Transcriptomic analysis of benign prostatic hyperplasia identifies critical pathways in prostatic overgrowth and 5-alpha reductase inhibitor resistance.

BACKGROUND: The medical therapy of prostatic symptoms (MTOPS) trial randomized men with symptoms of benign prostatic hyperplasia (BPH) and followed response of treatment with a 5α-reductase inhibitor (5ARI), an alpha-adrenergic receptor antagonist (α-blocker), the combination of 5ARI and α-blocker or no medical therapy (none). Medical therapy reduced risk of clinical progression by 66% but the reasons for nonresponse or loss of therapeutic response in some patients remains unresolved. Our previous work showed that prostatic glucocorticoid levels are increased in 5ARI-treated patients and that glucocorticoids can increased branching of prostate epithelia in vitro. To understand the transcriptomic changes associated with 5ARI treatment, we performed bulk RNA sequencing of BPH and control samples from patients who received 5ARI versus those that did not. Deconvolution analysis was performed to estimate cellular composition. Bulk RNA sequencing was also performed on control versus glucocorticoid-treated prostate epithelia in 3D culture to determine underlying transcriptomic changes associated with branching morphogenesis. METHOD: Surgical BPH (S-BPH) tissue was defined as benign prostatic tissue collected from the transition zone (TZ) of patients who failed medical therapy while control tissue termed Incidental BPH (I-BPH) was obtained from the TZ of men undergoing radical prostatectomy for low-volume/grade prostatic adenocarcinoma confined to the peripheral zone. S-BPH patients were divided into four subgroups: men on no medical therapy (none: n = 7), α-blocker alone (n = 10), 5ARI alone (n = 6) or combination therapy (α-blocker and 5ARI: n = 7). Control I-BPH tissue was from men on no medical therapy (none: n = 8) or on α-blocker (n = 6). A human prostatic cell line in 3D culture that buds and branches was used to identify genes involved in early prostatic growth. Snap-frozen prostatic tissue taken at the time of surgery and 3D organoids were used for RNA-seq analysis. Bulk RNAseq data were deconvoluted using CIBERSORTx. Differentially expressed genes (DEG) that were statistically significant among S-BPH, I-BPH, and during budding and branching of organoids were used for pathway analysis. RESULTS: Transcriptomic analysis between S-BPH (n = 30) and I-BPH (n = 14) using a twofold cutoff (p < 0.05) identified 377 DEG (termed BPH377) and a cutoff < 0.05 identified 3377 DEG (termed BPH3377). Within the S-BPH, the subgroups none and α-blocker were compared to patients on 5ARI to reveal 361 DEG (termed 5ARI361) that were significantly changed. Deconvolution analysis of bulk RNA seq data with a human prostate single cell data set demonstrated increased levels of mast cells, NK cells, interstitial fibroblasts, and prostate luminal cells in S-BPH versus I-BPH. Glucocorticoid (GC)-induced budding and branching of benign prostatic cells in 3D culture was compared to control organoids to identify early events in prostatic morphogenesis. GC induced 369 DEG (termed GC359) in 3D culture. STRING analysis divided the large datasets into 20-80 genes centered around a hub. In general, biological processes induced in BPH supported growth and differentiation such as chromatin modification and DNA repair, transcription, cytoskeleton, mitochondrial electron transport, ubiquitination, protein folding, and cholesterol synthesis. Identified signaling pathways were pooled to create a list of DEG that fell into seven hubs/clusters. The hub gene centrality was used to name the network including AP-1, interleukin (IL)-6, NOTCH1 and NOTCH3, NEO1, IL-13, and HDAC/KDM. All hubs showed connections to inflammation, chromatin structure, and development. The same approach was applied to 5ARI361 giving multiple networks, but the EGF and sonic hedgehog (SHH) hub was of particular interest as a developmental pathway. The BPH3377, 5ARI363, and GC359 lists were compared and 67 significantly changed DEG were identified. Common genes to the 3D culture included an IL-6 hub that connected to genes identified in BPH hubs that defined AP1, IL-6, NOTCH, NEO1, IL-13, and HDAC/KDM. CONCLUSIONS: Reduction analysis of BPH and 3D organoid culture uncovered networks previously identified in prostatic development as being reinitiated in BPH. Identification of these pathways provides insight into the failure of medical therapy for BPH and new therapeutic targets for BPH/LUTS.

Glucocorticoids are induced while dihydrotestosterone levels are suppressed in 5-alpha reductase inhibitor treated human benign prostate hyperplasia patients.

