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    Incidence of Atrial Fibrillation in Large Vessel Occlusion and Large Embolic Stroke of Undetermined Source
    (Springer Nature, 2023-01-12) Seachrist, Eric J.; Petrone, Ashley; Nevin, Connor; Ranasinghe, Tamra; Jacob, Sneha; Ferari, Christopher; Adcock, Amelia; Urology, School of Medicine
    Introduction: Large vessel occlusion (LVO) stroke is a common presentation of acute ischemic stroke and is often unknown or cryptogenic in etiology. There is a strong association between atrial fibrillation (AF) and cryptogenic LVO stroke, making it a unique stroke subgroup. Therefore, we propose that any LVO stroke meeting the criteria for an embolic stroke of an undetermined source (ESUS) be classified as large ESUS (LESUS). The purpose of this retrospective cohort study was to report the etiology of anterior LVO strokes that underwent endovascular thrombectomy. Methods: This was a single-center retrospective cohort study characterizing the etiology of acute anterior circulation LVO strokes that received emergent endovascular thrombectomy from 2011 to 2018. Patients with LESUS designation at hospital discharge were changed to cardioembolic etiology if AF was discovered during the two-year follow-up period. Results: Overall, 155 (45%) of 307 patients in the study were found to have AF. New onset AF was discovered in 12 (23%) of 53 LESUS patients after hospitalization. Furthermore, eight (35%) of 23 LESUS patients who received extended cardiac monitoring were found to have AF. Conclusion: Nearly half the patients with LVO stroke who received endovascular thrombectomy were found to have AF. With the use of extended cardiac monitoring devices after hospitalization, AF is frequently discovered in patients with LESUS and may change the secondary stroke prevention strategy.
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    Age-based risk of end-stage kidney disease in patients with myelomeningocele
    (Elsevier, 2023-04) Adams, Cyrus M.; Misseri, Rosalia; Roth, Joshua D.; Whittam, Benjamin M.; Guckien, Zoe E.; King, Shelly J.; Kaefer, Martin; Rink, Richard C.; Szymanski, Konrad M.; Urology, School of Medicine
    Objective We aimed to quantify end-stage kidney disease (ESKD) risk after infancy in individuals with myelomeningocele (MMC) followed by urology in the modern medical era and to assess if ESKD risk was higher after surgery related to a hostile bladder. Methods We retrospectively reviewed patients with MMC followed by urology at our institution born ≥ 1972 (when clean intermittent catheterization was introduced) past 1 year of age (when mortality is highest, sometimes before establishing urology care). ESKD was defined as requiring permanent peritoneal/hemodialysis or renal transplantation. Early surgery related to hostile bladder included incontinent vesicostomy, bladder augmentation, detrusor Botulinum A toxin injection, ureteral reimplantation, or nephrectomy for recurrent urinary tract infections. Survival analysis and proportional hazards regression were used. Sensitivity analyses included: risk factor analysis with only vesicostomy, timing of surgery, including the entire population without minimal follow-up (n = 1054) and only patients with ≥ 5 years of follow-up (n = 925). Results Overall, 1029 patients with MMC were followed for a median of 17.0 years (49% female, 76% shunted). Seven patients (0.7%) developed ESKD at a median 24.3 years old (5 hemodialysis, 1 peritoneal dialysis, 1 transplantation). On survival analysis, the ESKD risk was 0.3% at 20 years old and 2.1% at 30 years old (Figure). This was ∼100 times higher than the general population (0.003% by 21 years old, p < 0.001). Patients who underwent early surgery for hostile bladder had higher ESKD risk (HR 8.3, p = 0.001, 6% vs. 1.5% at 30 years). On exploratory analyses, gender, birth year, shunt status and wheelchair use were not associated with ESKD risk (p ≥ 0.16). Thirty-year ESKD risk was 10% after early vesicostomy vs. 1.4% among children without one (p = 0.001). Children undergoing bladder surgery between 1.5 and 5 years old had a higher risk of ESKD. No other statistically/clinically significant differences were noted. Comment Patients with MMC remain at risk of progressive renal damage throughout life. We relied on the final binary ESKD outcome to quantify this risk, rather than imprecise glomerular filtration rate formulas. Analysis was limited by few people developing ESKD, inconsistent documentation of early urodynamic findings and indications for bladder-related surgery. Conclusions While ESKD is relatively uncommon in the MMC population receiving routine urological care, affecting 2.1% of individuals in the first 3 decades, it is significantly higher than the general population. Children with poor bladder function are likely at high risk, underlining the need for routine urological care, particularly in adulthood.
