Perioperative risk predictors for gender affirming surgery in the NSQIP database.

INTRODUCTION: Gender affirming surgeries (GAS), such as phalloplasty (PLPs) and vaginoplasty (VGPs), are important aspects of medical care for transgender patients. Here, we aim to better characterize patient demographics and surgical outcomes for PLPs and VGPs using the National Surgical Quality Improvement Program (NSQIP). We hypothesized that frailty indices would be predictive of perioperative PLP and VGP risk and outcomes for PLPs and VGPs. MATERIALS AND METHODS: Primary GAS, specifically PLPs and VGPs performed from 2006-2020 were identified in NSQIP. Baseline frailty was based on NSQIP's modified frailty index (mFI) and preoperative morbidity probability (morbprob) variable. RESULTS: Fifty-eight PLPs and 468 VGPs were identified. The overall 30-day complication rate for PLP was 26%, with 17% of total patients experiencing minor complications and 16% experiencing major complications. The overall, minor, and major complication rates for VGP were 14%, 7%, and 9% respectively. Readmissions and reoperations occurred in 7% PLP and 5% VGP patients. No deaths occurred in either group within 30 days. The mFI scores were not predictive of 30-day complications or LOS. NSQIP morbprob was predictive of 30-day complications for both PLP (OR 4.0, 95% CI 1.08-19.59, p = 0.038) and VGP (OR 2.39, 95% CI 1.46-3.97, p = 0.0005). NSQIP's morbprob was also predictive of extended LOS for PLP patients (6.3 ± 1.3 days, p = 0.03). CONCLUSIONS: This study describes patient characteristics and complication rates of PLPs and VGPs. The NSQIP preoperative morbprob is an effective predictor of surgical complications and is better than the mFI.

Peri-operative outcomes following radical prostatectomy in the setting of advanced prostate cancer.

OBJECTIVE: To compare the peri-operative outcomes of radical prostatectomy (RP) for locally advanced, node-positive, and metastatic prostate cancer (PCa), as determined through pathological staging, using the American College of Surgeons National Surgical Quality Improvement Project. METHODS: We identified RP procedures performed between 2019 and 2021. Patients were stratified by pathological staging to compare the effect of locally advanced disease (T3-4), node positivity (N+) and metastasis (M+) vs localised PCa (T1-2 N0 M0). Baseline demographics and 30-day outcomes, including operating time, length of hospital stay (LOS), 30-day mortality, readmissions, reoperations, major complications, minor complications and surgery-specific complications, were compared between groups. RESULTS: Pathological staging data were available for 9276 RPs. Baseline demographics were comparable. There was a slightly higher rate of minor complications in the locally advanced cohort, but no significant difference in major complications, 30-day mortality, readmissions, or rectal injuries. Node positivity was associated with longer operating time, LOS, and some slightly increased rates of 30-day complications. RP in patients with metastatic disease appeared to be similarly safe to RP in patients with M0 disease, although it was associated with a longer LOS and slightly increased rates of certain complications. CONCLUSIONS: For patients with pathologically determined locally advanced, node-positive, and metastatic PCa, RP appears to be safe, and is not associated with significantly higher rates of 30-day mortality or major complications compared to RP for localised PCa. This study adds to the growing body of literature investigating the role of RP for advanced PCa; further studies are needed to better characterise the risks and benefits of surgery in such patients.

A Narrative Review on Robotic Surgery as Treatment for Renal Cell Carcinoma with Inferior Vena Cava Thrombus.

Renal cell carcinoma (RCC) is a common diagnosis, of which a notable portion of patients present with an extension into the venous circulation causing an inferior vena cava (IVC) tumor thrombus. Venous extension has significant implications for staging and subsequent treatment planning, with recommendations for more aggressive surgical removal, although associated surgical morbidity and mortality is relatively increased. The methods for surgical removal of RCC with IVC thrombus remain complex, particularly surrounding the use of robot-assisted surgery. Robot assistance for radical nephrectomy in this context is recently emerging. Thrombus level has important implications for surgical technique and prognosis. Other preoperative considerations may include location, laterality, size, and wall invasion. The urology literature on treatment of such tumors is largely limited to case series and institutional studies that describe the feasibility of various surgical options for these complex tumors. Further understanding of the outcomes and patient-specific risk factors would shed increased light on the optimal treatment for such cases. This narrative review provides a thorough overview on the previously reported use of robot-assisted nephrectomy in RCC with IVC thrombus to inform further studies which may optimize outcomes and guide shared decision-making.