BACKGROUND: The development of benign prostatic hyperplasia (BPH) and medication-refractory lower urinary tract symptoms (LUTS) remain poorly understood. This study attempted to characterize the pathways associated with failure of medical therapy for BPH/LUTS. METHODS: Transitional zone tissue levels of cholesterol and steroids were measured in patients who failed medical therapy for BPH/LUTS and controls. Prostatic gene expression was measured using qPCR and BPH cells were used in organoid culture to study prostatic branching. RESULTS: BPH patients on 5-α-reductase inhibitor (5ARI) showed low levels of tissue dihydrotestosterone (DHT), increased levels of steroid 5-α-reductase type II (SRD5A2), and diminished levels of androgen receptor (AR) target genes, prostate-specific antigen (PSA), and transmembrane serine protease 2 (TMPRSS2). 5ARI raised prostatic tissue levels of glucocorticoids (GC), whereas alpha-adrenergic receptor antagonists (α-blockers) did not. Nuclear localization of GR in prostatic epithelium and stroma appeared in all patient samples. Treatment of four BPH organoid cell lines with dexamethasone, a synthetic GC, resulted in budding and branching. CONCLUSIONS: After failure of medical therapy for BPH/LUTS, 5ARI therapy continued to inhibit androgenesis but a 5ARI-induced pathway increased tissue levels of GC not seen in patients on α-blockers. GC stimulation of organoids indicated that the GC receptors are a trigger for controlling growth of prostate glands. A 5ARI-induced pathway revealed GC activation can serve as a master regulator of prostatic branching and growth.

The prostaglandin pathway is activated in patients who fail medical therapy for benign prostatic hyperplasia with lower urinary tract symptoms.

BACKGROUND: Little is known about how benign prostatic hyperplasia (BPH) develops and why patients respond differently to medical therapy designed to reduce lower urinary tract symptoms (LUTS). The Medical Therapy of Prostatic Symptoms (MTOPS) trial randomized men with symptoms of BPH and followed response to medical therapy for up to 6 years. Treatment with a 5α-reductase inhibitor (5ARI) or an alpha-adrenergic receptor antagonist (α-blocker) reduced the risk of clinical progression, while men treated with combination therapy showed a 66% decrease in risk of progressive disease. However, medical therapies for BPH/LUTS are not effective in many patients. The reasons for nonresponse or loss of therapeutic response in the remaining patients over time are unknown. A better understanding of why patients fail to respond to medical therapy may have a major impact on developing new approaches for the medical treatment of BPH/LUTS. Prostaglandins (PG) act on G-protein-coupled receptors (GPCRs), where PGE2 and PGF2 elicit smooth muscle contraction. Therefore, we measured PG levels in the prostate tissue of BPH/LUTS patients to assess the possibility that this signaling pathway might explain the failure of medical therapy in BPH/LUTS patients. METHOD: Surgical BPH (S-BPH) was defined as benign prostatic tissue collected from the transition zone (TZ) of patients who failed medical therapy and underwent surgical intervention to relieve LUTS. Control tissue was termed Incidental BPH (I-BPH). I-BPH was TZ obtained from men undergoing radical prostatectomy for low-volume, low-grade prostatic adenocarcinoma (PCa, Gleason score ≤ 7) confined to the peripheral zone. All TZ tissue was confirmed to be cancer-free. S-BPH patients divided into four subgroups: patients on α-blockers alone, 5ARI alone, combination therapy (α-blockers plus 5ARI), or no medical therapy (none) before surgical resection. I-BPH tissue was subgrouped by prior therapy (either on α-blockers or without prior medical therapy before prostatectomy). We measured prostatic tissue levels of prostaglandins (PGF2α , PGI2 , PGE2 , PGD2 , and TxA2 ), quantitative polymerase chain reaction levels of mRNAs encoding enzymes within the PG synthesis pathway, cellular distribution of COX1 (PTGS1) and COX2 (PTGS2), and tested the ability of PGs to contract bladder smooth muscle in an in vitro assay. RESULTS: All PGs were significantly elevated in TZ tissues from S-BPH patients (n = 36) compared to I-BPH patients (n = 15), regardless of the treatment subgroups. In S-BPH versus I-BPH, mRNA for PG synthetic enzymes COX1 and COX2 were significantly elevated. In addition, mRNA for enzymes that convert the precursor PGH2 to metabolite PGs were variable: PTGIS (which generates PGI2 ) and PTGDS (PGD2 ) were significantly elevated; nonsignificant increases were observed for PTGES (PGE2 ), AKR1C3 (PGF2α ), and TBxAS1 (TxA2 ). Within the I-BPH group, men responding to α-blockers for symptoms of BPH but requiring prostatectomy for PCa did not show elevated levels of COX1, COX2, or PGs. By immunohistochemistry, COX1 was predominantly observed in the prostatic stroma while COX2 was present in scattered luminal cells of isolated prostatic glands in S-BPH. PGE2 and PGF2α induced contraction of bladder smooth muscle in an in vitro assay. Furthermore, using the smooth muscle assay, we demonstrated that α-blockers that inhibit alpha-adrenergic receptors do not appear to inhibit PG stimulation of GPCRs in bladder muscle. Only patients who required surgery to relieve BPH/LUTS symptoms showed significantly increased tissue levels of PGs and the PG synthetic enzymes. CONCLUSIONS: Treatment of BPH/LUTS by inhibition of alpha-adrenergic receptors with pharmaceutical α-blockers or inhibiting androgenesis with 5ARI may fail because of elevated paracrine signaling by prostatic PGs that can cause smooth muscle contraction. In contrast to patients who fail medical therapy for BPH/LUTS, control I-BPH patients do not show the same evidence of elevated PG pathway signaling. Elevation of the PG pathway may explain, in part, why the risk of clinical progression in the MTOPS study was only reduced by 34% with α-blocker treatment.

