Clinical and sociodemographic characteristics as predictors for quality of life in transmasculine and transfeminine individuals receiving gender-affirming hormone therapy.

Healthcare systems and providers have increasingly acknowledged the role and impact of social determinants in overall health. However, gender-diverse individuals face persistent health disparities due to their identities. There is limited research on the impact of clinical and sociodemographic characteristics on mood and quality of life (QoL) for transgender (TG) individuals. Our study aims to understand and better elucidate social and clinical characteristics of transmasculine (TM) and transfeminine (TF) individuals and their impact on quality of life and depressive symptoms. In this cross-sectional study, 298 TF and TM individuals on gender-affirming hormone therapy (GAHT) were surveyed about their demographic characteristics (age, gender identity, body mass index (BMI), and education), social needs, mood, and quality of life. Multivariable regression modelling was performed to assess the effect of each variable listed above on three domains of QoL (psychological, environmental, and physical) as well as depressive symptoms. We find that QoL scores are similar between TM and TF individuals, with scores in the psychological domain particularly low in both cohorts. TM individuals report higher rates of stress and restroom avoidance than TF individuals. In particular, psychological well-being (measured by the psychological domain of QoL and depressive symptoms) is significantly associated with increased BMI, financial instability, and stress in TM individuals while for TF individuals, psychological well-being is associated with stress and social integration. These data suggest that social circumstances are key drivers of QoL and psychological well-being among gender-diverse individuals receiving GAHT with specific differences between TF and TM individuals. This information may be utilized by healthcare providers and policymakers to address and improve clinical care and social policies to improve health equity for gender-diverse individuals.

Methodological rigour in preclinical urology: a systematic review reporting research quality over a 14-year period.

OBJECTIVE: To investigate the prevalence and trends of essential study design elements in preclinical urological studies, as well as key factors that may improve methodological rigour, as the demand for methodological rigour in preclinical studies is increasing since research reproducibility and transparency in the medico-scientific field are being questioned. METHODS AND RESULTS: PubMed was searched to include preclinical urological studies published between July 2007 to June 2021. A total of 3768 articles met the inclusion criteria. Data on study design elements and animal models used were collected. Citation density was also examined as a surrogate marker of study influence. We performed an analysis of the prevalence of seven critical study design elements and temporal patterns over 14 years. Randomisation was reported in 50.0%, blinding in 15.0%, sample size estimation in 1.0%, inclusion of both sexes in 6.3%, statistical analysis in 97.1%, housing and husbandry in 47.7%, and inclusion/exclusion criteria in 5.0%. Temporal analysis showed that the implementation of these study design elements has increased, except for inclusion of both sexes and inclusion/exclusion criteria. Reporting study design elements were associated with increased citation density in randomisation and statistical analysis. CONCLUSIONS: The risk of bias is prevalent in 14-year publications describing preclinical urological research, and the quality of methodological rigour is barely related to the citation density of the article. Yet five study design elements (randomisation, blinding, sample size estimation, statistical analysis, and housing and husbandry) proposed by both the National Institutes of Health and Animal Research: Reporting of In Vivo Experiments guidelines have been either well reported or are being well reported over time. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022233125.

Disparities in cause-specific mortality by race and sex among bladder cancer patients from the SEER database.

PURPOSE: Previous literature shows that more bladder cancer patients overall die from causes other than the primary malignancy. Given known disparities in bladder cancer outcomes by race and sex, we aimed to characterize differences in cause-specific mortality for bladder cancer patients by these demographics. METHODS: We identified 215,252 bladder cancer patients diagnosed with bladder cancer from 2000 to 2017 in the SEER 18 database. We calculated cumulative incidence of death from seven causes (bladder cancer, COPD, diabetes, heart disease, external, other cancer, other) to assess differences in cause-specific mortality between race and sex subgroups. We used multivariable Cox proportional hazards regression and Fine-Gray competing risk models to compare risk of bladder cancer-specific mortality between race and sex subgroups overall and stratified by cancer stage. RESULTS: 17% of patients died from bladder cancer (n = 36,923), 30% died from other causes (n = 65,076), and 53% were alive (n = 113,253). Among those who died, the most common cause of death was bladder cancer, followed by other cancer and diseases of the heart. All race-sex subgroups were more likely than white men to die from bladder cancer. Compared to white men, white women (HR: 1.20, 95% CI: 1.17-1.23) and Black women (HR: 1.57, 95% CI: 1.49-1.66) had a higher risk of dying from bladder cancer, overall and stratified by stage. CONCLUSION: Among bladder cancer patients, death from other causes especially other cancer and heart disease contributed a large proportion of mortality. We found differences in cause-specific mortality by race-sex subgroups, with Black women having a particularly high risk of dying from bladder cancer.

