023, residency programs offered 43 interviews each, compared to an average of 35 in the 15 years prior. Programs have been receiving more applications each year, from a low of 225 in 2019 to a peak of 347 in 2022. This resulted in an interview offer rate of 13% between 2021 and 2023, compared to 16% in the five years prior. Applicants applied to a mean of 88 programs in 2023, increasing each year since 40 in 2006. Applicants attended 12 interviews on average between 2021 and 2023, compared to 13 in the two years prior. Self-reported applicant data similarly demonstrated that, compared to the four years prior, applicants between 2021 and 2023 applied to more programs (81 vs. 70), had a lower interview offer rate (22% vs. 32%), and a higher interview acceptance rate (90% vs. 75%). CONCLUSIONS: During the years with VIs, programs offered more interviews and applicants attended fewer on average, indicating a larger applicant pool was interviewed. Despite the introduction of PS, applicants applied to more programs in 2022 and 2023 than ever before.

The value of residency program characteristics changes throughout urology training.

INTRODUCTION: The purpose of this study was to determine which characteristics of urology residency programs are most highly valued by medical students and residents, and how these change during training. MATERIALS AND METHODS: We distributed a survey to urology residents and medical students interested in urology via program director email and social media. The survey collected demographic data, future career plans, and asked respondents to rank the relative importance of six categories of residency program characteristics and specific characteristics within each category. RESULTS: Among the six categories of residency characteristics, resident experience was ranked most important by both medical students and residents, followed by geography and clinical experience which were tied. Medical students ranked clinic experience and formal mentorship with greater importance while residents placed higher value on the active role of clinical faculty and help from advanced practice providers. Trainees planning for an academic career ranked research experiences and resident diversity as more important than those entering private practice. CONCLUSIONS: Residents and medical students mostly agreed on the relative importance of residency program characteristics. The differences observed suggest that as trainees gain experience they place greater importance on informal relationships with faculty and value characteristics that enhance surgical training such as support from advanced practice providers and less time in clinic. These findings may guide programs on what information to include on their websites and presentations.

Female sexual health digital resources: women and health care providers need more options.

INTRODUCTION: Female sexual health and female sexual dysfunction (FSD) are usually poorly diagnosed and treated because of the numerous barriers providers and patients face. Internet platforms, such as mobile applications (apps) are potential tools that help overcome these barriers and improve patient access to education and management options for FSD. OBJECTIVES: The aim of this review was to identify existing applications on female sexual health and evaluate their educational content and services. METHODS: We searched the internet and Apple App Store using multiple keywords. A panel of physicians specialized in the treatment of FSD reviewed the apps for content quality, the scientific basis of provided information, interactivity, usability, and whether they would recommend it as a reference tool for patients. RESULTS: Of the 204 apps identified, 17 met the inclusion criteria and were reviewed further. The selected apps were organized into groups based on common themes such as educational (n = 6), emotions and communication (n = 2), relaxation and meditation (n = 4), general sexual health (n = 2), and social and fun (n = 3). All apps from the educational category provided scientific information in collaboration with health experts. When assessed for usability, 1 app received good and 5 received excellent scores based on the System Usability Scale. Most apps (n = 5) provided information on pathology and treatments of orgasmic dysfunction, but only 1 app, created by a physician, provided comprehensive information on all the types of FSD. CONCLUSION: Digital technology could be an effective way to overcome barriers to accessing information and ultimately care for female sexual health. Our review demonstrated that there is still a need for more accessible educational resources addressing female sexual health and FSD for patients and providers.

Focal prostate cancer therapy in the era of multiparametric MRI: a review of options and outcomes.

BACKGROUND: The goal of prostate cancer focal therapy is to achieve oncologic control while reducing the rate of adverse events associated with whole-gland treatments. Numerous focal therapy modalities are currently available with early data demonstrating highly variable rates of cancer control and preservation of sexual/urinary function. METHODS: All English language clinical trial publications evaluating various focal therapies for localized prostate cancer were reviewed. The literature search was limited to studies from the modern era of MRI-guided treatment, as MRI is hypothesized to improve tumor localization and targeting. Primary outcomes were post-treatment cancer-free rates, in-field/out-of-field recurrence rates, and rates of conversion to radical therapy. Secondary outcomes were related to functional status and adverse events. RESULTS: Numerous focal therapies were identified with clinical data including high-intensity focused ultrasound, transurethral ultrasound ablation, focal laser ablation, focal cryotherapy, irreversible electroporation, and photodynamic therapy. Recurrence rates among all technologies were low to moderate (0-51%) and rates of freedom from radical treatment were highly variable (46-98%). Rates of erectile dysfunction and incontinence generally ranged from 0 to 44% and 0 to 12%, respectively, with variability between focal therapy modalities. Caution should be exercised when comparing studies as outcomes are strongly associated with patient selection. No individual focal therapy is currently recommended by society guidelines. Randomized controlled trials are ongoing in search of a standard of care. CONCLUSION: For localized MRI-visible prostate cancer, early clinical trial data demonstrate that focal therapy can provide good to moderate cancer control while having preferable side effect profiles compared to whole-gland treatments. While current studies do not make head-to-head comparisons between technologies, early data suggest a potential for these technologies to provide adequate cancer control in a well-selected patient population. The oncologic outcomes of some focal therapies appear promising; however, longer-term follow-up data are needed to assess the durability of early outcomes.

