Higher Morbidity and Mortality in Females With Fournier's Gangrene Compared to Males: Insights From National Inpatient Sample Data.

PURPOSE: To compare Fournier's gangrene in female and male patients, and identify mortality-associated characteristics in both. MATERIALS AND METHODS: We employed National Inpatient Sample data (2016-2020) to identify Fournier's gangrene cases and extracted demographic, comorbidity, and procedural variables. Multivariable regression models were utilized to identify mortality risk factors for both cohorts. RESULTS: We identified 2875 females (31%) and 6451 males (69%) with Fournier's gangrene corresponding to an estimated 14,375 (95% CI 13,784-14,966) and 32,255 (95% CI 31,390-33,120) cases, respectively. Females were more likely to die than males (7.1% vs 5.7%, P < .0001, respectively). Median incidence rates were 1.7 (IQR 1.5-1.8) and 4 (IQR 3.6-4.3) cases per 100,000 person-years for females and males, respectively. Females had higher median age, longer hospital stays, more charges, procedures, and fecal diversion rates, but lower routine discharges than males (P < .05). Non-White females had increased mortality odds compared to White females (odds ratio [OR] 1.49, 95% CI 1.07-2.07, P = .019). Prolonged interval until initial perineal debridement correlated with higher mortality odds in both females and males (OR 1.02, 95% CI 1-1.04, P = .034 vs OR 1.03, 95% CI 1.01-1.05, P < .0001). Diabetes lowered mortality odds in females and males (OR 0.68, 95% CI 0.47-0.99, P = .046 vs OR 0.54, 95% CI 0.41-0.7, P < .0001). CONCLUSIONS: In females, Fournier's gangrene incidence surpasses previous reports, with slightly worse outcomes compared to males, emphasizing the need for precise clinical assessment and early intensive interventions.

Multi-Institutional Outcomes of Dorsal Onlay Buccal Mucosal Graft Urethroplasty in Patients With Postprostatectomy, Postradiation Anastomotic Stenosis.

PURPOSE: The treatment of urethral stenosis after a combination of prostatectomy and radiation therapy for prostate cancer is understudied. We evaluate the clinical and patient-related outcomes after dorsal onlay buccal mucosal graft urethroplasty (D-BMGU) in men who underwent prostatectomy and radiation therapy. MATERIALS AND METHODS: A multi-institutional, retrospective review of men with vesicourethral anastomotic stenosis or bulbomembranous urethral stricture disease after radical prostatectomy and radiation therapy from 8 institutions between 2013 to 2021 was performed. The primary outcomes were stenosis recurrence and development of de novo stress urinary incontinence. Secondary outcomes were surgical complications, changes in voiding, and patient-reported satisfaction. RESULTS: Forty-five men were treated with D-BMGU for stenosis following prostatectomy and radiation. There was a total of 7 recurrences. Median follow-up in patients without recurrence was 21 months (IQR 12-24). There were no incidents of de novo incontinence, 28 patients were incontinent pre- and postoperatively, and of the 6 patients managed with suprapubic catheter preoperatively, 4 were continent after repair. Following repair, men had significant improvement in postvoid residual, uroflow, International Prostate Symptom Score, and International Prostate Symptom Score quality-of-life domain. Overall satisfaction was +2 or better in 86.6% of men on the Global Response Assessment. CONCLUSIONS: D-BMGU is a safe, feasible, and effective technique in patients with urethral stenosis after a combination of prostatectomy and radiation therapy. Although our findings suggest this technique may result in lower rates of de novo urinary incontinence compared to conventional urethral transection and excision techniques, head-to-head comparisons are needed.

The Impact of Social Deprivation on Anterior Urethral Stricture Recurrence After Urethroplasty - A Trauma and Urologic Reconstructive Network of Surgeons (TURNS) Analysis.