Addressing the need for preclinical study of penile prosthesis infection: a new animal model and narrative review.

Background and Objective: Erectile dysfunction (ED) is a common condition in men, and many patients refractory to conservative treatment may undergo penile prostheses (PPs) placement. The primary concern following PP implantation is device infection. Although antibiotic and hydrophilic coatings have reduced the incidence of inflatable PP (IPP) infections, there remains room for improvement. Optimization of PP outcomes requires a practical in vivo model to better understand mechanisms of infection and to test new infection control strategies. We aimed to describe a new rabbit model which contains a functional IPP and review previously reported animal PP models. Methods: An IPP was placed into rabbit flanks and cycled for functionality testing. Rabbits were evaluated for signs of pain and distress over 14 days. Separately, narrative review methodology was utilized to search the PubMed and Scopus databases for all publications through March 21, 2023, which studied PP within an in vivo setting. Three independent reviewers ultimately selected 12 papers from 1992-2021 for inclusion. Key Content and Findings: Several animal studies highlighted the initial functionality or feasibility of devices for ED before their introduction in the clinical setting. There are several subsequent studies aimed at optimizing the type of antibiotic use or coating material using segments of PP material in an in vivo setting. However, the literature lacks a contemporary animal model containing a functional IPP. Our novel rabbit model offers a safe, practical way to implant a functioning IPP and investigate new perioperative infection prevention and treatment strategies before trials in the clinical setting. Conclusions: Animal models have played a key role in testing medical devices, including PPs, prior to their clinical introduction. Our review uncovered no modern animal studies involving placement of a functional PP. A new animal model can facilitate study of evolving microorganism profiles, novel methods to enhance antibiotic delivery, and proposed treatment options.

Racial Disparities in Diagnosis and Treatment of Depression Associated with Androgen Deprivation Therapy for Prostate Cancer.

OBJECTIVE: To analyze potential racial disparities in the diagnosis and management of depression associated with androgen deprivation therapy. METHODS: TriNetX health record network was queried for prostate cancer patients treated with androgen deprivation therapy from 2003-2023. Differences in rates of depression diagnosis and treatment were compared between White and Black patients. Means, odds ratios, and t tests were calculated in univariate analysis with 95% confidence intervals (CI). RESULTS: Data were queried from 93 health care organizations to yield 78,313 prostate cancer patients treated with androgen deprivation therapy. Patients on androgen deprivation therapy had 60% greater odds of developing depression vs other patients [9% vs 6%; odds ratio (OR) 1.6; 95% CI (1.5-1.7); P <.0001]. Of those with depression secondary to androgen deprivation therapy, only 35% were treated with antidepressants. After starting androgen deprivation therapy, White patients had 30% greater odds of being diagnosed with depression, compared to Black patients [10% vs 8%; OR 1.3; 95% CI (1.2-1.4); P <.001]. White patients also had higher odds of being treated with a first line antidepressant than Black patients [56% vs 48%; OR 1.4, 95% CI (1.2-1.6), P <.001]. CONCLUSION: This analysis confirms a significant association between androgen deprivation therapy and the development of clinical depression, and highlights its medical undertreatment. Importantly, our findings also indicate significant racial disparities in the identification and treatment of depression. Routine screening initiatives that account for social determinants of health may alleviate this disparity. Limitations of this study include retrospective design and lack of data describing severity of depression, which might correlate with need for medication.

Perioperative and Complication Related Outcomes for Robotic-Assisted vs Open Radical Cystectomy: A Comparative National Surgical Quality Improvement Project Analysis.

