Faculty Bibliography

INTRODUCTION/BACKGROUND:Bladder outlet obstruction (BOO) in women includes functional and anatomic etiologies. Primary bladder neck obstruction (PBNO), Fowler's syndrome (FS), and dysfunctional voiding (DV) are some examples of functional obstructions, whereas pelvic organ prolapse (POP), periurethral masses, and intragenic causes are some of the anatomic causes. METHODS:This literature review describes the etiologies of female BOO, unique aspects of the workup and diagnosis, and the data for the standard surgical treatments and newer surgical techniques to treat women. Urethral stenosis and sling-related obstruction are treated in the other articles of this series. Where possible the focus is the efficacy and outcomes. RESULTS:Treatment of PBNO using a transurethral incision of the bladder neck and injection of botulinum toxin in the bladder neck decreases the BOO. After the failure of conservative approaches, sacral neuromodulation (SNM) is effective for FS, while DV may benefit from SNM or botulinum toxin injections. Concerning POP, most surgeries have been reported to significantly improve a pre-existent BOO but the level of evidence is low. Benign urethral and periurethral masses may provoke BOO, and surgical excision usually resolves this condition. CONCLUSION/CONCLUSIONS:Although most surgical treatments of BOO for functional and benign anatomical etiologies in women seem to be effective, data are scarce even for more common conditions like POP. Further studies are required to give better advice on the choice of surgical technique for these patients.

BACKGROUND:In 1999, 1 year after the approval of the first oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), the first Princeton Consensus Conference was held to address the clinical management of men with ED who also had cardiovascular disease. These issues were readdressed in the second and third conferences. In the 13 years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug-drug interactions, but also a potential cardioprotective effect of these drugs. AIM/OBJECTIVE:In March 2023, an interdisciplinary group of scientists and practitioners met for the fourth Princeton Consensus Guidelines at the Huntington Medical Research Institutes in Pasadena, California, to readdress the cardiovascular workup of men presenting with ED as well as the approach to treatment of ED in men with known cardiovascular disease. METHOD/METHODS:A series of lectures from experts in the field followed by Delphi-type discussions were developed to reach consensus. OUTCOMES/RESULTS:Consensus was reached regarding a number of issues related to erectile dysfunction and the interaction with cardiovascular health and phosphodiesterase-5 inhibitors. RESULTS:An algorithm based on recent recommendations of the American College of Cardiology and American Heart Association, including the use of computed tomography coronary artery calcium scoring, was integrated into the evaluation of men presenting with ED. Additionally, the issue of nitrate use was further considered in an algorithm regarding the treatment of ED patients with coronary artery disease. Other topics included the psychological effect of ED and the benefits of treating it; the mechanism of action of the PDE5 inhibitors; drug-drug interactions; optimizing use of a PDE5 inhibitors; rare adverse events; potential cardiovascular benefits observed in recent retrospective studies; adulteration of dietary supplements with PDE5 inhibitors; the pros and cons of over-the-counter PDE5 inhibitors; non-PDE5 inhibitor therapy for ED including restorative therapies such as stem cells, platelet-rich plasma, and shock therapy; other non-PDE5 inhibitor therapies, including injection therapy and penile prostheses; the issue of safety and effectiveness of PDE5 inhibitors in women; and recommendations for future studies in the field of sexual dysfunction and PDE5 inhibitor use were discussed. CLINICAL IMPLICATIONS/CONCLUSIONS:Algorithms and tables were developed to help guide the clinician in dealing with the interaction of ED and cardiovascular risk and disease. STRENGTHS AND LIMITATIONS/UNASSIGNED:Strengths include the expertise of the participants and consensus recommendations. Limitations included that participants were from the United States only for this particular meeting. CONCLUSION/CONCLUSIONS:The issue of the intersection between cardiovascular health and sexual health remains an important topic with new studies suggesting the cardiovascular safety of PDE5 inhibitors.

BACKGROUND:Blood homeostasis requires the daily production of millions of terminally differentiated effector cells that all originate from hematopoietic stem cells (HSCs). HSCs are rare and exhibit unique self-renewal and multipotent properties, which depend on their ability to maintain quiescence through ill-defined processes. Defective control of cell cycle progression can eventually lead to bone marrow failure or malignancy. In particular, the molecular mechanisms tying cell cycle re-entry to cell fate commitment in HSCs remain elusive. Previous studies have identified chromatin coordination as a key regulator of differentiation in embryonic stem cells. RESULTS:phase of the cell cycle, which correlates with the engagement of specific signaling pathways, including aberrant expression of cell adhesion molecules and the interferon signaling program in LT-HSCs. In addition, we uncover the Sin3B-dependent accessibility of genomic elements controlling HSC differentiation, which points to cell cycle progression possibly dictating the priming of HSCs for differentiation. CONCLUSIONS:Our findings provide new insights into controlled cell cycle progression as a potential regulator of HSC lineage commitment through the modulation of chromatin features.