INTRODUCTION AND OBJECTIVES: Several factors influence recurrence after urethral stricture repair. The impact of socioeconomic factors on stricture recurrence after urethroplasty is poorly understood. This study aims to assess the impact that social deprivation, an area-level measure of disadvantage, has on urethral stricture recurrence after urethroplasty. METHODS: We performed a retrospective review of patients undergoing urethral reconstruction by surgeons participating in a collaborative research group. Home zip code was used to calculate Social Deprivation Indices (SDI; 0-100), which quantifies the level of disadvantage across several sociodemographic domains collected in the American Community Survey. Patients without zip code data were excluded from the analysis. The Cox Proportional Hazards model was used to study the association between SDI and the hazard of functional recurrence, adjusting for stricture characteristics as well as age and body mass index. RESULTS: Median age was 46.0 years with a median follow up of 367 days for the 1452 men included in the study. Patients in the fourth SDI quartile (worst social deprivation) were more likely to be active smokers with traumatic and infectious strictures compared to the first SDI quartile. Patients in the fourth SDI quartile had 1.64 times the unadjusted hazard of functional stricture recurrence vs patients in the first SDI quartile (95% CI 1.04-2.59). Compared to anastomotic ± excision, substitution only repair had 1.90 times the unadjusted hazard of recurrence. The adjusted hazard of recurrence was 1.08 per 10-point increase in SDI (95% CI 1.01-1.15, P = .027). CONCLUSIONS: Patient social deprivation identifies those at higher risk for functional recurrence after anterior urethral stricture repair, offering an opportunity for preoperative counseling and postoperative surveillance. Addressing these social determinants of health can potentially improve outcomes in reconstructive surgery.

Fragility of overactive bladder medication clinical trials: A systematic review.

PURPOSE: Overactive bladder (OAB) syndrome significantly impairs quality of life, often necessitating pharmacological interventions with associated risks. The fragility of OAB trial outcomes, as measured by the fragility index (FI: smallest number of event changes to reverse statistical significance) and quotient (FQ: FI divided by total sample size expressed as a percentage), is critical yet unstudied. MATERIALS AND METHODS: We conducted a systematic search for randomized controlled trials on OAB medications published between January 2000 and August 2023. Inclusion criteria were trials with two parallel arms reporting binary outcomes related to OAB medications. We extracted trial details, outcomes, and statistical tests employed. We calculated FI and FQ, analyzing associations with trial characteristics through linear regression. RESULTS: We included 57 trials with a median sample size of 211 participants and a 12% median lost to follow-up. Most studies investigated anticholinergics (37/57, 65%). The median FI/FQ was 5/3.5%. Larger trials were less fragile (median FI 8; FQ 1.0%) compared to medium (FI: 4; FQ 2.5%) and small trials (FI: 4; FQ 8.3%). Double-blinded studies exhibited higher FQs (median 2.9%) than unblinded trials (6.7%). Primary and secondary outcomes had higher FIs (median 5 and 6, respectively) than adverse events (FI: 4). Each increase in 10 participants was associated with a +0.19 increase in FI (p < 0.001). CONCLUSIONS: A change in outcome for a median of five participants, or 3.5% of the total sample size, could reverse the direction of statistical significance in OAB trials. Studies with larger sample sizes and efficacy outcomes from blinded trials were less fragile.

Consumer product-related female genital injuries in the USA from 2013 to 2022.