MOSESTM Technology for Holmium Laser Enucleation of the Prostate: A Prospective Double-Blind Randomized Controlled Trial.

PURPOSE: Holmium laser enucleation of the prostate has proven to be efficacious and safe for the treatment of benign prostatic hyperplasia. New laser technologies, such as the MOSES™ pulse laser system, improve energy delivery and may improve operative times. We sought to prospectively evaluate holmium laser enucleation of the prostate using MOSES technology in a double-blind randomized controlled trial. MATERIALS AND METHODS: This is a single-center, prospective, double-blind, randomized controlled trial comparing holmium laser enucleation of the prostate using MOSES technology to holmium laser enucleation of the prostate. Patients were randomized in a 1:1 fashion. The study was powered to evaluate for a difference in operative time. Secondary end points included enucleation, morcellation, and hemostasis times, as well as blood loss, functional outcomes and complications 6 weeks postoperatively. RESULTS: A total of 60 patients were analyzed without difference in preoperative characteristics in either group (holmium laser enucleation of the prostate using MOSES technology: 30/60, 50%, holmium laser enucleation of the prostate: 30/60, 50%). Shorter total operative time was seen in the holmium laser enucleation of the prostate using MOSES technology group compared to the holmium laser enucleation of the prostate group (mean: 101 vs. 126 minutes, p <0.01). This difference remained significant on multiple linear regression. Additionally, the holmium laser enucleation of the prostate using MOSES technology group had shorter enucleation times (mean: 68 vs. 80 minutes, p=0.03), hemostasis time (mean: 18 vs. 29 minutes, p <0.01), and less blood loss (mean: -6.3 vs. -9.0%, p=0.03), measured by a smaller change in hematocrit postoperatively, compared to the traditional holmium laser enucleation of the prostate. There was no difference in functional or safety outcomes at followup. CONCLUSIONS: We report the results of a prospective, double-blind, randomized controlled trial comparing holmium laser enucleation of the prostate using MOSES technology to traditional holmium laser enucleation of the prostate. MOSES technology resulted in an improvement in operative time and a reduction in blood loss with comparable functional outcomes and complications compared to traditional holmium laser enucleation of the prostate.

Predicting complications following radical cystectomy with the ACS NSQIP universal surgical risk calculator.

INTRODUCTION: Radical cystectomy (RC) is a challenging procedure with significant morbidity, though remains the standard of care treatment for many patients with bladder cancer. There has been debate regarding the utility of universal risk calculators to aid in point-of-care prediction of complications in individual patients preoperatively. We retrospectively evaluated the predictive value of the ACS NSQIP universal surgical risk calculator in our patients who underwent RC. METHODS: A prospective cohort of patients undergoing RC was retrospectively reviewed between October 2014 and August 2017. Only patients who underwent a RC for genitourinary cancer without significant deviation from NSQIP surgery codes 51590, 51595, and 51596 (n = 29) were included. The accuracy of the risk calculator was assessed by ROC AUC and Brier scores for both NSQIP and Clavien-Dindo defined complications. Additionally, each NSQIP risk factor was individually assessed for association with postoperative complications. RESULTS: 223 patients who underwent open or robotic RC (n = 18) were included for analysis. Determined by AUC C-stat and Brier scores, prediction was good for cardiac complications (0.80 and 0.021), fair for pneumonia (0.75 and 0.017), poor for UTI (0.64 and 0.078), 30-day mortality (0.62 and 0.013), any complication (0.60 and 0.19) and serious complication (0.60 and 0.17). There was a significant discordance between the rate of NSQIP predicted vs. Clavien-Dindo observed any and serious complications: 28.8% vs. 67.3%, and 25.3% vs. 11.7%, respectively. CONCLUSION: The NSQIP universal surgical risk calculator did not perform with enough accuracy to consider adoption into clinical practice.

Ureteral stents: the good the bad and the ugly.

