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Objective: To compare appointment availability and wait times between private equity-owned and non-private equity-owned urology clinics for 2 common urologic complaints., Methods: We identified all PE-owned urology clinic locations as of June 2022 (n = 390). For each PE-owned location, a geographically matched, non-PE-owned clinic was identified. Each office was called using a "secret shopper" method with a standardized script, requesting an appointment on behalf of their Medicare-aged father for evaluation of gross hematuria or elevated prostate-specific antigen (PSA). The primary outcome was appointment availability, and the secondary outcome was wait time until soonest appointment., Results: PE-owned and non-PE-owned clinics treated the presenting complaints with similar frequency (gross hematuria: 85% vs 88%, P = .3, elevated PSA: 93% vs 94%, P = .5). Wait time in days until the next available appointment was similar for PE-owned clinics compared to non-PE clinics for both complaints (gross hematuria: 16 vs 13, P = .06, elevated PSA: 18 vs 19, P = .7). If available, the time in days until the soonest next appointment with an advanced practice provider was also similar between PE-owned and non-PE clinics (gross hematuria: 13 vs 11, P = .07, elevated PSA: 13 vs 12, P = .6)., Conclusion: Overall, there were no large-scale differences in access to outpatient urologic care between PE-owned clinics and non-PE-owned clinics. Access to care in PE-owned clinics is likely clinically similar to geographic-matched controls for Medicare patients with gross hematuria or elevated PSA., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To examine changes in late- versus early-stage diagnosis of cancer associated with the introduction of mandatory Medicaid managed care (MMC) in Pennsylvania., Data Sources and Study Setting: We analyzed data from the Pennsylvania cancer registry (2010-2018) for adult Medicaid beneficiaries aged 21-64 newly diagnosed with a solid tumor. To ascertain Medicaid and managed care status around diagnosis, we linked the cancer registry to statewide hospital-based facility records collected by an independent state agency (Pennsylvania Health Care Cost Containment Council)., Study Design: We leveraged a natural experiment arising from county-level variation in mandatory MMC in Pennsylvania. Using a stacked difference-in-differences design, we compared changes in the probability of late-stage cancer diagnosis among those residing in counties that newly transitioned to mandatory managed care to contemporaneous changes among those in counties with mature MMC programs., Data Collection/extraction Methods: N/A., Principal Findings: Mandatory MMC was associated with a reduced probability of late-stage cancer diagnosis (-3.9 percentage points; 95% CI: -7.2, -0.5; p = 0.02), particularly for screening-amenable cancers (-5.5 percentage points; 95% CI: -10.4, -0.6; p = 0.03). We found no significant changes in late-stage diagnosis among non-screening amenable cancers., Conclusions: In Pennsylvania, the implementation of mandatory MMC for adult Medicaid beneficiaries was associated with earlier stage of diagnosis among newly diagnosed cancer patients with Medicaid, especially those diagnosed with screening-amenable cancers. Considering that over half of the sample was diagnosed with late-stage cancer even after the transition to mandatory MMC, Medicaid programs and managed care organizations should continue to carefully monitor receipt of cancer screening and design strategies to reduce barriers to guideline-concordant screening or diagnostic procedures., (© 2024 Health Research and Educational Trust.)

Introduction: We sought to implement a multipronged behavioral intervention to reduce and tailor antibiotic use for 2 common urologic outpatient procedures., Methods: This study was a nonblinded intervention study that consisted of a preintervention phase (November 2018-January 2019), an intervention phase (January 2020-December 2020) in which a multipronged behavioral intervention was implemented, and a postintervention phase (January 2021-March 2021). We examined antibiotic use for cystoscopy and transrectal prostate biopsy at 3 separate urologic outpatient clinics. A multipronged behavioral intervention consisted of formal physician education, modification of the electronic health order sets, clinic staff education, literature review, development and introduction of patient questionnaires, and individual audit feedback. The primary outcome was 30-day infections. Secondary outcomes were adherence to the recommended antibiotic protocols, questionnaire completion, and Escherichia coli outpatient antibiograms., Results: A total of 2374 patients underwent 3047 cystoscopies, and 547 patients underwent 559 prostate biopsies. The proportions of cystoscopy patients receiving antibiotic prophylaxis and prostate biopsy patients receiving augmented antibiotic prophylaxis decreased 33% and 35%, respectively. The odds of postcystoscopy infection were not different between the preintervention and intervention phases and were lower in the postintervention phase. The odds of postbiopsy infection were not changed between the preintervention and intervention phases or between the preintervention and postintervention phases., Conclusions: Implementing a multipronged behavioral intervention reduced and tailored antibiotic use without an increase in 30-day infections. These findings suggest that outpatient antibiotic stewardship and facilitating rapid adoption of guidelines can be accomplished via this approach.

Sarracenia purpurea is a carnivorous plant historically used to treat smallpox infections. Our previous data found S. purpurea had broad spectrum antiviral activity in vitro. S. purpurea is one of several hundred identified carnivorous species of plants. Carnivorous plants have evolved through convergent evolution in at least ten independent events, usually in response to harsh environments where nutrition from prey is required for growth. These prey are known vectors of plant viruses that might introduce novel biotic stressors and defense pathways in carnivorous plants. This study evaluated the antiviral activity of several non-carnivorous and carnivorous plants from four evolutionarily distinct clades. Results demonstrated that carnivorous plants have evolved antiviral activity, a trait that is not present in related species of non-carnivorous plants. The antiviral trait may be due to the plant-prey relationship with insect vectors and an evolutionary need for carnivorous plants to have more robust antiviral defense systems., Competing Interests: Declaration of competing interest 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.)