Background: Radical cystectomy (RC) is standard of care for muscle-invasive bladder cancer, but it comes with significant perioperative risk, with half of the patients experiencing major postoperative complications. Robot-assisted radical cystectomies (RARCs) have aimed to decrease patient morbidity and been increasingly adopted in North America. Currently, both open radical cystectomies (ORCs) and RARCs are frequently performed. The aim of this study is to contribute to the existing literature using newly available data from the American College of Surgeons National Surgical Quality Improvement Project (NSQIP), representing one of the most recent, largest multi-institutional studies, while uniquely accounting for a variety of factors, including type of urinary diversion, cancer staging, and neoadjuvant chemotherapy. Methods: RC procedures performed between 2019 and 2021 were identified in NSQIP and the corresponding cystectomy-targeted database. Cases in the ORC group were planned open procedures, and cases in the RARC group were robot assisted, including unplanned conversion to open cases for intention to treat. Chi-square and t-tests were performed to compare baseline demographics and operative parameters. Multivariate analysis was performed for outcomes, including major complications, minor complications, and 30-day mortality rates, while adjusting for baseline differences significant on univariate analysis. Results: Five thousand three hundred forty-three RC cases were identified. Of these, 70% underwent planned ORC, while 30% received RARC. RARC was associated with longer operative times and shorter hospital length of stay compared with ORC. On multivariate analysis, there was no difference between the cohorts in 30-day rates of major complications, hospital readmissions, need for reoperation, or mortality. ORC was, however, associated with higher rates of minor complications, bleeding, superficial surgical site infections, and anastomotic leak. Conclusions: In the NSQIP database, ORC is associated with higher rates of 30-day minor complications, most notably bleeding, compared with RARC. However, there is no difference in regard to perioperative major morbidity or mortality rates. This study is unique in the size of the cohorts compared, timeliness of data (2019-2021), applicability to a variety of different practice settings across the country, and ability to control for factors, such as type of urinary diversion and pathological bladder cancer staging, as well as use of neoadjuvant chemotherapy. This study was approved by the Institutional Review Board (IRB) specific to Thomas Jefferson University.

Recurring cystitis cystica and cystitis glandularis masquerading as urothelial carcinoma.

We report a rare case of cystitis cystica and glandularis mimicking low-grade urothelial carcinoma that was found incidentally and treated with resection and fulguration via transurethral resection of bladder tumor (TURBT). When early recurrence was found on surveillance cystoscopy 3 months later, the patient was treated with repeat TURBT and intravesical gemcitabine. Surveillance cystoscopy 4 months later revealed cystitis cystica and cystitis glandularis yet again. We highlight the diagnosis and management of multiple early recurrences of cystitis cystica in this patient, particularly our treatment with gemcitabine and close surveillance.

Squamous cell carcinoma of the renal pelvis masquerading as xanthogranulomatous pyelonephritis.

We report a rare case of a 56-year-old male with a history of hypertension who initially presented to the emergency department with abdominal pain and was radiologically diagnosed with left xanthogranulomatous pyelonephritis (XGP) in a non-functioning kidney with a staghorn calculus. Pathological evaluation of his kidney revealed squamous cell carcinoma (SCC) of the renal pelvis with invasion into the renal parenchyma. We highlight the presentation, diagnosis, and management of this rare condition.

Gender Diversity in Urology Residency Program Leadership Is Associated With Gender Diversity in Residency Cohort.

OBJECTIVE: To evaluate the association of program director (PD) gender on the proportion of female residents in urology residency programs. METHODS: Demographics for program faculty and current residents matched in the 2017-2022 cycles at United States' accredited urology residency programs were collected from institutional websites. Data verification was completed using the American Urological Association's (AUA) list of accredited programs and the programs' official social media channels. Proportion of female residents across cohorts was compared using two-tailed Student's t-tests. RESULTS: One hundred forty-three accredited programs were studied, and 6 were excluded for lack of data. Thirty (22%) of the 137 programs studied have female PDs. Of 1799 residents, 571 (32%) are women. There has been an upward trend in the proportion of females matched from 26% in 2018 to 30% in 2019, 33% in 2020, 32% in 2021, to 38% in 2022. When compared to programs with male PDs, those with female PDs had a significantly higher proportion of female residents (36.2% vs 28.8%, p = .02). CONCLUSION: Nearly one-quarter of urology residency PDs are female, and approximately one-third of current urology residents are women, a proportion that has been increasing. Programs with female PDs are more likely to match female residents, whether those programs with female leadership rank female applicants more favorably or female applicants rank those programs higher. Given the ongoing gender disparities in urology, these findings indicate notable benefit in supporting female urologists in academic leadership positions.

The Impact of COVID-19 on the Urology Residency Match and Geographic Proximity of Applicants.