PURPOSE OF REVIEW: Ureteral stents are necessary in the routine practice of an urologist. Choosing the correct stent and being aware of the options available will allow urologists to provide the best possible care for patients and value to the healthcare system. This review seeks to educate urologists regarding improvements in stent technology currently available or in development. RECENT FINDINGS: Research from around the world is underway to discover an ideal stent - one that is comfortable for patients, resists infection and encrustation and is affordable for hospital systems. Stent design alterations and stent coatings are revealing reductions in encrustation and bacterial colonization. Biodegradable stents and magnetic stents are being tested to prevent the discomfort of cystoscopic removal. Intraureteral stents are proving efficacious while eliminating an irritating coil from the bladder and the symptoms associated with it. SUMMARY: The studies highlighted in this review provide encouraging results in the pursuit of the ideal stent while opening discussion around new concepts and further areas of research.

Comparison of flexible ureteroscopy damage rates for lower pole renal stones by laser fiber type.

OBJECTIVES: Laser lithotripsy, often used during ureteronephroscopy (URNS), requires the Ho:YAG optical fiber transmit energy via total internal reflection (TIR). In critical lower pole deflections, energy may refract into the cladding causing fiber failure and scope damage. New optical fiber technology aims to have increased tolerance for high degrees of flexion. We compared two brands of laser fibers with sub-300 micron cores (Sureflex, Boston Flexiva) to determine failure rates and scope repair costs. METHODS: A retrospective cohort study comparing these two fibers for patients at a single academic institution who underwent flexible URNS with laser lithotripsy was performed from September 2013 to October 2015. Preoperative imaging was evaluated for stone burden and location. Intraoperative variables were collected, including energy use, lower pole lasering, laser fiber malfunction, and scope damage. The primary outcome was scope damage caused by laser fiber malfunction. Secondary outcome was scope repair costs. Fisher's exact test and two tailed t-tests were used. RESULTS: Of 223 subjects, 143 met inclusion criteria, and 8 had laser fiber failure. All failures occurred with the Sureflex fiber (8 of 63, 13%) vs the Boston Flexiva fiber (0 of 80, 0%) (P < 0.01). Malfunctions occurred in 8 of 79 lower pole stone applications versus 0 of 64 non-lower pole stone laser applications (P < 0.01). No other risk factor was different between fiber cohorts, except energy setting. Scope repair cost averaged $9155 CDN, yielding an average repair cost per case of $1144 CDN for the Sureflex versus $0 for the Boston fiber (P < 0.01). CONCLUSIONS: Both optical fibers perform well in non-lower pole locations. However, the challenge for laser fibers in lower pole URNS is to maintain TIR. Fiber failure reflects an inability to maintain reflection and is not based on energy used or stone burden. The Boston Flexiva laser fiber has fewer failures, resulting in $0 repair cost per case, compared to the Sureflex fiber in URNS with an average repair cost of $1144 CDN per case. Lasers Surg. Med. 50:798-801, 2018. © 2018 Wiley Periodicals, Inc.

Investigation of aminoglycoside resistance inducing conditions and a putative AmrAB-OprM efflux system in Burkholderia vietnamiensis.

BACKGROUND: Burkholderia cepacia complex (BCC) bacteria are highly virulent, typically multidrug-resistant, opportunistic pathogens in cystic fibrosis (CF) patients and other immunocompromised individuals. B. vietnamiensis is more often susceptible to aminoglycosides than other BCC species, and strains acquire aminoglycoside resistance during chronic CF infection and under tobramycin and azithromycin exposure in vitro, apparently from gain of antimicrobial efflux as determined through pump inhibition. The aims of the present study were to determine if oxidative stress could also induce aminoglycoside resistance and provide further observations in support of a role for antimicrobial efflux in aminoglycoside resistance in B. vietnamiensis. FINDINGS: Here we identified hydrogen peroxide as an additional aminoglycoside resistance inducing agent in B. vietnamiensis. After antibiotic and hydrogen peroxide exposure, isolates accumulated significantly less [3H] gentamicin than the susceptible isolate from which they were derived. Strains that acquired aminoglycoside resistance during infection and after exposure to tobramycin or azithromycin overexpressed a putative resistance-nodulation-division (RND) transporter gene, amrB. Missense mutations in the repressor of amrB, amrR, were identified in isolates that acquired resistance during infection, and not in those generated in vitro. CONCLUSIONS: These data identify oxidative stress as an inducer of aminoglycoside resistance in B. vietnamiensis and further suggest that active efflux via a RND efflux system impairs aminoglycoside accumulation in clinical B. vietnamiensis strains that have acquired aminoglycoside resistance, and in those exposed to tobramycin and azithromycin, but not hydrogen peroxide, in vitro. Furthermore, the repressor AmrR is likely just one regulator of the putative AmrAB-OprM efflux system in B. vietnamiensis.

Perioperative outcomes of primary renal tumour resections: comparison of in-hours to out-of-hours surgery.