Introduction and Objectives: Radical cystectomy readmission rates remain high, with around 25% of patients readmitted to index and nonindex hospitals in 30 days. Nonindex readmissions have been associated with poorer outcomes, including longer lengths of stay and higher mortality rates. This study aimed to examine the associations of social factors (e.g., sex, race, socioeconomic status, insurance type, and resident location) on readmission to index versus nonindex hospitals and discharge disposition., Methods: We conducted a population-based retrospective study using the Pennsylvania Cancer Registry (PCR) to identify patients diagnosed with nonmetastatic muscle-invasive bladder cancer who underwent radical cystectomy in Pennsylvania between 2010 and 2018. Readmitted patients were identified using the Pennsylvania Health Care Cost Containment Council data (PHC4). The primary outcome was readmission location (i.e., index or nonindex hospital) following radical cystectomy. We used chi-square tests for categorical variables, Wilcoxon rank sum test for continuous variables, multivariable logistic regression model to assess predictors of being readmitted to an index hospital and calculating the predicted probability of being admitted to an index hospital depending on discharge disposition., Results: A total of 517 patients were readmitted within 30-days after radical cystectomy. The majority of readmissions were index readmissions (83%). Median readmission hospital stay was 4 days (interquartile range [IQR] 4) for index and 5 days (IQR 7) for nonindex hospitals, P = 0.01. Patients readmitted to index hospitals had fewer comorbidities (median weighted Elixhauser Comorbidity Index 2 (IQR 2)) and lived in urban areas (89%). Discharge with home care was associated with a higher odds of index readmission (odds ratio, [OR] 2.40; 95% confidence interval, [CI] 1.25-4.52)., Conclusions: Patients residing in urban areas and with fewer comorbidities were more likely to be readmitted to index hospitals than nonindex hospitals. Socioeconomic status and insurance type did not correlate with the type of readmission. Finally, being discharged with home health care was found to be a predictor of readmission to an index hospital., Competing Interests: Declaration of competing interest 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 Elsevier Inc. All rights reserved.)

Objective: To investigate stereotactic body radiation (SBRT) adoption for prostate cancer. As evidence supporting SBRT mounts, its utilization and impact relative to other prostate cancer treatments is unknown., Methods: We used SEER-Medicare to identify patients diagnosed with localized prostate cancer from 2008 to 2017. We then identified physician networks by identifying the primary treating physician of each patient based on primary treatment, then linking each physician to a practice. We examined trends in prostate cancer treatment between networks performing SBRT or not using chi-squared tests and logistic regression models., Results: There were 35,972 patients who received treatment for prostate cancer at 234 physician networks. Of these patients, 30,635 were treated in a non-SBRT network (n = 190), while 5337 received treatment in a SBRT network (n = 44). Patients who received care in an SBRT network were more likely to live in metropolitan areas ≥1 million (70% vs 46%, P <.001), have a higher median income >$60,000 (62% vs 42%, P <.001), and live in the northeast (35% vs 12%) or west (40% vs 38%, P <.001) compared to non-SBRT networks. In SBRT networks, more patients received IMRT (31% vs 23%), and fewer patients received prostatectomy (16% vs 23%) or active surveillance (15% vs 19%) compared to non-SBRT networks. Black men were 45% less likely to receive SBRT (OR=0.55, CI: 0.36-0.85) compared to White men., Conclusion: SBRT utilization is increasing relative to other prostate cancer treatments. Prostate cancer treatment mix is different in networks that offer SBRT, and SBRT is less available to some patient groups, raising concern for novel treatment inequity., Competing Interests: Declaration of Competing Interest 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 Elsevier Inc. All rights reserved.)

Prostate cancer is the second most diagnosed cancer and the fifth leading cause of cancer death among men worldwide. In the 1980s, the development and implementation of Prostate-Specific Antigen (PSA) testing for diagnosing prostate cancer led to a surge in the number of prostate cancer diagnoses. We explore the trends in recommendations and new innovations in adjunctive testing for prostate cancer screening., Competing Interests: Declaration of competing interest Our research group was asked to write a review article detailing the change in prostate cancer screening practices over the past several years. We are sincerely grateful for this opportunity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: This study aims to determine if there is a difference in prostate cancer nomogram-adjusted risk of biochemical recurrence (BCR) and/or adverse pathology (AP) between African American (AAM) and Caucasian men (CM) undergoing radical prostatectomy (RP)., Methods: A retrospective review was performed of men undergoing RP in the Pennsylvania Urologic Regional Collaborative between 2015 and 2021. Cox proportional hazard regression models were used to compare the rate of BCR after RP, and logistic regression models were used to compare rates of AP after RP between CM and AAM, adjusting for the CAPRA, CAPRA-S, and MSKCC pre- and post-operative nomogram scores., Results: Rates of BCR and AP after RP were analyzed from 3190 and 5029 men meeting inclusion criteria, respectively. The 2-year BCR-free survival was lower in AAM (72.5%) compared to CM (79.0%), with a hazard ratio (HR) of 1.38 (95% CI 1.16-1.63, p < 0.001). The rate of BCR was significantly greater in AAM compared to CM after adjustment for MSKCC pre-op (HR 1.29; 95% CI 1.08-1.53; p = 0.004), and post-op nomograms (HR 1.26; 95% CI 1.05-1.49; p < 0.001). There was a trend toward higher BCR rates among AAM after adjustment for CAPRA (HR 1.13; 95% CI 0.95-1.35; p = 0.17) and CAPRA-S nomograms (HR 1.11; 95% 0.93-1.32; p = 0.25), which did not reach statistical significance. The rate of AP was significantly greater in AAM compared to CM after adjusting for CAPRA (OR 1.28; 95% CI 1.10-1.50; p = 0.001) and MSKCC nomograms (OR 1.23; 95% CI 1.06-1.43; p = 0.007)., Conclusion: This analysis of a large multicenter cohort provides further evidence that AAM may have higher rates of BCR and AP after RP than is predicted by CAPRA and MSKCC nomograms. Accordingly, AAM may benefit with closer post-operative surveillance and may be more likely to require salvage therapies., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To examine differential changes in receipt of surgery at National Cancer Institute (NCI)-designated comprehensive cancer centers (NCI-CCC) and Commission on Cancer (CoC) accredited hospitals for patients with cancer more likely to be newly eligible for coverage under Affordable Care Act (ACA) insurance expansions, relative to those less likely to have been impacted by the ACA., Data Sources and Study Setting: Pennsylvania Cancer Registry (PCR) for 2010-2019 linked with discharge records from the Pennsylvania Health Care Cost Containment Council (PHC4)., Study Design: Outcomes include whether cancer surgery was performed at an NCI-CCC or a CoC-accredited hospital. We conducted a difference-in-differences analysis, estimating linear probability models for each outcome that control for residence in a county with above median county-level pre-ACA uninsurance and the interaction between county-level baseline uninsurance and cancer treatment post-ACA to capture differential changes in access between those more and less likely to become newly eligible for insurance coverage (based on area-level proxy). All models control for age, sex, race and ethnicity, cancer site and stage, census-tract level urban/rural residence, Area Deprivation Index, and year- and county-fixed effects., Data Collection/extraction Methods: We identified adults aged 26-64 in PCR with prostate, lung, or colorectal cancer who received cancer-directed surgery and had a corresponding surgery discharge record in PHC4., Principal Findings: We observe a differential increase in receiving care at an NCI-CCC of 6.2 percentage points (95% CI: 2.6-9.8; baseline mean = 9.8%) among patients in high baseline uninsurance areas (p = 0.001). Our estimate of the differential change in care at the larger set of CoC hospitals is positive (3.9 percentage points [95% CI: -0.5-8.2; baseline mean = 73.7%]) but not statistically significant (p = 0.079)., Conclusions: Our findings suggest that insurance expansions under the ACA were associated with increased access to NCI-CCCs., (© 2024 The Authors. Health Services Research published by Wiley Periodicals LLC on behalf of Health Research and Educational Trust.)