BACKGROUND: Consumer product-related genital injuries in females across all age groups are understudied. Existing research focuses primarily on paediatric populations. We aimed to determine characteristics, trends and predictors of hospitalisation. METHODS: The National Electronic Injury Surveillance System database was queried for female genital injuries from 2013 to 2022. We stratified our population into four age groups (<18, 18-34, 35-54, >54 years). Automated text matching and manual reviews were employed for variable extraction. χ2 tests and logistic regression were conducted, accounting for survey design and weights. RESULTS: 9054 cases representing a national estimate of 252 329 injuries (95% CI 188 059 to 316 599) were identified. Paediatric injuries were most common (61%) and seniors had the highest hospitalisation rates (28%). Falls were common in paediatric (51%) and senior (48%) groups, whereas self-induced and topical application injuries were more frequent among adults aged 18-34 and 35-54. Injuries predominantly involved playground equipment and bicycles in children, razors and massage devices in adults aged 18-34 and 35-54 and household structures in seniors. Hospitalisation increased over the decade from 7% to 9%; significant predictors of hospitalisation were Asian race (OR=3.39, 95% CI 1.83 to 6.30), fractures (OR=7.98, 95% CI 4.85 to 13.1) and urethral injury (OR=3.15, 95% CI 1.30 to 7.63). CONCLUSIONS: Our study identifies distinct patterns in female genital injuries across ages. In the paediatric cohort, injuries are often linked to playgrounds and bicycles. For adults, grooming products are frequently implicated. Seniors commonly suffer injuries from household structures such as bathtubs. These patterns may inform discussions on tailored preventive strategies.

Comparing GPT-4 and Human Researchers in Health Care Data Analysis: Qualitative Description Study.

BACKGROUND: Large language models including GPT-4 (OpenAI) have opened new avenues in health care and qualitative research. Traditional qualitative methods are time-consuming and require expertise to capture nuance. Although large language models have demonstrated enhanced contextual understanding and inferencing compared with traditional natural language processing, their performance in qualitative analysis versus that of humans remains unexplored. OBJECTIVE: We evaluated the effectiveness of GPT-4 versus human researchers in qualitative analysis of interviews with patients with adult-acquired buried penis (AABP). METHODS: Qualitative data were obtained from semistructured interviews with 20 patients with AABP. Human analysis involved a structured 3-stage process-initial observations, line-by-line coding, and consensus discussions to refine themes. In contrast, artificial intelligence (AI) analysis with GPT-4 underwent two phases: (1) a naïve phase, where GPT-4 outputs were independently evaluated by a blinded reviewer to identify themes and subthemes and (2) a comparison phase, where AI-generated themes were compared with human-identified themes to assess agreement. We used a general qualitative description approach. RESULTS: The study population (N=20) comprised predominantly White (17/20, 85%), married (12/20, 60%), heterosexual (19/20, 95%) men, with a mean age of 58.8 years and BMI of 41.1 kg/m2. Human qualitative analysis identified "urinary issues" in 95% (19/20) and GPT-4 in 75% (15/20) of interviews, with the subtheme "spray or stream" noted in 60% (12/20) and 35% (7/20), respectively. "Sexual issues" were prominent (19/20, 95% humans vs 16/20, 80% GPT-4), although humans identified a wider range of subthemes, including "pain with sex or masturbation" (7/20, 35%) and "difficulty with sex or masturbation" (4/20, 20%). Both analyses similarly highlighted "mental health issues" (11/20, 55%, both), although humans coded "depression" more frequently (10/20, 50% humans vs 4/20, 20% GPT-4). Humans frequently cited "issues using public restrooms" (12/20, 60%) as impacting social life, whereas GPT-4 emphasized "struggles with romantic relationships" (9/20, 45%). "Hygiene issues" were consistently recognized (14/20, 70% humans vs 13/20, 65% GPT-4). Humans uniquely identified "contributing factors" as a theme in all interviews. There was moderate agreement between human and GPT-4 coding (κ=0.401). Reliability assessments of GPT-4's analyses showed consistent coding for themes including "body image struggles," "chronic pain" (10/10, 100%), and "depression" (9/10, 90%). Other themes like "motivation for surgery" and "weight challenges" were reliably coded (8/10, 80%), while less frequent themes were variably identified across multiple iterations. CONCLUSIONS: Large language models including GPT-4 can effectively identify key themes in analyzing qualitative health care data, showing moderate agreement with human analysis. While human analysis provided a richer diversity of subthemes, the consistency of AI suggests its use as a complementary tool in qualitative research. With AI rapidly advancing, future studies should iterate analyses and circumvent token limitations by segmenting data, furthering the breadth and depth of large language model-driven qualitative analyses.