Noncancerous Genitourinary Conditions as a Public Health Priority: Conceptualizing the Hidden Burden.

OBJECTIVE: To provide a conceptual framework to guide investigations into burdens of noncancerous genitourinary conditions (NCGUCs), which are extensive and poorly understood. METHODS: The National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop of diverse, interdisciplinary researchers and health professionals to identify known and hidden burdens of NCGUCs that must be measured to estimate the comprehensive burden. Following the meeting, a subgroup of attendees (authors of this article) continued to meet to conceptualize burden. RESULTS: The Hidden Burden of Noncancerous Genitourinary Conditions Framework includes impacts across multiple levels of well-being and social ecology, including individual (ie, biologic factors, lived experience, behaviors), interpersonal (eg, romantic partners, family members), organizational/institutional (eg, schools, workplaces), community (eg, public restroom infrastructure), societal (eg, health care and insurance systems, national workforce/economic output), and ecosystem (eg, landfill waste) effects. The framework acknowledges that NCGUCs can be a manifestation of underlying biological dysfunction, while also leading to biological impacts (generation and exacerbation of health conditions, treatment side effects). CONCLUSION: NCGUCs confer a large, poorly understood burden to individuals and society. An evidence-base to describe the comprehensive burden is needed. Measurement of NCGUC burdens should incorporate multiple levels of well-being and social ecology, a life course perspective, and potential interactions between NCGUCs and genetics, sex, race, and gender. This approach would elucidate accumulated impacts and potential health inequities in experienced burdens. Uncovering the hidden burden of NCGUCs may draw attention and resources (eg, new research and improved treatments) to this important domain of health.

The Inflection Point Model: A Model to Explore the Hidden Burdens of Non-Cancerous Genitourinary Conditions.

OBJECTIVE: To propose a conceptual model to identify points along the condition course where actions or inaction affect downstream burdens of non-cancerous genitourinary conditions (NCGUC). MATERIALS AND METHODS: The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) convened an interdisciplinary meeting to comprehensively consider the burdens of NCGUCs. Subsequently, the authors met monthly to conceptualize the model. RESULTS: Inflection points (IP) describe time points during a condition course that are sensitive to change. Our proposed Inflection Point Model (IPM) helps conceptualize burden/benefit trade-offs in any related decision and provides a platform to identify the downstream aggregate burden of a NCGUC across multiple socio-ecological levels at a single time point, which may be summed across the condition course to measure cumulative burden. Two personae demonstrate the utility of this model to better understand impacts of 2 common NCGUCs. CONCLUSION: The IPM may be applied in multiple contexts: narrowly to explore burden of a single NCGUC at a single IP; or more broadly, to address multiple conditions, multiple IPs, or multiple domains/levels of social ecology. Applying the IPM may entail combining population data describing prevalence of NCGUCs, associated behaviors, and resulting outcome patterns that can be combined with suitable mathematical models to quantify aggregate and cumulative burden. The IPM challenges stakeholders to expand from the individual to include broader levels of social ecology. Application of the IPM will undoubtedly identify data gaps and research needs that must be fulfilled to delineate and address the burden of NCGUCs.

Evaluation of the relationship of cholinergic metabolites in urine and urgency urinary incontinence.