OBJECTIVE: To determine the impacts of COVID-19 pandemic-related changes and program-specific characteristics on the geographic diversity of the 2021 and 2022 urology match classes. METHODS: We gathered publicly available information to compare match outcomes in 2021 and 2022 to the previous 5 application cycles (2016-2020). Variables included residency program class size, program and resident AUA section, and program and resident medical school. Univariate comparisons were made with Fisher's t-tests. Odds ratios were calculated following multivariable analysis. RESULTS: Comparing the previous 5 application cycles to the 2 pandemic years individually and together showed no significant changes in home or in-section matches. However, when comparisons were stratified by small (1-2 residents) vs large (3+ residents) programs, a significant increase in at-home and in-section matches was observed for small programs in 2021. Large programs did not experience significant changes in match patterns. Multivariate analysis showed that small programs had significantly lower odds of matching applicants from home institutions and within AUA sections. Additionally, certain AUA sections demonstrated significantly increased likelihood of accepting in-section applicants. CONCLUSION: The changes from in-person to virtual application cycles during the pandemic particularly affected small residency programs in 2021. With easing restrictions and logistical improvements in the 2022 cycle, locoregional match rates partially shifted back to prepandemic patterns, though not completely. Although the pandemic did not affect geographic diversity in urology as much as in other surgical subspecialties, these findings and further study should be considered to optimize upcoming cycles.

Association of baseline self-reported fatigue with overall survival after stereotactic body radiation therapy for localized prostate cancer.

Introduction: Stereotactic Body Radiation Therapy (SBRT) has emerged as a definitive therapy for localized prostate cancer (PCa). However, more data is needed to predict patient prognosis to help guide which patients will benefit most from treatment. The FACIT-Fatigue (FACIT-F) is a well validated, widely used survey for assessing fatigue. However, the role of fatigue in predicting PCa survival has yet to be studied. Herein, we investigate the role of FACIT-F as a baseline predictor for overall survival (OS) in patients undergoing SBRT for localized PCa. Methods: A retrospective review was conducted of 1358 patients who received SBRT monotherapy between January 2008 to April 2021 at an academic, tertiary referral center. FACIT-F scores (range 0 to 52) were summed for patients who answered all 13-items on the survey. FACIT-F total scores of ≥35 represented severe fatigue. Patients receiving androgen deprivation therapy were excluded. Differences in fatigue groups were evaluated using chi-squared tests. OS rates were determined using the Kaplan-Meier method and predictors of OS were evaluated using Cox proportional hazard method. Results: Baseline full FACIT-F scores and survival data was available for 891 patients. 5-year OS was 87.6% and 95.2%, respectively, for the severely fatigued and non-fatigued groups. Chi-squared analysis of fatigue groups showed no significant difference in the following categories: D'Amico risk group, age, ethnicity, grade group, T-stage, or PSA density. Severe fatigue was associated with a significant decrease in OS (hazard ratio 2.76; 95%CI 1.55 - 4.89). The Cox proportional hazard model revealed that age and FACIT-F were both statistically significant (p <0.05). Conclusion: Baseline FACIT-F scores are significantly associated with OS. Higher FACIT-F scores, representing less fatigued patients, are associated with an overall survival benefit. These results indicate that the FACIT-F survey could serve as an additional metric for clinicians in determining prognostic factors for patients undergoing SBRT.

Patient Factors Impacting Perioperative Outcomes for T1b-T2 Localized Renal Cell Carcinoma May Guide Decision for Partial versus Radical Nephrectomy.

There remains debate surrounding partial (PN) versus radical nephrectomy (RN) for T1b-T2 renal cell carcinoma (RCC). PN offers nephron-sparing benefits but involves increased perioperative complications. RN putatively maximizes oncologic benefit with complex tumors. We analyzed newly available nephrectomy-specific NSQIP data to elucidate predictors of perioperative outcomes in localized T1b-T2 RCC. We identified 2094 patients undergoing nephrectomy between 2019-2020. Captured variables include surgical procedure and approach, staging, comorbidities, prophylaxis, peri-operative complications, reoperations, and readmissions. 816 patients received PN while 1278 received RN. Reoperation rates were comparable; however, PN patients more commonly experienced 30-day readmissions (7.0% vs. 4.7%, p = 0.026), bleeds (9.19% vs. 5.56%, p = 0.001), renal failure requiring dialysis (1.23% vs. 0.31%, p = 0.013) and urine leak or fistulae (1.10% vs. 0.31%, p = 0.025). Infectious, pulmonary, cardiac, and venothromboembolic event rates were comparable. Robotic surgery reduced occurrence of various complications, readmissions, and reoperations. PN remained predictive of all four complications upon multivariable adjustment. Several comorbidities were predictive of complications including bleeds and readmissions. This population-based cohort explicates perioperative outcomes following nephrectomy for pT1b-T2 RCC. Significant associations between PN, patient-specific factors, and complications were identified. Risk stratification may inform management to improve post-operative quality of life (QOL) and RCC outcomes.