A Contemporary Analysis of Combat-related Urological Injuries: Data From the Department of Defense Trauma Registry.

PURPOSE: There has been little to no literature published on combat-related genitourinary injuries beyond 2013. With the goal of enhancing medical readiness prior to deployment and making recommendations to improve the long-term rehabilitation of service members as they become civilians, we sought to describe the incidence of combat-related genitourinary injuries and interventions from January 1, 2007, to March 17, 2020. MATERIALS AND METHODS: We conducted a retrospective analysis of the Department of Defense Trauma Registry, which is a prospectively maintained database, for the time between 2007 and 2020. We used predefined search criteria to primarily identify any casualties that arrived at a military treatment facility with urological-based injuries. RESULTS: The registry contained 25,897 adult casualties, of which 7.2% sustained urological injuries. The median age was 25. Explosive injuries (64%) and firearms (27%) predominated. The median injury severity score was 18 (IQR 10-29). Most patients survived until hospital discharge (94%). The most frequently injured organs were the scrotum (60%), testes (53%), penis (30%), and kidneys (30%). Massive transfusion protocols were activated in 35% of all patients who sustained a urological injury and accounted for 28% of all protocols between 2007 and 2020. CONCLUSIONS: The incidence of genitourinary trauma persistently increased for both military and civilian personnel as the U.S. remained actively engaged in major military conflicts during this period. Patients with genitourinary trauma in this data set were often associated with high injury severity scores and required an increased number of immediate and long-term resources for survival and rehabilitation.

The roaring 2020s: a new decade of systemic therapy for renal cell carcinoma.

PURPOSE OF REVIEW: The genomic and immunologic profiling of renal cell carcinoma (RCC) has provided the impetus for advancements in systemic treatments using combination therapy - either with immune check point inhibitor (ICI) + ICI or with ICI + targeted therapy. This approach has been examined in several landmark trials, treating both clear cell (ccRCC) and nonclear cell (nccRCC) histologies. In this review, we highlight systemic therapy advancements made in this new decade, the 2020s. RECENT FINDINGS: Targeting the programmed death receptor 1/PD-L1 pathway has created more tolerable and effective immunotherapy regimens, expanding the applications of ICIs. These new applications, paired with trial data, include ICI monotherapy in nccRCC and adjuvant pembrolizumab in resected, high-risk RCC. In addition, ICI + ICI and ICI + TKI combination therapy have demonstrated oncologic efficacy in advanced ccRCC and sarcomatoid RCC. Similar progress has been noted regarding new targeted therapies. Along the hypoxia inducible factor pathway, belzutifan has received FDA approval in von Hippel-Lindau-associated RCC. In addition, in papillary RCC, agents such as cabozantinib target the MET proto-oncogene pathway and have demonstrated impressive oncologic outcomes. SUMMARY: The 2020s utilize the molecular profiling of advanced RCC as a scaffold for recent trials in immunotherapy and targeted therapies. Going forward, emphasizing patient-reported outcomes and careful clinical trial construction remain critical to improve systemic therapy in RCC.

Quantifying Publication Rates and Time to Publication for American Urological Association Podium Presentations.

PURPOSE: The American Urological Association (AUA) Annual Meeting serves as the premier platform for presenting unpublished research in urology. Among selected abstracts, podium presentations represent the most impactful submissions. While podium presentations receive a large audience through conference attendance and social media posts, it is unclear how often they manifest as publications in peer-reviewed journals. MATERIALS AND METHODS: Podium presentations from the 2017 AUA Annual Meeting were reviewed. Abstracts were assessed for publication between January 1, 2015 and May 31, 2020 allowing for a 3-year window of publication and accounting for publications prior to the submission deadline. Abstract authors were individually searched with key terms being added sequentially until <30 results were generated in PubMed®. Abstracts were deemed published if at least 1 author and 1 conclusion matched a manuscript. Publication rate, time to publication, and 2019 journal impact factor were collected. Statistical analysis was performed by linear and logistic regression. RESULTS: Of 872 podium presentations, 453 (51.9%) were published within 3 years. Median time from submission to publication was 12.5 months (IQR: 7.5-20.5). The number of articles published at 1, 2 and 3 years from submission was 203, 368 and 430, respectively. The median journal impact factor of publications was 3.2 (IQR: 2.0-5.8). Oncology studies (OR=1.21 [95% CI: 0.91-1.60], p=0.186) had similar rates of publication compared to non-oncology studies. CONCLUSIONS: While AUA podium presentations disseminate valuable data, approximately half were not published in peer-reviewed journals within 3 years. Therefore, care must be taken when promoting findings or adopting new practices based on these presentations alone.

