Transperineal versus Transrectal MRI/TRUS fusion-guided prostate biopsy in a large, ethnically diverse, and multiracial cohort.

PURPOSE: To compare transperineal (TP) vs transrectal (TR) magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) fusion-guided prostate biopsy (PBx) in a large, ethnically diverse and multiracial cohort. MATERIALS AND METHODS: Consecutive patients who underwent multiparametric (mp) MRI followed by TP or TR TRUS-fusion guided PBx, were identified from a prospective database (IRB #HS-13-00663). All patients underwent mpMRI followed by 12-14 core systematic PBx. A minimum of two additional target-biopsy cores were taken per PIRADS≥3 lesion. The endpoint was the detection of clinically significant prostate cancer (CSPCa; Grade Group, GG≥2). Statistical significance was defined as p<0.05. RESULTS: A total of 1491 patients met inclusion criteria, with 480 undergoing TP and 1011 TR PBx. Overall, 11% of patients were Asians, 5% African Americans, 14% Hispanic, 14% Others, and 56% White, similar between TP and TR (p=0.4). For PIRADS 3-5, the TP PBx CSPCa detection was significantly higher (61% vs 54%, p=0.03) than TR PBx, but not for PIRADS 1-2 (13% vs 13%, p=1.0). After adjusting for confounders on multivariable analysis, Black race, but not the PBx approach (TP vs TR), was an independent predictor of CSPCa detection. The median maximum cancer core length (11 vs 8mm; p<0.001) and percent (80% vs 60%; p<0.001) were greater for TP PBx even after adjusting for confounders. CONCLUSIONS: In a large and diverse cohort, Black race, but not the biopsy approach, was an independent predictor for CSPCa detection. TP and TR PBx yielded similar CSPCa detection rates; however the TP PBx was histologically more informative.

Role of buccal mucosa graft ureteroplasty in the surgical management of pyeloplasty failure.

Objective: Secondary pyeloplasty for recurrent ureteropelvic junction obstructions may be a safe and feasible surgical option for patients. This study aimed to demonstrate outcomes of utilizing a non-transecting buccal mucosa graft ureteroplasty for management of recurrent ureteropelvic junction obstruction after prior failed pyeloplasty. Methods: We performed a retrospective review of our Collaborative of Reconstructive Robotic Ureteral Surgery database for all consecutive patients who underwent buccal mucosa graft ureteroplasty between April 2012 and June 2022 for management of recurrent ureteropelvic junction obstructions after prior failed pyeloplasty. The primary outcome included surgical success which was defined as the absence of flank pain and no obstruction on imaging. Results: Overall, ten patients were included in our analysis. The median stricture length was 2.5 (interquartile range [IQR] 1.8-4.0) cm. The median operative time was 230.5 (IQR 199.5-287.0) min and median estimated blood loss was 50.0 (IQR 28.8-102.5) mL. At a median follow-up of 10.3 (IQR 6.2-14.8) months, 80% of patients were surgically successful and there were no major (Clavien-Dindo Grade>2) complications. Conclusion: Buccal mucosa graft ureteroplasty is a valuable non-transecting surgical option for patients with recurrent ureteropelvic junction obstructions who failed prior pyeloplasty and has comparable outcomes to the literature regarding standard transecting techniques.

Description of a novel robotic early post-prostatectomy anastomotic repair technique and institutional outcomes.

Objective: A vesicourethral anastomotic leak (VUAL) is a known complication following robotic-assisted radical prostatectomy. The natural history of a VUAL has been well described and is frequently managed with prolonged catheterization. With increasing emphasis on patient reported outcomes, catheter duration and VUAL are associated with significant short-term quality of life impairment. We aimed to present a case series of our robotic early post-prostatectomy anastomotic repair technique, defined as revision within 6 weeks from index surgery. Methods: A single institution prospective database identified eleven patients with a VUAL from July 2016 to October 2022 who underwent robotic early post-prostatectomy anastomotic repair by a single surgeon. Patients were diagnosed with a VUAL on pre-operative CT urogram or CT/fluoroscopic cystogram. The primary outcome was resolution of the anastomotic leak, defined as no contrast extravasation on post-operative cystography. Secondary outcomes included post-repair catheter duration and continence on the last follow-up defined as pad(s) per day. Results: The mean time to intervention after robotic-assisted radical prostatectomy was 21 days. Eight of the eleven (72.7%) patients had no evidence of extravasation on post-repair cystogram. The range from intervention to first cystogram was 7-20 days. The median catheter duration for those with successful intervention was 10 days. The median catheter duration for those with the leak on initial post-operative cystogram was 20 days. At a mean follow-up time of 25 months, eight (72.7%) patients reported using no pads per day, and three (27.3%) patients reported one pad per day. Conclusion: Management of a VUAL has traditionally relied on prolonged catheter drainage and the tincture of time. As the role of robotic reconstruction has been shown to be a viable modality for management of bladder neck contracture, it is important to reconsider prior dogmas of urologic care. Our case series suggests that an early repair is safe and has a high success rate. Early robotic intervention gives providers an additional tool in aiding patient recovery.