Postoperative Rehabilitation of Posterior Cruciate Ligament Surgery: A Systematic Review.

Posterior cruciate ligament (PCL) injuries can be debilitating knee injuries, having involvement in up to 44% of traumatic knee injuries. However, isolated PCL injuries are relatively infrequent. Therefore, effective evidence-based rehabilitation protocols have proven to be elusive. This systematic review aims to summarize the latest evidence on postoperative rehabilitation protocols for patients undergoing PCL reconstruction. Studies included in this paper included those published from 1991 to 2019 with a grade 1 to 5 level of evidence discussing the postoperative PCL rehabilitation. A multidatabase search using largely PubMed and Ovid was conducted using relevant keywords such as "PCL," "postoperative," and "rehabilitation," initially leading to 955 papers, which were narrowed by relevance to 12 final published studies used in the analysis. Through careful review of the evidence, crucial principles of rehabilitation, such as an initial focus on protecting the graft during strengthening, as well as an optimized PCL reconstruction protocol are presented here. Rehabilitation following PCL reconstruction continues to be limited by a lack of high-quality evidence-based publications.

Mechanism of ß2AR regulation by an intracellular positive allosteric modulator.

Drugs targeting the orthosteric, primary binding site of G protein-coupled receptors are the most common therapeutics. Allosteric binding sites, elsewhere on the receptors, are less well-defined, and so less exploited clinically. We report the crystal structure of the prototypic ß2-adrenergic receptor in complex with an orthosteric agonist and compound-6FA, a positive allosteric modulator of this receptor. It binds on the receptor's inner surface in a pocket created by intracellular loop 2 and transmembrane segments 3 and 4, stabilizing the loop in an α-helical conformation required to engage the G protein. Structural comparison explains the selectivity of the compound for ß2- over the ß1-adrenergic receptor. Diversity in location, mechanism, and selectivity of allosteric ligands provides potential to expand the range of receptor drugs.

Small-Molecule Positive Allosteric Modulators of the ß2-Adrenoceptor Isolated from DNA-Encoded Libraries.

Conventional drug discovery efforts at the ß2-adrenoceptor (ß2AR) have led to the development of ligands that bind almost exclusively to the receptor's hormone-binding orthosteric site. However, targeting the largely unexplored and evolutionarily unique allosteric sites has potential for developing more specific drugs with fewer side effects than orthosteric ligands. Using our recently developed approach for screening G protein-coupled receptors (GPCRs) with DNA-encoded small-molecule libraries, we have discovered and characterized the first ß2AR small-molecule positive allosteric modulators (PAMs)-compound (Cmpd)-6 [(R)-N-(4-amino-1-(4-(tert-butyl)phenyl)-4-oxobutan-2-yl)-5-(N-isopropyl-N-methylsulfamoyl)-2-((4-methoxyphenyl)thio)benzamide] and its analogs. We used purified human ß2ARs, occupied by a high-affinity agonist, for the affinity-based screening of over 500 million distinct library compounds, which yielded Cmpd-6. It exhibits a low micro-molar affinity for the agonist-occupied ß2AR and displays positive cooperativity with orthosteric agonists, thereby enhancing their binding to the receptor and ability to stabilize its active state. Cmpd-6 is cooperative with G protein and ß-arrestin1 (a.k.a. arrestin2) to stabilize high-affinity, agonist-bound active states of the ß2AR and potentiates downstream cAMP production and receptor recruitment of ß-arrestin2 (a.k.a. arrestin3). Cmpd-6 is specific for the ß2AR compared with the closely related ß1AR. Structure-activity studies of select Cmpd-6 analogs defined the chemical groups that are critical for its biologic activity. We thus introduce the first small-molecule PAMs for the ß2AR, which may serve as a lead molecule for the development of novel therapeutics. The approach described in this work establishes a broadly applicable proof-of-concept strategy for affinity-based discovery of small-molecule allosteric compounds targeting unique conformational states of GPCRs.