Association of Lymph Node Count and Survival after Primary Retroperitoneal Lymphadenectomy for Nonseminomatous Testicular Cancer.

PURPOSE: Retroperitoneal lymph node dissection (RPLND) for men with clinical stage (CS) I or II testicular nonseminomatous germ cell tumor (NSGCT) has both staging and therapeutic implications. We aimed to investigate the impact of lymph node count (LNC) on outcome after primary RPLND for men with CS I or II NSGCT using a nationally representative data set. MATERIALS AND METHODS: A retrospective analysis of men who received a primary RPLND for CS I or II NSGCT was performed using the National Cancer Database. The Kaplan-Meier method was used to determine overall survival (OS) according to LNC. Logistic regression analyses were used to identify factors associated with LNC >20 and factors predictive of lymph node-positive (pN+) disease after primary RPLND. RESULTS: Of 1,376 men who comprised our analytical cohort, 50.1% and 49.9% had 1-20 lymph nodes (LNs) and >20 LNs removed, respectively. Five-year OS rates were 96.4% and 99.1% for men with 1-20 and >20 LNs resected, respectively (p=0.004). A higher proportion of men with >20 LNs removed were treated at academic centers, had private insurance, presented with higher AJCC (American Joint Committee on Cancer) CS and were more likely to have pN+ disease, compared to those with 1-20 LNs removed. Factors significantly associated with pN+ disease after RPLND include higher AJCC CS and LNC (per 10-count increase). CONCLUSIONS: Higher LNC after primary RPLND significantly increases the likelihood of identifying pN+ disease and is associated with improved OS. Our data support the therapeutic implications of a thoroughly performed RPLND in the primary setting.

A challenging frontier - the genomics and therapeutics of nonclear cell renal cell carcinoma.

PURPOSE OF REVIEW: As molecular profiling of renal cell carcinoma (RCC) continues to elucidate novel targets for nonclear cell histologies, understanding the landscape of these targets is of utmost importance. In this review, we highlight the genomic landscape of nonclear cell RCC and its implications for current and future systemic therapies. RECENT FINDINGS: Several genomic studies have described the mutational burden among nonclear cell histologies. These studies have highlighted the importance of MET in papillary RCC and led to several clinical trials evaluating the efficacy of MET inhibitors for papillary RCC. The success of immune checkpoint inhibitors, such as ipilimumab and nivolumab, in clear cell RCC has led to ongoing trials evaluating these novel therapeutics in nonclear cell RCC. SUMMARY: Genomic profiling has allowed for the evaluation of novel targets for nonclear cell RCC. This evolving therapeutic landscape is being explored in promising, ongoing trials that have the potential for changing how nonclear cell RCC is managed.

From Diagnosis to Therapy-PET Imaging for Pheochromocytomas and Paragangliomas.

PURPOSE OF REVIEW: Pheochromocytoma and paraganglioma (PPGLs) are neuroendocrine tumors with diverse clinical presentations. PPGLs can be sporadic but often are associated with various syndromes, which can have variable clinical presentations. A thorough workup is therefore critical for staging, treatment, and follow-up. Imaging is an essential part of the workup and diagnosis of PPGLs. RECENT FINDINGS: Improvements in cross-sectional imaging with radionuclides have increased specificity and sensitivity for identifying and treating PPGLs. Furthermore, a variety of targets on PPGLs has allowed for optimal imaging with radionuclides that can be used for staging and treatment. Currently, radionuclides are being evaluated for staging and treatment of PPGLs. Developing novel radionuclides that can identify disease sites and target them simultaneously provides a potential for improving survival and outcomes in patients with PPGLs. Given the clinical diversity among PPGLs, expanding the therapeutic arsenal against locally advanced or metastatic PPGLs can allow clinicians to evaluate and treat PPGLs thoroughly.