PURPOSE: Primary resection is typically performed for children with localised suspected Wilms tumours. Resource limitation may necessitate performing these operations nights and weekends. We hypothesise that outcomes will be worse in patients having nephrectomies out-of-hours (OOH) compared to those in-hours (IH). METHODS: With IRB ethics approval, primary renal tumour resections performed on oncology patients from 1989-2011 were reviewed retrospectively. IH operations were defined as Monday-Friday 0745-1530 hours. Outcomes included major intraoperative complications, capsule rupture, and blood loss. Data were analysed using Fischer Exact and Mann-Whitney U tests. RESULTS: There were 64 patients with renal tumours who underwent primary resection. Forty-five procedures were performed IH, and 19 OOH. Groups were similar in age, ASA status, tumour size and grade. In a comparison of major intraoperative complications, capsule rupture, and mean blood loss, differences were 2 vs. 26% (p = 0.007), 27 vs. 42% (p = 0.12), 178 vs. 244 ml (p = 0.15) for IH and OOH respectively. There was one perioperative mortality (OOH). CONCLUSIONS: Primary renal tumour resections performed OOH were associated with an increase in major complications compared to those performed in standard hours. Avoidance of OOH operating where possible may reduce morbidity for children undergoing primary renal tumour resections.

Accuracy and Readability of Kidney Stone Patient Information Materials Generated by a Large Language Model Compared to Official Urologic Organizations.

OBJECTIVE: To compare the readability and accuracy of large language model generated patient information materials (PIMs) to those supplied by the American Urological Association (AUA), Canadian Urological Association (CUA), and European Association of Urology (EAU) for kidney stones. METHODS: PIMs from AUA, CUA, and EAU related to nephrolithiasis were obtained and categorized. The most frequent patient questions related to kidney stones were identified from an internet query and input into GPT-3.5 and GPT-4. PIMs and ChatGPT outputs were assessed for accuracy and readability using previously published indexes. We also assessed changes in ChatGPT outputs when a reading level was specified (grade 6). RESULTS: Readability scores were better for PIMs from the CUA (grade level 10-12), AUA (8-10), or EAU (9-11) compared to the chatbot. GPT-3.5 had the worst readability scores at grade 13-14 and GPT-4 was likewise less readable than urologic organization PIMs with scores of 11-13. While organizational PIMs were deemed to be accurate, the chatbot had high accuracy with minor details omitted. GPT-4 was more accurate in general stone information, dietary and medical management of kidney stones topics in comparison to GPT-3.5, while both models had the same accuracy in the surgical management of nephrolithiasis topics. CONCLUSION: Current PIMs from major urologic organizations for kidney stones remain more readable than publicly available GPT outputs, but they are still higher than the reading ability of the general population. Of the available PIMs for kidney stones, those from the AUA are the most readable. Although Chatbot outputs for common kidney stone patient queries have a high degree of accuracy with minor omitted details, it is important for clinicians to understand their strengths and limitations.

An analysis of benign prostatic hyperplasia surgical treatment reimbursement trends across Canada: Examining provincial changes over the recent decade with comparison to cost of living changes.

INTRODUCTION: A variety of procedures for the endoscopic surgical treatment of symptomatic benign prostatic hyperplasia (BPH) refractory to medical therapy have existed for decades. The present study examines trends in surgeon compensation for these treatments within Canada. METHODS: The physician fee schedule for BPH surgery across 10 Canadian provinces for the years 2010 and 2023 were obtained. A descriptive study examining first, the provincial reimbursement for transurethral resection of prostate (TURP) and laser ablative/enucleation surgery; second, the difference in TURP reimbursement between 2010 and 2023; and third, the annual change in TURP reimbursement juxtaposed with the annual change in the provincial Consumer Price Index (CPI) and annual salary for the working population aged 35-44. RESULTS: Seven of 10 Canadian provinces reimburse laser BPH surgery equally to TURP. The average provincial TURP reimbursement is $545, ranging from $451 in Ontario to $688 in Saskatchewan. Since 2010, TURP reimbursement has varied by province from a 0% net change in Ontario to an increase of 21% in Nova Scotia. Reimbursement for TURP has increased at a slower pace than the local CPI, and for half of the provinces at a slower pace than the annual salary for people aged 35-44. CONCLUSIONS: The compensation model for endoscopic BPH surgery does not have a unified structure in Canada that is consistent across provinces, nor does it keep up with inflation, possibly impacting future recruitment, increasing geographic disparities, and most importantly, limiting the adoption of new BPH therapies.

Kidney Stone Prevalence Based on Self-Report and Electronic Health Records: Insight into the Prevalence of Active Medical Care for Kidney Stones.