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    The role of urethral ligation after AUS failure and end stage urethra
    (Springer, 2022-11) Arnold, Peter J.; Soyster, Mary E.; Burns, Ramzy T.; Mellon, Matthew J.; Urology, School of Medicine
    Purpose To provide our single-center experience with an approach to refractory stress urinary incontinence (SUI) with permanent urethral ligation (PUL) and suprapubic tube (SPT) placement, in hopes of contributing to the limited body of research surrounding this surgical treatment option for patients with end-stage urethra (ESU). Methods All patients undergoing PUL with SPT placement from 01/01/2018 to 04/30/2022 were identified from an institutional database. Institutional Review Board exempt status was granted for the conduct of this study. Patients were seen postoperatively at 1 month and 1 year. If there were any concerns of incontinence, an antegrade urethrogram via the SPT was performed. Descriptive statistics were used to evaluate patients. Results Seven patients underwent PUL with SPT in our timeframe and were included in the study. All patients previously had an AUS placed, and two patients had a urethral sling previously placed. The median follow-up time was 21 months, ranging between 2 and 48 months. Complications included bladder spasms (43%) and continued leakage per urethra (14%). Of the 7 patients, 6 have reported continence through their urethra at their most recent follow-up. Conclusion This initial data suggest that PUL with SPT placement may be a viable surgical approach to treating refractory SUI, especially for patients with ESU who wish to avoid the morbidity associated with more formal supravesical diversion. Further study of this technique and longer follow-up is required to determine its long-term efficacy and tolerability for patients.
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    Ranking Important Factors for Using Postoperative Chemotherapy in Nonmuscle Invasive Bladder Cancer: Conjoint Analysis Results From the Michigan Urological Surgery Improvement Collaborative (MUSIC)
    (Wolters Kluwer, 2022) Cary, Clint; Tong, Yan; Linsell, Susan; Ghani, Khurshid; Miller, David C.; Weiner, Michael; Koch, Michael O.; Perkins, Susan M.; Zimet, Gregory; Urology, School of Medicine
    Purpose: National and international guidelines recommend the use of 1 dose of intravesical chemotherapy immediately following surgery for nonmuscle invasive bladder cancer, which is performed infrequently on a population level. We sought to understand the importance of potential environmental and clinical dimensions involved in the decision to offer this therapy. Materials and methods: Urologists from the Michigan Urological Surgery Improvement Collaborative (MUSIC) rated 8 distinct clinical vignettes involving patients with nonmuscle invasive bladder cancer. A ratings-based conjoint analysis method was used to evaluate the clinical vignette responses. Each vignette included 4 clinical dimensions and 2 environmental dimensions, with each dimension consisting of 2 possible attributes. The relative importance of each attribute was derived from the regression model and ranked in order. Results: A total of 58 urologists answered the clinical vignettes which represents >75% of MUSIC sites. The median age of urologists was 53, most were male, and median years in practice was 20 years post residency. An environmental attribute, having a recovery room protocol for instilling and disposing of the chemotherapy, ranked as the most influential attribute for giving postoperative chemotherapy (utility=8.6). The clinical attribute yielding the strongest preference for giving chemotherapy was tumor grade (utility=4.9). These preferences varied by different subgroups of urologists, particularly regarding the type of practice a urologist was in. Conclusions: This study demonstrates that urologists have clear preferences for when they offer postoperative immediate chemotherapy. Factors beyond just clinical variables play a role in this decision making process such as the structure of the recovery room.