Impact of pathologic lymph node-positive renal cell carcinoma on survival in patients without metastasis: Evidence in support of expanding the definition of stage IV kidney cancer.

BACKGROUND: Stage III renal cell carcinoma (RCC) encompasses both lymph node-positive (pT1-3N1M0) and lymph node-negative (pT3N0M0) disease. However, prior institutional studies have indicated that among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease. The objective of the current study was to validate these findings using a large, nationally representative sample of patients with kidney cancer. METHODS: Patients with AJCC stage III or stage IV RCC were identified using the National Cancer Data Base (NCDB). Patients were categorized as having lymph node-positive stage III (pT1-3N1M0), lymph node-negative stage III (pT3N0M0), or stage IV metastatic (pT1-3 N0M1) disease. Cox proportional hazards models compared outcomes while adjusting for comorbidities. Kaplan-Meier estimates illustrated relative survival when comparing staging groups. RESULTS: A total of 8988 patients met the inclusion criteria, with 6587 patients classified as having lymph node-negative stage III disease, 2218 as having lymph node-positive stage III disease, and 183 as having stage IV disease. Superior survival was noted among patients with lymph node-negative stage III disease, but similar survival was noted between patients with lymph node-positive stage III and stage IV RCC, with 5-year survival rates of 61.9% (95% confidence interval [95% CI], 60.3%-63.4%), 22.7% (95% CI, 20.6%-24.9%), and 15.6% (95% CI, 11.1%-23.8%), respectively. CONCLUSIONS: Current RCC staging systems group pT1-3N1M0 and pT3N0M0 disease as stage III disease. However, the results of the current validation study suggest the need for further stratification and even placement of patients with pT1-3N1M0 disease into the stage IV category. Staging that accurately reflects oncologic prognosis may help clinicians better counsel and select patients who might derive the most benefit from lymphadenectomy, adjuvant systemic therapy, more rigorous imaging surveillance, and clinical trial participation.

Challenges and opportunities in the management of metastatic renal cell carcinoma: combination therapy and the role of cytoreductive surgery.

PURPOSE OF REVIEW: As the biology of metastatic renal cell carcinoma (mRCC) continues to be elucidated, novel treatments focused around immunotherapies and targeted therapies will continue to emerge. In this review, we will highlight recent treatment advances and their implications for surgical and systemic therapy. RECENT FINDINGS: Several new treatments, including the tyrosine kinase inhibitor cabozantinib, the combination of a programmed cell death protein 1 antibody (nivolumab) with a cytotoxic T-lymphocyte-associated antigen 4 antibody (ipilimumab), and the combination of axitinib with pembrolizumab or avelumab have been approved by the US Food and Drug Administration as first-line therapy for the treatment of mRCC. Although promising survival benefits have been seen with these new therapies, careful patient selection is still critical. SUMMARY: The introduction of novel therapies and the investigation of combinatorial therapies have shifted the treatment paradigm for advanced RCC. Present trials have provided promising data that could lead to further therapeutic advances.

Opportunities and Challenges in Activity-Based Protein Profiling of Mycobacteria.

