Mechanisms of Improving Collateral Blood Flow During Ischemic Stroke

Undergraduate Scholarship Competitions Administered by the ASC Honors ProgramMore than 795,000 Americans suffer a stroke annually, and it is the third leading cause of death in the United States1. There are two types of stroke, hemorrhagic and ischemic. Hemorrhagic stroke is caused by the rupture of blood vessels within the brain, as opposed to ischemic strokes, which are caused by a blockage within the vessel. Of all strokes presented clinically, 86% are ischemic by nature1. Currently, there are few treatments for ischemic stroke. The prevailing early treatments include thrombolytic therapy and antiplatelet therapy such as low dose aspirin2,3. These treatments are each flawed. Tissue plasminogen activator (tPA) is currently the only FDA-approved thrombolytic therapy for the acute treatment of ischemic stroke4. This treatment is approved for less than 10% of patients, and is given to less than 4%4. In addition, greater than 65% of hospitals in America have never administered tPA to patients due to low efficacy as well as potential harmful side effects5. Antiplatelets, such as low dose aspirin, are another treatment option. These are drugs, and therefore have negative side effects associated with long-term use such as increased risk of hemorrhagic stroke6, and gastrointestinal bleeding7. As a result, there is a distinct lack of safe therapeutic options for both the early and long-term treatment of ischemic stroke patients. Cerebrovascular collaterals refer to the network of blood vessels that are clinically documented to perfuse stroke-affected tissue during ischemic stroke and reduce brain injury8. While strategies to improve collateral blood flow during stroke are of significant therapeutic interest, mechanisms and a means to improve circulation through these blood vessels during stroke remain unknown. This honors thesis proposal rests on a key in vivo observation that supplementation of a lesser-characterized natural vitamin E, alpha-tocotrienol (TCT), improves cerebrovascular collateral blood flow and attenuates stroke injury8. TCT therefore serves as a powerful tool to study cerebrovascular collateral remodeling during stroke. The overall objective of this honors thesis will be to characterize the effects of TCT on cerebrovascular collateral perfusion during stroke and to identify a mechanistic basis for TCT improvement of cerebrovascular collateral circulation. Many previously identified arteriogenic markers, including Tissue inhibitor of metalloproteinase 1 (TIMP1), will be investigated as a known molecular target of interest for induction of collateral growth in the brain. FITC-lectin tagging of cerebrovascular collaterals will be used for laser capture microdissection experiments and downstream molecular study of arteriogenic targets. This approach will enable the specific collection of perfused cerebrovascular collaterals from stroke-affected tissue for mechanistic study.Funding from research grants awarded to Dr. Cameron RinkNo embargoAcademic Major: Biolog

Stress Urinary Incontinence post-Holmium Laser Enucleation of the Prostate: a Single-Surgeon Experience.

PURPOSE: To identify incidence and predictors of stress urinary incontinence (SUI) following Holmium laser enucleation of the prostate (HoLEP). MATERIALS AND METHODS: We performed a retrospective review of 589 HoLEP patients from 2012-2018. Patients were assessed at pre-operative and post-operative visits. Univariate and multivariate regression analyses were performed to identify predictors of SUI. RESULTS: 52/589 patients (8.8%) developed transient SUI, while 9/589 (1.5%) developed long-term SUI. tSUI resolved for 46 patients (88.5%) within the first six weeks and in 6 patients (11.5%) between 6 weeks to 3 months. Long-term SUI patients required intervention, achieving continence at 16.4 months on average, 44 men (70.9%) with incontinence were catheter dependent preoperatively. Mean prostatic volume was 148.7mL in tSUI patients, 111.6mL in long-term SUI, and 87.9mL in others (p \u3c 0.0001). On univariate analysis, laser energy used (p \u3c 0.0001), laser on time (p=0.0204), resected prostate weight (p \u3c 0.0001), overall International Prostate Symptom Score (IPSS) (p=0.0005), and IPSS QOL (p=0.02) were associated with SUI. On multivariate analysis, resected prostate weight was predictive of any SUI and tSUI, with no risk factors identified for long-term SUI. CONCLUSION: Post-HoLEP SUI occurs in ~10% of patients, with 1.5% continuing beyond six months. Most patients with tSUI recover within the first six weeks. Prostate size \u3e100g and catheter dependency are associated with increased risk tSUI. Larger prostate volume is an independent predictor of any SUI, and tSUI

Perspectives and Experiences of Transgender and Non-binary Individuals on Seeking Urological Care.