INTRODUCTION AND HYPOTHESIS: To investigate differences in urine cholinergic metabolites in women with urinary urgency incontinence (UUI) and responders (R) and non-responders (NR) to anti-cholinergic medications (AC). METHODS: Patients with UUI and age-matched controls were evaluated pre- and post-treatment using OABSS, UDI-6 and IIQ-7. Controls were defined as having a cumulative OABSS of zero. Patients with UUI were treated with AC and followed for 12 weeks. Responders were those with a > 50% decrease in the total OABSS score. Urine samples were collected from all participants for evaluation. Metabolite detection was accomplished using commercial assay kits. Wilcoxon-rank sum test and Fisher's exact test were used to express differences between groups. Spearman's rho correlation coefficient was used to determine the relationship between acetylcholine (Ach), choline (Ch), acetylcholinesterase (AchE) and questionnaire scores. RESULTS: We recruited 39 with UUI and 33 controls. We found concentrations of Ch [29.0 (IQR: 24.2-42.5) µmol vs. 15.2 (IQR: 7.5-24.1) µmol] and Ach [65.8 (IQR: 30.4-101.8) nmol and 33.1 (IQR: 11.9-43.8) nmol] were higher in the UUI group compared to controls (p = 0.003 and p < 0.001, respectively] and no differences in AchE concentrations. In the UUI group, 43.6% responded to AC after 12 weeks of therapy. There were no differences in Ch or AchE levels between R and NR; Ach levels were higher in the R group [82.1 nmol (IQR: 54.8-118.1) vs. 50.3 nmol (IQR: 29.9-68.2), p = 0.007]. Ch and Ach were positively associated with pre-treatment OABSS parameters. CONCLUSIONS: Urine Ach is higher in responders to anti-cholinergic therapy, and urine cholinergic metabolites were higher in the UUI patients compared to controls.

Abdominal and vaginal pelvic support with concomitant hysterectomy for uterovaginal pelvic prolapse: a comparative systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: While approximately 225,000 pelvic organ prolapse (POP) surgeries are performed annually in the US, there is no consensus on the optimal route for pelvic support for the initial treatment of uterovaginal prolapse (UVP). Our objective is to compare the outcomes of abdominal sacrocolpopexy (ASC) to vaginal pelvic support (VPS) with either uterosacral ligament suspension (USLS) or sacrospinous ligament fixation (SSF) in combination with hysterectomy for treating apical prolapse. METHODS: A systematic search was performed through March 2021. Studies comparing ASC with VPS for treatment of UVP were included in the review. The primary outcome was the rate of overall anatomic prolapse failure per studies' definition. Secondary outcomes included evaluating isolated recurrent vaginal wall prolapse, postoperative POP-Q points, total vaginal length (TVL), and Pelvic Floor Distress Inventory (PFDI-20) scores. Random effect analyses were generated utilizing R 4.0.2. RESULTS: Out of 4225 total studies, 4 met our inclusion criteria, including 226 patients in the ASC group and 199 patients in the VPS group. ASC was not found to be associated with a higher rate of vaginal wall prolapse recurrence (OR = 0.6; 95% CI = 0.2-2.4; P = 0.33). There was no significant difference between groups for anterior or apical vaginal wall prolapse recurrence (P = 0.58 and P = 0.97, respectively). ASC was associated with significantly longer TVL (mean difference [MD]: 1.01; 95% CI = 0.33-1.70; P = 0.02) and better POP-Q Ba scores [MD = -0.23; 95% CI = -0.37; -0.10; P = 0.01]. CONCLUSIONS: ASC and vaginal pelvic support (either USLS or SSF) have comparable anatomical outcomes. However, weak evidence of a difference in TVL and Ba was found. The strength of the evidence in this study is based on the small number of observational studies. A large, randomized trial is highly warranted.

Gender Disparities in Bladder Cancer-Specific Survival in High Poverty Areas Utilizing Ohio Cancer Incidence Surveillance System (OCISS).

