How Can We Identify Extraprostatic Extension (EPE) Before Surgery? The Use of a Preoperative Prostate MRI EPE Scoring System to Assess Postprostatectomy Locally Advanced Prostate Cancer.

Background: Distinguishing between organ-confined disease and extraprostatic extension (EPE) is crucial for the treatment of patients with prostate cancer. EPE is associated with an increased risk of biochemical recurrence, positive surgical margins, and metastatic disease. An MRI-based EPE scoring system was developed by Mehralivand in 2019; however, it has not been adopted in the Urology community. The purpose of this study is to evaluate the association of MRI-based EPE scoring with the pathologic EPE (pEPE) after radical prostatectomy. Methods: We conducted a retrospective review on a prospectively collected database of male patients who underwent a prostate MRI with EPE scoring by a trained genitourinary radiologist and subsequent robotic radical prostatectomy at our institution from September 2020 to December 2022. The associations between MRI EPE (mEPE) score and the presence of EPE on surgical pathology (pEPE) were examined using multivariable logistic regression. Results: A total of 194 patients met inclusion criteria with a median age of 63 years and prostate specific antigen (PSA) 7 ng/mL. Among those with mEPE score 3, 96% had pEPE. Those patients with an mEPE score ≥2 had an increased risk of pEPE compared with those with mEPE score 0 (odds ratio 3.79; 95% confidence interval 1.28-11.3) Furthermore, those with an mEPE score 3 were significantly more likely to have pEPE compared with those with mEPE score 0, 1 and 2 independently. Conclusion: MRI EPE is a straightforward tool that strongly correlates with the presence of pEPE. If validated prospectively, this scoring system could assist in counseling patients regarding nerve-sparing approach.

Evaluating PubMed-Indexed Publications of Applicants Successfully Matching into the Top 50 Urology Residency Programs in the 2021-2023 Cycles.

Background and objective Urology residency match occurs through the American Urological Association (AUA), and hence information about the success of applicants in finding a match is not readily available. The average number of publications a successful urology applicant has when applying for residency is unknown. In light of this, we conducted this study to examine the number of PubMed-indexed research projects involving US senior medical students who successfully matched into the top 50 urology residency programs in the 2021, 2022, and 2023 match cycles. We also assessed these applicants based on their medical schools and gender. Methods Doximity Residency Navigator was used to generate the top 50 residency programs as sorted by reputation. Newly matched residents were found using program Twitter accounts and residency program websites. PubMed was queried for peer-reviewed publications of incoming interns. Results The average number of publications across all incoming interns in the three years was 3.65. The average number of urology-specific publications was 1.86 and that of first-author urology publications was 1.11. The median number of total publications for matched applicants was 2, and applicants with a total of five publications were in the 75th percentile for research productivity. Conclusion A successful applicant had two PubMed-indexed urology papers on average and also had a urology-specific first-author paper in the cycles we surveyed. There has been an increase in publications per applicant when comparing the results to previous application cycles, which can be attributed to post-pandemic changes.

Reproductive Health and Coronavirus Disease 2019-Induced Economic Contracture: Lessons From the Great Recession.

The coronavirus disease 2019 (COVID-19) pandemic has magnified disparities in care, including within reproductive health. There has been limited research on the implications of the financial calamity COVID-19 has precipitated on reproductive health, including restricted access to contraception and prenatal care, as well as adverse perinatal outcomes resulting from economic contracture. We therefore examined the Great Recession (the period of economic downturn from 2007-2009 also referred to as the 2008 recession) to discuss how the current financial difficulties may influence reproductive health now and in the years to come. The existing literature examining the impacts of economic downturn on reproductive health provides a resounding body of evidence supporting the need for state and federal investment in comprehensive reproductive health care. Policies directed at expanding access to programs such as Special Supplemental Nutrition Program for Women, Infants, and Children and Medicaid (WIC), extending Medicaid coverage to 12 months' postpartum, continuing coverage for telehealth services, and lowering barriers to access through mobile care units would help mitigate anticipated effects of a recession on reproductive health.

Clinical Prediction Models for Valvular Heart Disease.

Background While many clinical prediction models (CPMs) exist to guide valvular heart disease treatment decisions, the relative performance of these CPMs is largely unknown. We systematically describe the CPMs available for patients with valvular heart disease with specific attention to performance in external validations. Methods and Results A systematic review identified 49 CPMs for patients with valvular heart disease treated with surgery (n=34), percutaneous interventions (n=12), or no intervention (n=3). There were 204 external validations of these CPMs. Only 35 (71%) CPMs have been externally validated. Sixty-five percent (n=133) of the external validations were performed on distantly related populations. There was substantial heterogeneity in model performance and a median percentage change in discrimination of -27.1% (interquartile range, -49.4%--5.7%). Nearly two-thirds of validations (n=129) demonstrate at least a 10% relative decline in discrimination. Discriminatory performance of EuroSCORE II and Society of Thoracic Surgeons (2009) models (accounting for 73% of external validations) varied widely: EuroSCORE II validation c-statistic range 0.50 to 0.95; Society of Thoracic Surgeons (2009) Models validation c-statistic range 0.50 to 0.86. These models performed well when tested on related populations (median related validation c-statistics: EuroSCORE II, 0.82 [0.76, 0.85]; Society of Thoracic Surgeons [2009], 0.72 [0.67, 0.79]). There remain few (n=9) external validations of transcatheter aortic valve replacement CPMs. Conclusions Many CPMs for patients with valvular heart disease have never been externally validated and isolated external validations appear insufficient to assess the trustworthiness of predictions. For surgical valve interventions, there are existing predictive models that perform reasonably well on related populations. For transcatheter aortic valve replacement (CPMs additional external validations are needed to broadly understand the trustworthiness of predictions.

Translocation of the papillomavirus L2/vDNA complex across the limiting membrane requires the onset of mitosis.

The human papillomavirus type 16 (HPV16) L2 protein acts as a chaperone to ensure that the viral genome (vDNA) traffics from endosomes to the trans-Golgi network (TGN) and eventually the nucleus, where HPV replication occurs. En route to the nucleus, the L2/vDNA complex must translocate across limiting intracellular membranes. The details of this critical process remain poorly characterized. We have developed a system based on subcellular compartmentalization of the enzyme BirA and its cognate substrate to detect membrane translocation of L2-BirA from incoming virions. We find that L2 translocation requires transport to the TGN and is strictly dependent on entry into mitosis, coinciding with mitotic entry in synchronized cells. Cell cycle arrest causes retention of L2/vDNA at the TGN; only release and progression past G2/M enables translocation across the limiting membrane and subsequent infection. Microscopy of EdU-labeled vDNA reveals a rapid and dramatic shift in vDNA localization during early mitosis. At late G2/early prophase vDNA egresses from the TGN to a pericentriolar location, accumulating there through prometaphase where it begins to associate with condensed chromosomes. By metaphase and throughout anaphase the vDNA is seen bound to the mitotic chromosomes, ensuring distribution into both daughter nuclei. Mutations in a newly defined chromatin binding region of L2 potently blocked translocation, suggesting that translocation is dependent on chromatin binding during prometaphase. This represents the first time a virus has been shown to functionally couple the penetration of limiting membranes to cellular mitosis, explaining in part the tropism of HPV for mitotic basal keratinocytes.