OBJECTIVE: To describe perspectives and experiences related to urology care-seeking of transgender and non-binary (TGNB) individuals assigned male at birth. MATERIALS AND METHODS: This HIPAA-compliant study was IRB approved and followed Consolidated Criteria for Reporting Qualitative Studies (COREQ) guidelines. Through semistructured interviews, perspectives, and experiences of individuals related to urology care-seeking were explored. Open-ended questions were designed to elicit a range of responses rather than quantifiable data. Thematic codes were developed and explicitly defined. Codes pertaining to patient experiences were assessed and described. RESULTS: Twenty-five TGNB individuals assigned male at birth were interviewed. Participants reported an array of factors that informed and inhibited care-seeking, factors that framed individual urologic care experiences, and their overall impression of the healthcare system\u27s ability to effectively and respectfully serve the TGNB population. Specifically, participants reported that prior negative healthcare experiences dissuaded them from seeking care such as feeling discriminated against and having a lack of trust in providers. Additionally, participants reported feeling a need and responsibility to educate providers on both their medical needs and psychosocial experiences. Participants were also unclear how best to identify trans-friendly urologists who are culturally competent and have appropriate medical knowledge. CONCLUSION: TGNB individuals face significant barriers to care for unique healthcare needs. TGNB participants described care avoidance and reported experiences of healthcare discrimination. These data highlight the importance for urologists to understand the perspectives and historical experiences of these individuals who may seek urological care

Impact of Tumor Regional Involvement on Active Surveillance Outcomes: Validation of the Cumulative Cancer Location Metric in a US Population.

BACKGROUND: Treatment progression for men on active surveillance (AS) for prostate cancer (PCa) is driven primarily by grade and volume progression on isolated prostate biopsies (PBx). As PCa is a multifocal disease, regional disease progression over time should be accounted for. OBJECTIVE: To validate the utility of the cumulative cancer location (CCLO) metric, which assesses regional core involvement, as described by Erickson et al (Cumulative cancer locations is a novel metric for predicting active surveillance outcomes: a multicenter study. Eur Urol Oncol 2018;1:268-75), in predicting AS outcomes in a North American cohort. DESIGN, SETTING, AND PARTICIPANTS: A single-institutional retrospective chart review of all AS patients evaluated between 2015 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: CCLO defined as the total number of cancer-positive sextant locations among all PBx to that point in time (range 1-6). Baseline demographics and clinical characteristics of the entire cohort were stratified by CCLOΔ, defined as the difference between the first and the last CCLO. CCLOΔ then correlated with progression to treatment and treatment outcomes. RESULTS AND LIMITATIONS: A total of 261 men met the inclusion criteria. Though the mean number of biopsies was slightly higher in the CCLOΔ 3-5 cohort than in the CCLOΔ 0-2 cohort (p =  0.006), mean AS follow-up time (3.3 yr) was not significantly different (p =  0.327). As CCLOΔ increased, the proportion of men remaining on AS decreased, while the proportion of men receiving treatment increased (p \u3c  0.001). In men undergoing radical prostatectomy, a higher CCLOΔ was not associated with higher rates of Gleason 7-10 (p =  0.38) or pT3 (p =  0.52) disease. However, as CCLOΔ increased, upgrading from final PBx to RP pathology increased, while downgrading decreased (p =  0.12). In Kaplan-Meier analyses, lower CCLOΔ and lower initial cancer location scores were associated with the highest 5-yr treatment-free survival rates (p \u3c  0.001). CONCLUSIONS: Higher regional cancer core involvement is associated with higher rates of progression to treatment in AS patients. The CCLO metric is a potentially useful modality in stratifying AS patients among the North American cohort for treatment, while not compromising disease outcomes. PATIENT SUMMARY: In the North American population, cumulative cancer-positive locations among biopsies can be used to predict active surveillance outcomes in men with prostate cancer

Twitter and Academic Urology in the United States and Canada: A Comprehensive Assessment of the Twitter-verse in 2019.

