Metabolic syndrome and the urinary microbiome of patients undergoing percutaneous nephrolithotomy.

Objective: To identify possible stone-promoting microbes, we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome (MetS). The association between MetS and urinary stone disease is well established, but the exact pathophysiologic relationship remains unknown. Recent evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis risk. Methods: At the time of percutaneous nephrolithotomy, bladder urine and stone fragments were collected from patients with and without MetS. Both sample types were subjected to expanded quantitative urine culture (EQUC) and 16 S ribosomal RNA gene sequencing. Results: Fifty-seven patients included 12 controls (21.1%) and 45 MetS patients (78.9%). Both cohorts were similar with respect to demographics and non-MetS comorbidities. No controls had uric acid stone composition. By EQUC, bacteria were detected more frequently in MetS stones (42.2%) compared to controls (8.3%) (p=0.041). Bacteria also were more abundant in stones of MetS patients compared to controls. To validate our EQUC results, we performed 16 S ribosomal RNA gene sequencing. In 12/16 (75.0%) sequence-positive stones, EQUC reliably isolated at least one species of the sequenced genera. Bacteria were detected in both "infectious" and "non-infectious" stone compositions. Conclusion: Bacteria are more common and more abundant in MetS stones than control stones. Our findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.

Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer.

Introduction: Intravesical therapy (IVT), including Bacillus Calmette-Guérin (BCG), is the standard of care for high grade (HG) non-muscle invasive bladder cancer (NMIBC). Despite the use of IVT, many patients recur after treatment. The bladder microbiome and its role in disease processes has recently risen to prominence. We aim to characterize changes that occur in the bladder microbiome over the course of intravesical therapy and assess whether these changes correlate with outcomes in patients with NMIBC. Methods: Patients with NMIBC undergoing induction BCG or intravesical therapy were prospectively enrolled from January 2019 to March 2020. Patients with clinical T2 or greater pathology or active urinary tract infection at enrollment were excluded. Twenty-nine patients had catheterized (bladder) urine samples collected prior to induction intravesical therapy and prior to each IVT instillation. Twenty-seven received BCG while 2 received intravesical gemcitabine. Bacteria were identified using 16S ribosomal RNA gene sequencing. Bladder microbiome changes were evaluated and differences between patients who recurred and patients who did not recur after IVT were investigated. Results: Across the 29 patients analyzed, bacterial richness decreased significantly following intravesical therapy (Richness, P=0.01). Evenness and overall diversity did not change significantly (Pielou, P=0.62; Shannon, P=0.13). Patients who experienced recurrence had a higher relative abundance of Aerococcus in their urine (P<0.01), while those who did not recur had significantly more Ureaplasma (P=0.01) and Escherichia/Shigella species (P=0.05). Patients with decreased levels of alpha diversity were more likely to fall within the non-recurrence cohort. Conclusion: IVT for NMIBC appears to change the urinary microbiome by decreasing richness while not altering evenness or overall diversity. The presence of Aerococcus species may be predictive of a poor cancer response to IVT, while the presence of Ureaplasma and Escherichia/Shigella may predict a favorable response to IVT. Further studies are warranted to elucidate and confirm the significance of changes in the bladder microbiome.

Workforce Issues in Urology.

The future supply of urologists is not on pace to account for future demands of urologic care. This impending urologic shortage sits on a backdrop of multiple other workforce issues. In this review, we take an in-depth look at several pressing issues facing the urologic workforce, including the impending urology shortage, gender and diversity concerns, growing levels of burnout, and the effects of the coronavirus pandemic. In doing so, we highlight specific areas of clinical practice that may need to be addressed from a health care policy standpoint.

Putting Patients Ahead by Leaving Nothing Behind: An Emerging Treatment Paradigm in Minimally Invasive Surgical Therapy for Benign Prostatic Hyperplasia.

Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) are highly prevalent in older men. The long-term clinical utility of lifestyle modification and oral medications for LUTS is limited. There is a great clinical need for safe, effective, and durable BPH therapies for men who unsuccessfully attempt conservative measures. Enthusiasm for transurethral resection of the prostate has declined due to surgical risk, high rates of postoperative sexual dysfunction, and the perceived invasive nature therein. Consequently, interest has grown in developing minimally invasive surgical treatments (MISTs) that are efficacious but with a more favorable risk profile in order to better align with patient preferences. This review evaluates currently available MISTs for BPH. Further, we critically examine a "Leave Nothing Behind" philosophy in MIST for BPH since implantation of permanent metallic devices may be associated with increased long-term failure rates.