Clinical and Preclinical Therapies for Bladder Cancer Following Bacillus Calmette-Guérin Failure.

PURPOSE: Intravesical bacillus Calmette-Guérin is the current first-line treatment for high-grade nonmuscle-invasive bladder cancer; however, a substantial proportion of patients are unresponsive to bacillus Calmette-Guérin treatment. While cystectomy is often recommended in bladder cancer following bacillus Calmette-Guérin failure, there are numerous established therapeutic agents and pre-commercialized trials describing treatments for nonmuscle-invasive bladder cancer following failed bacillus Calmette-Guérin treatment. Our objective in this systematic review is to characterize the efficacy of these therapeutic agents by reporting their corresponding complete response rates and toxicity profiles. MATERIALS AND METHODS: We conducted a systematic review of all available clinical trials evaluating therapies to treat recurring nonmuscle-invasive bladder cancer after previous intravesical bacillus Calmette-Guérin. Bacillus Calmette-Guérin failure patients who had previously failed 1 or more courses of prior bacillus Calmette-Guérin therapy were included. Studies that were not in the English language, included muscle-invasive bladder cancer patient populations, or lacked a post-treatment evaluation of response were excluded. We used PubMed/Medline, the Cochrane Library, and Embase to search for relevant studies. No formal risk of bias assessment was conducted. Complete response rates for 3, 6, 12, and 24 months post-treatment evaluation, progression rates, cystectomy rates, and 12 complications are reported. RESULTS: A total of 70 studies with 73 reports evaluating 27 treatment options were retained for final analysis. These treatments were reported in 5 categories including intravesical chemotherapy, combination therapy, hyperthermia paired with intravesical chemotherapy, immunotherapy, and novel agents, with published years ranging from 1998 to 2021. Single intravesical chemotherapy and the combination of multiple intravesical chemotherapy agents demonstrate varied complete response rates of 10%-83% at 12 months. Limited clinical data evaluating hyperthermia paired with chemotherapy demonstrate 12-month complete response rates of 50%-85%. Despite these reported response rates, progression rates ranged from 0%-18%. Moreover, immunotherapeutic agents demonstrate progression rates of 7% to 22% at a median of 12 months of follow-up. Novel agents displayed a wide range of complete response rates (6% to 91%) at 12 months based on the treatment used. Total grade 3 toxicity rates range from 0%-55% for intravesical chemotherapy and combination intravesical chemotherapy agents, 0%-15% for hyperthermia paired with chemotherapy agents, 12%-13% for immunotherapy agents, and 0%-17% for novel agents. CONCLUSIONS: Bladder-preserving treatments accomplish moderate success in nonmuscle-invasive bladder cancer following bacillus Calmette-Guérin failure. As the majority of available clinical trials are single-armed uncontrolled cohorts and contain a limited number of patients, strength and comparability of the data are limited. In general, intravesical chemotherapy and hyperthermia paired with mitomycin C demonstrate some of the highest complete response rates at 12 and 24 months. Similarly, among the pre-commercialized novel agents, N-803 and gene therapy display promising results and may serve as potential future treatment for nonmuscle-invasive bladder cancer following failed bacillus Calmette-Guérin treatment. In terms of toxicity/complication rates, both commercially available and unavailable treatments showcase low toxicity profiles for bladder cancer following bacillus Calmette-Guérin failure. The comprehensive analysis provided by this systematic review can serve as a reference for treatment decisions and clinical trial design in the bacillus Calmette-Guérin-unresponsive domain.

Definitive treatment choice among Black immigrants with prostate cancer: Analysis of patient surveys distributed at a single safety-net institution.