OBJECTIVE: To better understand the interplay of socioeconomic and demographic traits on bladder cancer outcomes utilizing the Ohio state cancer registry, Ohio Cancer Incidence Surveillance System (OCISS). METHODS: We obtained demographic, clinical and outcome data on 47,182 bladder cancer cases diagnosed from 1996 to 2016 from OCISS. Multivariable Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between sex, race and poverty and survival, adjusting age, stage, and primary treatment. RESULTS: Within the OCISS database, there were 47,182 patients with a diagnosis of bladder cancer identified, with females representing 12,056 (26%) of the population. There were a total of 9255(35.2%) deaths due to bladder cancer, with median follow-up time of 4.4 years. After adjusting for confounding variables, women were statistically significantly less likely to die from any cause (HR: 0.94, 95% CI: 0.91-0.96), compared with men, but more likely to die from bladder cancer (HR: 1.21, 95% CI: 1.15-1.27). We also found that after adjusting for confounding variables, including sex and poverty, black race was statistically significantly associated with a higher risk of overall (HR: 1.12, 95% CI: 1.06-1.18) and bladder cancer-specific mortality (HR: 1.25, 95% CI: 1.15-1.36). CONCLUSION: Using the OCISS database, female gender, self-reported black race, and neighborhood poverty level were associated with worse bladder cancer-specific survival. By recognizing these disparities, we can prospectively address risk factors in efforts to improve survival among these patient populations.

Diagnostic Yield of Incremental Biopsy Cores and Second Lesion Sampling for In-Gantry MRI-Guided Prostate Biopsy.

BACKGROUND. In-gantry MRI-guided biopsy (MRGB) of the prostate has been shown to be more accurate than other targeted prostate biopsy methods. However, the optimal number of cores to obtain during in-gantry MRGB remains undetermined. OBJECTIVE. The purpose of this study was to assess the diagnostic yield of obtaining an incremental number of cores from the primary lesion and of second lesion sampling during in-gantry MRGB of the prostate. METHODS. This retrospective study included 128 men with 163 prostate lesions who underwent in-gantry MRGB between 2016 and 2019. The men had a total of 163 lesions sampled with two or more cores, 121 lesions sampled with three or more cores, and 52 lesions sampled with four or more cores. A total of 40 men underwent sampling of a second lesion. Upgrade on a given core was defined as a greater International Society of Urological Pathology (ISUP) grade group (GG) relative to the previously obtained cores. Clinically significant prostate cancer (csPCa) was defined as ISUP GG 2 or greater. RESULTS. The frequency of any upgrade was 12.9% (21/163) on core 2 versus 10.7% (13/121) on core 3 (p = .29 relative to core 2) and 1.9% (1/52) on core 4 (p = .03 relative to core 3). The frequency of upgrade to csPCa was 7.4% (12/163) on core 2 versus 4.1% (5/121) on core 3 (p = .13 relative to core 2) and 0% (0/52) on core 4 (p = .07 relative to core 3). The frequency of upgrade on core 2 was higher for anterior lesions (p < .001) and lesions with a higher PI-RADS score (p = .007); the frequency of upgrade on core 3 was higher for apical lesions (p = .01) and lesions with a higher PI-RADS score (p = .01). Sampling of a second lesion resulted in an upgrade in a single patient (2.5%; 1/40); both lesions were PI-RADS category 4 and showed csPCa. CONCLUSION. When performing in-gantry MRGB of the prostate, obtaining three cores from the primary lesion is warranted to optimize csPCa diagnosis. Obtaining a fourth core from the primary lesion or sampling a second lesion has very low yield in upgrading cancer diagnoses. CLINICAL IMPACT. To reduce patient discomfort and procedure times, operators may refrain from obtaining more than three cores or second lesion sampling.

"Robotic fatigue?" - The impact of case order on positive surgical margins in robotic-assisted laparoscopic prostatectomy.