Purpose: Older cancer survivors have substantial needs for ongoing care, but they may encounter difficulties accessing care due to cost concerns. We examined whether near-universal insurance coverage through Medicare-a key source of health insurance coverage in this population-is associated with improvements in care access and affordability among older cancer survivors around age 65., Methods: In a nationally representative sample of cancer survivors (aged 50-80) from 2006-2018 National Health Interview Survey, we employed a quasi-experimental, regression discontinuity design to estimate changes in insurance coverage, delayed/skipped care due to cost, and worries about or problems paying medical bills at age 65., Results: Medicare coverage sharply increased from 8.3% at age 64 to 98.2% at age 65, ensuring near-universal insurance coverage (99.5%). Medicare eligibility at age 65 was associated with reductions in delayed/skipped care due to cost (discontinuity, - 5.7 percentage points or pp; 95% CI, - 8.1, - 3.3; P < .001), worries about paying for medical bills (- 7.7 pp; 95% CI, - 12.0, - 3.2; P = .001), and problems paying medical bills (- 3.2 pp; 95% CI, - 6.1, - 0.2; P = .036). However, a sizable proportion reported any access or affordability problems (29.7%) between ages 66 and 80., Conclusions: Near-universal Medicare coverage at age 65 was associated with a reduction-but not elimination-of access and affordability problems among cancer survivors., Implications for Cancer Survivors: These findings reaffirm the role of Medicare in improving access and affordability for older cancer survivor and highlight opportunities for reforms to further alleviate financial burden of care in this population., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To identify antibiotic prescribing patterns at the time of foley catheter removal after radical prostatectomy and implement a multi-pronged behavioral intervention to standardize antibiotic use., Methods: This was a single-institution study examining the prescribing of antibiotics at the time of foley catheter removal after radical prostatectomy. Pre-intervention data were collected retrospectively to establish baselines for antibiotic prescribing, patient characteristics, and urinary tract infection rates. A single dose of an oral antibiotic taken at the time of foley catheter removal was recommended as the standard antibiotic protocol. A multi-pronged behavioral intervention was used to encourage compliance with our protocol. Adherence to the protocol, quantity of antibiotics prescribed, and rate of urinary tract infection were recorded prospectively. Durability of the intervention was evaluated during a post-intervention phase., Results: A total of 416 patients and 6 surgeons were included in the study. Accordance with the standardized antibiotic protocol was 59% in the pre-intervention phase and 91% in the intervention phase (P = .03). No patients in the intervention or post-intervention phase were prescribed more than one dose of an antibiotic. The rate of urinary tract infection did not differ across the study phases., Conclusion: Implementation of a multi-pronged behavioral intervention resulted in a high rate of surgeon compliance with a standardized antibiotic protocol. This led to a significant reduction in antibiotic use with no change in the rate of urinary tract infection after foley catheter removal after radical prostatectomy., Competing Interests: Declaration of Competing Interest No authors have any conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Disparities in prostate, bladder, and kidney cancer outcomes are associated with access to care. Telemedicine can improve access but may be underutilized by certain patient populations. Our objective was to determine if the patient populations who suffer worse oncologic outcomes are the same as those who are less likely to use telemedicine., Methods: Using an institutional database, we identified all prostate, bladder and kidney cancer encounters from March 14, 2020 to October 31, 2021 (n = 15,623; n = 4, 14; n = 3,830). Telemedicine was used in 13%, 8%, and 12% of these encounters, respectively. We performed random effects modeling analysis to examine patient and provider characteristics associated with telemedicine use. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were reported as measures of association., Results: Among prostate, bladder, and kidney cancer patients, Black patients had lower odds of a telemedicine encounter (OR 0.51, 95% CI 0.37-0.69; OR 0.22, 95% CI 0.07-0.70; OR 0.46, 95% CI 0.24-0.86), and patients residing in small and isolated small rural towns areas had higher odds of a telemedicine encounter (OR 1.44, 95% CI 1.09-1.91; OR 2.12, 95% CI 1.14-3.94; OR 1.89, 95% CI 1.12-3.19). Compared to providers in practice ≤5 years, providers in practice for 6 to 15 years had significantly higher odds of a telemedicine encounter for prostate and bladder cancer patients (OR 4.10, 95% CI 1.4511.58; OR 3.42, 95% CI 1.09-10.77)., Conclusion: The lower rates of telemedicine use among Black patients could exacerbate pre-existing disparities in prostate, bladder, and kidney cancer outcomes., Competing Interests: Declaration of competing interest 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 © 2023 Elsevier Inc. All rights reserved.)

Poxviruses are notorious for having acquired/evolved numerous genes to counteract host innate immunity. Chordopoxviruses have acquired/evolved at least three different inhibitors of host necroptotic death: E3, which blocks ZBP1-dependent necroptotic cell death, and vIRD and vMLKL that inhibit necroptosis downstream of initial cell death signaling. While this suggests the importance of the necroptotic cell death pathway in inhibiting chordopoxvirus replication, several chordopoxviruses have lost one or more of these inhibitory functions. Monkeypox/mpox virus (MPXV) has lost a portion of the N-terminus of its E3 homologue. The N-terminus of the vaccinia virus E3 homologue serves to inhibit activation of the interferon-inducible antiviral protein, ZBP1. This likely makes MPXV unique among the orthopoxviruses in being sensitive to interferon (IFN) treatment in many mammals, including humans, which encode a complete necroptotic cell death pathway. Thus, IFN sensitivity may be the Achille's Heel for viruses like MPXV that cannot fully inhibit IFN-inducible, ZBP1-dependent antiviral pathways., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Objective: To develop a multipronged, evidence-based protocol to reduce readmission risk and readmission intensity, as represented by the duration of the index readmission, after radical cystectomy., Materials and Methods: A per-protocol study was performed. The protocol included preoperative nutritional supplementation, early stent removal, and a follow-up phone call within 4-5days of discharge. The preprotocol period was from February 1, 2020 to July 31, 2021 and the postprotocol period was from December 1, 2020 to November 31, 2021. Using multivariate regression models, we compared outcomes among patients treated with radical cystectomy before and after protocol initiation., Results: We identified 70 preprotocol patients and 126 postprotocol patients. After adjusting for age, sex, BMI, and frailty score, there was a significant reduction in 90-day readmission intensity (7 vs 5days; P = .048) among postprotocol patients., Conclusion: After implementation of an evidence-based protocol for patients undergoing radical 90-day readmission intensity decreased significantly. This protocol may move the needle forward on reducing readmissions, but a larger randomized trial is needed., Competing Interests: Declaration of Competing Interest 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 © 2023. Published by Elsevier Inc.)

