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Category: Ankle Arthritis; Ankle; Hindfoot Introduction/Purpose: Ankle and hindfoot arthrodesis are common interventions for degenerative and inflammatory foot and ankle conditions. These include, but are not limited to osteoarthritis, inflammatory arthritis, deformity, and instability. While we know the addition of bone graft is critical for successful union, we do not fully understand how graft selection affects union rates. Demineralized bone matrix (DBM) is commonly chosen due to its ease of availability and osteoconductive and osteoinductive properties. In our study, we aim to determine if adding BMAc, and thus osteogenic properties, to a DBM allograft improves union rates following ankle and hindfoot arthrodesis. Methods: After receiving IRB approval from our institution, we collected the records of patients who underwent arthrodesis of the hindfoot (subtalar, calcaneocuboid, talonavicular) or ankle during a 10-year time period. Patients were then divided into two groups: arthrodesis performed with the use of DBM and arthrodesis performed with DMB-BMAc. Cases using other graft options such as bulk allograft, autograft, or bone morphogenic protein (BMP) were excluded. Fusion was determined by standard radiographic and clinical criteria and CT scans were utilized in cases which fusion could not be determined. Patients were followed for a minimum of 6 months. If fusion was not complete at that time clinical and radiographic exams were performed at the 9- and 12-month period. Patients were analyzed for sucussesful arthrodesis. Complications and revisions were recorded and analyzed. Results: A total of 124 patients who met the inclusion criteria were identified. In 49 patients only DBM was utilized, and 75 patients BMC was added to the DBM. At 12 months post operatively the group utilizing only DBM had a union rate of 90% while the union rate of the BMAc/DBM had a union rate of 88% (p=0.985) There was no difference in the rate of complications between the two groups and the groups were matched in terms of age, smoking status, DM, sex and BMI. Additionally, in our cohort there was a trend toward increased non-union and complication rate in smokers, although this did not reach statistical significance. Conclusion: Ankle and hindfoot arthrodesis are a reliable treatment option for patients with specific foot and ankle pathology. Our study reports a fusion rate in line with previous studies. The addition of BMAc from the pelvis, attempting to improve the biology of the fusion site, to DBM does not seem to affect fusion rates.

Category: Other; Sports Introduction/Purpose: Surgical management of Achilles ruptures with minimally invasive techniques reduces soft tissue injury and complication rates compared to open repair. No consensus in current literature identifies the optimal minimally invasive Achilles rupture repair technique to reduce complication rates. The Percutaneous Achilles Repair System (PARS) (Arthrex Inc; Naples, FL) utilizes knots to secure tension at the site of rupture. The more recently developed Midsubstance Speedbridge Implant System (MSB) (Arthrex Inc; Naples, FL) utilizes interference screws to tension the repair. Our institution performs a high volume of Achilles repairs by these two techniques. We hypothesized that complication rates and risk of complications would be similar between patients who underwent MSB repair technique and patients who underwent PARS repair technique. Methods: We retrospectively reviewed all 434 patients who underwent Achilles rupture repair between January 1st, 2018 and January 1st, 2023 at our institution. Patients were excluded if surgical indications included tendinopathies, open injuries, or concomitant fractures, or if their operation included tendon transfers, gastrocnemius recessions, or open repairs. Groups identified for inclusion were defined as those who underwent PARS technique (n=212) and those who underwent MSB technique (n=104). The Fisher exact test was used to compare incidence of heel pain at last visit and incidence of complications including deep vein thrombosis (DVT), pulmonary embolism (PE), sural nerve injury, rerupture, and reoperation between PARS and MSB techniques. We combined the listed complications to create a discrete variable indicating whether a patient experienced any one complication. Using logistic regression with a log-link, we evaluated the relative risk of experiencing any one complication between PARS and MSB techniques. Results: There was a significantly lower relative risk of experiencing any one complication in the MSB group compared to the PARS group (RR=0.31, 95% CI 0.11-0.88). There was no significant difference of incidence of each complication between groups. The rates of complications in the MSB group were 0% deep vein thrombosis (DVT), 0% rerupture, 1.0% (1/104) sural nerve injury, 2.9% (3/104) wound complication, and 2.9% (3/104) reoperation. The rates of complications in the PARS group were 0.9% (2/212) DVT, 1.9% (4/212) rerupture, 1.9% (4/212) sural nerve injury, 4.2% (9/212) wound complication, and 2.8% (6/212) reoperation. MSB demonstrated a significantly higher incidence of heel pain at last follow-up (P=0.01). Males experienced a lower relative risk of complication compared to females (RR=0.39, 95% CI 0.17-0.90). Conclusion: The MSB and PARS minimally invasive Achilles repair techniques are safe and effective at surgically managing Achilles ruptures. In the largest known study to compare PARS and MSB repair technique complications, we found that the MSB technique reduces the overall risk of a complication from minimally invasive Achilles rupture repairs.

Category: Ankle; Trauma Introduction/Purpose: Studies have evaluated the impact of ankle fracture subtype and level of athletic competition on ability and time to return to sporting activity. Limited studies have analyzed whether pre-injury activity level influences return to activity for the general population. Our study investigates whether pre-injury activity level is associated with post-recovery activity level regardless of fracture subtype characterized by the Weber classification. We hypothesize that pre-injury activity level of patients will not be associated with post-recovery activity level regardless of fracture subtype among patients with fractures anatomically reduced during operative repair. This investigation is the largest retrospective cohort study evaluating the influence of pre-injury activity level on return to any activity for the general population. Methods: We retrospectively reviewed all 782 patients who underwent surgical repair of an ankle fracture at Northwestern Memorial Hospital from 2016-2021. Two foot and ankle fellowship trained orthopedic surgeons independently reviewed all radiographs. Patients were stratified by Weber fracture subtype, fixation technique, and reduction quality at final follow-up. Patients with multiple injuries at time of presentation, pilon variants, and who identified as part of vulnerable populations were excluded. Of the 703 patients included, 218 completed a post-operative questionnaire querying their activity level (sedentary, light, moderate, and high) before and after surgery and any current activity limitations. The 200 closed fractures were included for final analysis. 117 of the 200 patients had anatomic reduction of the ankle at minimum one year follow-up and reported no activity limitations due to fear of reinjury. Fisher’s exact test and Pearson’s chi-square test with Yates continuity correction were used for bivariate comparisons between groups. Results: 70% of patients reported returning to pre-injury activity level. Pre-injury activity level was significantly associated with return to activity (p=0.02). Across all groups, the highest proportion able to return to pre-injury activity level was those with sedentary/light activity (81.9%) and the lowest proportion was those with high activity (60.5%). When patients who experienced activity limitations due to fear of reinjury were excluded (N =159), no statistically significant association was found between pre-injury activity level and return to activity (p=0.1). Analysis of only those with anatomic reduction at minimum one-year follow-up who reported no fear of reinjury (N =117) found no significant association between pre-injury activity level and return to pre-injury activity level (p=0.1). Weber fracture subtype (N =200) was not associated with return to pre-injury activity level (p=0.16). Conclusion: Proper surgical fixation and anatomic reduction can return most patients of the general population back to pre-injury levels of activity regardless of pre-injury level of activity and fracture subtype. Patients who have lower activity demands can have higher expectations to return to their normal activity level compared to those who are more vigorously active. Fear of reinjury may influence patients’ abilities to return to activity, as when proper surgical fixation and reduction are achieved in patients with no fear of reinjury, pre-injury level of activity is no longer associated with ability to return to pre-injury activity level.

Category: Ankle; Trauma Introduction/Purpose: It remains unclear whether ankle fracture pattern as described by the Weber classification—a reproducible method describing the level of fracture with respect to the distal tibiofibular syndesmosis—impacts outcomes. Patient Reported Outcome Measurement Information System (PROMIS) is a validated measure of outcomes after foot and ankle surgery. To our knowledge, no study has compared PROMIS scores between Weber subtypes. Our study thus examines whether Weber fracture subtype impacts surgical outcomes as measured by PROMIS scores. We hypothesize that both Weber B and Weber C fracture patterns will not have a significant difference in PROMIS scores when anatomically reduced during operative repair. This study is the largest evaluating PROMIS scores of Weber fracture subtypes. Methods: All 782 patients who underwent surgical repair of an ankle fracture at Northwestern between January 1, 2016 and December 31, 2021 were retrospectively reviewed. Two foot and ankle fellowship trained orthopedic surgeons independently reviewed all radiographs and stratified them by Weber fracture subtype, fixation technique, and reduction quality at final follow-up. Patients with multiple injuries at time of presentation, pilon variants, and who identified as a part of vulnerable populations were excluded. Of the 703 patients included, 218 completed a post-operative PROMIS physical function (PF) and pain interference (PI) computerized adaptive test. Subsequently, only the 200 closed Weber B and Weber C fractures were included for final analysis. The Mann-Whitney U test was used to compare differences in PROMIS scores. The Kruskal-Wallis test was used when comparisons were between three or more groups. Results: No significant difference existed between Weber B and Weber C fractures anatomically reduced intraoperatively in terms of mean PF (52.19 ± 9.84 vs. 53.59 ± 9.46, p=0.52) and PI (48.30 ± 8.74 vs. 46.77 ± 7.86, p=0.33). Analysis of those with anatomic reduction at minimum one-year follow-up found no significant difference between Weber B’s and Weber C’s with regard to mean PF (51.46 ± 9.97 vs. 53.67 ± 9.51, p=0.32) and PI (47.76 ± 9.15 vs. 47.68 ± 7.75, p=0.67). Compared to lower BMIs, BMIs of 30 or greater had significantly worse mean PF (p=0.02) and PI (p=0.01). Compared to males, females had worse mean PF (49.88 ± 7.99 vs. 57.92 ± 10.78, p< 0.001) and PI (49.10 ± 8.56 vs. 45.54 ± 8.03, p< 0.01). Conclusion: Weber classification remains a reliable method for categorizing fracture subtypes. We can conclude that anatomic reduction and fixation can return patients with both Weber C and Weber B fractures back to population mean functional outcomes. Although Weber C fractures with known syndesmotic injury result in larger soft tissue trauma, anatomic surgical reduction and fixation can achieve equivalent outcomes to patients with lower energy Weber B fractures. BMI, sex, and age affect functional outcomes following operative repair and may help surgeons guide patient expectations during recovery.