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    Comparison of Contemporary Surgical Outcomes Between Holmium Laser Enucleation of the Prostate and Robotic-Assisted Simple Prostatectomy
    (Springer Nature, 2023) Shelton, T. Max; Drake, Connor; Vasquez, Ruben; Rivera, Marcelino; Urology, School of Medicine
    Purpose of review: This study reviews contemporary literature on RASP and HoLEP to evaluate perioperative outcomes, common complications, cost analytics, and future directions of both procedures. Recent findings: RASP is indicated for prostates > 80 mL, while HoLEP is size-independent. No notable differences were found in operative time, PSA nadir (surrogate for enucleation volume), re-catheterization rates, or long-term durability. Prolonged incontinence and bladder neck contracture rates are low for both surgeries. Patients experience similar satisfaction outcomes and improvements in uroflowmetry and post-void residual volumes. HoLEP demonstrates shorter hospitalizations, lower transfusion rates, lower costs, and higher rates of same-day discharge. RASP offers a shorter learning curve and lower rates of early postoperative urinary incontinence. HoLEP is a size-independent surgery that offers advantages for patients seeking a minimally invasive procedure with the potential for catheter-free same-day discharge. Future directions with single-port simple prostatectomy may offer parity in same-day discharge, but further research is needed to determine broader feasibility.
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    A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease
    (Nature, 2023-07-19) Canela, Victor Hugo; Bowen, William S.; Ferreira, Ricardo Melo; Syed, Farooq; Lingeman, James E.; Sabo, Angela R.; Barwinska, Daria; Winfree, Seth; Lake, Blue B.; Cheng, Ying-Hua; Gaut, Joseph P.; Ferkowicz, Michael; LaFavers, Kaice A.; Zhang, Kun; Coe, Fredric L.; Worcester, Elaine; Jain, Sanjay; Eadon, Michael T.; Williams, James C., Jr.; El-Achkar, Tarek M.; Urology, School of Medicine
    Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers.
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    Genetic Risk Assessment for Hereditary Renal Cell Carcinoma: Clinical Consensus Statement
    (Wiley, 2021) Bratslavsky, Gennady; Mendhiratta, Neil; Daneshvar, Michael; Brugarolas, James; Ball, Mark W.; Metwalli, Adam; Nathanson, Katherine L.; Pierorazio, Phillip M.; Boris, Ronald S.; Singer, Eric A.; Carlo, Maria I.; Daly, Mary B.; Henske, Elizabeth P.; Hyatt, Colette; Middleton, Lindsay; Morris, Gloria; Jeong, Anhyo; Narayan, Vivek; Rathmell, W. Kimryn; Vaishampayan, Ulka; Lee, Bruce H.; Battle, Dena; Hall, Michael J.; Hafez, Khaled; Jewett, Michael A.S.; Karamboulas, Christina; Pal, Sumanta K.; Hakimi, A. Ari; Kutikov, Alexander; Iliopoulos, Othon; Linehan, W. Marston; Jonasch, Eric; Srinivasan, Ramaprasad; Shuch, Brian; Urology, School of Medicine
    Background: Although renal cell carcinoma (RCC) is believed to have a strong hereditary component, there is a paucity of published guidelines for genetic risk assessment. A panel of experts was convened to gauge current opinions. Methods: A North American multidisciplinary panel with expertise in hereditary RCC, including urologists, medical oncologists, clinical geneticists, genetic counselors, and patient advocates, was convened. Before the summit, a modified Delphi methodology was used to generate, review, and curate a set of consensus questions regarding RCC genetic risk assessment. Uniform consensus was defined as ≥85% agreement on particular questions. Results: Thirty-three panelists, including urologists (n = 13), medical oncologists (n = 12), genetic counselors and clinical geneticists (n = 6), and patient advocates (n = 2), reviewed 53 curated consensus questions. Uniform consensus was achieved on 30 statements in specific areas that addressed for whom, what, when, and how genetic testing should be performed. Topics of consensus included the family history criteria, which should trigger further assessment, the need for risk assessment in those with bilateral or multifocal disease and/or specific histology, the utility of multigene panel testing, and acceptance of clinician-based counseling and testing by those who have experience with hereditary RCC. Conclusions: In the first ever consensus panel on RCC genetic risk assessment, 30 consensus statements were reached. Areas that require further research and discussion were also identified, with a second future meeting planned. This consensus statement may provide further guidance for clinicians when considering RCC genetic risk assessment. Lay summary: The contribution of germline genetics to the development of renal cell carcinoma (RCC) has long been recognized. However, there is a paucity of guidelines to define how and when genetic risk assessment should be performed for patients with known or suspected hereditary RCC. Without guidelines, clinicians struggle to define who requires further evaluation, when risk assessment or testing should be done, which genes should be considered, and how counseling and/or testing should be performed. To this end, a multidisciplinary panel of national experts was convened to gauge current opinion on genetic risk assessment in RCC and to enumerate a set of recommendations to guide clinicians when evaluating individuals with suspected hereditary kidney cancer.