Objective: To report the outcomes of performing transperineal prostate biopsy in the office setting using the novel anesthetic technique of tumescent local anesthesia. We report anxiety, pain, and embarrassment of patients who underwent this procedure compared to patients who underwent a transrectal prostate biopsy using standard local anesthesia., Materials and Methods: Consecutive patients undergoing either a transperineal prostate biopsy under tumescent local anesthesia or a transrectal prostate biopsy with standard local anesthetic technique were prospectively enrolled. The tumescent technique employed dilute lidocaine solution administered using a self-filling syringe. Patients were asked to rate their pain before, during, and after their procedure using a visual analog scale. Patient anxiety and embarrassment was assessed using the Testing Modalities Index Questionnaire., Results: Between April 2021 and June 2022, 430 patients underwent a transperineal prostate biopsy using tumescent local anesthesia and 65 patients underwent a standard transrectal prostate biopsy. Patients who underwent a transperineal biopsy had acceptable but significantly higher pain scores than those who underwent a transrectal prostate biopsy (3.9 vs 1.6, P-value <.01). These scores fell to almost zero immediately following their procedure. Additionally, transperineal biopsy patients were more likely to experience anxiety (71% vs 45%, P < .01) and embarrassment (32% vs 15%, P < .01)., Conclusion: Transperineal biopsy using local tumescent anesthesia is safe and well-tolerated. Despite the benefits, patients undergoing a transperineal prostate biopsy under tumescent anesthesia still experienced worse procedural pain, anxiety, and embarrassment. Additional studies examining other adjunctive interventions to improve patient experience during transperineal prostate biopsy are needed., Competing Interests: Declaration of Competing Interest Matthew Allaway: CEO of Perineologic. Michael Gorin: Former Paid Consultant for Perineologic. The other authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To better understand the association between high-volume surgical kidney cancer centers and decreased mortality. To identify quality metrics that mediate this association., Methods: We designed a cohort of 14,044 patients who were diagnosed with kidney cancer between 2004 and 2013 and underwent a partial or radical nephrectomy using SEER-Medicare data. Hospitals were divided into quartiles based on their total nephrectomy volume for the study period. We investigated 6 quality metrics as potential mediators of the association between hospital volume and mortality using a mediation model., Results: At the highest volume centers, survival was higher at 1-, 3-, 5-, and 10-year time intervals, respectively (91% vs 89%, 80% vs 76%, 70% vs 66%, 45% vs 38%, P < .001) compared to the lowest quartile nephrectomy centers. Receipt of partial nephrectomy for stage ≤T1a tumors explains 52.3% of the total association between hospital nephrectomy volume and mortality. Additionally, patients at the highest-volume centers were more likely to be younger (20% vs 26% 80≤ years old, P < .001), white (82% vs 78%, P < .001), reside in more densely populated counties (≥1 million residents, 62% vs 42%, P > .001), have a shorter mean length of stay (5.03 vs 5.88days, P < .001) when compared to those in the lowest-volume quartile., Conclusion: This analysis of SEER-Medicare data is the first to suggest that partial nephrectomy in the setting of T1a tumors mediates the association between hospital volume and mortality. Quality metrics that reduce mortality should be harnessed to develop more efficient and higher-quality health systems., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To determine agreement between variables capturing the primary payer at cancer diagnosis across the Pennsylvania Cancer Registry (PCR) and statewide facility discharge records (Pennsylvania Health Care Cost Containment Council [PHC4]) for adults younger than 65 years, and to specifically examine factors associated with misclassification of Medicaid status in the registry given the role of managed care., Study Design: Cross-sectional analysis of the primary cancer cases among adults aged 21 to 64 years in the PCR from 2010 to 2016 linked to the PHC4 facility visit records., Methods: We assessed agreement of payer at diagnosis (Medicare, Medicaid, private, other, uninsured, unknown) across data sources, including positive predictive value (PPV) and sensitivity, using the PHC4 records as the gold standard. The probability of misclassifying Medicaid in registry was estimated using multivariate logit models., Results: Agreement of payers was high for private insurance (PPV, 89.7%; sensitivity, 83.6%), but there was misclassification and/or underreporting of Medicaid in the registry (PPV, 80%; sensitivity, 58%). Among cases with "other" and "unknown" insurance, 73.8% and 62.1%, respectively, had private insurance according to the PHC4 records. Medicaid managed care was associated with a statistically significant increase of 12.6 percentage points (95% CI, 9.4-15.8) in the probability of misclassifying Medicaid enrollment as private insurance in the registry., Conclusions: Findings suggest caution in conducting and interpreting research using insurance variables in cancer registries.