Generative AI Platform for Automating Social Media Posts From Urology Journal Articles: A Cross-Sectional Study and Randomized Assessment.

PURPOSE: This cross-sectional study assessed a generative-AI platform to automate the creation of accurate, appropriate, and compelling social-media (SoMe) posts from urological journal articles. MATERIALS AND METHODS: One hundred SoMe-posts from the top 3 journals in urology X (Twitter) profiles were collected from Aug-2022 to Oct-2023 A freeware GPT-tool was developed to auto-generate SoMe posts, which included title-summarization, key findings, pertinent emojis, hashtags, and DOI links to the article. Three physicians independently evaluated GPT-generated posts for achieving tetrafecta of accuracy and appropriateness criteria. Fifteen scenarios were created from 5 randomly selected posts from each journal. Each scenario contained both the original and the GPT-generated post for the same article. Five questions were formulated to investigate the posts' likability, shareability, engagement, understandability, and comprehensiveness. The paired posts were then randomized and presented to blinded academic authors and general public through Amazon Mechanical Turk (AMT) responders for preference evaluation. RESULTS: Median (IQR) time for post auto-generation was 10.2 seconds (8.5-12.5). Of the 150 rated GPT-generated posts, 115 (76.6%) met the correctness tetrafecta: 144 (96%) accurately summarized the title, 147 (98%) accurately presented the articles' main findings, 131 (87.3%) appropriately used emojis and hashtags 138 (92%). A total of 258 academic urologists and 493 AMT responders answered the surveys, wherein the GPT-generated posts consistently outperformed the original journals' posts for both academicians and AMT responders (P < .05). CONCLUSIONS: Generative-AI can automate the creation of SoMe posts from urology journal abstracts that are both accurate and preferable by the academic community and general public.

Contractility assessment using aligned human iPSC-derived cardiomyocytes.

INTRODUCTION: Cardiac safety assessment, such as lethal arrhythmias and contractility dysfunction, is critical during drug development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been shown to be useful in predicting drug-induced proarrhythmic risk through international validation studies. Although cardiac contractility is another key function, fit-for-purpose hiPSC-CMs in evaluating drug-induced contractile dysfunction remain poorly understood. In this study, we investigated whether alignment of hiPSC-CMs on nanopatterned culture plates can assess drug-induced contractile changes more efficiently than non-aligned monolayer culture. METHODS: Aligned hiPSC-CMs were obtained by culturing on 96-well culture plates with a ridge-groove-ridge nanopattern on the bottom surface, while non-aligned hiPSC-CMs were cultured on regular 96-well plates. Next-generation sequencing and qPCR experiments were performed for gene expression analysis. Contractility of the hiPSC-CMs was assessed using an imaging-based motion analysis system. RESULTS: When cultured on nanopatterned plates, hiPSC-CMs exhibited an aligned morphology and enhanced expression of genes encoding proteins that regulate contractility, including myosin heavy chain, calcium channel, and ryanodine receptor. Compared to cultures on regular plates, the aligned hiPSC-CMs also showed both enhanced contraction and relaxation velocity. In addition, the aligned hiPSC-CMs showed a more physiological response to positive and negative inotropic agents, such as isoproterenol and verapamil. DISCUSSION: Taken together, the aligned hiPSC-CMs exhibited enhanced structural and functional properties, leading to an improved capacity for contractility assessment compared to the non-aligned cells. These findings suggest that the aligned hiPSC-CMs can be used to evaluate drug-induced cardiac contractile changes.

Evaluation of germicidal ultraviolet-C disinfection in a real-world outpatient health care environment.

BACKGROUND: The coronavirus disease 2019 pandemic has highlighted the need for effective infection control in outpatient health care settings. Germicidal ultraviolet-C (GUV) light, known for inactivating microorganisms by damaging their deoxyribonucleic acid or ribonucleic acid, offers a potential solution. This study examines the efficacy of GUV air disinfection systems in real-world outpatient environments. METHODS: We deployed upper-room and far-UV GUV fixtures in 3 outpatient facilities, assessing their impact on bacterial loads through air and surface sampling and bioindicator tests. Occupancy was also monitored. RESULTS: While manual air and surface sampling did not show a significant difference in bacterial loads between control and Ultraviolet C-treated groups, bioindicator tests demonstrated a high level of spore inactivation (up to 99.7% for upper-room GUV and 96.26% for far-UV). Occupancy levels did not significantly influence these outcomes. DISCUSSION: The discrepancy between bioindicator efficacy and environmental sampling results suggests limitations in the latter's ability to accurately capture environmental bioburden. Bioindicators proved to be reliable for in-situ validation of Ultraviolet C surface disinfection. CONCLUSIONS: Bioindicators are effective for validating GUV surface disinfection efficacy in health care settings, though further research is needed to optimize environmental sampling methods for assessing GUV's impact on real-world bacterial loads.

