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Introduction: Bowel regimens (BR) before radical cystectomy (RC) are currently not recommended by Enhanced Recovery After Surgery (ERAS) protocols, as prior studies have shown BRs lead to worsened outcomes. However, many of those studies have used historic literature before recent surgical advancements such as minimally invasive RC and have not investigated the impact BRs have by type of urinary diversion. Our goal is to determine the outcomes of preoperative BR in patients undergoing RC based on diversion type using a modern patient cohort., Methods: RCs performed between 2019 and 2020 with BR information available were identified in the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP). Patients were grouped by type of BR received: no BR, both mechanical bowel preparation (MBP) and preoperative oral antibiotic BR (OABR), MBP only, and OABR only. We conducted propensity score matching based on factors influencing the operative approach. Baseline demographics and 30-day complication rates were compared between matched groups. We analyzed hospital length of stay (LOS) via multivariate regression with a Poisson distribution., Results: In total, 2054 RCs were identified with 2.4% receiving OABR, 21.3% receiving MBP, 5.3% receiving both, and 71.0% receiving no BR. For patients with ileal conduit diversions, outcomes with BRs appeared mixed, as OABR leads to increased LOS. For patients with neobladder diversions, BRs were not associated with any worsened outcomes and were associated with reduced length of stay., Conclusions: BRs such as OABR may associated with improved outcomes in patients receiving RC with neobladder diversion, a finding that warrants further investigation., (© 2025 The Japanese Urological Association.)

Introduction: Placing ureteral stents at the ureteroileal anastomosis for radical cystectomy with ileal conduit (RCIC) has long been common practice. Recently, some providers have begun omitting stents. We sought to investigate differences in perioperative and 30-day outcomes between patients who underwent RCIC with and without stents placed at the ureteroileal anastomosis., Methods: We identified RCICs performed between 2019 and 2021 in the National Surgical Quality Improvement Program database and corresponding Cystectomy-Targeted Participant Use File. Baseline demographics, comorbidities, and operative parameters were compared via Pearson's χ 2 and t tests between stented and stentless RCICs. Outcomes of interest, including rates of UTIs, acute kidney injury, renal failure requiring dialysis, ileoileal anastomotic leaks, ureteral obstruction, urinary leak or fistula formation, reoperations, and 30-day hospital readmissions, were compared using Pearson's χ 2 . All statistical tests were 2-tailed with P < .05 considered significant., Results: A total of 5418 RCICs were identified. Four hundred ninety-eight (9.2%) were stentless. There were no differences in baseline demographics or comorbidities. Significantly fewer stented patients had robotic-assisted operations (23% vs 29%, P < .01). Stented patients had lower rates of urinary leak or fistula formation (3.1% vs 4.8%, P = .04). There was no significant difference in 30-day rates of UTIs, acute kidney injuries, renal failure, ileoileal anastomotic leaks, ureteral obstruction, reoperations, and readmissions. Limitations include retrospective design and lack of longitudinal tracking past 30 days., Conclusions: Stentless patients had noninferior outcomes compared to stented patients in most important 30-day outcomes. Our analysis suggests that stents may not be necessary in ileal conduit urinary diversion procedures.

