Patient-Reported Outcome Measures Following Hyperbaric Oxygen Therapy for Radiation Cystitis: Early Results From the Multicenter Registry for Hyperbaric Oxygen Therapy.

PURPOSE: Our purpose was to determine changes in patient-reported hematuria and urinary symptoms after hyperbaric oxygen (HBO2) treatment for radiation cystitis (RC). MATERIALS AND METHODS: We analyzed prospectively collected data from the Multicenter Registry for Hyperbaric Oxygen Therapy Consortium accumulated within a week of beginning and ending HBO2. Measures included the modified Radiation Therapy Oncology Group (RTOG) Hematuria Scale, Urinary Distress Inventory Short Form, and EuroQol Five Dimension Five Level instrument. RTOG hematuria and Urinary Distress Inventory Short Form scores were compared using the sign test. Logistic regression was used to evaluate characteristics associated with hematuria improvement. RESULTS: A total of 470 registry patients had RC. The median age, number of HBO2 sessions, and years after radiation were 73 (IQR 12) years, 39 (IQR 10) sessions, and 5 (IQR 8) years, respectively. Eighty-four percent of patients (393/470) had prostate cancer‒related radiation. EuroQol Five Dimension Five Level scores improved from 0.83 (IQR 0.14) to 0.85 (IQR 0.22; P < .001. Three hundred seventy patients had complete RTOG hematuria scores that improved from 2 (IQR 2) to 0 (IQR 2; P < .001. Two hundred forty-six patients had complete Urinary Distress Inventory Short Form ratings that decreased from 33.3 (IQR 44) to 22.2 (IQR 33; P < .001). Regression analysis of those with visible hematuria before HBO2 showed lower improvement odds associated with higher HBO2 hematuria scores (odds ratio [OR] 0.44, 95% CI 0.26-0.73; P < .01), a smoking history (OR 0.44, 95% CI 0.21-0.92; P = .03), or a nonprostate cancer history (OR 0.32, 95% CI 0.10-0.99; P = .05). CONCLUSIONS: HBO2 for RC improved reported hematuria, urinary function, and quality of life. Higher baseline hematuria scores, smoking, and nonprostate cancer history were associated with lower odds of hematuria improvement.

Trends Among Female Pelvic Medicine and Reconstructive Surgery Fellowships and Graduates.

IMPORTANCE: Understanding differences in female pelvic medicine and reconstructive surgery (FPMRS) urology and gynecology-based fellowships is important because both are accredited by the American Board of Medical Subspecialties. OBJECTIVE: The aim of the study was to characterize urology-based and gynecology-based FPMRS fellowships. MATERIAL AND METHODS: An institutional review board-approved 21-item survey was emailed to Accreditation Council for Graduate Medical Education-accredited FPMRS fellowship program directors from January 8 through March 9, 2021. The survey aimed to characterize fellowships through a series of common and specialty-specific questions. Responses were collected with Qualtrics and analyzed using STATA/MP Version 16.1. RESULTS: The response rate was 75% (52/69). Many programs accept both gynecology- and urology-trained applicants (urology-based fellowships, 45.4%; gynecology-based fellowships, 68.3%) since the Accreditation Council for Graduate Medical Education accreditation in 2012. Within the gynecology-based cohort, there have been 10 urology-trained graduates among 7 programs (n = 1-2). Barriers to accepting urology applicants were limited gynecologic knowledge/experience (n = 14) and length of training (n = 11). Thirty-seven (94.8%) reported their graduates log more than 30 hysterectomies and 8.3% (n = 3) log 3 or more urinary diversions.Within the urology-based cohort, there have been 16 gynecology-trained graduates among 4 programs (n = 2-7). Lack of urologic clinical knowledge (n = 4) and training length (n = 2) were cited as barriers to accepting gynecology-trained applicants. Three (27%) reported that their graduates log more than 30 hysterectomies, while 8 (72.7%) reported that graduates log 3 or more urinary diversions. CONCLUSIONS: Despite many FPMRS programs stating that they accept gynecology or urology-trained applicants, few fellows graduate from outside specialty FPMRS training programs. Several barriers were identified that may prevent trainees acceptance outside of their residency specialty. Procedural training experience differs between urology- and gynecology-based fellowships.

Treatment of urethral stricture disease in women: A multi-institutional collaborative project from the SUFU research network.