Category: Other; Sports Introduction/Purpose: The optimal surgical management of Achilles ruptures remains controversial. The Percutaneous Achilles Repair System (PARS) (Arthrex Inc; Naples, FL) utilizes knots to secure tension at the rupture site. The more recently developed Midsubstance Speedbridge Implant System (MSB) (Arthrex Inc; Naples, FL) utilizes interference screws to tension the repair. Prior studies have compared patient reported outcomes (PROs) utilizing the Patient Reported Outcomes Information System (PROMIS) computerized adaptive tests of physical function (PF) and pain interference (PI) and the Achilles Tendon Total Rupture Score (ATRS) between open and minimally invasive repair techniques. No study has compared PF, PI, and ATRS PROs between PARS and MSB techniques. We hypothesized that PROs would be similar between patients who underwent MSB repair and patients who underwent PARS repair. Methods: All 434 patients who underwent Achilles rupture repair between January 1st, 2018 and January 1st, 2023 at our institution were emailed a weblink via REDCap to complete the PROMIS PF and PI and the ATRS questionnaire measures. Excluded surgical indications were tendinopathies, open injuries, or concomitant fractures. Open repairs, tendon transfers, or gastrocnemius recessions were also excluded. A total of 119 included patients completed all surveys. Groups were defined as those who underwent repair with PARS technique (n=78) and those who underwent MSB technique (n=41). The Mann-Whitney U test assessed differences in distribution of PF, PI, and ATRS scores between groups. Between groups, we compared postoperative complications using the Fischer exact test and months to return to preinjury level of activity using the Student’s t-test for independent samples. Results: There was no significant difference in PF, PI, and ATRS measures between PARS and MSB (P > .05). Mean PARS group PF, PI, and ATRS scores were 58.77, 44.21, and 85.99, respectively. Mean MSB group PF, PI, and ATRS scores were 55.26, 44.01, and 82.51, respectively. Mean months to return to preinjury level of activity was 9.28 for PARS and 9.4 for MSB (P = 0.96). Each postoperative complication had no significant difference of incidence between groups (P > .05). The rates of complications for PARS and MSB, respectively, were 0.9% (2/212) and 0% deep vein thrombosis, 1.9% (4/212) and 0% rerupture, 1.9% (4/212) and 1.0% (1/104) sural nerve injury, 4.2% (9/212) and 2.9% (3/104) wound complication, and 2.8% (6/212) and 2.9% (3/104) reoperation. Conclusion: This is the largest study to compare patient reported outcomes between PARS and MSB minimally invasive Achilles tendon rupture repairs. Both techniques achieve physical function patient reported outcomes that are greater than the population mean and pain interference that is lower than the population mean. Each technique has low rates of postoperative complications and similar ATRS scores. Overall, the MSB and PARS minimally invasive Achilles repair techniques are safe and effective strategies for surgically managing Achilles ruptures.

Background: Pilon fractures are associated with high-energy injuries, and there is presently much debate as to optimal fixation strategies and timing of intervention. There is little evidence comparing the type of fibular fixation during pilon fracture fixation. The purpose of this study was to compare fibular fixation methods in complex pilon injuries as it relates to pilon union rates and development of post-traumatic arthritis. Methods : This was a retrospective review from an urban Level 1 trauma center from January 2009 to May 2019, including patients age ≥ 18 who sustained a pilon fracture with an associated fibula fracture. Patients were allocated into one of three groups based on fibular fracture treated with plating, intramedullary device, or no fixation. Radiographic analysis was performed postoperatively and at final follow up to evaluate for tibial or fibular nonunion, malunion, talocrural angle, and ankle Kellgren-Lawrence grade. Results : Of the 107 patients in this study, 42 underwent surgical fixation of their fibular fracture. There were no differences with respect to tibial or fibular union rates amongst the three groups. Furthermore, there were no differences in the presence of radiographic ankle arthritis at final follow up. However, Kellgren-Lawrence arthritis grading did appear to be a more severe grade in patients who did not undergo fibular fixation ( p = 0.001). Conclusions : Fibular intramedullary fixation does not appear to influence tibial or fibular nonunion rates as compared to plating in complex pilon injuries.

Objective: To evaluate the perioperative complications of single-port robot-assisted radical prostatectomy (SP-RARP)., Patients and Methods: A retrospective review was performed on the prospectively maintained, Institutional Review Board-approved, multi-institutional Single-Port Advanced Research Consortium (SPARC) database. A total of 1103 patients were identified who underwent three different approaches of SP-RARP between 2019 and 2022 using the purpose-built SP robotic platform. In addition to baseline clinical, perioperative outcomes, this study comprehensively analysed for any evidence of intraoperative complication, as well as postoperative complication and readmission within 90 days of the respective surgery., Results: Of the 244, 712, and 147 patients who underwent transperitoneal, extraperitoneal, and transvesical SP-RARP, respectively, intraoperative complications were noted in five patients (0.4%), all of which occurred during the transperitoneal approach. Two patients had bowel serosal tears, two had posterior button-holing of the bladder necessitating repair, and one patient had an obturator nerve injury. Postoperative complications were noted in 143 patients (13%) with major complications (Clavien-Dindo Grade ≥III) only identified in 3.7% of the total cohort. The most common complications were lymphocele (3.9%), acute urinary retention (2%), and urinary tract infection (1.9%). The 90-day re-admission rate was 3.9%., Conclusion: The SP-RARP is a safe and effective procedure with low complication and readmission rates regardless of the approach. These results are comparable to current multi-port RARP literature., (© 2023 BJU International.)

Tauopathies, including Alzheimer's disease (AD) and Frontotemporal Dementia (FTD), are histopathologically defined by the aggregation of hyperphosphorylated pathological tau (pTau) as neurofibrillary tangles in the brain. Site-specific phosphorylation of tau occurs early in the disease process and correlates with progressive cognitive decline, thus serving as targetable pathological epitopes for immunotherapeutic development. Previously, we developed a vaccine (Qβ-pT181) displaying phosphorylated Thr181 tau peptides on the surface of a Qβ bacteriophage virus-like particle (VLP) that induced robust antibody responses, cleared pathological tau, and rescued memory deficits in a transgenic mouse model of tauopathy. Here we report the characterization and comparison of two additional Qβ VLP-based vaccines targeting the dual phosphorylation sites Ser199/Ser202 (Qβ-AT8) and Ser396/Ser404 (Qβ-PHF1). Both Qβ-AT8 and Qβ-PHF1 vaccines elicited high-titer antibody responses against their pTau epitopes. However, only Qβ-PHF1 rescued cognitive deficits, reduced soluble and insoluble pathological tau, and reactive microgliosis in a 4-month rTg4510 model of FTD. Both sera from Qβ-AT8 and Qβ-PHF1 vaccinated mice were specifically reactive to tau pathology in human AD post-mortem brain sections. These studies further support the use of VLP-based immunotherapies to target pTau in AD and related tauopathies and provide potential insight into the clinical efficacy of various pTau epitopes in the development of immunotherapeutics., Competing Interests: Competing interests All authors declare no competing financial or non-financial interests.

Introduction: Retzius-sparing prostatectomy was promoted with the early continence result. The long-term oncologic outcome is still unknown. In this study, we aimed to compare the intermediate-term oncologic outcomes of these two approaches in patients' cohort who were treated as part of a randomized controlled trial. Methods: A total of 120 patients were previously randomized equally to receive Retzius-sparing robot-assisted laparoscopic radical prostatectomy (RS-RARP) vs standard robot-assisted laparoscopic radical prostatectomy (S-RARP) between January 2015 and April 2016. Baseline, surgical, and pathologic characteristics as well as oncologic outcomes were assessed. The analysis was done based on the treatment received. Result: Sixty-three patients underwent S-RARP, whereas 57 patients underwent RS-RARP. There was no statistically significant difference in the baseline nor surgical characteristics. The median follow-up was 71.24 (interquartile range: 59.75-75.75) months. There were more pathologic T3 diseases in RS-RARP. There was no significant difference in the positive margin status nor in the biochemical recurrence (BCR) rate among both groups. After S-RARP and RS-RARP, 6 and 10 patients had BCR, and the 5 years BCR-free survival was 91% and 85%, respectively ( p  = 0.21). Conclusion: In this cohort, there was no difference in BCR in the patients who received either technique. Further multi-institutional studies with a larger sample size and longer follow-up are required.