The New American Urological Association Benign Prostatic Hyperplasia Clinical Guidelines: 2019 Update.

PURPOSE OF REVIEW: The goal of this paper was to analyze the efficacy of the current modalities available to surgically treat lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). RECENT FINDINGS: There have been significant surgical advancements for the treatment of BPH, including an increasing development and utilization of minimally invasive surgical techniques (MISTs). These procedures have varying outcomes that are critical to understand. In addition, MISTs have important adverse effects, though have minimized effects on sexual function when compared to more invasive surgical techniques. It is important for all urologists to be familiar with the surgical techniques available to treat BPH and the updated American Urological Association (AUA) Guidelines. Further studies evaluating efficacy, safety, and sexual functioning will help guide care in the future and evolve practice.

Surgical Reintervention Rate after Prostatic Urethral Lift: Systematic Review and Meta-Analysis Involving over 2,000 Patients.

PURPOSE: The surgical reintervention rate after prostatic urethral lift is not well characterized but has been estimated at 2% to 3% per year. We performed a systematic review and meta-analysis to determine the surgical reintervention rate after prostatic urethral lift. MATERIALS AND METHODS: We systematically searched MEDLINE®, Embase® and the Cochrane Central Register of Controlled Trials for studies of men treated with prostatic urethral lift reporting at least 1 year of maximum followup data. We performed a random effects meta-analysis to estimate the annual rate of surgical reintervention after prostatic urethral lift, including those performed for lower urinary tract symptoms or involving device explant, additions or replacement. The robustness of the meta-analysis conclusions was evaluated in a one-study removed analysis and heterogeneity was investigated with a subgroup analysis. RESULTS: In 11 studies (2,016 patients) 153 surgical reinterventions were performed, among which transurethral resection of the prostate/laser (51.0%), repeat prostatic urethral lift (32.7%) and device explant (19.6%) were most common. The annual rate of surgical reintervention was 6.0% per year (95% CI 3.0-8.9). These results were not significantly influenced by any single study. The annual rate of surgical intervention was significantly influenced by the mean duration of patient followup. Surgical reintervention rates were 4.3% per year in studies with 1 year or less mean followup, 10.7% per year in studies with more than 1 year to 3 years mean followup and 5.8% per year in a single study with more than 3 years mean followup (p=0.04). CONCLUSIONS: The surgical reintervention rate with prostatic urethral lift is 6.0% per year and is higher in studies with longer followup durations.

Penile Prosthesis Implantation and Timing Disparities After Radical Prostatectomy: Results From a Statewide Claims Database.

BACKGROUND: Many patients with erectile dysfunction (ED) after radical prostatectomy (RP) improve with conservative therapy but some do not; penile prosthesis implantation rates have been sparsely reported, and have used nonrepresentative data sets. AIM: To characterize rates and timing of penile prosthesis implantation after RP and to identify predictors of implantation using a more representative data set. METHODS: The Healthcare Cost and Utilization Project State Inpatient and State Ambulatory Surgery databases for Florida from 2006 to 2015 were used. Patients undergoing RP (2006-2012) were tracked longitudinally for penile prosthesis implantation. Patient and clinical data were analyzed using multivariable logistic regression. OUTCOMES: The primary outcome was risk-adjusted predictors of prosthesis implantation, and the secondary outcome was predictors of the highest quartile of time between RP and penile prosthesis. RESULTS: Of 29,288 men who had RP, 1,449 (4.9%) patients underwent subsequent prosthesis. The mean time from RP to prosthesis was 2.6 years (median: 2.1; interquartile range [IQR]: 1.2-3.5). Adjusted predictors of prosthesis implantation included open RP (odds ratio [OR]: 1.5, P < .01), African American race (OR: 1.7, P < .01) or Hispanic ethnicity (OR: 3.2, P < .01), and Medicare (OR: 1.4, P < .01) insurance. Oler patients (age >70 years; OR: 0.7, P < .01) and those from the highest income quartile relative to the lowest (OR: 0.8, P < .05) were less likely to be implanted. Adjusted predictors of longer RP-to-implantation time (highest quartile: median: 4.7 years; IQR: 3.9-6.0 years) included open RP (OR: 1.78, P < .01), laparoscopic RP (OR: 4.67, P < .01), Medicaid (OR: 3.03, P < .05), private insurance (OR: 2.57, P < .01), and being in the highest income quartile (OR: 2.52, P < .01). CLINICAL IMPLICATIONS: These findings suggest ED treatment healthcare disparities meriting further investigation; upfront counseling on all ED treatment modalities and close monitoring for conservative treatment failure may reduce lost quality of life years. STRENGTHS & LIMITATIONS: This study is limited by its use of administrative data, which relies on accurate coding and lacks data on ED questionnaires/prior treatments, patient-level cost, and oncologic outcomes. Quartile-based analysis of income and time between RP and prosthesis limits the conclusions that can be drawn. CONCLUSION: Less than 5% of post-RP patients undergo penile prosthesis implantation, with open RP, Medicare, African American race, and Hispanic ethnicity predicting post-RP implantation; living in the wealthiest residential areas predicts lower likelihood of implantation compared to the least wealthy areas. Patients with the longest time between RP and prosthesis are more likely to live in the wealthiest areas or have undergone open/laparoscopic RP relative to robotic RP. Bajic P, Patel PM, Nelson MH, et al. Penile Prosthesis Implantation and Timing Disparities After Radical Prostatectomy: Results From a Statewide Claims Database. J Sex Med 2020;17:1175-1181.