BACKGROUND: Large-scale prostate cancer (PCa) database reviews have found a consistent discrepancy in the mortality rate in Black patients compared to their White counterparts. Furthermore, differences in PCa treatment and outcomes among Black men of different ethnic origins have also been identified. Due to the heterogeneity of PCa-impacted communities and the unclear impact of patient immigration status on treatment outcomes, we sought to determine the demographic factors associated with treatment choice for definitive treatment of PCa in our single institution's patient population of Black immigrants. METHODS: We distributed surveys to all patients in the Kings County Hospital Center urologic oncology clinic from February 2019 to February 2020 and collected relevant health information via EMR. The survey collected demographic information regarding age, education, health insurance, employment status, socioeconomic status, country of birth, and years living in the United States (US). RESULTS: Out of the 253 patients surveyed, the majority of patients surveyed were Black and foreign born. There were no significant differences in demographic data between US-born and foreign-born patients except number of years living in the United States. In the intermediate risk group, patients living in the United States for <10 years chose surgery significantly more often than US-born patients (90.9% vs. 50.0%, p = 0.036). On multivariate analysis, patients that chose surgery were more likely to be older when diagnosed (odds ratio [OR] = 1.21) and less likely to be born in the United States than in African or Caribbean countries (OR = 0.054). CONCLUSIONS: In our study of a majority-Black population, we found that patients born in the United States were less likely than their foreign counterparts to opt for surgery, as previous studies have shown. The choice of definitive treatment modality for Black men with intermediate risk PCa was found to be influenced by age at diagnosis and immigration status.

Perspectives of Residency Applicants and Program Directors on the Role of Social Media in the 2021 Urology Residency Match.

OBJECTIVES: To perform a survey assessing the use of, attitudes towards, and perceived utility of social media (SoMe) in the 2021 urology residency match. METHODS: We distributed surveys to urology residency applicants and program directors (PDs) via the Urology Match 2021 Google Spreadsheet and email. The survey collected demographic information as well as SoMe activity, perceived pressure to use SoMe, match results, and attitudes regarding the utility of SoMe in the match process. RESULTS: A total of 108/528 (20%) applicants registered for the 2021 match and 61/142 (43%) PDs completed the survey. More applicants than PDs felt that SoMe helped them gain better insight into residency programs or applicants, respectively. Fewer applicants than PDs felt that SoMe activity provided a benefit to them in the match process. No significant relationship was found between SoMe viewing frequency, posting frequency, or tweetorial use with match outcomes. The majority of PDs believed that SoMe played a more important role in the 2021 match process than previous years while 15% and 12% reported that an applicant's SoMe activity helped or hurt the chances of matching to their program respectively. CONCLUSIONS: SoMe, particularly Twitter, was widely used in the 2021 match by both applicants and PDs. A majority of applicants and PDs believed that SoMe use aided them in some way in the match process, yet there was no relationship between the volume or type of applicant SoMe activity and match outcomes.

Catching a Big Fish with a Small Net: Factors Associated with First-Choice Match from Urology Residency Applicants' Self-Reported Data.

INTRODUCTION: We sought to determine the accuracy of self-reported urology applicant match data and determine which factors were most influential on successful application outcomes. METHODS: A publicly accessible Google spreadsheet entitled "Urology Residency Applicant Spreadsheet" containing self-reported urology residency applicant characteristics and match outcomes was analyzed for differences across the years 2017+2018 (pre-aggregated)-2020. These data were compared to published data from the American Urological Association and the Association of American Medical Colleges. Statistical modeling of the self-reported data was performed to determine which applicant characteristics were predictive of match outcomes. RESULTS: Averages of self-reported data were similar to published match data with a bias towards more competitive applicants. The factors associated with increased interview offer rate were: Step 1 score, Step 2 score, number of research items, class quartile, and Alpha Omega Alpha membership. Logistic regression modeling correctly predicted an applicant matching to their first-choice program with 74.7% accuracy, with significant negative predictors being the number of programs to which the applicant applied and interviews offered from waitlist or cancellations, and positive predictors being the number of interview offers received. CONCLUSIONS: Many applicants "apply broadly" with the goal of improving their match outcomes, but we found that applying to more programs is associated with a decreased likelihood of the applicant matching to their first-choice program. Applicant characteristics such as United States Medical Licensing Examination® scores were not related to first-choice match, suggesting that program selection, among other factors, is vital in the match process.

Pathological downstaging as a novel endpoint for the development of neoadjuvant chemotherapy for upper tract urothelial carcinoma.