OBJECTIVE: To provide the first comprehensive analysis of the Twitter-verse amongst academic urologists and programs in North America. METHODS: Using national accreditation and individual program websites, all active urology residency programs (USA & Canada) and academic Urology faculty at these programs were identified. Demographic data for each program (AUA section, resident class size) and physician (title, fellowship training, Scopus H-index and citations) were documented. Twitter metrics (Twitter handle, date joined, # tweets, # followers, # following, likes) for programs and physicians were catalogued (data capture: March-April 2019). Descriptive analyses and temporal trends in Twitter utilization amongst programs and physician were assessed. Multivariable (MV) logistic regression was used to identify predictors of Twitter use. RESULTS: 156 academic programs (143 USA, 13 Canada) and 2214 academic faculty (2015 USA, 199 Canada) were identified. Twitter utilization is currently 49.3% and 34.1% amongst programs and physicians, respectively, and continues to increase. On MV analysis, programs with 3-5 residents/year and programs with a higher percentage of faculty Twitter engagement were more likely to have Twitter accounts. From a physician perspective, those with fellowship training, lower academic rank (clinical instructor, assistant professor, associate professor vs. professor) and higher H-indices were more likely to have individual Twitter accounts. CONCLUSION: There is a steady increase in Twitter engagement amongst Urology programs and academic physicians. Faculty Twitter utilization is an important driver of program Twitter engagement. Twitter SoMe activity is strongly associated with academic productivity, and may in fact drive academic metrics. Within Urology, SoMe presence appears to be proportional to academic activity

Incorporating mpMRI biopsy data into established pre-RP nomograms: potential impact of an increasingly common clinical scenario

Background: We examine the practical application of multiparametric MRI (mpMRI) prostate biopsy data using established pre-RP nomograms and its potential implications on RP intraoperative decision-making. We hypothesize that current nomograms are suboptimal in predicting outcomes with mpMRI targeted biopsy (TBx) data. Materials and methods: Patients who underwent mpMRI-based TBx prior to RP were assessed using the MSKCC and Briganti nomograms with the following iterations: (1) Targeted (T) (targeted only), (2) Targeted and Systematic (TS) and (3) Targeted Augmented (TA) (targeted core data; assumed negative systematic cores for 12 total cores). Nomogram outcomes, lymph node involvement (LNI), extracapsular extension (ECE), organ-confined disease (OCD), seminal vesicle invasion (SVI), were compared across iterations. Clinically significant impact on management was defined as a change in LNI risk above or below 2% (Δ2) or 5% (Δ5). Results: A total of 217 men met inclusion criteria. Overall, the TA iteration had more conservative nomogram outcomes than the T. Moreover, TA better predicted RP pathology for all four outcomes when compared with the T. In the entire cohort, Δ2 and Δ5 were 16.6–25.8% and 20.3–39.2%, respectively. In the subset of 190 patients with targeted and systematic cores, TA was a better approximation of TS outcomes than T in 71% (MSKCC) and 82% (Briganti) of patients. Conclusion: In established pre-RP nomograms, mpMRI-based TBx often yield variable and discordant results when compared with systematic biopsies. Future nomograms must better incorporate mpMRI TBx core data. In the interim, augmenting TBx data may serve to bridge the gap

Setting the Standards: Examining Research Productivity Among Academic Urologists in the USA and Canada in 2019.