Background: Multidisciplinary models of care have been advocated for prostate cancer (PC) to promote shared decision-making and facilitate quality care. Yet, how this model applies to low-risk disease where the preferred management is expectant remains unclear. Accordingly, we examined recent practice patterns in specialty visits for low/intermediate-risk PC and resultant use of active surveillance (AS)., Methods: Using SEER-Medicare, we ascertained whether patients saw urology and radiation oncology (i.e., multispecialty care) versus urology alone, based on self-designated specialty codes, for newly diagnosed PC from 2010 to 2017. We also examined the association with AS, defined as the absence of treatment within 12 months of diagnosis. Time trends were analyzed using Cochran-Armitage test. Chi-squared and logistic regression analyses were applied to compare sociodemographic and clinicopathologic characteristics between these models of care., Results: The proportion of patients seeing both specialists was 35.5% and 46.5% for low- and intermediate-risk patients respectively. Trend analysis showed a decline in multispecialty care in low-risk patients (44.1% to 25.3% years 2010-2017; P < 0.001). Between 2010 and 2017, the use of AS increased 40.9% to 68.6% (P < 0.001) and 13.1% to 24.6% (P < 0.001) for patients seeing urology and those seeing both specialists respectively. Age, urban residence, higher education, SEER region, co-morbidities, frailty, Gleason score, predicted receipt of multispecialty care (all P < 0.02)., Conclusions: Uptake of AS among men with low-risk PC has occurred primarily under the purview of urologists. While selection is certainly at play, these data suggest that multispecialty care may not be required to promote the utilization of AS for men with low-risk PC., Competing Interests: Declaration of Competing Interest The database infrastructure used for this project was supported by the CER Strategic Initiative of UNC's Clinical &Translational Science Award (UL1TR002489). Soohyun Hwang and Dr. Tan were further supported by a Discovery Grant from Advancing Cancer Treatment (A21-1380-001). There are no other conflict of interest disclosures for the authors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To measure the changes in treatment patterns for non-muscle invasive bladder cancer before and during the Bacillus Calmette-Guerin (BCG) drug shortage., Materials and Methods: We used a 5% random sample of Medicare beneficiaries and identified 7971 bladder cancer patients (2648 pre-BCG shortage and 5323 during the shortage) ≥66 years of age who received intravesical treatment within 1 year of diagnosis between 2010 and 2017. The BCG shortage period was defined from July 2012 ongoing. Full induction treatment with BCG, mitomycin C, gemcitabine, or other intravesical agents was defined as receiving ≥5 of 6 treatments within 60 days. State-level BCG use before and during the drug shortage was compared in US states reporting at least 50 patients in each period. Independent variables included year of index date, age, sex, race, rurality, and region of residence., Results: BCG utilization rates decreased 5.9% in the shortage period (95% CI (-8.2%)-(-3.7%)). The proportion of patients that completed a full induction course of BCG decreased from 31.0% in the pre-shortage period to 27.6% in the shortage period (P = .002). 84% of reporting states (16 of 19) had decreased BCG utilization ranging between 5% and 36% compared to pre-shortage rates., Conclusion: During the BCG drug shortage, eligible bladder cancer patients were less likely to receive gold standard intravesical BCG with a large variation in treatment patterns between US states., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: While active surveillance, a form of expectant management (EM), is preferred for patients with low-risk prostate cancer (PCa), some favor a more risk-adapted approach that recognizes patient preferences and condition-specific factors. However, previous research has shown non-patient-related factors often drive PCa treatment. In this context, we characterized trends in AS with respect to disease risk and health status., Methods and Materials: Using SEER-Medicare data, we identified men 66 years and older diagnosed with localized low- and intermediate-risk PCa from 2008 to 2017 and examined receipt of EM, defined as the absence of treatment (i.e., surgery, cryotherapy, radiation, chemotherapy, and androgen deprivation therapies) within 1 year of diagnosis. We performed bivariable analysis to compare trends in use for EM vs. treatment, stratified by disease risk (i.e., Gleason 3+3, 3+4, 4+3; PSA<10, 10-20) and health status (i.e., NCI Comorbidity Index (NCI), frailty, life expectancy). We then ran a multivariable logistic regression model to examine determinants of EM., Results: Within this cohort, 26,364 (38%) were categorized as low-risk (i.e., Gleason 3+3 and PSA<10) and 43,520 (62%) as intermediate-risk (i.e., all others). Over the study period, use of EM significantly increased across all risk groups, except for Gleason 4+3 (P = 0.662), as well across all health status groups. However, linear trends did not differ significantly between frail vs. nonfrail patients for both those categorized as low-risk (P = 0.446) and intermediate-risk (P = 0.208). Trends also did not differ between NCI 0 vs. 1 vs. >1 for low-risk PCa (P = 0.395). In the multivariable models, EM was associated with increasing age and being frail for men with both low- and intermediate risk disease. Conversely, EM selection was negatively associated with higher comorbidity score., Conclusions: EM increased significantly over time for patients with low- and favorable intermediate-risk disease, with the most notable differences based on age and Gleason score. In contrast, trends in uptake of EM did not differ substantively by health status, suggesting that physicians may not be effectively incorporating patient health into PCa treatment decisions. Additional work is needed to develop interventions that recognize health status as an essential component of a risk-adapted approach., Competing Interests: Declaration of Competing Interest The database infrastructure used for this project was funded by the CER Strategic Initiative of UNC's Clinical and Translational Science Award (UL1TR002489), the UNC School of Medicine, and the UNC Lineberger Comprehensive Cancer Center's University Cancer Research Fund (UCRF) via the State of North Carolina. The research was further supported by a Discovery Grant from Advancing Cancer Treatment. These funding sources had no role in the design, conduct, analysis, or decision to publish the manuscript. There are no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To examine the association of area-level socioeconomic status, rural-urban residence, and type of insurance with overall and cancer-specific mortality among patients with muscle-invasive bladder cancer., Methods: Using the Pennsylvania Cancer Registry, which collects demographic, insurance, and clinical information on every patient with cancer within the state, we identified all patients diagnosed with non-metastatic muscle-invasive bladder cancer between 2010 and 2016 based on clinical and pathologic staging. We used the Area Deprivation Index (ADI) as a surrogate for socioeconomic status and Rural-Urban Commuting Area codes to classify urban, large town, and rural communities. ADI was reported in quartiles, with 4 representing the lowest socioeconomic status. We fit multivariable logistic regression and Cox models to assess the relationship of these social determinants with overall and cancer-specific survival adjusting for age, sex, race, stage, treatment, rural-urban classification, insurance and ADI., Results: We identified 2597 patients with non-metastatic muscle-invasive bladder cancer. On multivariable analysis, Medicare (hazards ratio [HR] 1.15), Medicaid (HR 1.38), ADI 3 (HR 1.16) and ADI 4 (HR 1.21) were independent predictors of greater overall mortality (all P < 0.05). Female sex and receipt of non-standard treatment were associated with increased overall mortality and bladder cancer-specific mortality. There was no significant difference in both overall and cancer-specific survival between patients who were non-Hispanic White compared to non-White or between those from urban areas, large towns, or rural locations., Conclusion: Lower socioeconomic status and Medicare and Medicaid insurance were associated with a greater risk of overall mortality while rural residence was not a significant factor. Implementation of public health programs may help reduce the gap in mortality for low SES at-risk populations., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Rural populations routinely rank poorly on common health indicators. While it is understood that rural residents face barriers to health care, the exact nature of these barriers remains unclear. To further define these barriers, a qualitative study of primary care physicians practicing in rural communities was performed., Methods: Semistructured interviews were conducted with primary care physicians practicing in rural areas within western Pennsylvania, the third largest rural population within the USA, using purposively sampling. Data were then transcribed, coded, and analyzed by thematic analysis., Results: Three key themes emerged from the analysis addressing barriers to rural health care: (1) cost and insurance, (2) geographic dispersion, and (3) provider shortage and burnout. Providers mentioned strategies that they either employed or thought would be beneficial for their rural communities: (1) subsidize services, (2) establish mobile and satellite clinics (particularly for specialty care), (3) increase utilization of telehealth, (4) improve infrastructure for ancillary patient support (ie social work services), and (5) increase utilization of advanced practice providers., Conclusion: There are numerous barriers to providing rural communities with quality health care. Barriers that are encountered are multidimensional. Patients are unable to obtain the care they need because of cost-related barriers. More providers need to be recruited to rural areas to combat the shortage and burnout. Advanced care-delivery methods such as telehealth, satellite clinics, or advanced practice providers can help bridge the gaps caused by geographic dispersion. Policy efforts should target all these aspects in order to appropriately address rural healthcare needs.