Objective: To report urinary bother, urinalysis changes, disease-free survival (DFS), and overall survival (OS) over 2 years for subjects enrolled in a phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab for recurrent or persistent high-grade non-muscle invasive bladder cancer (HGNMIBC)., Methods: Eighteen patients consented to the study. Five were screen failures. Clinical activity was determined using cystoscopy and cytology with a biopsy of suspicious lesions. Urinalysis and International Prostate symptom score were assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and 3 and 6 months from treatment completion. IPSS was analyzed using a mixed-model repeated measures analysis. A Chi-square test was used to compare urinalysis results at each interval., Results: The pathologic disease stage after restaging transurethral resection and before treatment was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). There was no increase in reported urinary bother throughout treatment. Quality of life measurements demonstrated no change in subjective burden. On urinalysis, we did not observe significant differences at 3 months compared to baseline evaluation. At 12 months, the DFS and OS were 69.23% and 92.31%, respectively. At 24 months, the DFS and OS were 38.46% and 92.31%, respectively., Conclusions: Treatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response data is promising and await confirmation in the phase III study (Keynote 676)., Competing Interests: Disclosure Southern Illinois University School of Medicine received research funding from MERCK and Co., Inc. for this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Medical personnel often experience stress when responding to a medical emergency. A known stress-response is a measurable reduction in heart rate variability. It is currently unknown if crisis simulation can elicit the same stress response as real clinical emergencies. We aim to compare heart rate variability changes amongst medical trainees during simulated and real medical emergencies. We performed a single center prospective observational study, enrolling 19 resident physicians. Heart rate variability was measured in real time, using a 2-lead heart rate monitor (Bodyguard 2, Firstbeat Technologies Ltd) worn during 24 h critical care call shifts. Data was collected at baseline, during crisis simulation and when responding to medical emergencies. 57 observations were made to compare participant's heart rate variability. Each heart rate variability metric changed as expected in response to stress. Statistically significant differences were observed between baseline and simulated medical emergencies in Standard Deviation of the N-N interval (SDNN), Root mean square standard deviation of the N-N interval (RMSSD), Percentage of successive R-R intervals that differ by more than 50 ms (PNN50), Low Frequency (LF) and Low Frequency: High Frequency ratios (LF:HF). No statistically significant differences between simulated and real medical emergencies were identified in any heart rate variability metrics. We have shown using objective results, that simulation can elicit the same psychophysiological response as actual medical emergencies. Therefore, simulation may represent a reasonable way to practice not only essential skills in a safe environment but has the additional benefit of creating a realistic, physiological response in medical trainees., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Antibody complementarity determining regions (CDRs) participate in antigen recognition, but not all participate equally in antigen binding. Here we describe a technique for discovering strong, specific binding partners to defined motifs within the CDRs of chimeric, engineered antibodies using affinity selection and counter-selection of epitopes displayed on bacteriophage MS2-based virus-like particles (VLPs). As an example, we show how this technique can be used to identify families of VLPs that interact with antibodies displaying the CDRs encoded by the germline precursor of a broadly neutralizing monoclonal antibody against HIV-1., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To establish a consensus for initial evaluation and follow-up of patients on active surveillance (AS) for T1 renal masses (T1RM)., Methods: A modified Delphi method was used to gather information about AS of T1RM, with a focus on patient selection, timing/type of imaging modality, and triggers for intervention. A consensus panel of Michigan Urological Surgery Improvement Collaborative-affiliated urologists who routinely manage renal masses was formed. Areas of consensus (defined >80% agreement) about T1RM AS were established iteratively via 3 rounds of online questionnaires., Results: Twenty-six Michigan Urological Surgery Improvement Collaborative urologists formed the panel. Consensus was achieved for 321/587 scenarios (54.7%) administered through 124 questions. Life expectancy, age, comorbidity, and renal function were most important for patient selection, with life expectancy ranking first. All tumors <3 cm and all patients with life expectancy <1 year were considered appropriate for AS. Appropriateness also increased with elevated perioperative risk, increasing tumor complexity, and/or declining renal function. Consensus was for multiphasic axial imaging initially (contrast CT for GFR >60 or MRI for GFR >30) with first repeat imaging at 3-6 months and subsequent imaging timing determined by tumor size. Consensus was for chest imaging for tumors >3 cm initially and >5 cm at follow up. Renal biopsy was not felt to be a requirement for entering AS, but useful in several scenarios. Consensus indicated rapid tumor growth as an appropriate trigger for intervention., Conclusion: Our consensus panel was able to achieve areas of consensus to help define a clinically useful and specific roadmap for AS of T1RM and areas for further discussion where consensus was not achieved., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To evaluate the risk of postoperative hernia following different approaches of single-port robot-assisted radical prostatectomy (SP-RARP)., Methods: A retrospective review was performed on patients who underwent SP-RARP between February 2019 and December 2022. Demographic and clinical information was collected from the multi-institutional, prospectively-maintained Single-Port Advanced Research Consortium (SPARC) database. Data were analyzed using IBM Statistical Packaging for Social Sciences (SPSS) version 29.0 with descriptive statistics as presented., Results: A total of 1103 patients were identified, consisting of 244 (22.1%), 712 (64.6%), and 147 (13.3%) cases performed via transperitoneal, extraperitoneal (EP), and transvesical (TV) approaches, respectively. During a median follow-up time of 11 months (interquartile range 5.7-17.1 months), only two cases of incisional hernia were reported. Both cases occurred following transperitoneal SP-RARP with one patient requiring surgical repair. There remains no evidence of postoperative hernia following EP and TV SP-RARP at the completion of our review., Conclusion: SP-RARP was associated with low risk for postoperative hernia. The risk was lower following TV and EP SP-RARP where the peritoneum is preserved., Competing Interests: Declaration of Competing Interest Michael Stifelman: Consultant for VTI, performs educational activities for Ethicon, and is on the Scientific Advisory Board for Intuitive. Mutahar Ahmed: Consultant/Advisor at Intuitive, Aminox/Clarix, and VTI. Simone Crivellaro: Consultant for Intuitive. Jihad H. Kaouk: Speaker for Intuitive and Consultant for VTI. All the other authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In a phase I dose escalation and safety study (NCT02555397), a replication-competent oncolytic adenovirus expressing yCD, TK and hIL-12 (Ad5-yCD/mutTKSR39rep-hIL-12) was administered in 15 subjects with localized recurrent prostate cancer (T1c-T2) at increasing doses (1 × 1010, to 1 × 1012 viral particles) followed by 7-day treatment of 5-fluorocytosine (5-FC) and valganciclovir (vGCV). The primary endpoint was toxicity through day 30 while the secondary and exploratory endpoints were quantitation of IL-12, IFNγ, CXCL10 and peripheral blood mononuclear cells (PBMC). The study maximum tolerated dose (MTD) was not reached indicating 1012 viral particles was safe. Total 115 adverse events were observed, most of which (92%) were grade 1/2 that did not require any treatment. Adenoviral DNA was detected only in two patients. Increase in IL-12, IFNγ, and CXCL10 was observed in 57%, 93%, and 79% patients, respectively. Serum cytokines demonstrated viral dose dependency, especially apparent in the highest-dose cohorts. PBMC analysis revealed immune system activation after gene therapy in cohort 5. The PSA doubling time (PSADT) pre and post treatment has a median of 1.55 years vs 1.18 years. This trial confirmed that replication-competent Ad5-IL-12 adenovirus (Ad5-yCD/mutTKSR39rep-hIL-12) was well tolerated when administered locally to prostate tumors., Competing Interests: KNB and SOF hold a patent “Methods and Composition for Cancer Therapy Using a Novel Adenovirus” (#7,815,902 B2) for an adenovirus like the one used in this study, BM: Research support from Varian, ViewRay and Philips (no direct conflict), FS: Varian Medical Systems, Inc- Honorarium and travel reimbursement for lectures and talks, Varian Noona- Medical Advisory Board member- receive honorarium, CW: Clara Hwang: Stock holdings in Johnson and Johnson; research funding to institution from Merck, Bausch Health, Genentech, Bayer, and AstraZeneca, consultant fees from Tempus, Genzyme, and EMD Sorono, speaking fees from OncLive/MJH Life Sciences, travel fees from Merck, all outside the submitted work. SN: The work presented was partly supported by NIH-R21-CA252010 (co-PIs: MD Green and S Nyati). SB: The work presented was partly supported by NIH-R01-CA218596 (co-PIs: JR Ewing and S Brown). HA: participate in research activities with Novartis, Merck, Astra-Zeneca, Grail, and Pfizer. Receives consultation Honorarium from Astra-Zeneca, Seagen, Pfizer, OBI, cardinal health and Regeneron. HS, MA, JP, PL: no COI. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Nyati et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study investigated the effect of induced attitude ambivalence on the relationship between the personalized norm feedback (PNF) intervention and heavy drinking by college students. College students consume more alcohol and engage in binge drinking at greater rates than most segments of the population. Given the harmful effects of binge drinking and other risky drinking behaviors, it is important to implement effective interventions to reduce alcohol consumption. PNF is an effective intervention for reducing heavy drinking where students compare their drinking and perceptions of normative drinking with actual drinking norms. Past research suggests that inducing ambivalence makes norms a stronger predictor of behavior. We hypothesized that induced attitudinal ambivalence before the PNF intervention would lower intentions to consume alcohol. This study was a one-way design with ambivalence about drinking (high vs low) as the independent variable and intentions to drink alcohol in the future as the dependent variable ( N  = 338, 76 % female, M age  = 19.76, SD  = 2.61). All participants received the PNF intervention after the ambivalence manipulation and before the intentions to drink alcohol measure. Results from the generalized linear model revealed a significant effect for ambivalence, p  =.028. As predicted, participants in the high ambivalence condition intended to drink fewer drinks in one sitting in the future compared to those in the low ambivalence condition. These results suggest that ambivalence may play an important role in make PNF interventions more effective, though more research is necessary to untangle the relationship between ambivalence and norms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Ltd.)