Mycobacteria, from saprophytic to pathogenic species, encounter diverse environments that demand metabolic versatility and rapid adaptation from these bacteria for their survival. The human pathogen Mycobacterium tuberculosis, for example, can enter a reversible state of dormancy in which it is metabolically active, but does not increase in number, and which is believed to enable its survival in the human host for years, with attendant risk for reactivation to active tuberculosis. Driven by the need to combat mycobacterial diseases like tuberculosis, efforts to understand such adaptations have benefitted in recent years from application of activity-based probes. These studies have been inspired by the potential of these chemical tools to uncover protein function for previously unannotated proteins, track shifts in protein activity as a function of environment, and provide a streamlined method for screening and developing inhibitors. Here we seek to contextualize progress thus far with achieving these goals and highlight the unique challenges and opportunities for activity-based probes to further our understanding of protein function and regulation, bacterial physiology, and antibiotic development.

Virus particle release from glycosphingolipid-enriched microdomains is essential for dendritic cell-mediated capture and transfer of HIV-1 and henipavirus.

UNLABELLED: Human immunodeficiency virus type 1 (HIV-1) exploits dendritic cells (DCs) to promote its transmission to T cells. We recently reported that the capture of HIV-1 by mature dendritic cells (MDCs) is mediated by an interaction between the glycosphingolipid (GSL) GM3 on virus particles and CD169/Siglec-1 on MDCs. Since HIV-1 preferentially buds from GSL-enriched lipid microdomains on the plasma membrane, we hypothesized that the virus assembly and budding site determines the ability of HIV-1 to interact with MDCs. In support of this hypothesis, mutations in the N-terminal basic domain (29/31KE) or deletion of the membrane-targeting domain of the HIV-1 matrix (MA) protein that altered the virus assembly and budding site to CD63(+)/Lamp-1-positive intracellular compartments resulted in lower levels of virion incorporation of GM3 and attenuation of virus capture by MDCs. Furthermore, MDC-mediated capture and transmission of MA mutant viruses to T cells were decreased, suggesting that HIV-1 acquires GSLs via budding from the plasma membrane to access the MDC-dependent trans infection pathway. Interestingly, MDC-mediated capture of Nipah and Hendra virus (recently emerged zoonotic paramyxoviruses) M (matrix) protein-derived virus-like particles that bud from GSL-enriched plasma membrane microdomains was also dependent on interactions between virion-incorporated GSLs and CD169. Moreover, capture and transfer of Nipah virus envelope glycoprotein-pseudotyped lentivirus particles by MDCs were severely attenuated upon depletion of GSLs from virus particles. These results suggest that GSL incorporation into virions is critical for the interaction of diverse enveloped RNA viruses with DCs and that the GSL-CD169 recognition nexus might be a conserved viral mechanism of parasitization of DC functions for systemic virus dissemination. IMPORTANCE: Dendritic cells (DCs) can capture HIV-1 particles and transfer captured virus particles to T cells without establishing productive infection in DCs, a mechanism of HIV-1 trans infection. We have recently identified CD169-mediated recognition of GM3, a host-derived glycosphingolipid (GSL) incorporated into the virus particle membrane, as the receptor and ligand for the DC-HIV trans infection pathway. In this study, we have identified the matrix (MA) domain of Gag to be the viral determinant that governs incorporation of GM3 into HIV-1 particles, a previously unappreciated function of the HIV-1 MA. In addition, we demonstrate that the GSL-CD169-dependent trans infection pathway is also utilized as a dissemination mechanism by henipaviruses. GSL incorporation in henipaviruses was also dependent on the viral capsid (M) protein-directed assembly and budding from GSL-enriched lipid microdomains. These findings provide evidence of a conserved mechanism of retrovirus and henipavirus parasitization of cell-to-cell recognition pathways for systemic virus dissemination.

Ergonomics in Urology: Current Landscape and Future Directions.

Optimal ergonomics are essential to improving clinical performance and longevity among urologists, as poor ergonomics can contribute to work-related injury and physician burnout. While a majority of urologists experience muscular injury throughout their career, women and trainees are disproportionately affected. These disparities are exacerbated by the lack of formal ergonomics education within urologic training programs. This review provides an overview of practical approaches to optimize ergonomics across working environments for urologists and trainees. We highlight intraoperative techniques and novel devices which have been shown to reduce work-related injury, and we identify knowledge gaps to guide future areas of ergonomic research.