PURPOSE: Multiple robotic-assisted surgeries are often performed within a single operating day; however, the impact of this practice on patient outcomes has not been examined. We aim to determine whether outcomes for robotic-assisted laparoscopic prostatectomy (RALP) differed when performed sequentially. MATERIALS AND METHODS: A multi-institutional, retrospective cohort study was conducted involving a total of 8 academic centers between years 2015 and 2018. Participants were adult males undergoing RALP for localized prostate cancer on operative days in which 2 RALP cases were performed sequentially by the same resident-attending team. The primary outcome of the study was presence of positive surgical margin (PSM). Secondary outcomes were lymph node yield, operative time, and estimated blood loss. The primary analysis was a random effects meta-analysis model for PSM. RESULTS: Overall, 898 RALP cases (449 sequential pairs) were included in the study. There was no significant difference in PSM rate (27.2% vs. 30.3%, P= 0.338) between first and second case groups, respectively. Utilizing random effects meta-analysis, the second case cohort had no increased risk of PSM (OR 0.761.231.97, P= 0.40). Higher blood loss was noted in the second case cohort (186.7 ml vs. 221.7 ml, P = 0.002). Additionally, factors associated with PSM were increasing prostate specific antigen, higher percent tumor involvement, extraprostatic extension, and seminal vesicle invasion. CONCLUSION: Case sequence was not associated with PSM, lymph node yield, or operative time for RALP. Disease specific factors and institutional experience are associated with increased risk for positive surgical margin which can aid providers in scheduling of patients.

Transcriptomic Analysis of Human Mesenchymal Stem Cell Therapy in Incontinent Rat Injured Urethra.

Periurethral human mesenchymal stem cell (hMSC) injections are associated with functional improvement in animal models of postpartum stress urinary incontinence (SUI). However, limited data exist on the role of hMSCs in modulating gene expression in tissue repair after urethral injury. To this end, we quantified temporal gene expression modulation in hMSCs, and in injured rat urethral tissue, using RNA-seq in an animal model of SUI, over a 3-day period following urethral injury, and local hMSC injection. We injected PKH fluorescent-labeled hMSC into the periurethral space of rats following a 4 h vaginal distention (VD) (three rats per time point). Control rats underwent VD injury only, and all animals were euthanized at 12, 24, 36, 72 h postinjury. Rat urethral and vaginal tissues were frozen and sectioned. Fluorescent labeled hMSCs were distinguished from adjacent, unlabeled rat urethral tissue. RNA was prepared from hMSCs and urethral tissue obtained by laser dissection of frozen tissue sections and sequenced on an Illumina HiSeq 2500. Differentially expressed genes (DEGs) over 72 h were evaluated using a two-group t-test (p < 0.05). Our transcriptional analyses identified candidate genes involved in tissue injury that were broadly sorted by injury and exposure to hMSC throughout the first 72 h of acute phase of injury. DEGs in treated urethra, compared with untreated urethra, were functionally associated with tissue repair, angiogenesis, neurogenesis, and oxidative stress suppression. DEGs included a variety of cytokines, extracellular matrix stabilization and regeneration genes, cytokine signaling modification, cell cycle regulation, muscle differentiation, and stabilization. Moreover, our results revealed DEG changes in hMSCs (PKH-labeled) harvested from injured urethra. The expressions are related to DNA damage repair, transcription activation, stem cell regulation, cell survival, apoptosis, self-renewal, cell proliferation, migration, and injury response. Impact statement Stress urinary incontinence (SUI) affects nearly half of women over 40, resulting in reduced quality of life and increased health care cost. Development of SUI is multifactorial and strongly associated with vaginal delivery. While stem cell therapy in animal models of SUI and limited preliminary clinical trials demonstrate functional improvement of SUI, the role of stem cell therapy in modulating tissue repair is unclear impeding advanced clinical trials. Our work provides a new understanding of the transcriptional mechanisms with which human mesenchymal stem cells improve acute injury repair thus guiding the development of cell-based therapies for women with nonacute established SUI.

Gene expression in stress urinary incontinence: a systematic review.