Introduction: Healthcare teams include both leaders and followers, with followers making up the majority of the healthcare team. There are five followership styles which have been described by Kelly (1992) based on critical thinking and active engagement. We aim to explore if a relationship exists between followership style and burnout, and also with job satisfaction of followers within the critical care setting. Additionally, we aim to quantify the distribution of followership types amongst followers within the critical care setting., Methods: Participants were recruited in person at random to participate in a single centered, cross sectional, four-part survey to determine their followership type (Kelly followership type), burnout (Maslach Burnout Inventory) and job satisfaction (Brayfiled-Rothe Survey and Work and Meaning Inventory). Correlations between followership type and burnout as well as followership type and job satisfaction were then determined., Results: A total of 64 participants (27 residents and 37 critical care nurses) took part in the study. There was a weak-moderate correlation between independent critical thinking and personal accomplishment (R = 0.297), and moderate correlation to meaningful work (R = 0.390), and job satisfaction (R = -0.300). Active engagement was moderately correlated with personal accomplishment (R = 0.302), meaningful work (R = 0.448) and job satisfaction (R = -0.418). Neither independent critical thinking nor active engagement showed significant correlation with depersonalization and emotional exhaustion subscales. Most participants were characterized into effective/exemplary followership type with no statistically significant differences between nurses and residents., Conclusion: This research shows that by creating an environment which promotes critical thinking and active engagement, nurses and residents may display less burnout, and enhanced job satisfaction., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To aid in the diagnosis and treatment of patients with metastatic tumor seeding, an exceedingly rare phenomenon following minimally invasive urological surgery, additional case reports are needed., Materials and Methods: We report our experience with patients determined to have peritoneal carcinomatosis following robotic-assisted radical prostatectomy (RARP) and provide a descriptive summary of these unique cases., Results: Five cases of peritoneal carcinomatosis were identified, all of which occurred relatively late-between 8 and 13 years-following RARP. Four of the 5 cases had T3 disease at the time of prostatectomy. 68 Ga-PSMA PET identified peritoneal carcinomatosis in 3 of 5 cases., Conclusion: Certain clinical factors, such as advanced pathologic stage at the time of prostatectomy, may predict risk for carcinomatosis following RARP. Additionally, next-generation imaging modalities, such as PSMA PET, may aid in identifying these metastases and are likely to identify increasing numbers of these patients as next-generation imaging becomes more widely available. Continued documentation and classification of this atypical presentation are needed to improve our understanding and management of this phenomenon., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Objective: Request for refills of opioids is one of the indicators of possible misuse. We aimed to investigate racial variations in request for refills of opioids after hospital discharge from robotic-assisted laparoscopic radical prostatectomy (RALP)., Methods: We conducted a retrospective study of a contemporary cohort of patients treated with RALP for prostate cancer and post-operative standardized pain control that employed nonopioid medications. Patients' request for refills of opioids (within 30 days) after discharge was examined, accounting for race, age, pain control after surgery, alcohol intake, marijuana consumption, pre-existing behavioral health diagnoses, and pre-existing chronic pain disorders using multivariate analysis. p-Value of < 0.05 was considered significant., Results: We included a total of 282 adult patients in this study. African Americans (AA) patients comprised 24.5 percent of our post-prostatectomy individuals. Of the total cohort, 94.3 percent of patients reported adequate pain control in the hospital after surgery, and only 5.7 percent requested refills of opioid medications after discharge. No racial variations in request of refills were identified. Only pre-existing chronic pain disorders were found to be a significant predictor of requesting an opioid medication refill for pain control after discharge from the hospital., Conclusions: A combination of minimally invasive surgery and nonopioid heavy pain management leads to low level of post-hospital discharge request for refills of opioid medication in patients treated with RALP across racial groups. Awareness and better control of chronic pain perioperatively are needed to ensure better postdischarge pain control.

Objective: High-risk (HR) prostate cancer (CaP) patients are at greatest risk for occult metastases and disease progression. Radical prostatectomy (RP) provides benefit, but remains of unknown oncologic value compared with other options. We investigated outcomes of RP for HR, very-high-risk (VHR), or metastatic CaP., Methods: Included are 1,635 patients undergoing RP between January 2012 and December 2018 (prior to widespread availability of CaP-specific PET imaging). VHR CaP was defined as having ≥2HR features, >4cores of biopsy Gleason ≥4+4, or primary Gleason pattern 5. Metastatic CaP was defined by radiographic evidence of N1 and/or M1 CaP and grouped as cN1M any and cN0M1. Pre-treatment, perioperative, and early oncologic data were compared. Patient/tumor characteristics were compared according to risk groups using Chi-squared and Wilcoxon rank-sum tests. Kaplan-Meier analysis of cancer progression and multivariable analyses were performed., Results: Length of stay >2days and readmission following RP was 10.8% and 5.5% for patients with HR or higher CaP. Median time to progression was 3.9 months (IQR:1.6-13.9), and 2-year progression-free probability was 67% for HR, 53% for VHR, 51% for cN1M any , and 58% for cN0M1. In multivariable analysis, VHR (hazard ratio:1.70; P < 0.0001) and cN1M any (1.96, P < 0.0001) were highly significant predictors of progression, while cN0M1 was not (P = 0.54), compared with non-metastatic HR CaP. Limitations include selection biases and imprecision of imaging methodologies., Conclusions: Most patients with HR or higher CaP remain progression-free 2 years after RP, with acceptable perioperative outcomes. Progression-free survival was similar in cN1 and VHR patients, better with non-metastatic HR CaP, and between these for cN0M1 patients indicating the imprecise clinical staging occurring with conventional imaging modalities alone., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To examine the ability of machine learning methods to predict upgrading of Gleason score on confirmatory magnetic resonance imaging-guided targeted biopsy (MRI-TB) of the prostate in candidates for active surveillance., Subjects and Methods: Our database included 592 patients who received prostate multiparametric magnetic resonance imaging in the evaluation for active surveillance. Upgrading to significant prostate cancer on MRI-TB was defined as upgrading to G 3+4 (definition 1 - DF1) and 4+3 (DF2). Machine learning classifiers were applied on both classification problems DF1 and DF2., Results: Univariate analysis showed that older age and the number of positive cores on pre-MRI-TB were positively correlated with upgrading by DF1 (P-value ≤ 0.05). Upgrading by DF2 was positively correlated with age and the number of positive cores and negatively correlated with body mass index. For upgrading prediction, the AdaBoost model was highly predictive of upgrading by DF1 (AUC 0.952), while for prediction of upgrading by DF2, the Random Forest model had a lower but excellent prediction performance (AUC 0.947)., Conclusion: We show that machine learning has the potential to be integrated in future diagnostic assessments for patients eligible for AS. Training our models on larger multi-institutional databases is needed to confirm our results and improve the accuracy of these models' prediction., Competing Interests: Conflicts of interest The authors have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Radical prostatectomy (RP) is the most common definitive treatment for men with intermediate-risk prostate cancer and is frequently complicated by erectile dysfunction., Objective: To develop and validate models to predict 12- and 24-month post-RP sexual function., Design Setting and Participants: Using Michigan Urological Surgery Improvement Collaborative (MUSIC) registry data from 2016 to 2021, we developed dynamic, multivariate, random-forest models to predict sexual function recovery following RP. Model factors (established a priori) included baseline patient characteristics and repeated assessments of sexual satisfaction, and Expanded Prostate Cancer Index Composite 26 (EPIC-26) overall scores and sexual domain questions., Outcome Measurements and Statistical Analysis: We evaluated three outcomes related to sexual function: (1) the EPIC-26 sexual domain score (range 0-100); (2) the EPIC-26 sexual domain score dichotomized at ≥73 for "good" function; and (3) a dichotomized variable for erection quality at 12 and 24 months after RP. A gradient-boosting decision tree was used for the prediction models, which combines many decision trees into a single model. We evaluated the performance of our model using the root mean squared error (RMSE) and mean absolute error (MAE) for the EPIC-26 score as a continuous variable, and the area under the receiver operating characteristic curve (AUC) for the dichotomized EPIC-26 sexual domain score (SDS) and erection quality. All analyses were conducted using R v3.6.3., Results and Limitations: We identified 3983 patients at 12 months and 2494 patients at 24 months who were randomized to the derivation cohort at 12 and 24 months, respectively. Using baseline information only, our model predicted the 12-month EPIC-26 SDS with RMSE of 24 and MAE of 20. The AUC for predicting EPIC-26 SDS ≥73 (a previously published threshold) was 0.82. Our model predicted 24-month EPIC-26 SDS with RMSE of 26 and MAE of 21, and AUC for SDS ≥73 of 0.81. Inclusion of post-RP data improved the AUC to 0.91 and 0.94 at 12 and 24 months, respectively. A web tool has also been developed and is available at https://ml4lhs.shinyapps.io/askmusic&#95;prostate&#95;pro/., Conclusions: Our model provides a valid way to predict sexual function recovery at 12 and 24 months after RP. With this dynamic, multivariate (multiple outcomes) model, accurate predictions can be made for decision-making and during survivorship, which may reduce decision regret., Patient Summary: Our prediction model allows patients considering prostate cancer surgery to understand their probability before and after surgery of recovering their erectile function and may reduce decision regret., (© 2022 The Author(s).)

