Faculty Bibliography

[This corrects the article DOI: 10.1016/j.euros.2023.05.007.].

As the climate crisis deepens, its adverse effects on human health are becoming evident, including impacts on cancer pathogenesis and treatment. This study explored the link between individuals' awareness of the health impacts of climate change and interest in cancer screening. Using the 2021 Health Information National Trends Survey, our study demonstrated a statistically significant association between recognition of climate change as a personal health threat and interest in cancer screening. Although the study's retrospective nature and self-reported data pose some limitations, these findings signal a promising avenue for future research on the intersection of climate and cancer risk. This research supports the development of public health interventions that incorporate components of environmental health literacy alongside cancer screening efforts.

Type 2 diabetes (T2D) is a chronic metabolic disorder in which insulin resistance and impaired insulin secretion result in altered metabolite balance, specifically elevated levels of circulating glucose and succinate, which increases the risk of many pathologies, including periodontitis. Succinate, a tricarboxylic acid (TCA) cycle intermediate, can be produced and metabolized by both host cells and host microbiota, where elevated levels serve as an inflammation and pathogen threat signal through activating the succinate G protein-coupled receptor, SUCNR1. Modulating succinate-induced SUCNR1 signaling remains a promising therapeutic approach for pathologies resulting in elevated levels of succinate, such as T2D and periodontitis. Here, we demonstrate hyperglycemia and elevated intracellular succinate in a T2D mouse model and determine gut microbiome composition. Drawing on previous work demonstrating the ability of a novel SUCNR1 antagonist, compound 7a, to block inflammation and alleviate dysbiosis in a mouse model, we examined if compound 7a has an impact on the growth and virulence gene expression of bacterial and fungal human microbiota in vitro, and if 7a could reduce bone loss in a periodontitis-induced mouse model. T2D mice harbored a significantly different gut microbiome, suggesting the altered metabolite profile of T2D causes shifts in host-microbial community structure, with enrichment in succinate producers and consumers and mucin-degrading bacteria. Bacterial and fungal cultures showed that 7a did not influence growth or virulence gene expression, suggesting the therapeutic effects of 7a are a direct result of 7a interacting with host cells and that alterations in microbial community structure are driven by reduced host SUCNR1 signaling. This work further suggests that targeting SUCNR1 signaling is a promising therapeutic approach in metabolic, inflammatory, or immune disorders with elevated succinate levels.

OBJECTIVES/OBJECTIVE:To evaluate the interaction of patient age and Prostate Imaging-Reporting and Data System (PI-RADS) score in determining the grade of prostate cancer (PCa) identified on magnetic resonance imaging (MRI)-targeted biopsy in older men. PATIENTS AND METHODS/METHODS:From a prospectively accrued Institutional Review Board-approved comparative study of MRI-targeted and systematic biopsy between June 2012 and December 2022, men with at least one PI-RADS ≥3 lesion on pre-biopsy MRI and no prior history of PCa were selected. Ordinal and binomial logistic regression analyses were performed. RESULTS:A total of 2677 men met study criteria. The highest PI-RADS score was 3 in 1220 men (46%), 4 in 950 men (36%), and 5 in 507 men (19%). The median (interquartile range [IQR]) patient age was 66.7 (60.8-71.8) years, median (IQR) prostate-specific antigen (PSA) level was 6.1 (4.6-9.0) ng/mL, median (IQR) prostate volume was 48 (34-68) mL, and median (IQR) PSA density was 0.13 (0.08-0.20) ng/mL/mL. Clinically significant (cs)PCa and high-risk PCa were identified on targeted biopsy in 1264 (47%) and 321 (12%) men, respectively. Prevalence of csPCa and high-risk PCa were significantly higher in the older age groups. On multivariable analyses, patient age was significantly associated with csPCa but not high-risk PCa; PI-RADS score and the interaction of age and PI-RADS score were significantly associated with high-risk PCa but not csPCa. CONCLUSION/CONCLUSIONS:In our cohort, the substantial rate of high-risk PCa on MRI-ultrasound fusion targeted biopsies in older men, and its significant association with MRI findings, supports the value of pre-biopsy MRI to localise disease that could cause cancer mortality even in older men.

IMPORTANCE/OBJECTIVE:Urinary incontinence (UI) is a common and treatable medical condition among women, but only approximately one third of women seek care. OBJECTIVE:The objective of this study was to determine factors associated with care-seeking behavior in women with UI. STUDY DESIGN/METHODS:This was a cross-sectional study using patient-reported survey data collected by the National Association for Continence from November 2018 to January 2019. This survey included 60 questions and was conducted using SurveyMonkey. Descriptive statistics were used for baseline characteristics, the χ2 test was used for categorical variables, and multivariate logistic regression was used to determine predictors of care-seeking behavior. RESULTS:Four hundred eighty-five women completed the survey, 30.7% were not care seeking, and 69.3% were care seeking for UI. Most women were 55 years or older and had UI for more than 4 years. Care-seeking women had more overactive bladder symptoms. Women who sought care were more likely to report feelings of anger, depression, hopelessness, isolation, and report greater social effects from UI than non-care-seeking women. Less than 10% of women who sought care were asked about their UI by a medical professional. In the multivariate logistic regression expenditure of $5 or more on monthly incontinence maintenance, daily UI and older age were associated with seeking care. CONCLUSIONS:Most women in our study population sought care for UI. Factors associated with seeking care were expenditure greater than $5 per month on incontinence, daily UI, and age. This information demonstrates the need for effective implementation of screening interventions to increase treatment access.