Objective: To develop and evaluate a risk-based antibiotic prophylaxis protocol for patients undergoing transrectal prostate biopsy., Methods: We created a risk-based protocol for antibiotic prophylaxis before transrectal prostate biopsy. Patients were screened for infection risk-factors with a self-administered questionnaire. The protocol was implemented from January 1, 2020 to March 31, 2020. We compared patient risk-factors, antibiotic regimens, and 30-day infection rates for patients undergoing transrectal prostate biopsies during the intervention and for a 3-month period before the intervention., Results: There were 116 prostate biopsies in the preintervention group and 104 in the intervention group. Although there was no significant difference in the number of high-risk patients between the 2 groups (48% vs 55%; P = .33), the percentage of patients treated with augmented prophylaxis decreased from 74% to 45% (P = 0.03). The duration of antibiotic administration and the median number of doses prescribed also decreased significantly. Despite significant decreases in antibiotic use, there were no differences in infection rates (5% vs 5%; P = .90) or sepsis rates (1% vs 2%; P = .60)., Conclusion: We developed a risk-based protocol for prophylactic antibiotics before prostate biopsy. The protocol was associated with less antibiotic use but did not lead to an increase in infectious complications., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To report the incidence and risk factors for secondary neoplasm after transplantation for sickle cell disease., Methods: Included are 1,096 transplants for sickle cell disease between 1991 and 2016. There were 22 secondary neoplasms. Types included leukemia/myelodysplastic syndrome (MDS; n = 15) and solid tumor (n = 7). Fine-Gray regression models examined for risk factors for leukemia/MDS and any secondary neoplasm., Results: The 10-year incidence of leukemia/MDS was 1.7% (95% CI, 0.90 to 2.9) and of any secondary neoplasm was 2.4% (95% CI, 1.4 to 3.8). After adjusting for other risk factors, risks for leukemia/MDS (hazard ratio, 22.69; 95% CI, 4.34 to 118.66; P = .0002) or any secondary neoplasm (hazard ratio, 7.78; 95% CI, 2.20 to 27.53; P = .0015) were higher with low-intensity (nonmyeloablative) regimens compared with more intense regimens. All low-intensity regimens included total-body irradiation (TBI 300 or 400 cGy with alemtuzumab, TBI 300 or 400 cGy with cyclophosphamide, TBI 200, 300, or 400 cGy with cyclophosphamide and fludarabine, or TBI 200 cGy with fludarabine). None of the patients receiving myeloablative and only 23% of those receiving reduced-intensity regimens received TBI., Conclusion: Low-intensity regimens rely on tolerance induction and establishment of mixed-donor chimerism. Persistence of host cells exposed to low-dose radiation triggering myeloid malignancy is one plausible etiology. Pre-existing myeloid mutations and prior inflammation may also contribute but could not be studied using our data source. Choosing conditioning regimens likely to result in full-donor chimerism may in part mitigate the higher risk for leukemia/MDS.

Importance: Disruptions in cancer surgery during the COVID-19 pandemic led to widespread deferrals and cancellations, creating a surgical backlog that presents a challenge for health care institutions moving into the recovery phase of the pandemic., Objective: To describe patterns in surgical volume and postoperative length of stay for major urologic cancer surgery during the COVID-19 pandemic., Design, Setting, and Participants: This cohort study identified 24 001 patients 18 years or older from the Pennsylvania Health Care Cost Containment Council database with kidney cancer, prostate cancer, or bladder cancer who received a radical nephrectomy, partial nephrectomy, radical prostatectomy, or radical cystectomy between the first quarter (Q1) of 2016 and Q2 of 2021. Postoperative length of stay and adjusted surgical volumes were compared before and during the COVID-19 pandemic., Main Outcomes and Measures: The primary outcome was adjusted surgical volume for radical and partial nephrectomy, radical prostatectomy, and radical cystectomy during the COVID-19 pandemic. The secondary outcome was postoperative length of stay., Results: A total of 24 001 patients (mean [SD] age, 63.1 [9.4] years; 3522 women [15%], 19 845 White patients [83%], 17 896 living in urban areas [75%]) received major urologic cancer surgery between Q1 of 2016 and Q2 of 2021. Of these, 4896 radical nephrectomy, 3508 partial nephrectomy, 13 327 radical prostatectomy, and 2270 radical cystectomy surgical procedures were performed. There were no statistically significant differences in patient age, sex, race, ethnicity, insurance status, urban or rural status, or Elixhauser Comorbidity Index scores between patients who received surgery before and patients who received surgery during the pandemic. For partial nephrectomy, a baseline of 168 surgeries per quarter decreased to 137 surgeries per quarter in Q2 and Q3 of 2020. For radical prostatectomy, a baseline of 644 surgeries per quarter decreased to 527 surgeries per quarter in Q2 and Q3 of 2020. However, the likelihood of receiving radical nephrectomy (odds ratio [OR], 1.00; 95% CI, 0.78-1.28), partial nephrectomy (OR, 0.99; 95% CI, 0.77-1.27), radical prostatectomy (OR, 0.85; 95% CI, 0.22-3.22), or radical cystectomy (OR, 0.69; 95% CI, 0.31-1.53) was unchanged. Length of stay for partial nephrectomy decreased from baseline by a mean of 0.7 days (95% CI, -1.2 to -0.2 days) during the pandemic., Conclusions and Relevance: This cohort study suggests that partial nephrectomy and radical prostatectomy surgical volume decreased during the peak waves of COVID-19, as did postoperative length of stay for partial nephrectomy.