Objective: The objective of the study is to identify the rate of significant prostate cancer (PCa) detection in PI-RADS3 lesions in AA patients stratified by PSAD threshold of < 0.15 vs. ≥ 0.15 ng/ml 2  and lesion diameter of < 1 cm vs ≥ 1 cm., Methods: We analyzed our institutional database of MRI-TB to identify the rate of significant prostate cancer (PCa) detection in PI-RADS3 lesions in AA patients stratified by PSAD threshold of < 0.15 vs. ≥ 0.15 ng/ml 2  and lesion diameter of < 1 cm vs ≥ 1 cm. Significant prostate cancer was defined as Gleason grade group 2 or higher on MRI-TB of the PI-RADS 3 lesion., Results: Of 768 patients included in the database, 211 (27.5%) patients identified themselves as AAs. Mean age of AA patients was 63 years and mean PSAD was 0.21. Sixty nine (32.7%) AA patients were found to have PI-RADS 3 lesions. Mean PSAD of AA patients with PI-RADS 3 lesions was 0.21 ng/ml 2  as well. Fifty percent of AA patients with PI-RADS 3 lesions had PSAD ≥ 0.15 ng/ml 2 . Significant PCa detection rate for AA patients with PI-RADS 3 lesions was 9% for PSAD of ≥ 0.15 vs. 0.03% percent for AA patients with PSAD < 0.15 ng/ml 2  (OR 7.056, CI 1.017-167.9, P = 0.04). Stratification by lesion diameter (< 1 cm vs. > 1 cm) resulted in missing 0% of significant PCa when only AA patients with PSAD ≥ 0.15 ng/ml 2 and lesion diameter ≥ 1 cm received MRI-TB., Conclusions: We report on the performance of a reported PSAD density threshold in detecting significant PCa in one of the largest series of AA patients receiving MRI-TB of the prostate. Our results have direct clinical implications when counseling AA patients with PI-RADS 3 lesion on whether they should undergo MRI-TB of such lesions., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: To analyze the impact of neoadjuvant chemotherapy on survival and recurrence patterns in muscle-invasive bladder cancer after robot-assisted radical cystectomy., Materials and Methods: The International Robotic Cystectomy Consortium database was reviewed to identify patients who underwent robot-assisted radical cystectomy for muscle-invasive bladder cancer between 2002 and 2019. Survival outcomes, response rates, and recurrence patterns were compared between patients who received neoadjuvant chemotherapy and those who did not. Survival distributions were estimated using Kaplan-Meier analyses and compared using the log-rank test., Results: A total of 1370 patients with muscle-invasive bladder cancer were identified, of whom 353 (26%) received neoadjuvant chemotherapy. After a median follow-up of 27 months, neoadjuvant chemotherapy recipients had higher 3-year overall survival (74% vs 57%; log-rank P < 0.01), 3-year cancer-specific survival (83% vs 73%; log-rank P = 0.03), and 3-year relapse-free survival (64% vs 48%; log-rank P < 0.01). Neoadjuvant chemotherapy was a predictor of higher overall survival, cancer-specific survival, and relapse-free survival in univariate but not multivariate analysis. Pathological downstaging (46% vs 23%; P < 0.01), complete responses (24% vs 8%; P < 0.01), and margin negativity (95% vs 91%; P < 0.01) at robot-assisted radical cystectomy were more common in the neoadjuvant chemotherapy group. Neoadjuvant chemotherapy recipients had lower distant (15% vs 22%; P < 0.01) but similar locoregional (12% vs 13%; P = 0.93) recurrence rates., Conclusions: In this analysis from a large international database, patients with muscle-invasive bladder cancer who received neoadjuvant chemotherapy before robot-assisted radical cystectomy had higher rates of survival, pathological downstaging, and margin-negative resections. They also experienced fewer distant recurrences., (© 2021 The Japanese Urological Association.)

Importance: Of patient-reported outcomes for individuals undergoing radical prostatectomy, sexual function outcomes are among the most reported and the most detrimental to quality of life. Understanding variations at the patient and surgeon level may inform collaborative quality improvement., Objective: To describe patient- and surgeon-level sexual function outcomes for patients undergoing radical prostatectomy in the Michigan Urological Surgery Improvement Collaborative (MUSIC) and to examine the correlation between surgeon case volume and sexual function outcomes., Design, Setting, and Participants: This is a prospective cohort study using the MUSIC registry and patient-reported sexual function outcome data. Patient- and surgeon-level variation in sexual function outcomes were examined among patients undergoing radical prostatectomy from May 2014 to August 2019. Sexual function outcome data were collected using validated questionnaires, which were completed before surgery and at 3, 6, 12, and 24 months' follow-up following surgery. All participants were male. Race and ethnicity data were self-reported and were included to examine potential variation in outcomes by race and/or ethnicity. Data were analyzed from January 2021 to March 2021., Main Outcomes and Measures: There were 4 outcomes in this study, including the 26-item Expanded Prostate Cancer Index Composite (EPIC-26) sexual function scores at 3, 6, 12, and 24 months' follow-up; patient-level sexual function recovery at 12- and 24-month follow-up; surgeon-level variation in sexual function outcomes at 12- and 24-month follow-up; and correlation between surgeon case volume and sexual function outcomes., Results: A total of 1426 male patients met inclusion criteria for this study. The median (IQR) age was 64 (58-68) years. A total of 115 participants (8%) were Black, 1197 (84%) were White, 25 (2%) were of another race or ethnicity (consolidated owing to low numbers), and 89 (6%) were of unknown race or ethnicity. Among patients undergoing bilateral nerve-sparing radical prostatectomy, mean (SD) EPIC-26 sexual function scores at 12- and 24-month follow-up (12 months, 39 [28]; 24 months, 63 [29]) did not return to baseline levels. There was wide variation in EPIC-26 sexual function scores at both 12-month follow-up (range, 23-69; P < .001) and 24-month follow-up (range, 27-64; P < .001). Similar variations were found in EPIC-26 sexual function scores and recovery of sexual function by surgeon. Recovery rates ranged from 0% to 40% of patients at 12-month follow-up (18 surgeons; P < .001) and 3% to 44% of patients at 24-month follow-up (12 surgeons; P < .001). Surgeon case volume and sexual function outcomes were not significantly correlated. On multivariable analysis, the following variables were associated with better recovery at 24-month follow-up: younger age (P < .001), lower baseline EPIC-26 sexual function score (P < .001), lower Gleason score (P = .05), and nonobesity (P = .03)., Conclusions and Relevance: In this study, there was significant patient- and surgeon-level variation in sexual function recovery over 2 years following radical prostatectomy. Variation in surgeon-level sexual function outcomes presents an opportunity and model for surgical collaborative quality improvement.

Introduction: Contrast-induced acute kidney injury (CI-AKI) is a major clinical complication of percutaneous cardiovascular procedures requiring iodinated contrast. Despite its relative frequency, practicing physicians are unlikely to identify or treat this condition., Methods: In a 2-round clinical trial of simulated patients, we examined the clinical utility of a urine-based assay that measures liver-type fatty acid-binding protein (L-FABP), a novel marker of CI-AKI. We sought to determine if interventional cardiologists' ability to diagnose and treat potential CI-AKI improved using the biomarker assay for 3 different patient types: pre-procedure, peri-procedure, and post-procedure patients., Results: 154 participating cardiologists were randomly divided into either control or intervention. At baseline, we found no difference in the demographics or how they identified and treated potential complications of AKI, with both groups providing less than half the necessary care to their patients (46.4% for control vs. 47.6% for intervention, p = 0.250). The introduction of L-FABP into patient care resulted in a statistically significant improvement of 4.6% (p = 0.001). Compared to controls, physicians receiving L-FABP results were 2.9 times more likely to correctly identify their patients' risk for AKI (95% CI 2.1-4.0) and were more than twice as likely to treat for AKI by providing volume expansion and withholding nephrotoxic medications. We found the greatest clinical utility in the pre-procedure and peri-procedure settings but limited value in the post-procedure setting., Conclusion: This study suggests L-FABP as a clinical marker for assessing the risk of potential CI-AKI, has clinical utility, and can lead to more accurate diagnosis and treatment., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Unwarranted variability in clinical practice is a challenging problem in practice today, leading to poor outcomes for patients and low-value care for providers, payers, and patients., Objective: In this study, we introduced a novel tool, QualityIQ, and determined the extent to which it helps primary care physicians to align care decisions with the latest best practices included in the Merit-Based Incentive Payment System (MIPS)., Methods: We developed the fully automated QualityIQ patient simulation platform with real-time evidence-based feedback and gamified peer benchmarking. Each case included workup, diagnosis, and management questions with explicit evidence-based scoring criteria. We recruited practicing primary care physicians across the United States into the study via the web and conducted a cross-sectional study of clinical decisions among a national sample of primary care physicians, randomized to continuing medical education (CME) and non-CME study arms. Physicians "cared" for 8 weekly cases that covered typical primary care scenarios. We measured participation rates, changes in quality scores (including MIPS scores), self-reported practice change, and physician satisfaction with the tool. The primary outcomes for this study were evidence-based care scores within each case, adherence to MIPS measures, and variation in clinical decision-making among the primary care providers caring for the same patient., Results: We found strong, scalable engagement with the tool, with 75% of participants (61 non-CME and 59 CME) completing at least 6 of 8 total cases. We saw significant improvement in evidence-based clinical decisions across multiple conditions, such as diabetes (+8.3%, P<.001) and osteoarthritis (+7.6%, P=.003) and with MIPS-related quality measures, such as diabetes eye examinations (+22%, P<.001), depression screening (+11%, P<.001), and asthma medications (+33%, P<.001). Although the CME availability did not increase enrollment in the study, participants who were offered CME credits were more likely to complete at least 6 of the 8 cases., Conclusions: Although CME availability did not prove to be important, the short, clinically detailed case simulations with real-time feedback and gamified peer benchmarking did lead to significant improvements in evidence-based care decisions among all practicing physicians., Trial Registration: ClinicalTrials.gov NCT03800901; https://clinicaltrials.gov/ct2/show/NCT03800901., (©Trever Burgon, Linda Casebeer, Holly Aasen, Czarlota Valdenor, Diana Tamondong-Lachica, Enrico de Belen, David Paculdo, John Peabody. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 23.12.2021.)