INTRODUCTION/UNASSIGNED:Overactive bladder (OAB) patients who do not achieve satisfactory results with second-line OAB medications should be offered third-line therapies (percutaneous tibial nerve stimulation, sacral neuromodulation, onabotulinumtoxinA bladder injection [BTX-A]). We aimed to determine which clinical factors affect progression from second- to third-line OAB therapy. METHODS/UNASSIGNED:Between 2014 and 2020, the AUA Quality Registry was queried for adult patients with idiopathic OAB. For the primary outcome, patient and provider factors associated with increased odds of progression from second- to third-line therapy were assessed. Secondary outcomes included median time for progression to third-line therapy and third-line therapy utilization across subgroups. RESULTS/UNASSIGNED:A total of 641,122 patients met inclusion criteria and were included in analysis. Of these, only 7487 (1.2%) received third-line therapy after receiving second-line therapy. On multivariate analysis, patients aged 65 to 79, women, White race, history of dual anticholinergic and β3 agonist therapy, metropolitan area, government insurance, and single specialty practice had the greatest odds of progressing to third-line therapy. Black and Asian race, male gender, and rural setting had lower odds of progressing to third-line therapy. BTX-A was the most common therapy overall (40% BTX-A, 32% sacral neuromodulation, 28% percutaneous tibial nerve stimulation). The median time of progression from second- to third-line therapy was 15.4 months (IQR 5.9, 32.4). Patients < 50 years old and women progressed fastest to third-line therapy. CONCLUSIONS/UNASSIGNED:Very few patients received third-line therapies, and the time to progression from second- to third-line therapies is > 1 year. The study findings highlight a potential need to improve third-line therapy implementation.

PURPOSE/OBJECTIVE:Germline genetic testing (GT) is important for prostate cancer (PCA) management, clinical trial eligibility, and hereditary cancer risk. However, GT is underutilized and there is a shortage of genetic counselors. To address these gaps, a patient-driven, pretest genetic education webtool was designed and studied compared with traditional genetic counseling (GC) to inform strategies for expanding access to genetic services. METHODS:Technology-enhanced acceleration of germline evaluation for therapy (TARGET) was a multicenter, noninferiority, randomized trial (ClinicalTrials.gov identifier: NCT04447703) comparing a nine-module patient-driven genetic education webtool versus pretest GC. Participants completed surveys measuring decisional conflict, satisfaction, and attitudes toward GT at baseline, after pretest education/counseling, and after GT result disclosure. The primary end point was noninferiority in reducing decisional conflict between webtool and GC using the validated Decisional Conflict Scale. Mixed-effects regression modeling was used to compare decisional conflict between groups. Participants opting for GT received a 51-gene panel, with results delivered to participants and their providers. RESULTS:= .01), suggesting the patient-driven webtool was noninferior to GC. Overall, 145 (89.5%) GC and 120 (78.4%) in the webtool arm underwent GT, with pathogenic variants in 15.8% (8.7% in PCA genes). Satisfaction did not differ significantly between arms; knowledge of cancer genetics was higher but attitudes toward GT were less favorable in the webtool arm. CONCLUSION/CONCLUSIONS:The results of the TARGET study support the use of patient-driven digital webtools for expanding access to pretest genetic education for PCA GT. Further studies to optimize patient experience and evaluate them in diverse patient populations are warranted.

PURPOSE/UNASSIGNED:Although the majority of US adults obtain health information on the internet, the quality of information about prostate cancer is highly variable. Black adults are underrepresented in online content about prostate cancer despite a higher incidence of and mortality from the disease. The goal of this study was to explore the perspectives of Black patients with prostate cancer on the importance of racial representation in online content and other factors influencing trust. MATERIALS AND METHODS/UNASSIGNED:We conducted 7 virtual focus groups with Black patients with prostate cancer in 2022 and 2023. Participants completed an intake questionnaire with demographics followed by a group discussion, including feedback on purposefully selected online content. Transcripts were independently analyzed by 2 investigators experienced in qualitative research using a constant comparative method. RESULTS/UNASSIGNED:Most participants use online sources to look for prostate cancer information. Racial representation is an important factor affecting trust in the content. A lack of Black representation has consequences, including misperceptions about a lower risk of prostate cancer and discouraging further information-seeking. Other key themes affecting trust in online content included the importance of a reputable source of information, professional website structure, and soliciting money. CONCLUSIONS/UNASSIGNED:Underrepresentation of Black adults in prostate cancer content has the potential to worsen health disparities. Optimal online communications should include racially diverse representation and evidence-based information in a professional format from reputable sources without financial conflict.

Podcasts represent a new source of information for patients and families dealing with prostate cancer, but no studies have been conducted evaluating the quality of information in them. Evaluating for: (1) quality based on the validated DISCERN criteria, (2) understandability and actionability based on the Patient Education Materials Assessment Tool (PEMAT), (3) misinformation, and (4) commercial bias, we concluded that podcasts are currently not good sources of information for lay health consumers.