OBJECTIVE: To compare rates of patient-reported kidney stone disease to Electronic Health Records (EHR) kidney stone diagnosis using a common dataset to evaluate for socio-demographic differences, including between those with and without active care. METHODS: From the All of Us research database, we identified 21,687 adult participants with both patient-reported and EHR data. We compared differences in age, sex, race, education, employment status and healthcare access between patients with self-reported kidney stone history without EHR data to those with EHR-based diagnoses. RESULTS: In this population, the self-reported prevalence of kidney stones was 8.6% overall (n = 1877), including 4.6% (n = 1004) who had self-reported diagnoses but no EHR data. Among those with self-reported kidney stone diagnoses only, the median age was 66. The EHR-based prevalence of kidney stones was 5.7% (n = 1231), median age 67. No differences were observed in age, sex, education, employment status, rural/urban status, or ability to afford healthcare between groups with EHR diagnosis or self-reported diagnosis only. Of patients who had a self-reported history of kidney stones, 24% reported actively seeing a provider for kidney stones. CONCLUSION: Kidney stone prevalence by self-report is higher than EHR-based prevalence in this national dataset. Using either method alone to estimate kidney stone prevalence may exclude some patients with the condition, although the demographic profile of both groups is similar. Approximately 1 in 4 patients report actively seeing a provider for stone disease.

Innovations in Endourologic Stone Surgery: Contemporary Practice Patterns from a Global Survey.

Objective: The purpose of this study is to evaluate the current availability of technology for urolithiasis treatment and ureteroscopy (URS). Perioperative practice patterns, availability of ureteroscopic technologies, pre- and poststenting practices, and methods to alleviate stent-related symptoms (SRS) were assessed via a survey of members of the Endourological Society. Methods: We distributed a 43-question survey online via the Qualtrics platform to members of the Endourological Society. The survey consisted of questions pertaining to the following topics: general (6), equipment (17), preoperative URS (9), intraoperative URS (2), and postoperative URS (9). Results: A total of 191 urologists responded to the survey and 126 completed all questions of the survey (66%). Fifty-one percent (65/127) of urologists were fellowship trained and dedicated an average of 58% of their practice to stone management. In terms of procedures, most urologists performed URS most commonly (68%), followed by percutaneous nephrolithotomy (23%) and extracorporeal shockwave lithotripsy (11%). Ninety percent (120/133) of respondent urologists purchased a new ureteroscope within the last 5 years (16% single-use scopes, 53% reusable, and 31% purchased both). Fifty-three percent (70/132) of the respondents stated that they would be interested in a ureteroscope that can sense intrarenal pressure, with an additional 28% (37/132) stating they would be interested depending on the cost. Seventy-four percent (98/133) of responders purchased a new laser within the last 5 years, and 59% (57/97) changed their lasering technique due to the new laser. Urologists are performing primary ureteroscopy for obstructing stones in 70% of cases, and prefer prestenting patients for subsequent URS in 30% (on average after 21 days). Seventy-one percent (90/126) of responders insert a ureteral stent after uncomplicated URS, which is removed, on average, after 8 days in uncomplicated cases and 21 days after complicated URS. Most urologists give analgesics, alpha-blockers, and anticholinergics for SRS and <10% prescribe opioids. Conclusion: Our survey revealed urologists' eagerness for the early adoption of novel technologies and adherence to conservative practice patterns focused on patient safety.

Development and preliminary usability testing of an electronic conversation guide incorporating patient values and prognostic information in preparation for older people's decision-making near the end of life.

Initiating end-of-life conversations can be daunting for clinicians and overwhelming for patients and families. This leads to delays in communicating prognosis and preparing for the inevitable in old age, often generating potentially harmful overtreatment and poor-quality deaths. We aimed to develop an electronic resource, called Communicating Health Alternatives Tool (CHAT) that was compatible with hospital medical records software to facilitate preparation for shared decision-making across health settings with older adults deemed to be in the last year of life. The project used mixed methods including: literature review, user-directed specifications, web-based interface development with authentication and authorization; clinician and consumer co-design, iterative consultation for user testing; and ongoing developer integration of user feedback. An internet-based conversation guide to facilitate clinician-led advance care planning was co-developed covering screening for short-term risk of death, patient values and preferences, and treatment choices for chronic kidney disease and dementia. Printed summary of such discussion could be used to begin the process in hospital or community health services. Clinicians, patients, and caregivers agreed with its ease of use and were generally accepting of its contents and format. CHAT is available to health services for implementation in effectiveness trials to determine whether the interaction and documentation leads to formal decision-making, goal-concordant care, and subsequent reduction of unwanted treatments at the end of life.

Decision-making and improvements in health-related quality of life in patients with kidney stones: comparing surgery versus observation using a mixed methods analysis.