Objectives: We conducted the first phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab in patients with high-grade non-muscle-invasive bladder cancer (HGNMIBC) who had persistent or recurrent disease after prior intravesical therapy with BCG. The primary endpoint was the safety of this combination. The secondary endpoint was clinical activity at three months following BCG treatment., Methods: Eighteen patients were consented for the study, five of which were screen failures. Six doses of pembrolizumab were administered every 3 weeks over 16 weeks concurrently with six weekly doses of BCG beginning at week 7. Patient safety was evaluated from the time of consent through 30 days following pembrolizumab treatment. Clinical activity was determined using cystoscopy and biopsy of suspicious lesions., Results: Treatment-related adverse events included one grade 4 adverse event (AEs) (adrenal insufficiency). There were nine grade 3 AEs (chest discomfort, pulmonary embolism, arthritis, wrist edema, injection site reaction, bilateral wrist pain, cardiomyopathy, hypokalemia, urinary tract infection). There were 49 grade 1 and 30 grade 2 AEs (88% of AEs). Eleven patients finished the treatment, and two patients died during the study. Of 13 patients treated, nine patients (69%) had no evidence of disease at 3 months following BCG treatment., Conclusions: We report for the first time that combining BCG and pembrolizumab in treating HGNMIBC is safe allowing complete treatment of most patients. A phase III trial has opened to test the efficacy of this combination in HGNMIBC (KEYNOTE-676)., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality. Much of the disease burden comes from exacerbations requiring hospitalization. Unwarranted care variation and divergence from evidence-based COPD management guidelines among hospitalists is a leading driver of the poor outcomes and excess costs associated with COPD-related hospitalizations. We engaged with Novant Health hospitalists to determine if measurement and feedback using fixed-choice simulated patients improves evidence-based care delivery and reduces costs. We created a series of gamified acute-care COPD case simulations with real-time feedback over 16 weeks then performed a year-over-year analytic comparison of the cost, length of stay (LOS), and revisits over the six months prior to the introduction of the simulated patients, the four months while caring for the simulated patients, and the six months after. In total, 245 hospitalists from 15 facilities at Novant Health participated. At baseline, the overall quality-of-care was measured as 58.4% + 12.3%, with providers correctly identifying COPD exacerbation in 92.4% of cases but only identifying the grade and group in 61.9% and 49.5% of cases, respectively. By the study end, the quality-of-care had improved 10.5% ( p < 0.001), including improvements in identifying the grade (+9.7%, p = 0.044) and group (+8.4%, p = 0.098). These improvements correlated with changes in real-world performance data, including a 19% reduction in COPD-related pharmacy costs. Overall, the annualized impact of COPD improvements led to 233 fewer inpatient days, 371 fewer revisit days, and inpatient savings totaling nearly $1 million. Engaging practicing providers with patient simulation-based serial measurements and gamified evidence-based feedback potentially reduces inpatient costs while simultaneously reducing patient LOS and revisit rates.

The ligand-binding surface of the B cell receptor (BCR) is formed by encoded and non-encoded antigen complementarity determining regions (CDRs). Genetically reproducible or 'public' antibodies can arise when the encoded CDRs play deterministic roles in antigen recognition, notably within human broadly neutralizing antibodies against HIV and influenza virus. We sought to exploit this by engineering virus-like-particle (VLP) vaccines that harbor multivalent affinity against gene-encoded moieties of the BCR antigen binding site. As proof of concept, we deployed a library of RNA bacteriophage VLPs displaying random peptides to identify a multivalent antigen that selectively triggered germline BCRs using the human V H gene IGVH1-2*02. This VLP selectively primed IGHV1-2*02 BCRs that were present within a highly diversified germline antibody repertoire within humanized mice. Our approach thus provides methodology to generate antigens that engage specific BCR configurations of interest, in the absence of structure-based information., Competing Interests: BC and DP have an equity stake in Flagship Laboratories 72. RMB, DR and NL were employed by Bristol Myers Squibb. 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 © 2021 Ronsard, Yousif, Peabody, Okonkwo, Devant, Mogus, Barnes, Rohrer, Lonberg, Peabody, Chackerian and Lingwood.)

Contrast-induced acute kidney injury (CI-AKI) occurs in up to 10% of cardiac catheterizations and coronary interventions, resulting in increased morbidity, mortality, and cost. One main reason for these complications and costs is under-recognition of CI-AKI risk and under-treatment of patients with impaired renal status. 157 interventional cardiologists each cared for three simulated patients with common conditions requiring intravascular contrast media in three typical settings: pre-procedurally, during the procedure, and post-procedure. We evaluated their ability to assess the risk of developing CI-AKI, make the diagnosis, and treat CI-AKI, including proper volume expansion and withholding nephrotoxic medications. Overall, the quality-of-care scores averaged 46.0% ± 10.5, varying between 18% to 78%. The diagnostic scores for accurately assessing risk of CI-AKI were low at 57.1% ± 21.2% and the accuracy of diagnosis pre-existing chronic kidney disease was 50.2%. Poor diagnostic accuracy led to poor treatment: proper volume expansion done in only 30.7% of cases, in-hospital repeat creatinine evaluation performed in 32.1%, and avoiding nephrotoxic medications occurred in 14.2%. While volume expansion was relatively similar across the three settings (P = 0.287), the cardiologists were less likely to discontinue nephrotoxic medications in pre-procedurally (9.7%) compared to the other settings (27.0%), and to order in-hospital creatinine testing in peri-procedurally (18.8%) compared to post-procedure (57.8%) (P < 0.05 for both). The overall care of patients at risk for contrast-induced acute kidney injury varied widely and showed room for improvement. Improving care for this condition will require greater awareness by cardiologists and better diagnostic tools to guide them., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Virus-like particles from a variety of RNA bacteriophages have turned out to be useful platforms for delivery of vaccine antigens in a highly immunogenic format. Here we update the current state of development of RNA phage VLPs as platforms for presentation of diverse antigens by genetic, enzymatic, and chemical display methods.

Objective: To assess the prognostic ability of lymphovascular invasion (LVI) as a predictor of overall survival (OS)., Materials and Methods: We included 126,682 prostate cancer (CaP) cM0 patients who underwent radical prostatectomy with lymph node dissection between 2010 and 2015, within the National Cancer Database. Patients who received androgen deprivation therapy were included. Patients were divided into four sub-cohorts based on LVI and lymph node invasion (LNI) status: pL 0 N 0 , pL 1 N 0 , pL 0 N 1 , and pL 1 N 1 . Kaplan-Meier curves estimated OS and Cox-regression analysis tested the relationship between LVI and OS., Results: Median (IQR) age and PSA at diagnosis were 62 (57-66) years and 5.7 (4.5-8.9) ng/ml, respectively. Most patients had pT2 stage (68.5%), and pathological Gleason 3+4 (46.7%). 10.0% and 4.0% patients had LVI and LNI, respectively. Median follow-up was 42 months (27-58). At 5-years, OS was 96.5% in pL 0 N 0 patients vs 93.1% pL 1 N 0 patients vs 93.3% in pL 0 N 1 patients vs 86.6% pL 1 N 1 patients. LVI was an independent predictor of OS (hazard ratio [HR]:1.28). LVI showed interaction with LNI, as LVI was associated with a higher overall-mortality in patients with LNI (HR:1.66), than in patients without LNI (HR:1.22). (all P<0.0001) CONCLUSIONS: Our report highlights the detrimental impact of LVI on OS. Patients with LVI alone fared similarly to patients with LNI alone. Patients with both LVI and LNI had worse OS than those with only LVI or LNI, implying a synergetic detrimental interaction. Our findings demonstrate an important utility that LVI can provide in deciding patients' prognoses., Competing Interests: Declaration of Competing Interest No conflicts of interest to disclose, (Copyright © 2021. Published by Elsevier Inc.)