OBJECTIVE:To build the Neiman Imaging Comorbidity Index (NICI), based on variables available in claims datasets, which provides good discrimination of an individual's chance of receiving advanced imaging (CT, MR, PET), and thus, utility as a control variable in research. METHODS:This retrospective study used national commercial claims data from Optum's deidentified Clinformatics Data Mart database from the period January 1, 2018 to December 31, 2019. Individuals with continuous enrollment during this 2-year study period were included. Lasso (least absolute shrinkage and selection operator) regression was used to predict the chance of receiving advanced imaging in 2019 based on the presence of comorbidities in 2018. A numerical index was created in a development cohort (70% of the total dataset) using weights assigned to each comorbidity, based on regression β coefficients. Internal validation of assigned scores was performed in the remaining 30% of claims, with comparison to the commonly used Charlson Comorbidity Index. RESULTS:The final sample (development and validation cohorts) included 10,532,734 beneficiaries, of whom 2,116,348 (20.1%) received advanced imaging. After model development, the NICI included nine comorbidities. In the internal validation set, the NICI achieved good discrimination of receipt of advanced imaging with a C statistic of 0.709 (95% confidence interval [CI] 0.708-0.709), which predicted advanced imaging better than the CCI (C 0.692, 95% CI 0.691-0.692). Controlling for age and sex yielded better discrimination (C 0.748, 95% CI 0.748-0.749). DISCUSSION/CONCLUSIONS:The NICI is an easily calculated measure of comorbidity burden that can be used to adjust for patients' chances of receiving advanced imaging. Future work should explore external validation of the NICI.

Introduction:ChatGPT is an artificial intelligence platform available to patients seeking medical advice. Traditionally, urology patients consulted official provider-created materials, particularly the Urology Care Foundationâ„¢ (UCF). Today, men increasingly go online due to the rising costs of health care and the stigma surrounding sexual health. Online health information is largely inaccessible to laypersons as it exceeds the recommended American sixth to eighth grade reading level. We conducted a comparative assessment of patient education materials generated by ChatGPT vs UCF regarding men's health conditions.Methods:All 6 UCF men's health resources were identified. ChatGPT responses were generated using patient questions obtained from UCF. Adjusted ChatGPT responses were generated by prompting, "Explain it to me like I am in sixth grade." Textual analysis was performed using sentence, word, syllable, and complex word count. Six validated formulae were used for readability analysis. Two physicians independently scored responses for accuracy, comprehensiveness, and understandability. Statistical analysis involved Wilcoxon matched-pairs test.Results:ChatGPT responses were longer and more complex. Both UCF and ChatGPT failed official readability standards, although ChatGPT performed significantly worse across all 6 topics (all P <.001). Conversely, adjusted ChatGPT readability typically surpassed UCF, even meeting the recommended level for 2 topics. Qualitatively, UCF and ChatGPT had comparable accuracy, although ChatGPT had better comprehensiveness and worse understandability.Conclusions:When comparing readability, ChatGPT-generated education is less accessible than provider-written content, although neither meets the recommended level. Our analysis indicates that specific artificial intelligence prompts can simplify educational materials to meet national standards and accommodate individual literacy.

CONTEXT.—/UNASSIGNED:The morphologic features of different entities in genitourinary pathology overlap, presenting a diagnostic challenge, especially when diagnostic materials are limited. Immunohistochemical markers are valuable when morphologic features alone are insufficient for definitive diagnosis. The World Health Organization classification of urinary and male genital tumors has been updated for 2022. An updated review of immunohistochemical markers for newly classified genitourinary neoplasms and their differential diagnosis is needed. OBJECTIVE.—/UNASSIGNED:To review immunohistochemical markers used in the diagnosis of genitourinary lesions in the kidney, bladder, prostate, and testis. We particularly emphasized difficult differential diagnosis and pitfalls in immunohistochemistry application and interpretation. New markers and new entities in the 2022 World Health Organization classifications of genitourinary tumors are reviewed. Recommended staining panels for commonly encountered difficult differential diagnosis and potential pitfalls are discussed. DATA SOURCES.—/UNASSIGNED:Review of current literature and our own experience. CONCLUSIONS.—/UNASSIGNED:Immunohistochemistry is a valuable tool in the diagnosis of problematic lesions of genitourinary tract. However, the immunostains must be carefully interpreted in the context of morphologic findings with a thorough knowledge of pitfalls and limitations.