The experience of patients who choose observation or surgery for kidney stones has not been well established. We compared these patients using qualitative interviews, the Wisconsin Quality of Life questionnaire (WISQOL), and the Cambridge Renal Stone Patient Reported Outcome Measure (CReSP). Adult patients with upper tract urinary calculi for whom observation or intervention were options underwent qualitative interviews at baseline and at 2 months. WISQOL and CReSP were administered at baseline, and at 6-16 weeks post operatively if surgery was selected. Comparisons in patient experiences and quality of life measures were performed between groups. Among 15 patients who opted for surgery and 10 patients who opted for observation, we identified major themes in patient experiences related to context, health care episodes, patient responses, and perceived outcomes. A conceptual framework for the domains of patient experience during kidney stone disease was developed, which can be used by clinicians and patients to shape discussion. Baseline standardized WISQOL and CReSP scores were comparable between groups. In the surgery group, both WISQOL and CReSP scores improved after surgery (WISQOL 58 to 83, higher is better, p = 0.003; CReSP 31 to 23, lower is better, p = 0.009). Patients who underwent surgery for kidney stones reported improvements in quality of life after treatment via WISQOL and CReSP. A conceptual framework was developed for the patient experience of kidney stones which provides a common language for patients and clinicians.

Antibiotics versus no treatment for asymptomatic bacteriuria in residents of aged care facilities: a systematic review and meta-analysis.

BACKGROUND: Asymptomatic bacteriuria (ASB) is common among residents of residential aged care facilities (RACFs). However, differentiating between an established urinary tract infection and ASB in older adults is difficult. As a result, the overuse of dipstick urinalysis, as well as the subsequent initiation of antibiotics, is common in RACFs. AIM: To find, appraise, and synthesise studies that reported the effectiveness, harms, and adverse events associated with antibiotic treatment for older patients with ASB residing in RACFs. DESIGN AND SETTING: A systematic review using standard Cochrane methods of RACF residents with ASB using antibiotics against placebo, or no treatment. METHOD: Three electronic databases (PubMed, EMBASE, and CENTRAL), clinical trial registries, and forward-backward reference checks of included studies were searched. RESULTS: Nine randomised controlled trials, comprising 1391 participants were included; two of which used a placebo comparator, and the remaining seven used no therapy control groups. There was a relatively small number of studies assessed per outcome and an overall moderate risk of bias. Outcomes related to mortality, development of ASB, and complications were comparable between the two groups. Antibiotic therapy was associated with a higher number of adverse effects (four studies; 303 participants; risk ratio [RR] 5.62, 95% confidence interval [CI] = 1.07 to 29.55, P = 0.04) and bacteriological cure (nine studies; 888 participants; RR 1.89, 95% CI = 1.08 to 3.32, P = 0.03). CONCLUSION: Overall, although antibiotic treatment was associated with bacteriological cure, it was also associated with significantly more adverse effects. The harms and lack of clinical benefit of antibiotic use for older patients in RACFs may outweigh the benefits.

Clinician Versus Nomogram Predicted Estimates of Kidney Stone Recurrence Risk.

Purpose: Kidney stone recurrence rates vary between patients. A patient's risk informs the frequency and intensity of preventative interventions. Clinicians routinely use clinical experience to estimate risk. We sought to compare clinician estimated recurrence risk with the recurrence of kidney stones (ROKS) nomogram. Materials and Methods: We surveyed members of the Endourological Society with clinical expertise in kidney stones. Respondents estimated the risk of recurrence for patients in three clinical vignettes corresponding to low, intermediate, and high recurrence risk from the nomogram. Clinician estimates were compared with ROKS estimates. Results: The majority of the 318 respondents were from North America (n = 127, 40%). The most commonly estimated recurrence was 50% at 5 years. The respondents' estimates were significantly different from the ROKS predicted recurrence rate for all cases (Case 1, 50% vs 93% p < 0.0001; Case 2, 50% vs 60% p < 0.0001; Case 3, 60% vs 22% p < 0.0001). The ROKS predicted estimates ranged from 22% to 93%, whereas the median urologist-derived 5-year risk estimates for each case ranged from 50% to 60%. The median range of estimates by respondents across cases was 20%, narrower than the 71% for the ROKS nomogram. The majority of respondents (95%) do not use nomograms in practice, mostly because of lack of awareness of useful nomograms (59%). Conclusions: This study suggests that clinicians may not be able to distinguish those with high and low recurrence risk when compared with peers and when compared with a nomogram. Clinical decision support tools are needed to enable clinicians to better estimate stone recurrence risk.

Systematic review automation tools improve efficiency but lack of knowledge impedes their adoption: a survey.