INTRODUCTION: A contribution of genetic factors to the development of stress urinary incontinence (SUI) is broadly acknowledged. This study aimed to: (1) provide insight into the genetic pathogenesis of SUI by gathering and synthesizing the available data from studies evaluating differential gene expression in SUI patients and (2) identify possible novel therapeutic targets and leads. METHODS: A systematic literature search was conducted through September 2017 for the concepts of genetics and SUI. Gene networking connections and gene-set functional analyses of the identified genes as differentially expressed in SUI were performed using GeneMANIA software. RESULTS: Of 3019 studies, 4 were included in the final analysis. A total of 13 genes were identified as being differentially expressed in SUI patients. Eleven genes were overexpressed: skin-derived antileukoproteinase (SKALP/elafin), collagen type XVII alpha 1 chain (COL17A1), plakophilin 1 (PKP1), keratin 16 (KRT16), decorin (DCN), biglycan (BGN), protein bicaudal D homolog 2 (BICD2), growth factor receptor-bound protein 2 (GRB2), signal transducer and activator of transcription 3 (STAT3), apolipoprotein E (APOE), and Golgi SNAP receptor complex member 1 (GOSR1), while two genes were underexpressed: fibromodulin (FMOD) and glucocerebrosidase (GBA). GeneMANIA revealed that these genes are involved in intermediate filament cytoskeleton and extracellular matrix organization. CONCLUSION: Many genes are involved in the pathogenesis of SUI. Furthermore, whole-genome studies are warranted to identify these genetic connections. This study lays the groundwork for future research and the development of novel therapies and SUI biomarkers in clinical practice.

Development and Validation of a Machine Learning Algorithm for Predicting Response to Anticholinergic Medications for Overactive Bladder Syndrome.

OBJECTIVE: To develop and externally validate a prediction model for anticholinergic response in patients with overactive bladder (OAB). METHODS: A machine learning model to predict the likelihood of anticholinergic treatment failure was constructed using a retrospective data set (n=559) of female patients with OAB who were treated with anticholinergic medications between January 2010 and December 2017. Treatment failure was defined as less than 50% improvement in frequency, urgency, incontinence episodes, and nocturia, and the patient's subjective impression of symptomatic relief. Patients were stratified by age (younger than 40 years, 40-60 years, and older than 60 years), and number of previously failed medications. K-fold stratified cross-validation was performed on each stratum using machine learning algorithms. Of these, the random forest model was the most accurate. This model was refined using internal cross validation within each stratum. The area under the curve (AUC) was calculated for each stratum and used to identify the optimal operating points for prediction of treatment failure. The random forest model was then externally validated using a prospectively collected data set (n=82) of women treated with anticholinergic medications at a different clinical site between January 2018 and December 2018. RESULTS: The global accuracy of the final model was 80.3% (95% CI 79.1-81.3), and the AUC was 0.77 (95% CI 0.74-0.79). Using the external validation data set, the model's sensitivity and specificity was 80.4% (95% CI 66.5-89.7%) and 77.4% (95% CI 58.6-89.7%), respectively. The model performed best in women aged younger than 40 years (AUC 0.84, 95% CI 0.81-0.84) and worst in women aged older than 60 years who had previously failed medication (AUC 0.71, 95% CI 0.67-0.75). CONCLUSION: Our externally validated machine learning prediction model can predict anticholinergic treatment failure during the standard 3-month treatment trial period with greater than 80% accuracy. The model can be accessed at https://oabweb.herokuapp.com/app/pre/.

Acute myocardial infarction quality of care: the Strong Heart Study.

OBJECTIVES: Evaluate the quality of care provided patients with acute myocardial infarction and compare with similar national and regional data. DESIGN: Case series. SETTING: The Strong Heart Study has extensive population-based data related to cardiovascular events among American Indians living in three rural regions of the United States. PARTICIPANTS: Acute myocardial infarction cases (72) occurring between 1/1/2001 and 12/31/2006 were identified from a cohort of 4549 participants. OUTCOME MEASURES: The proportion of cases that were provided standard quality of care therapy, as defined by the Healthcare Financing Administration and other national organizations. RESULTS: The provision of quality services, such as administration of aspirin on admission and at discharge, reperfusion therapy within 24 hours, prescription of beta blocker medication at discharge, and smoking cessation counseling were found to be 94%, 91%, 92%, 86% and 71%, respectively. The unadjusted, 30 day mortality rate was 17%. CONCLUSION: Despite considerable challenges posed by geographic isolation and small facilities, process measures of the quality of acute myocardial infarction care for participants in this American Indian cohort were comparable to that reported for Medicare beneficiaries nationally and within the resident states of this cohort.