Physiologically based modeling reveals different risk of respiratory depression after fentanyl overdose between adults and children.

Despite a rapid increase in pediatric mortality rate from prescription and illicit opioids, there is limited research on the dose-dependent impact of opioids on respiratory depression in children, the leading cause of opioid-associated death. In this article, we extend a previously developed translational model to cover pediatric populations by incorporating age-dependent pharmacokinetic, pharmacodynamic, and physiological changes compared to adults. Our model reproduced previous perioperative clinical findings that adults and children have similar risk of respiratory depression at the same plasma fentanyl concentration when specific endpoints (minute ventilation, CO2 tension in the blood) were used. However, our model points to a potential caveat that, in a perioperative setting, routine use of mechanical ventilation and supplemental oxygen maintained the blood and tissue oxygen partial pressures in patients and prevented the use of oxygen-related endpoints to evaluate the consequences of respiratory depression. In a community setting when such oxygenation procedures are not immediately available, our model suggests that the higher oxygen demand and reduced cerebrovascular reactivity could make children more susceptible to severe hypoxemia and brain hypoxia, even with the same plasma fentanyl concentration as adults. Our work indicates that when developing intervention strategies to protect children from opioid overdose in a community setting, these pediatric-specific factors may need to be considered.

Intranasal Naloxone Repeat Dosing Strategies and Fentanyl Overdose: A Simulation-Based Randomized Clinical Trial.

Importance: Questions have emerged as to whether standard intranasal naloxone dosing recommendations (ie, 1 dose with readministration every 2-3 minutes if needed) are adequate in the era of illicitly manufactured fentanyl and its derivatives (hereinafter, fentanyl). Objective: To compare naloxone plasma concentrations between different intranasal naloxone repeat dosing strategies and to estimate their effect on fentanyl overdose. Design, Setting, and Participants: This unblinded crossover randomized clinical trial was conducted with healthy participants in a clinical pharmacology unit (Spaulding Clinical Research, West Bend, Wisconsin) in March 2021. Inclusion criteria included age 18 to 55 years, nonsmoking status, and negative test results for the presence of alcohol or drugs of abuse. Data analysis was performed from October 2021 to May 2023. Intervention: Naloxone administered as 1 dose (4 mg/0.1 mL) at 0, 2.5, 5, and 7.5 minutes (test), 2 doses at 0 and 2.5 minutes (test), and 1 dose at 0 and 2.5 minutes (reference). Main Outcomes and Measures: The primary outcome was the first prespecified time with higher naloxone plasma concentration. The secondary outcome was estimated brain hypoxia time following simulated fentanyl overdoses using a physiologic pharmacokinetic-pharmacodynamic model. Naloxone concentrations were compared using paired tests at 3 prespecified times across the 3 groups, and simulation results were summarized using descriptive statistics. Results: This study included 21 participants, and 18 (86%) completed the trial. The median participant age was 34 years (IQR, 27-50 years), and slightly more than half of participants were men (11 [52%]). Compared with 1 naloxone dose at 0 and 2.5 minutes, 1 dose at 0, 2.5, 5, and 7.5 minutes significantly increased naloxone plasma concentration at 10 minutes (7.95 vs 4.42 ng/mL; geometric mean ratio, 1.95 [1-sided 97.8% CI, 1.28-∞]), whereas 2 doses at 0 and 2.5 minutes significantly increased the plasma concentration at 4.5 minutes (2.24 vs 1.23 ng/mL; geometric mean ratio, 1.98 [1-sided 97.8% CI, 1.03-∞]). No drug-related serious adverse events were reported. The median brain hypoxia time after a simulated fentanyl 2.97-mg intravenous bolus was 4.5 minutes (IQR, 2.1-∞ minutes) with 1 naloxone dose at 0 and 2.5 minutes, 4.5 minutes (IQR, 2.1-∞ minutes) with 1 naloxone dose at 0, 2.5, 5, and 7.5 minutes, and 3.7 minutes (IQR, 1.5-∞ minutes) with 2 naloxone doses at 0 and 2.5 minutes. Conclusions and Relevance: In this clinical trial with healthy participants, compared with 1 intranasal naloxone dose administered at 0 and 2.5 minutes, 1 dose at 0, 2.5, 5, and 7.5 minutes significantly increased naloxone plasma concentration at 10 minutes, whereas 2 doses at 0 and 2.5 minutes significantly increased naloxone plasma concentration at 4.5 minutes. Additional research is needed to determine optimal naloxone dosing in the community setting. Trial Registration: ClinicalTrials.gov Identifier: NCT04764630.