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    Oncological Follow-up Strategies for Testicular Germ Cell Tumours: A Narrative Review
    (Elsevier, 2022-09-07) Kaufmann, Ernest; Antonelli, Luca; Albers, Peter; Cary, Clint; Gillessen Sommer, Silke; Heidenreich, Axel; Oing, Christoph; Oldenburg, Jan; Pierorazio, Phillip Martin; Stephenson, Andrew J.; Fankhauser, Christian Daniel; Urology, School of Medicine
    Context: The aim of this review is to describe the proportion of testicular germ cell tumours (tGCTs) with recurrence, and the timing and anatomical sites of relapse across different disease stages and after different treatment options. We summarise published follow-up protocols and discuss current and future developments to personalise follow-up for patients with tGCT. Evidence acquisition: A systematic literature search was conducted and current guidelines and selected institutional follow-up protocols were reviewed. Evidence synthesis: Of 302 publications, we screened 68 full texts and included 29 studies; 22 of these were retrospective and seven were prospective in nature, contributing data for 20 570 patients. The number of patients included per study ranged from 119 to 2483. We compared the guideline follow-up protocols of the European Society for Medical Oncology, European Association of Urology, National Comprehensive Cancer Network, and American Urological Association, as well as institutional follow-up protocols. The protocols differed in terms of the number, time points, and type of follow-up investigations. Conclusions: Future research should assess how tGCT can be followed to ensure high adherence, define the role of miR-371a-3p microRNA during follow-up, and develop follow-up protocols after curative treatment in the metastatic setting. Patient summary: In this review of follow-up protocols for men with testis cancer, we observed different recommendations and discuss future research areas to improve follow-up for these patients.
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    Sarcoidosis: A rare cause of penile edema
    (Elsevier, 2022-07-19) Herodotou, Christopher A.; Burns, Ramzy T.; Whaley, Rumeal; Idrees, Muhammad; Mellon, Matthew J.; Urology, School of Medicine
    Reports of penile sarcoidosis are rare in the literature. We describe the case of a male who presented with several months of distal penile swelling and progressive inability to retract the foreskin. Firm, non-tender subcutaneous nodules were palpated near the base of the penis. The patient ultimately underwent penile skin resection, partial scrotal resection, and split thickness skin graft to the penis after failing multiple conservative treatments. Pathology revealed non-caseating granulomatous lesions which in addition to CT chest findings of bilateral hilar adenopathy suggested a diagnosis of penile sarcoidosis.
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    Piceatannol, a Dietary Polyphenol, Alleviates Adipose Tissue Loss in Pre-Clinical Model of Cancer-Associated Cachexia via Lipolysis Inhibition
    (MDPI, 2022-05-31) Kershaw, Jonathan C.; Elzey, Bennett D.; Guo, Xiao-Xuan; Kim, Kee-Hong; Urology, School of Medicine
    Cancer-associated cachexia (CAC) is the nutrition-independent loss of lean muscle and adipose tissues, and results in reduced chemotherapy effectiveness and increased mortality. Preventing adipose loss is considered a key target in the early stages of cachexia. Lipolysis is considered the central driver of adipose loss in CAC. We recently found that piceatannol, but not its analogue resveratrol, exhibits an inhibitory effect on lipolysis. The objective of this study was to investigate the role of piceatannol in cancer-associated lipolysis and cachexia-induced weight loss. Cancer cell-induced lipolysis in adipocytes was stimulated using cancer-conditioned media (CCM) or co-culture with human pancreatic cancer cells and the cachexia-associated cytokines TNF-α and interleukin-6 in 3T3-L1 adipocytes. C26 colon carcinoma-bearing mice were modeled using CAC in vivo. Piceatannol reduced cancer-associated lipolysis by at least 50% in both CCM and cytokine-induced lipolysis in vitro. Further gene and protein analysis confirmed that piceatannol modulated the stability of lipolytic proteins. Moreover, piceatannol protected tumor-bearing mice against weight-loss in early stages of CAC largely through preserving adipose tissue, with no effect on survival. This study demonstrates the use of a dietary compound to preserve adipose in models of early stage CAC and provides groundwork for further investigation of piceatannol or piceatannol-rich foods as alternative medicine in the preservation of body fat mass and future CAC therapy.