AIM: Female urethral stricture disease is rare and has several surgical approaches including endoscopic dilations (ENDO), urethroplasty with local vaginal tissue flap (ULT) or urethroplasty with free graft (UFG). This study aims to describe the contemporary management of female urethral stricture disease and to evaluate the outcomes of these three surgical approaches. METHODS: This is a multi-institutional, retrospective cohort study evaluating operative treatment for female urethral stricture. Surgeries were grouped into three categories: ENDO, ULT, and UFG. Time from surgery to stricture recurrence by surgery type was analyzed using a Kaplan-Meier time to event analysis. To adjust for confounders, a Cox proportional hazard model was fit for time to stricture recurrence. RESULTS: Two-hundred and ten patients met the inclusion criteria across 23 sites. Overall, 64% (n = 115/180) of women remained recurrence free at median follow-up of 14.6 months (IQR, 3-37). In unadjusted analysis, recurrence-free rates differed between surgery categories with 68% ENDO, 77% UFG and 83% ULT patients being recurrence free at 12 months. In the Cox model, recurrence rates also differed between surgery categories; women undergoing ULT and UFG having had 66% and 49% less risk of recurrence, respectively, compared to those undergoing ENDO. When comparing ULT to UFG directly, there was no significant difference of recurrence. CONCLUSION: This retrospective multi-institutional study of female urethral stricture demonstrates that patients undergoing endoscopic management have a higher risk of recurrence compared to those undergoing either urethroplasty with local flap or free graft.

A Review of Economic Evaluations of Erectile Dysfunction Therapies.

INTRODUCTION: Erectile dysfunction (ED) is a common and costly urologic condition with increasing prevalence as men age. Cost-effectiveness of ED therapies and whether cost-effectiveness varies for different populations of men remains underexplored. AIM: To review and summarize available published data on the economic evaluation of ED therapies and to identify gaps in the literature that still need to be addressed. METHODS: All relevant peer-reviewed publications and conference abstracts were reviewed and incorporated. RESULTS: There are a number of medical and surgical treatment options available for ED. The economic evaluation of phosphodiesterase-5 inhibitors, particularly sildenafil, has been well described. However, minimal research has been conducted to assess the cost-effectiveness of intracavernosal injections, intraurethral suppositories, penile prosthesis surgery, vacuum erection devices, and other emerging therapies in men with different causes of ED. CONCLUSION: Available economic evaluations of ED therapies are dated, do not reflect present-day physician, pharmaceutical, and device costs, fail to account for patient comorbidities, and may not be generalizable to today's ED patients. Substantial research is needed to evaluate the cost-effectiveness of ED treatments across different patient populations, countries, and reimbursement systems. Rezaee ME, Ward CE, Brandes ER, et al. A Review of Economic Evaluations of Erectile Dysfunction Therapies. Sex Med Rev 2019;8:497-503.

Trends in penile prosthesis implantation and analysis of predictive factors for removal.

PURPOSE: This study aims to analyze patient demographics, hospital characteristics, and clinical risk factors which predict penile prosthesis removal. We also examine costs of penile prosthesis removal and trends in inflatable versus non-inflatable penile prostheses implantation in the USA from 2003 to 2015. METHODS: Cross-sectional analysis from Premier Perspective Database was completed using data from 2003 to 2015. We compared the relative proportion of inflatable versus non-inflatable penile prostheses implanted. We separated the prosthesis removal group based on indication for removal-Group 1 (infection), Group 2 (mechanical complication), and Group 3 (all explants). All groups were compared to a control group of patients with penile implants who were never subsequently explanted. Multivariate analysis was performed to analyze patient and hospital factors which predicted removal. Cost comparison was performed between the explant groups. RESULTS: There were 5085 penile prostheses implanted with a stable relative proportion of inflatable versus non-inflatable prosthesis over the 13-year study period. There were 3317 explantations. Patient factors associated with prosthesis removal were non-black race, Charlson Comorbidity Index, diabetes, and HIV status. Hospital factors associated with removal included non-teaching status, hospital region, year of removal, and annual surgeon volume. Median hospitalization costs of all explantations were $10,878. Explantations due to infection cost $11,252 versus $8602 for mechanical complications. CONCLUSIONS: This large population-based study demonstrates a stable trend in inflatable versus non-inflatable prosthesis implantation. We also identify patient and hospital factors that predict penile prosthesis removal which has clinical utility for patient risk stratification and counseling.

A review of longitudinal clinical programs in US medical schools.