Background: Despite knowledge of the pathophysiology and clinical complications of connective tissue diseases (CTD), little is known regarding their impact on men's sexual health disorders., Aim: To investigate the prevalence of penile fracture (PF) in patients with Ehlers-Danlos Syndrome (EDS) and Marfan syndrome (MFS) in comparison with disease-free controls between 18 and 45 years of age., Methods: A multicenter, international, electronic health record network (TriNetX) was queried to identify adult male patients (between 18 and 45 years) with or without EDS and MFS between 1993 and 2023 using ICD-10 codes. The prevalence of PF was compared between patients with and without the diseases of interest. Prevalence ratios (PR) were generated with 95% confidence intervals., Outcome: Prevalence of PF in patients with EDS and MFS when compared to disease-free controls., Results: The number of patients with EDS, MFS, and control groups was 8060, 8642, and 20 184 547, respectively, with a mean age of 27.8 ± 7.58, 28.6 ± 7.4, and 31.6 ± 8.04 years. Men with EDS had a higher prevalence of PF (PR 30.18, 95% CI [17.08-53.19]; P < 0.0001). Similarly, men with MFS had a higher prevalence of PF (PR 23.4, 95% CI [12.6-43.7]; P < 0.0001)., Clinical Implications: This study demonstrates an association between CTD and men's sexual health disorders. It may be important to counsel such men about the risks of PF., Strengths and Limitations: This is the largest study to date to demonstrate an association between CTD and men's sexual health disorders. While the large sample sizes in this study contribute to the robustness of the findings, the study is limited by the use of a claims-based dataset, which does not provide further details about disease course and complications, and the use of a univariate analysis only., Conclusions: Patients with EDS and MFS are possibly at an elevated risk for PF. Due to the limitations of the TriNetX database, the analysis was limited to a univariate one, thus limiting the ability to control for confounders and limiting the generalizability of these findings. Further prospective research is needed to corroborate these findings., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To examine one academic institution's experiences with SpaceOAR placement, its associated complications, and periprocedural characteristics that affect outcomes for the purpose of quality improvement., Materials and Methods: We conducted a retrospective review of 233 patients who received SpaceOAR from four surgeons and one radiation oncologist between 2018 and 2021. Variables such as demographics, oncologic parameters, radiation plan, and radiographic assessment of hydrogel placement were recorded. The Charlson Comorbidity Index (CCI) was used to assess comorbidity risk. Mann-Whitney and Fisher's exact tests were performed to compare patients with and without complications., Results: Of the 233 patients who received SpaceOAR, 24 (10.3%) experienced toxicity. All complications were Clavien I or II, such as pelvic pain postplacement, pelvic fullness, bleeding, and lower urinary tract symptoms. 16 patients (6.9%) had some portion of the hydrogel injected into the rectal wall, but it was never clinically significant. The average CCI was 3.2 ± 0.95 for patients who experienced complications; the average CCI was 3.6 ± 1.6 ( p =0.48) in the group without complications. Of the physicians with higher procedure volumes, Physician #1 had the highest rate of patient-reported complications at 11 out of 68 (16.2%) and Physician #2 had the lowest rate of complications at 4 out of 96 placements (4.2%). Multivariate analysis found that patients who had received hormone therapy previously had less odds of reporting complications after SpaceOAR placement., Conclusions: The listed attending on the procedure had a significant correlation to complications with SpaceOAR placement on univariate analysis, and hormone therapy had some benefits to the tolerance for the procedure on multivariate analysis. Overall, the hydrogel placement was well tolerated with low incidence of mild and transient procedure-related toxicity., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Kerith R. Wang et al.)

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., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

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., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.

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.

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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-353/coif). The series “Genitourinary Prosthesis Infection” was commissioned by the editorial office without any funding or sponsorship. P.H.C. served as the unpaid Guest Editor of the series and serves as an unpaid editorial board member of Translational Andrology and Urology. P.H.C. consults for and receives research support from Coloplast and Boston Scientific. C.E.W. is a clinical consultant for Bracco Diagnostics and Canon Medical Systems USA. N.J.H. consults for SINTX technologies. F.F. receives research support from Bracco, the Butterfly Network, Canon Medical Systems USA, GE HealthCare, Lantheus Medical Imaging and Siemens Healthineers. He is also a consultant or advisor for Exact Therapeutics, Lantheus, Longeviti Neuro Solutions and Sonothera. The authors have no other conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

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.

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.

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., Competing Interests: Declaration of Competing Interest All authors report no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., Competing Interests: CONFLICTS OF INTEREST The authors (Nicholas J. Lanzotti and Jeffrey L. Ellis) declare no conflicts of interest pertaining to this publication., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.

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.

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., Competing Interests: SC is a consultant for Accuray, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Simhal, Sholklapper, Simhal, Zwart, Danner, Kumar, Aghdam, Suy, Hankins, Kowalczyk and Collins.)

Here, we report a case of a patient in their mid 30s who presented with an elevated creatinine and was found to have a massive bladder diverticulum. The patient underwent a robotic-assisted diverticulectomy. They were later found to have a primary bladder neck obstruction on video urodynamics, and subsequently, underwent bladder neck incision, leading to significant improvement in urinary symptoms. Primary bladder neck obstruction is an overlooked cause of bladder diverticulum. While cystoscopy and cross-sectional imaging are frequently used in the initial evaluation of bladder diverticula, in the absence of an anatomic obstruction such as prostate enlargement, video urodynamics should be performed to assess for primary bladder neck obstruction., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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 β 2 -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 β 2 - over the β 1 -adrenergic receptor. Diversity in location, mechanism, and selectivity of allosteric ligands provides potential to expand the range of receptor drugs., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Conventional drug discovery efforts at the β 2 -adrenoceptor ( β 2 AR) 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 β 2 AR 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 β 2 ARs, 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 β 2 AR 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 β -arrestin1 (a.k.a. arrestin2) to stabilize high-affinity, agonist-bound active states of the β 2 AR and potentiates downstream cAMP production and receptor recruitment of β -arrestin2 (a.k.a. arrestin3). Cmpd-6 is specific for the β 2 AR compared with the closely related β 1 AR. 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 β 2 AR, 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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 by The Author(s).)