BACKGROUND: Research productivity among academic urologists is strongly encouraged, but little data are available on productivity metrics within the field. OBJECTIVE: To provide the first comprehensive survey of research productivity among academic urologists in the USA and Canada. DESIGN, SETTING, AND PARTICIPANTS: Using the Accreditation Council for Graduate Medical Education, the Canadian Resident Matching Service, and individual program websites, all active accredited urology faculties were identified. For each individual, we collected data on American Urological Association section, title, gender, fellowship training, Scopus H-index, and citations. Comprehensive searches were completed during March-May 2019. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive statistics for demographic comparisons were performed using analysis of variance for continuous variables and chi-square test for categorical variables. Multivariable logistic regressions were used to identify the predictors of H-index greater than the median. RESULTS AND LIMITATIONS: A total of 2214 academic urology faculties (2015 in USA and 199 in Canada) were identified. The median and mean H-indices for the entire cohort of physicians were 11 and 16.1, respectively. On multivariable analysis, physicians in the North Central and Western Sections (vs mid-Atlantic), who were fellowship trained (vs no fellowship training), and of higher academic rank (professor and associate professor vs clinical instructor) were more likely to have H-index values greater than the median. Additionally, female physicians (vs male) were more likely to have H-index values less than the median. CONCLUSIONS: This study represents the first comprehensive assessment of research productivity metrics among academic urologists. These represent key benchmarks for trainees considering careers in academics and for practicing physicians gauging their own productivity in relation to their peers. PATIENT SUMMARY: In this study, we provide the first comprehensive assessment of research productivity among academic urologists in the USA and Canada. Our results help provide key benchmarks for trainees considering careers in academics and for practicing physicians gauging their own productivity in relation to peers

Stress Urinary Incontinence post-Holmium Laser Enucleation of the Prostate: a Single-Surgeon Experience

Purpose:To identify incidence and predictors of stress urinary incontinence (SUI) following Holmium laser enucleation of the prostate (HoLEP).Materials and methods:We performed a retrospective review of 589 HoLEP patients from 2012-2018. Patients were assessed at pre-operative and post-operative visits. Univariate and multivariate regression analyses were performed to identify predictors of SUI.Results:52/589 patients (8.8%) developed transient SUI, while 9/589 (1.5%) developed long-term SUI. tSUI resolved for 46 patients (88.5%) within the first six weeks and in 6 patients (11.5%) between 6 weeks to 3 months. Long-term SUI patients required intervention, achieving continence at 16.4 months on average, 44 men (70.9%) with incontinence were catheter dependent preoperatively. Mean prostatic volume was 148.7mL in tSUI patients, 111.6mL in long-term SUI, and 87.9mL in others (p < 0.0001). On univariate analysis, laser energy used (p < 0.0001), laser "on" time (p=0.0204), resected prostate weight (p < 0.0001), overall International Prostate Symptom Score (IPSS) (p=0.0005), and IPSS QOL (p=0.02) were associated with SUI. On multivariate analysis, resected prostate weight was predictive of any SUI and tSUI, with no risk factors identified for long-term SUI.Conclusion:Post-HoLEP SUI occurs in ~10% of patients, with 1.5% continuing beyond six months. Most patients with tSUI recover within the first six weeks. Prostate size >100g and catheter dependency are associated with increased risk tSUI. Larger prostate volume is an independent predictor of any SUI, and tSUI

Medical evaluation and management of male and female voiding dysfunction: a review.

A significant workforce shortage of urologists available to serve the US population has been projected to occur over the next decade. Accordingly, much of the management of urologic patients will need to be assumed by other specialties and practitioners. Since primary care physicians are often first evaluate common urologic complaints, it makes sense that these physicians are in an excellent position to intervene in the management of these patients when appropriate. One of the most common complaints in urology is voiding dysfunction. The incidence of voiding dysfunction increases with age, with conservative estimates showing that over 50% of elderly patients suffer. Despite this high prevalence and its negative impact on quality of life, however, few seek or receive treatment, as many do not readily disclose these impactful yet personal symptoms. We sought to summarize the typical presentation, evaluation, assessment and therapeutic options for both male and female patients presenting with voiding dysfunction

Medical evaluation and management of male and female voiding dysfunction: a review

A significant workforce shortage of urologists available to serve the US population has been projected to occur over the next decade. Accordingly, much of the management of urologic patients will need to be assumed by other specialties and practitioners. Since primary care physicians are often first evaluate common urologic complaints, it makes sense that these physicians are in an excellent position to intervene in the management of these patients when appropriate. One of the most common complaints in urology is voiding dysfunction. The incidence of voiding dysfunction increases with age, with conservative estimates showing that over 50% of elderly patients suffer. Despite this high prevalence and its negative impact on quality of life, however, few seek or receive treatment, as many do not readily disclose these impactful yet personal symptoms. We sought to summarize the typical presentation, evaluation, assessment and therapeutic options for both male and female patients presenting with voiding dysfunction