BACKGROUND: Longitudinal clinical experiences are a common component of undergraduate medical curricula, yet these programs have not been systematically characterized in US medical schools. OBJECTIVE: Our study sought to identify and characterize longitudinal clinical programs (LCPs) in US medical schools and measure associations between programs' structures and goals. DESIGN: Using a mixed-methods approach, we conducted a secondary analysis of data from publicly available websites. We conducted a systematic keyword search of the websites of 137 LCME-accredited US medical schools to identify LCPs. We included programs with student-patient interactions of at least six months. We categorized programs using qualitative thematic analysis and compared associations between program structures and goals. RESULTS: We identified 98 LCPs in 69 schools. Half (52.0%) of LCPs occurred during the core clinical year. Program structures included 'clinic attachments' (50.0%), 'longitudinal integrated clerkships' (26.5%), and 'patient attachments' (20.4%). We identified goals in 89 programs, including 'exposing students to specific topics, patient demographics, or practice settings' (78.7%); 'clinical or professional skill development' (65.2%); and 'understanding the patient experience' (19.1%). Patient attachments were associated with 'exposure to specific patient demographics' (P = .04) and 'understanding the patient experience' (P = .03). Pre-clinical programs were associated with clinical skills development (P = .01). CONCLUSIONS: Our study identifies the scope and nature of LCPs in US medical schools. Understanding connections between educational structures and goals may guide program design and research investigations of educational processes and outcomes.

Addressing the Requirements of High-Sensitivity Single-Molecule Imaging of Low-Copy-Number Proteins in Bacteria.

Single-molecule fluorescence super-resolution imaging and tracking provide nanometer-scale information about subcellular protein positions and dynamics. These single-molecule imaging experiments can be very powerful, but they are best suited to high-copy number proteins where many measurements can be made sequentially in each cell. We describe artifacts associated with the challenge of imaging a protein expressed in only a few copies per cell. We image live Bacillus subtilis in a fluorescence microscope, and demonstrate that under standard single-molecule imaging conditions, unlabeled B. subtilis cells display punctate red fluorescent spots indistinguishable from the few PAmCherry fluorescent protein single molecules under investigation. All Bacillus species investigated were strongly affected by this artifact, whereas we did not find a significant number of these background sources in two other species we investigated, Enterococcus faecalis and Escherichia coli. With single-molecule resolution, we characterize the number, spatial distribution, and intensities of these impurity spots.

Triazole Containing Novobiocin and Biphenyl Amides as Hsp90 C-Terminal Inhibitors.

Hsp90 C-terminal inhibitors are advantageous for the development of new cancer chemotherapeutics due to their ability to segregate client protein degradation from induction of the prosurvival heat shock response, which is a major detriment associated with Hsp90 N-terminal inhibitors under clinical investigation. Based upon prior SAR trends, a 1,2,3-triazole side chain was placed in lieu of the aryl side chain and attached to both the coumarin and biphenyl scaffold. Antiproliferative studies against SKBr3 and MCF-7 breast cancer cell lines demonstrated these triazole-containing compounds to exhibit improved activity. These compounds were shown to manifest Hsp90 inhibitory activity through Western blot analysis and represent a new scaffold upon which more potent inhibitors can be pursued.

RecO and RecR are necessary for RecA loading in response to DNA damage and replication fork stress.

RecA is central to maintaining genome integrity in bacterial cells. Despite the near-ubiquitous conservation of RecA in eubacteria, the pathways that facilitate RecA loading and repair center assembly have remained poorly understood in Bacillus subtilis. Here, we show that RecA rapidly colocalizes with the DNA polymerase complex (replisome) immediately following DNA damage or damage-independent replication fork arrest. In Escherichia coli, the RecFOR and RecBCD pathways serve to load RecA and the choice between these two pathways depends on the type of damage under repair. We found in B. subtilis that the rapid localization of RecA to repair centers is strictly dependent on RecO and RecR in response to all types of damage examined, including a site-specific double-stranded break and damage-independent replication fork arrest. Furthermore, we provide evidence that, although RecF is not required for RecA repair center formation in vivo, RecF does increase the efficiency of repair center assembly, suggesting that RecF may influence the initial stages of RecA nucleation or filament extension. We further identify single-stranded DNA binding protein (SSB) as an additional component important for RecA repair center assembly. Truncation of the SSB C terminus impairs the ability of B. subtilis to form repair centers in response to damage and damage-independent fork arrest. With these results, we conclude that the SSB-dependent recruitment of RecOR to the replisome is necessary for loading and organizing RecA into repair centers in response to DNA damage and replication fork arrest.