OBJECTIVES: To evaluate whether pathological downstaging (pDS) was more informative in predicting overall survival (OS) than pathological complete response (pCR) in patients treated with neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: The National Cancer Database was queried for patients with high-grade cN0M0 disease who had received NAC. pDS was defined as a decrease of at least one stage from cT to pT stage along with pN0, including pCR. A multivariable Cox model predicting OS was generated by fitting alternatively either pDS or pCR, and adjusted for potential confounders. The discrimination of the Cox models for predicting OS was evaluated using Harrell's C-index. The analyses were repeated in patients diagnosed as having cT2-4N0M0 disease. RESULTS: Among 264 patients meeting the inclusion criteria, 72 (27%) and 39 (15%) achieved pDS and pCR, respectively. On multivariable analysis, both pDS (hazard ratio [HR] 0.24, 95% confidence interval [CI] 0.13, 0.45; P < 0.001) and pCR (HR 0.37, 95% CI 0.18, 0.79; P = 0.01) were associated with OS. The model including pDS achieved better discrimination with respect to the model including pCR: C-index 76.4 vs 72.7, respectively. In the 128 patients diagnosed with cT2-4 disease, both pDS (HR 0.19, 95% CI 0.09, 0.40; P < 0.001) and pCR (HR 0.31, 95% CI 0.11, 0.85; P = 0.023) were confirmed as predictors of OS. The model including pDS was confirmed to discriminate better than the model including pCR: C-index 75 vs 68.9, respectively. CONCLUSION: The study showed that pDS after NAC for UTUC was more informative than pCR when predicting OS. These findings, although requiring prospective validation, can aid in the design of clinical trials seeking to refine the use of chemotherapy and other systemic therapies in this setting.

Homologous recombination is an intrinsic defense against antiviral RNA interference.

RNA interference (RNAi) is the major antiviral defense mechanism of plants and invertebrates, rendering the capacity to evade it a defining factor in shaping the viral landscape. Here we sought to determine whether different virus replication strategies provided any inherent capacity to evade RNAi in the absence of an antagonist. Through the exploitation of host microRNAs, we recreated an RNAi-like environment in vertebrates and directly compared the capacity of positive- and negative-stranded RNA viruses to cope with this selective pressure. Applying this defense against four distinct viral families revealed that the capacity to undergo homologous recombination was the defining attribute that enabled evasion of this defense. Independent of gene expression strategy, positive-stranded RNA viruses that could undergo strand switching rapidly excised genomic material, while negative-stranded viruses were effectively targeted and cleared upon RNAi-based selection. These data suggest a dynamic relationship between host antiviral defenses and the biology of virus replication in shaping pathogen prevalence.

Hippocampal-dependent neurocognitive impairment following cranial irradiation observed in pre-clinical models: current knowledge and possible future directions.

We reviewed the literature for studies pertaining to impaired adult neurogenesis leading to neurocognitive impairment following cranial irradiation in rodent models. This compendium was compared with respect to radiation dose, converted to equivalent dose in 2 Gy fractions (EQD2) to allow for direct comparison between studies. The effects of differences between animal species and the dependence on animal age as well as for time after irradiation were also considered. One of the major sites of de novo adult neurogenesis is the hippocampus, and as such, this review also focuses on assessing evidence related to the expression and potential effects of inflammatory cytokines on neural stem cells in the subgranular zone of the dentate gyrus and whether this correlates with neurocognitive impairment. This review also discusses potential strategies to mitigate the detrimental effects on neurogenesis and neurocognition resulting from cranial irradiation, and how the rationale for these strategies compares with the current outcome of pre-clinical studies.

A mouse model replicating hippocampal sparing cranial irradiation in humans: A tool for identifying new strategies to limit neurocognitive decline.

Cancer patients undergoing cranial irradiation are at risk of developing neurocognitive impairments. Recent evidence suggests that radiation-induced injury to the hippocampi could play an important role in this cognitive decline. As a tool for studying the mechanisms of hippocampal-dependent cognitive decline, we developed a mouse model replicating the results of the recent clinical RTOG 0933 study of hippocampal sparing whole-brain irradiation. We irradiated 16-week-old female C57BL/6J mice to a single dose of 10 Gy using either whole-brain irradiation (WBRT) or hippocampal sparing irradiation (HSI). These animals, as well as sham-irradiated controls, were subjected to behavioral/cognitive assessments distinguishing between hippocampal-dependent and hippocampal-independent functions. Irradiation was well tolerated by all animals and only limited cell death of proliferating cells was found within the generative zones. Animals exposed to WBRT showed significant deficits compared to sham-irradiated controls in the hippocampal-dependent behavioral task. In contrast, HSI mice did not perform significantly different from sham-irradiated mice (control group) and performed significantly better when compared to WBRT mice. This is consistent with the results from the RTOG 0933 clinical trial, and as such this animal model could prove a helpful tool for exploring new strategies for mitigating cognitive decline in cancer patients receiving cranial irradiation.

A 300 GHz collective scattering diagnostic for low temperature plasmas.

A compact and portable 300 GHz collective scattering diagnostic employing a homodyne detection scheme has been constructed and installed on the hot helicon experiment (HELIX). Verification of the homodyne detection scheme was accomplished with a rotating grooved aluminum wheel to Doppler shift the interaction beam. The HELIX chamber geometry and collection optics allow measurement of scattering angles ranging from 60 degrees to 90 degrees. Artificially driven ion-acoustic waves are also being investigated as a proof-of-principle test for the diagnostic system.