Background: Tissue-based gene expression (genomic) tests provide estimates of prostate cancer aggressiveness and are increasingly used for patients considering or engaged in active surveillance. However, little is known about patient experiences with genomic testing and its role in their decision-making. Methods: We performed a qualitative study consisting of in-depth, semi-structured interviews of patients with low- or favourable-intermediate-risk prostate cancer managed with active surveillance. We purposively sampled to include patients who received biopsy-based genomic testing as part of clinical care. The interview guide focused on experiences with genomic testing during patients' decision-making for prostate cancer management and understanding of genomic test results. We continued interviews until thematic saturation was reached, iteratively created a code key and used conventional content analysis to analyse data. Results: Participants' (n = 20) mean age was 68 years (range 51"“79). At initial biopsy, 17 (85%) had a Gleason grade group 1, and 3 (15%) had a grade group 2 prostate cancer. The decision to undergo genomic testing was driven by both participants and physicians' recommendations; however, some participants were unaware that testing had occurred. Overall, participants understood the role of genomic testing in estimating their prostate cancer risk, and the test results increased their confidence in the decision for active surveillance. Participants had some misconceptions about the difference between tissue-based gene expression tests and germline genetic tests and commonly believed that tissue-based tests measured hereditary cancer risk. While some participants expressed satisfaction with their physicians' explanations, others felt that communication was limited and lacked sufficient detail. Conclusion: Patients interact with and are influenced by the results of biopsy-based genomic testing during active surveillance for prostate cancer, despite gaps in understanding about test results. Our findings indicate areas for improvement in patient counselling in order to increase patient knowledge and comfort with genomic testing.

Introduction:The COVID-19 pandemic has fueled widespread incorporation of telehealth into urology practices. Vasectomy consultation via telehealth is convenient and improves access to care for male contraception. However, it does not allow for physical examination, inherently leading to possible day-of-procedure cancellations due to unforeseen anatomic concerns. This study aimed to compare vasectomy completion rates between patients undergoing virtual vs in-person consultation.Methods:All patients seen by a single provider at NYU Langone Health for vasectomy consultation between October 2016 and June 2022 were included in the study. Most patients seen before March 2020 had in-person consultations, whereas the majority of patients seen afterwards had virtual consultations without option for in-person visit due to the emergence of COVID-19. All patients seen virtually were examined in a consult room prior to being prepped for the vasectomy in the procedure room. Visit type, demographic information, and clinical outcomes data were collected for all patients. A chi-square test was used to compare the rate of vasectomy completion between those with in-person and virtual consultation. Analysis was performed using R, version 4.0.5.Results:Four hundred ninety-one patients were seen by a single provider for vasectomy consultation between October 2016 and June 2022. One hundred ninety-seven (40.1%) consultations were performed virtually and 294 (59.9%) consultations were performed in person. Three hundred seventy (75.4%) of all patients seen for consultation (both virtual and in person) ultimately underwent vasectomy. There was no evidence of difference in rate of completing vasectomy after virtual (75.6%) and in-person (75.2%) consultation (P =.91). Two of the 197 (1%) patients who consulted virtually had their vasectomy procedures cancelled on the day of the procedure based on their preoperative exam; one because of abnormal epididymal sensitivity after prior scrotal infection, the other because of a history of orchiopexy that the patient was not aware of until the surgeon started inquiring about scrotal scars present.Conclusions:Despite the lack of physical examination, virtual vasectomy consultation is both feasible and effective, with rates of vasectomy completion comparable to traditional in-person consultation.

Background: We previously reported a higher incidence of a pathogenic germline variant in the kinase insert domain receptor (KDR) in melanoma patients compared to the general population. Here, we dissect the impact of this genotype on melanoma tumor growth kinetics, tumor phenotype, and response to treatment with immune checkpoint inhibitors (ICIs) or targeted therapy. Methods: The KDR genotype was determined and the associations between the KDR Q472H variant (KDR-Var), angiogenesis, tumor immunophenotype, and response to MAPK inhibition or ICI treatment were examined. Melanoma B16 cell lines were transfected with KDR-Var or KDR wild type (KDR-WT), and the differences in tumor kinetics were evaluated. We also examined the impact of KDR-Var on the response of melanoma cells to a combination of VEGFR inhibition with MAPKi. Results: We identified the KDR-Var genotype in 81/489 (37%) patients, and it was associated with a more angiogenic (p = 0.003) and immune-suppressive tumor phenotype. KDR-Var was also associated with decreased PFS to MAPKi (p = 0.022) and a trend with worse PFS to anti-PD1 therapy (p = 0.06). KDR-Var B16 murine models had increased average tumor volume (p = 0.0027) and decreased CD45 tumor-infiltrating lymphocytes (p = 0.0282). The anti-VEGFR treatment Lenvatinib reduced the tumor size of KDR-Var murine tumors (p = 0.0159), and KDR-Var cells showed synergistic cytotoxicity to the combination of dabrafenib and lenvatinib. Conclusions: Our data demonstrate a role of germline KDR-Var in modulating melanoma behavior, including response to treatment. Our data also suggest that anti-angiogenic therapy might be beneficial in patients harboring this genotype, which needs to be tested in clinical trials.