Cellular stress granules arise in cells subjected to stress and promote cell survival. A cellular protein that localizes to stress granules is Z-DNA-binding protein 1 (ZBP1), which plays a major role in necroptosis, a programmed cell death pathway mediated by the kinase RIPK3. Here, we showed that the stress granule inducer arsenite activated RIPK3-dependent necroptosis. This pathway required ZBP1, which localized to arsenite-induced stress granules. RIPK3 localized to stress granules in the presence of ZBP1, leading to the formation of ZBP1-RIPK3 necrosomes, phosphorylation of the RIPK3 effector MLKL, and execution of necroptosis. Cells that did not form stress granules did not induce necroptosis in response to arsenite. Together, these results show that arsenite induces ZBP1-mediated necroptosis in a manner dependent on stress granule formation.

Importance: Patients with urologic diseases often experience financial toxicity, defined as high levels of financial burden and concern, after receiving care. The Price Transparency Final Rule, which requires hospitals to disclose both the commercial and cash prices for at least 300 services, was implemented to facilitate price shopping, decrease price dispersion, and lower health care costs., Objective: To evaluate compliance with the Price Transparency Final Rule and to quantify variations in the price of urologic procedures among academic hospitals and by insurance class., Design, Setting, and Participants: This was a cross-sectional study that determined the prices of 5 common urologic procedures among academic medical centers and by insurance class. Prices were obtained from the Turquoise Health Database on March 24, 2022. Academic hospitals were identified from the Association of American Medical Colleges website. The 5 most common urologic procedures were cystourethroscopy, prostate biopsy, laparoscopic radical prostatectomy, transurethral resection of the prostate, and ureteroscopy with laser lithotripsy. Using the corresponding Current Procedural Terminology codes, the Turquoise Health Database was queried to identify the cash price, Medicare price, Medicaid price, and commercial insurance price for these procedures., Exposures: The Price Transparency Final Rule, which went into effect January 1, 2021., Main Outcomes and Measures: Variability in procedure price among academic medical centers and by insurance class (Medicare, Medicaid, commercial, and cash price)., Results: Of 153 hospitals, only 20 (13%) listed a commercial price for all 5 procedures. The commercial price was reported most often for cystourethroscopy (86 hospitals [56%]) and least often for laparoscopic radical prostatectomy (45 hospitals [29%]). The cash price was lower than the Medicare, Medicaid, and commercial price at 24 hospitals (16%). Prices varied substantially across hospitals for all 5 procedures. There were significant variations in the prices of cystoscopy (χ23 = 85.9; P = .001), prostate biopsy (χ23 = 64.6; P = .001), prostatectomy (χ23 = 24.4; P = .001), transurethral resection of the prostate (χ23 = 51.3; P = .001), and ureteroscopy with laser lithotripsy (χ23 = 63.0; P = .001) by insurance type., Conclusions and Relevance: These findings suggest that, more than 1 year after the implementation of the Price Transparency Final Rule, there are still large variations in the prices of urologic procedures among academic hospitals and by insurance class. Currently, in certain situations, health care costs could be reduced if patients paid out of pocket. The Centers for Medicare & Medicaid Services may improve price transparency by better enforcing penalties for noncompliance, increasing penalties, and ensuring that hospitals report prices in a way that is easy for patients to access and understand.

Poxviruses have been long regarded as potent inhibitors of apoptotic cell death. More recently, they have been shown to inhibit necroptotic cell death through two distinct strategies. These strategies involve either blocking virus sensing by the host pattern recognition receptor, ZBP1 (also called DAI) or by influencing receptor interacting protein kinase (RIPK)3 signal transduction by inhibition of activation of the executioner of necroptosis, mixed lineage kinase-like protein (MLKL). Vaccinia virus E3 specifically blocks ZBP1 → RIPK3 → MLKL necroptosis, leaving virus-infected cells susceptible to the TNF death-receptor signaling (e.g., TNFR1 → FADD → RIPK1 → RIPK3 → MLKL), and, potentially, TLR3 → TRIF → RIPK3 → MLKL necroptosis. While E3 restriction of necroptosis appears to be common to many poxviruses that infect vertebrate hosts, another modulatory strategy not observed in vaccinia or variola virus manifests through subversion of MLKL activation. Recently described viral mimics of MLKL in other chordopoxviruses inhibit all three modes of necroptotic cell death. As with inhibition of apoptosis, the evolution of potentially redundant viral mechanisms to inhibit programmed necroptotic cell death emphasizes the importance of this pathway in the arms race between pathogens and their hosts., (© 2020. Springer Nature Switzerland AG.)

Objective: To show that zero-opioid discharges after both open and robotic cystectomy are feasible and to examine the impact of zero-opioid discharges on patient interaction with the physician's office., Materials and Methods: One hundred seven patients who underwent either open or robotic radical cystectomy from March 1, 2020 to December 30, 2020 were identified. Patient demographics, perioperative data, and 30 day pain related outcomes including phone calls, office visits, requests for pain medication, emergency department visits, and readmissions were abstracted from the chart. We then examined variables associated with a zero-opioid discharge., Results: Thirty-two patients were discharged with an opioid prescription (Median Oral Morphine Equivalents Prescribed = 90) and 75 were discharged without an opioid prescription. On regression analysis, age (OR 1.07, 95% CI [1.02-1.12]) and pathology (OR 0.36, 95% CI[0.14-0.9]) remained significantly associated with post-operative opioid prescriptions. There were no differences in the percent of patients presenting to the emergency department, being readmitted, calling the office, calling the office regarding pain, or requesting opioid prescriptions within 30 days of discharge, or the number of post-operative office visits (P >.05 for all)., Conclusion: Patients can safely be discharged home without opioids following cystectomy, regardless of robotic or open approach. Age and pathology are predictors of the need for an opioid prescription on discharge. These patients did not have increased follow-up visits, phone calls, or requests for pain medication., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To examine overall trends in opioid prescribing after ureteroscopy and compared opioid use between private and academic practice settings. We also analyzed the potential for spillover effect from an unrelated opioid-reduction initiative for major oncologic surgery., Methods: We conducted a retrospective chart review of all ureteroscopies performed within our system at four distinct time points from 2016-2019. We recorded the type and number of opioid pills prescribed and calculated oral morphine equivalents. Analysis included comparison between community and academic hospitals as well as pre- and post-initiative., Results: 555 patients undergoing ureteroscopy and 29 attending surgeons were included in the analysis. The median prescription size per ureteroscopy decreased throughout the study period in both the private and academic settings. From 2016-2017, median oral morphine equivalents (OMEs) decreased from 60 to 0 in the private setting and remained at 0 for the duration of the study period. Opioid reduction in the academic setting lagged behind private practitioners but median OMEs did steadily decrease to 0 in 2019. No significant spillover effect was observed., Conclusion: Since 2016, opioid prescribing following ureteroscopy has decreased in both the private and academic practice settings. Notably, private practice urologists achieved a median of 0 opioids 2 years prior to academic urologists. These data suggest that, in some circumstances, academic institutions may have been slower to respond to the opioid epidemic., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The Omicron SARS-CoV-2 variant has been designated as a variant of concern because its spike protein is heavily mutated. In particular, the Omicron spike is mutated at five positions (K417, N440, E484, Q493, and N501) that have been associated with escape from neutralizing antibodies induced by either infection with or immunization against the early Washington strain of SARS-CoV-2. The mouse-adapted strain of SARS-CoV-2, SARS2-N501Y MA30 , contains a spike that is also heavily mutated, with mutations at four of the five positions in the Omicron spike associated with neutralizing antibody escape (K417, E484, Q493, and N501). In this manuscript, we show that intranasal immunization with a pre-fusion stabilized Washington strain spike, expressed from a highly attenuated, replication-competent vaccinia virus construct, NYVAC-KC, fully protected mice against symptoms and death from SARS2-N501Y MA30 . Similarly, immunization by scarification on the skin fully protected against death, but not from mild disease. This data demonstrates that the Washington strain spike, when expressed from a highly attenuated, replication-competent poxvirus-administered without parenteral injection-can fully protect against the heavily mutated mouse-adapted SARS2-N501Y MA30 .