OBJECTIVE: We investigated systematic review automation tool use by systematic reviewers, health technology assessors and clinical guideline developerst. STUDY DESIGN AND SETTING: An online, 16-question survey was distributed across several evidence synthesis, health technology assessment and guideline development organizations. We asked the respondents what tools they use and abandon, how often and when do they use the tools, their perceived time savings and accuracy, and desired new tools. Descriptive statistics were used to report the results. RESULTS: A total of 253 respondents completed the survey; 89% have used systematic review automation tools - most frequently whilst screening (79%). Respondents' "top 3" tools included: Covidence (45%), RevMan (35%), Rayyan and GRADEPro (both 22%); most commonly abandoned were Rayyan (19%), Covidence (15%), DistillerSR (14%) and RevMan (13%). Tools saved time (80%) and increased accuracy (54%). Respondents taught themselves to how to use the tools (72%); lack of knowledge was the most frequent barrier to tool adoption (51%). New tool development was suggested for the searching and data extraction stages. CONCLUSION: Automation tools will likely have an increasingly important role in high-quality and timely reviews. Further work is required in training and dissemination of automation tools and ensuring they meet the desirable features of those conducting systematic reviews.

Defining postoperative ileus and associated risk factors in patients undergoing radical cystectomy with an Enhanced Recovery After Surgery (ERAS) program.

INTRODUCTION: Postoperative ileus (POI) is a common complication of radical cystectomy (RC), occurring in 1.6-23.5% of cases. It is defined heterogeneously in the literature. POI increases hospital length of stay and postoperative morbidity. Factors such as age, epidural use, length of procedure, and blood loss may impact POI. In this study, we aimed to evaluate risk factors that contribute to POI in a cohort of patients managed with a comprehensive Enhanced Recovery After Surgery (ERAS) protocol. METHODS: A retrospective review of consecutive patients who underwent RC from March 2015 to December 2016 at Vancouver General Hospital was performed. POI was defined a priori as insertion of nasogastric tube for nausea or vomiting, or failure to advance to a solid diet by the seventh postoperative day. To illustrate heterogeneity in previous studies, we also evaluated POI using other previously reported definitions in the RC literature. The influence of potential risk factors for POI, including patient comorbidities, American Society of Anesthesiologists score, gender, age, prior abdominal surgery or radiation, length of operation, diversion type, extent of lymph node dissection, removal date of analgesic catheter, blood loss, and fluid administration volume was analyzed. RESULTS: Thirty-six (27%) of 136 patients developed POI. Using other previously reported definitions for POI, the incidence ranged from <1-51%. Node-positive status and age at surgery were associated with POI on univariate analysis but not multivariable analysis. CONCLUSIONS: A large range of POI incidence was observed using previously published definitions of POI. We advocate for a standardized definition of POI when evaluating RC outcomes. POI occurs frequently even with a comprehensive ERAS protocol, suggesting that additional measures are needed to reduce the rate of POI.

A Multi-institutional Review of Single-access Percutaneous Nephrolithotomy for Complex Staghorn Stones.

BACKGROUND: With the heterogeneous distribution of novel surgical technologies and variable physician training, there is a need to re-evaluate contemporary outcomes of percutaneous nephrolithotomy (PCNL) for complex staghorn stones. OBJECTIVE: To evaluate contemporary outcomes of guideline-supported treatment for patients with staghorn kidney stones using single-access PCNL in multiple North American centers. DESIGN, SETTING AND PARTICIPANTS: We performed a multi-institutional retrospective review of staghorn stones managed from January 1, 2017 to January 1, 2019, inclusive. We excluded patients with more than a single percutaneous access per renal unit and those who underwent a concomitant contralateral procedure. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Safety (Clavien-Dindo complications) and efficacy in terms of a strictly defined stone-free rate were examined for single-access PCNL performed on staghorn stones with a Guy's stone score of 3-4. RESULTS AND LIMITATIONS: We evaluated 301 patients meeting the inclusion criteria with an average age of 57 yr (range 18-87). All stones had a Guy's stone score of 3 (36.2%) or 4 (63.8%). The mean (± standard deviation) stone burden was 191.4 ± 49.8 mm2. Of the 297 patients (98.6%) who underwent computed tomography on postoperative day 1, 132 (44.4%) showed no residual stone, 111 (37.3%) had a largest fragment <4 mm, and 54 (18.2%) had a fragment ≥4 mm after primary single-access PCNL. Secondary procedures were performed in 117 patients (38.9%). Imaging at 3 mo demonstrated that 210/257 patients (82%) were stone-free. The overall complication rate was 17.9%, with 11 patients (3.7%) experiencing Clavien-Dindo grade ≥3 complications. CONCLUSIONS: Single-access PCNL for complex staghorn stones is safe and effective. High stone-free rates with minimal morbidity are achievable with current techniques. PATIENT SUMMARY: This study confirms that single-access percutaneous nephrolithotomy provides excellent outcomes in the treatment of complex kidney stones. This surgical technique has both safe and effective outcomes that are reproducible across multiple centers in North America.