Drug-drug interactions (DDIs) are a serious problem in the healthcare system, leading to excess healthcare utilization and costs. We conducted a second prospective randomized, controlled trial to further establish the real-world clinical utility of a novel assay that objectively identifies potentially serious DDIs in real-world patients. Re-recruiting primary care physicians (PCPs) from our first randomized, controlled, simulated-patients study on DDIs, we experimentally introduced a definitive, urine-based mass spectrometry test intervention that the physicians could use when caring for their eligible patients. Patients were eligible if taking four or more prescription medications or suspected of taking other non-prescribed substances with potential medication interactions. The primary outcome was whether DDI testing changed clinical care. We explored a secondary outcome to see if the change in practice improved symptoms in patients with potential DDIs. A total of 169 control and 162 intervention patients were enrolled in the study, and their medical records were abstracted. In real-world patients, intervention physicians identified and/or treated a DDI at 3.0x the rate in their patient population compared to controls (21.6% vs. 7.1%, p < 0.001). Intervention physicians were more likely to discontinue or adjust the interacting agent compared to controls (62.9% vs. 8.3%, p = 0.001), and patient-reported symptoms also significantly declined (29.6% vs. 20.1%, p = 0.045). These results were nearly identical to concurrent measurements that used simulated patients, wherein intervention was more likely to both make a DDI diagnosis (56.3% vs. 21.6%, p < 0.001) and stop the interacting medications (58.3% versus 26.6%, p < 0.001). Bringing a new diagnostic test to market, particularly for an under-recognized clinical problem, requires robust data on both clinical validity and clinical utility. The results of this follow-up study showed that the use of DDI testing in real-world patients significantly improved (1) primary care patient management of drug interactions and (2) patient outcomes.

Importance: Understanding variation in patient-reported outcomes following radical prostatectomy may inform efforts to reduce morbidity after this procedure., Objective: To describe patient-reported urinary outcomes following radical prostatectomy in the diverse practice settings of a statewide quality improvement program and to explore whether surgeon-specific variations in observed outcomes persist after accounting for patient-level factors., Design, Setting, and Participants: This prospective population-based cohort study included 4582 men in the Michigan Urological Surgery Improvement Collaborative who underwent radical prostatectomy as primary management of localized prostate cancer between April 2014 and July 2018 and who agreed to complete validated questionnaires prior to surgery and at 3, 6, and 12 months after surgery. Data were analyzed from 2019 to June 2019., Exposures: Radical prostatectomy., Main Outcomes and Measures: Patient- and surgeon-level analyses of patient-reported urinary function 3 months after radical prostatectomy. Outcomes were measured using validated questionnaires with results standardized using previously published methods. Urinary function survey scores are reported on a scale from 0 to 100 with good function established as a score of 74 or higher., Results: For the 4582 men undergoing radical prostatectomy within the Michigan Urological Surgery Improvement Collaborative who agreed to complete surveys, mean (SD) age was 63.3 (7.1) years. Survey response rates varied: 3791 of 4582 (83%) responded at baseline, 3282 of 4137 (79%) at 3 months, 2975 of 3770 (79%) at 6 months, and 2213 of 2882 (77%) at 12 months. Mean (SD) urinary function scores were 88.5 (14.3) at baseline, 53.6 (27.5) at 3 months, 68.0 (25.1) at 6 months, and 73.7 (23.0) at 12 months. Regression analysis demonstrated that older age, lower baseline urinary function score, body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 or higher, clinical stage T2 or higher, and lack of bilateral nerve-sparing surgery were associated with a lower probability of reporting good urinary function 3 months after surgery. When evaluating patients with good baseline function, the rate at which individual surgeons' patients reported good urinary function 3 months after surgery varied broadly (0% to 54.5%; P < .001). Patients receiving surgery from top-performing surgeons were more likely to report good 3-month function. This finding persisted after accounting for patient risk factors., Conclusions and Relevance: In this study, patient- and surgeon-level urinary outcomes following prostatectomy varied substantially. Documenting surgeon-specific variations after accounting for patient factors may facilitate identification of surgical factors associated with superior outcomes.

Purpose: There have been concerns about higher incidence of local and retroperitoneal recurrences after robot-assisted radical cystectomy compared to open radical cystectomy. We report and detail relapses following robot-assisted radical cystectomy using a multinational database., Materials and Methods: A retrospective review of the International Robotic Cystectomy Consortium was performed. Data were reviewed for demographics, and perioperative, pathological and oncologic outcomes. Relapse rates and patterns were analyzed. Kaplan-Meier curves were used to depict relapse-free, local recurrence-free, distant metastasis-free and overall survival. Kaplan-Meier curves were further stratified by disease stage, lymph node status and margins. Multivariate stepwise Cox regression models were used to identify variables associated with relapse-free, local recurrence-free, distant metastasis-free and overall survival., Results: Of 2,107 patients 521 (25%) experienced disease relapse. Mean age (SD) was 68±10 years with a median followup of 26 (IQR 11-55) months for the study cohort. Local recurrences were observed in 11% and distant metastases in 18%. Early oncologic failure (within 3 months) occurred in 4% of patients. The most common sites of local recurrence and distant metastasis were the pelvis (5%) and lungs (6%)/extrapelvic lymph nodes (5%), respectively. Abdominal wall/port site metastasis occurred in 1.2% and peritoneal carcinomatosis in 1.2%. Five-year relapse-free, local recurrence-free, distant metastasis-free and overall survival was 66%, 84%, 74% and 60%, respectively. Patients with higher disease stage, positive lymph nodes and positive soft tissue surgical margins demonstrated worse relapse-free, local recurrence-free, distant metastasis-free and overall survival (log rank p <0.01 for all comparisons). Multivariate regression models identified that node positive status and disease stage (pT3 or greater) were significantly associated with relapse-free, local recurrence-free, distant metastasis-free and overall survival (p <0.01)., Conclusions: Disease stage remains the main variable associated with disease relapse and survival following radical cystectomy. Robot-assisted radical cystectomy was not associated with different patterns or higher relapse rates compared to historic open radical cystectomy data.

Objectives: We present postprostatectomy pathology results from a series of prostate cancer (Pca) Gleason grade group ≥2 patients who did not have findings suggestive of cancer on preoperative pelvic magnetic resonance imaging (MRI)., Methods: We performed an institutional retrospective study of prostate magnetic resonance imaging (MRI) examinations done from October 2015 to February 2018. We identified patients who underwent prostatectomy for Pca Gleason ≥3 + 4 diagnosed on prostate biopsy with no associated MRI findings suggestive of malignancy and analyzed their postprostatectomy pathologic findings and MRI imaging results., Results: At our institution, 850 men with Pca received MRI between 2015 and 2018, and 156/850 patients received robotic-assisted radical prostatectomy. Thirty-three patients (33/156 = 21%) had negative MRI for PIRAD 3 or greater but had a biopsy showing significant Pca. Their mean (range) age was 62.7 (50-86) years. Their median (interquartile range) PSA, and PSA density were, 4.6 (3.7) ng/mL and 0.12 (0.05) ng/mL/cm 2 , respectively; all not significantly different from patients with visible lesions on MRI who underwent surgery. On post prostatectomy pathology, 27/33 (82%) men had Pca Gleason score 7 or greater. The most common pattern was infiltrative growth with cancer glands intermingling between benign glands., Conclusion: We describe the pathologic and imaging findings in an extensive series of men with clinically significant Pca with no significant lesions on preoperative MRI. Our results support the importance of patient counseling on the risk of missing significant Pca on MRI in isolation from other clinical variables., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To examine the utilization of adjuvant radiotherapy (aRT) in contemporary prostate cancer patients with adverse pathological features at radical prostatectomy (RP)., Methods: We identified 189,240 patients with adverse features at RP (positive margin, stage ≥pT3a, and/or pN1 disease), from 2004 to 2015, within the National Cancer Database, and validated our findings within Surveillance, Epidemiology, and End Results (SEER) program. We examined the utilization of patients with aRT with adverse features at RP and patients with very aggressive disease (at least 2 of the following: ≥pT3b, pathological Gleason 8-10, and pN1). Regression analysis examined the relationship of various predictors of utilization adjusting to confounders. Pseudo R 2 analysis examined the magnitude of influence that each variable had on the decision to use aRT., Results: Within the National Cancer Database cohort, only 11.7% of our patients received aRT. In patients with very aggressive disease, aRT utilization rate was 28.9%. Within the SEER cohort, 16.3% of patients with any adverse features at time of RP received aRT. In patients with very aggressive disease, only 30% of patients received aRT. Further, year of diagnosis, Gleason grade, pathologic stage, and positive surgical margin were the variables that had the greatest influence on the decision to use aRT, and that positive surgical margin, type of institution at which care was received, and lymph node involvement were the most influential variables in patients with very aggressive disease., Conclusions: The current standard of care in the United States represents a significant underutilization of aRT in eligible patients with prostate cancer. Urgent efforts are necessary to address this quality-of-care concern., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Five-year kidney graft loss currently stands at about 30%. We evaluate the clinical utility of a blood test measuring donor-derived cell-free DNA that detects rejection earlier and, potentially, improves diagnostic and therapeutic accuracy., Methods: In a randomized controlled experiment, we measured the clinical practice of 175 practicing nephrologists, both with and without the use of dd-cfDNA testing. Providers cared for six simulated post-renal transplant patient cases whose ages ranged from 30 to 75 years and were 3-24 months post-transplant with typical presentations., Results: 154 nephrologists completed two rounds of simulated cases. At baseline, the study arms performed similarly, demonstrating no significant differences either in primary diagnosis (p = 0.853), decisions to biopsy or refer to transplant center (p = 1.000), or therapeutic management (p = 0.488). After introduction of the dd-cfDNA test, intervention nephrologists were more likely to arrive at the diagnosis of rejection (OR 4.00, 95% CI 1.93-8.30), make a correct decision on biopsy/transplant center referral (OR 11.07, 95% CI 4.87-25.16), and properly adjust therapeutic management (OR 2.37, 95% CI 1.07-5.24)., Conclusion: A sample of nationally representative, practicing nephrologists given dd-cfDNA to evaluate post-transplant patients were more likely to correctly diagnose early and subclinical allograft rejection, to send for biopsy or refer to transplant center, and to appropriately change treatment than those nephrologists without dd-cfDNA access.