Objectives: Transcervical resection of myoma (TCRM) is a widely implemented treatment for submucous fibroids. The aim of this study is to evaluate the effect of TCRM on menstrual bleeding, fibroid related symptoms and quality of life and hemoglobin (Hb) levels., Study Design: A prospective cohort study was conducted in three teaching hospitals and two academic hospitals in the Netherlands. Patients with HMB (PBAC score > 150) and submucous fibroids (type 0, 1, 2, 3, 4 and hybrid type 2-5) scheduled for TCRM were eligible. At baseline and 3 months after TCRM a Trans Vaginal Ultrasound (TVU) was performed and a Hb sample was taken. Patients filled out the Pictorial Blood Assessment Chart (PBAC) and the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire at baseline and up to 6 months after surgery. Primary outcome was improvement in PBAC score 6 months after surgery. Secondary outcomes were improvement in PBAC score and Hb level 3 months after surgery and UFS-QOL scores 3 and 6 months after surgery., Results: 126 patients were included and 104 were operated. PBAC were obtained from 98 patients. Six months after surgery, 56.6% of patients went from HMB to normal menstrual bleeding (PBAC < 150). A significant reduction in median PBAC scores of 427 (IQR 198 - 1392) (p <.0001) was found (86% improvement). UFS-QOL scores were obtained from 91 patients. Symptom severity improved from a median of 54 on a scale of 100 (IQR 44-66) at baseline to 22 (IQR 9-41) after 6 months (p <.0001) (59% improvement). Health related quality of life (HRQOL) improved from a median score of 44 on a scale of 100 (IQR 33-62) to 89 (IQR 67-97) 6 months after surgery (p <.0001) (102% improvement)., Conclusion: TCRM significantly reduces the amount of menstrual bleeding, severity of fibroid related symptoms and improves HRQOL in patients with submucous fibroids., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To identify patient-level factors that can lead to treatment disparities for muscle invasive bladder cancer, we examine factors associated with receipt of definitive therapy, type of definitive therapy, and neoadjuvant chemotherapy administration in a statewide cohort of muscle-invasive bladder cancer patients., Materials and Methods: We identified 2,434 patients diagnosed with non-metastatic muscle-invasive bladder cancer between 2010 and 2015 using the Pennsylvania Cancer Registry. We divided the cohort into three subsamples to examine receipt of treatment: definitive therapy among all muscle-invasive bladder cancer patients (n = 1548), cystectomy (n = 1254) vs. trimodal therapy (n = 294), and neoadjuvant chemotherapy among radical cystectomy patients (n = 1156). Multivariable logistic regression models controlling for patient-level covariates, including insurance status, and socioeconomic disadvantage (based on Area Deprivation Index from census tract data) were estimated to examine factors associated with each treatment outcome., Results: Only 64% of muscle-invasive bladder cancer patients underwent definitive therapy. Those receiving trimodal therapy were more likely to be covered by Medicare than those undergoing cystectomy. Uninsured patients were less likely to undergo definitive treatment and Medicare-insured patients were less likely to undergo cystectomy as their definitive therapy. Patients with greater socioeconomic disadvantage were less likely to receive definitive treatment, undergo cystectomy, or receive neoadjuvant chemotherapy. Over the course of the study period, there was increased neoadjuvant chemotherapy use, but a persistent gap by neighborhood socioeconomic status., Conclusions: Socioeconomic disadvantage and insurance status are patient-level factors associated with suboptimal treatment for muscle-invasive bladder cancer., Competing Interests: Disclosures Valentina Grajales, MD, MS: This work was supported in part by the 2020 Urology Care Foundation Residency Research Award Program and The Kahlert Foundation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Poxviridae have developed a plethora of strategies to evade innate and adaptive immunity. In this review, we focused on the vaccinia virus E3 protein, encoded by the E3L gene. E3 is present within the Chordopoxvirinae subfamily (with the exception of the avipoxviruses and molluscum contagiosum virus) and displays pleiotropic effects on the innate immune system. Initial studies identified E3 as a double-stranded RNA (dsRNA)-binding protein (through its C terminus), able to inhibit the activation of protein kinase dependent on RNA (PKR) and the 2'5'-oligoadenylate synthetase (OAS)/RNase L pathway, rendering E3 a protein counteracting the type I interferon (IFN) system. In recent years, N-terminal mutants of E3 unable to bind to Z-form nucleic acids have been shown to induce the cellular death pathway necroptosis. This pathway was dependent on host IFN-inducible Z-DNA-binding protein 1 (ZBP1); full-length E3 is able to inhibit ZBP1-mediated necroptosis. Binding to what was identified as Z-RNA has emerged as a novel mechanism of counteracting the type I IFN system and has broadened our understanding of innate immunity against viral infections. This article gives an overview of the studies leading to our understanding of the vaccinia virus E3 protein function and its involvement in viral pathogenesis. Furthermore, a short summary of other viral systems is provided.