Millions suffer daily from chronic pain diagnosed anatomically and treated with opioids. Research shows that underlying nutritional, metabolic and oxidative stressors, which drive the development or worsening of chronic pain, are not diagnosed despite the fact that treatment of these primary pain pathways relieves pain and increases function. One of the main reasons for this gap in care is the lack of a simple diagnostic assay to help clinicians make these diagnoses. We examined the clinical utility of a urine-based pain biomarker panel. Primary care physicians were randomized into the test group and compared to controls. We measured their ability to make the diagnosis and treat a total of nine standardized patients, with common but challenging cases of chronic pain, over two rounds of data collection in a pre-post design using a fixed-effects model. Intervention doctors received educational materials on a novel pain biomarker panel after the baseline round and had access to biomarker test results. Provider responses were measured against evidence-based criteria. The two study arms at baseline provided similar, poor care for three different primary pain pathways: nutritional deficiencies (5.0% control versus 9.2% intervention treated, p = 0.208), metabolic abnormalities (1.0% control versus 0% for intervention treated, p = 0.314), and oxidative stress (1.2% control versus 0% intervention treated, p = 0.152). After the introduction of the Foundation Pain Index (FPI) biomarker test, physicians in the intervention group were 41.5% more likely to make the diagnosis of a micronutrient deficiency, 29.4% more likely to identify a treatable metabolic abnormality and 26.1% more likely to identify an oxidative stressor. These diagnostic and treatment improvements were seen across all three case types, ranging from a relative +54% ( p = 0.004) for chronic neuropathic pain to +35% ( p = 0.007) in chronic pain from other causes to +38% ( p = 0.002) in chronic pain with associated mental health issues. Intervention doctors were also 75.1% more likely to provide a non-opioid treatment to patients on chronic opioids (O.R. 1.8, 95% C.I. 0.8-3.7), 62% less likely to order unnecessary imaging for their patients with low back pain (O.R. 0.38, 95% C.I. 0.15-0.97) and 66% less likely to order an unnecessary pain referral (O.R. 0.34, 95% C.I. 0.13-0.90). This experimental study showed significant clinical utility of a validated pain biomarker panel that determines nutritional deficiencies, metabolic abnormalities and oxidative stressors that drive underlying treatable causes of pain. When integrated into routine primary care practice, this testing approach could considerably improve diagnostic accuracy and provide more targeted, non-opioid treatments for patients suffering from chronic pain.

The pore-forming cytotoxin α-hemolysin, or Hla, is a critical Staphylococcus aureus virulence factor that promotes infection by causing tissue damage, excessive inflammation, and lysis of both innate and adaptive immune cells, among other cellular targets. In this study, we asked whether a virus-like particle (VLP)-based vaccine targeting Hla could attenuate S. aureus Hla-mediated pathogenesis. VLPs are versatile vaccine platforms that can be used to display target antigens in a multivalent array, typically resulting in the induction of high titer, long-lasting antibody responses. In the present study, we describe the first VLP-based vaccines that target Hla. Vaccination with either of two VLPs displaying a 21 amino-acid linear neutralizing domain (LND) of Hla protected both male and female mice from subcutaneous Hla challenge, evident by reduction in lesion size and neutrophil influx to the site of intoxication. Antibodies elicited by VLP-LND vaccination bound both the LND peptide and the native toxin, effectively neutralizing Hla and preventing toxin-mediated lysis of target cells. We anticipate these novel and promising vaccines being part of a multi-component S. aureus vaccine to reduce severity of S. aureus infection.

Objective: To describe and evaluate a risk-stratified triage pathway for inpatient urology consultations during the SARS-CoV-2 (COVID-19) pandemic. This pathway seeks to outline a urology patient care strategy that reduces the transmission risk to both healthcare providers and patients, reduces the healthcare burden, and maintains appropriate patient care., Materials and Methods: Consultations to the urology service during a 3-week period (March 16 to April 2, 2020) were triaged and managed via one of 3 pathways: Standard, Telemedicine, or High-Risk. Standard consults were in-person consults with non COVID-19 patients, High-Risk consults were in-person consults with COVID-19 positive/suspected patients, and Telemedicine consults were telephonic consults for low-acuity urologic issues in either group of patients. Patient demographics, consultation parameters and consultation outcomes were compared to consultations from the month of March 2019. Categorical variables were compared using Chi-square test and continuous variables using Mann-Whitney U test. A P value <.05 was considered significant., Results: Between March 16 and April 2, 2020, 53 inpatient consultations were performed. By following our triage pathway, a total of 19/53 consultations (35.8%) were performed via Telemedicine with no in-person exposure, 10/53 consultations (18.9%) were High-Risk, in which we strictly controlled the urology team member in-person contact, and the remainder, 24/53 consultations (45.2%), were performed as Standard in-person encounters. COVID-19 associated consultations represented 18/53 (34.0%) of all consultations during this period, and of these, 8/18 (44.4%) were managed successfully via Telemedicine alone. No team member developed COVID-19 infection., Conclusion: During the COVID-19 pandemic, most urology consultations can be managed in a patient and physician safety-conscious manner, by implementing a novel triage pathway., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: HbA1c is widely used as the standard measure to track glycemic control in patients with diabetes and pre-diabetes but measures average levels of glycated hemoglobin over two to three months, with limited utility in the presence of recent and/or short-term fluctuations in glycemic control, which are correlated with worse patient outcomes., Methods: We examined the clinical utility of 1-5-anhydroglucitol (1,5-AG) in six different, but common, case types of diabetes patients with short-term glycemic variability. We conducted a randomized controlled trial of simulated patients to examine the clinical practice patterns of primary care physicians before and after introducing 1,5-AG. The 145 participants were randomly assigned into standard care or standard care + 1,5-AG arms. Provider care was reviewed against explicit evidence-based care standards., Results: At baseline, we saw no difference between the two study arms in clinical quality of care provided (p = 0.997). After introduction of 1,5-AG, standard care + 1,5-AG providers performed 3.2% better than controls (p = 0.025. In diagnosis and treatment, there was a slight, but nonsignificant trend toward better care (+1.1%, p = 0.507) for intervention providers. Upon disaggregation by case, almost all the improvement occurred in the medication-induced hyperglycemia patients (+8.1%, p = 0.047)., Conclusions: A nationally representative sample of primary care physicians demonstrated that of six different cases used in this study, 1,5-AG was found to be most effective increasing awareness of poor glucose control in medication-induced hyperglycemia. If 1,5-AG is used in this particular circumstance, the overall savings to the healthcare system is estimated to be $28 million., (© 2020 The Authors.)

Purpose: Several guidelines recommend pelvic lymph node dissection (PLND) at robot-assisted radical prostatectomy (RARP) only when lymph node involvement (LN+) is >2%. Individual surgeon use of PLND is not well-known. We sought to examine variability in PLND performance and detection of LN+ across the Michigan Urological Surgery Improvement Collaborative., Methods: Data regarding all RARP (3/2012-9/2018) were prospectively collected, including patient and surgeon characteristics. Univariable and multivariable analyses of PLND rate and LN+ rate were performed., Results: Among 9,751 men undergoing RARP, 79.8% had PLND performed (n = 7,781), of which 5.2% were LN+ (n = 404). In univariate and multivariable analyses, predictors of PLND included higher Prostate-Specific Antigen (PSA), biopsy Gleason grade (bGG), number of positive cores, and maximum core involvement at P < 0.05 for each. Higher PSA, cT stage, bGG, number of positive cores, and maximum core involvement predicted LN+ when PLND was performed (P < 0.05 for each). There was significant surgeon variation in the proportion of PLND performed at RARP, yet neither surgeon-annualized RARP volume nor % of PLND performed was associated with LN+ disease (P > 0.05). Grade was associated with PLND (60.0%, 77.6%, 91.0%, 97.3%, and 98.5%; P < 0.001) and LN+ (0.7%, 2.5%, 5.8%, 8.6%, and 19.9%; P < 0.001) for bGG 1,2,3,4,5, respectively. Maximum core involvement also strongly predicted LN+ with rates of 1.5%, 3.8%, and 9.4% for <35%, 35% to 65%, and >65%, respectively (P < 0.001)., Conclusions: Nearly 80% of RARP in Michigan Urological Surgery Improvement Collaborative were performed with PLND, including 60% of bGG1 patients (with LN+ in only 0.7%), but significant variability exists between surgeons. Our data indicate limited benefit for favorable-risk CaP patients and support efforts to decrease PLND use going forward., (Copyright © 2019. Published by Elsevier Inc.)