A novel metric for treatment durability in clinical trials of minimally invasive treatments for benign prostatic hyperplasia.

Introduction: Clinical trial manuscripts commonly report results of individual endpoints. However, durability of a medical treatment may be difficult to determine when evaluating endpoint outcomes individually. We reviewed pivotal trial manuscripts of two minimally invasive benign prostatic hyperplasia (BPH) treatments and estimated the rate of treatment durability using a composite, symptom-centric metric.Methods: Data were derived from published pivotal trial reports of two minimally invasive BPH treatments - water vapor thermal therapy (WVTT) and prostatic urethral lift (PUL). We estimated the risk of medical or surgical retreatment using life-table methods, and the number of patients achieving the minimal clinically important difference (MCID) for the International Prostate Symptom Score (IPSS) using z-score methods. Treatment durability was defined as a MCID on the IPSS at the 4-year follow-up visit while free from medical or surgical retreatment.Results: Comparing WVTT to PUL, the rate of medical or surgical retreatment was 10.6% vs. 31.8%, the IPSS MCID was achieved in 82.2% vs. 79.5%, and treatment durability rates were 71.8% vs. 51.7%.Conclusions: Utilization of a composite treatment durability metric derived from endpoints commonly reported in the BPH literature may allow patients and their providers to make better informed treatment decisions.

Infectious Adverse Events Following the Placement of a Penile Prosthesis: A Systematic Review.

INTRODUCTION: Infection remains a prominent concern following penile implantation. Recognition of the risk factors for infection may help to guide surgeons toward reducing the risk of prosthetic contamination. AIM: To gain a further understanding of infectious adverse events following penile prosthesis, we performed a systematic literature review. METHODS: As part of the 2018 American Urological Association Erectile Dysfunction Clinical Guidelines and with the support of the American Urological Association, we performed a comprehensive review of the PubMed, Embase, and Cochrane databases to search for eligible articles published between January 1, 1965, and July 20, 2016, to identify articles reporting infectious adverse events following prosthesis placement. MAIN OUTCOME MEASURE: The main outcome measure was infectious adverse events following penile prosthesis placement. RESULTS: Ninety-one articles reporting infectious adverse events representing 97 study arms were identified. Prosthetic infection rates ranged from 0% to 24.6% across all series. Inflatable penile prostheses displayed a wider range (0-24.6%) than malleable devices (0-9.1%); the most frequently reported infection rate for inflatable devices was 5% or less. With the advent of device coatings and improved surgical techniques, infectious adverse events have decreased. Infections among diabetic patients also decreased throughout the reviewed body of literature, with the most recent series reporting rates consistent with those of non-diabetic patients. Furthermore, no glycosylated hemoglobin cutoff was found to infer increased or decreased risk of prosthesis infection. CONCLUSION: Overall penile prosthetic infectious adverse events have decreased as surgical techniques have improved and the use of antimicrobial coating has gained in popularity. These advances have demonstrated significant benefits for all patients, particularly diabetic patients who experience infection rates similar to those of non-diabetic patients in recent reports. Further technological advancements for the prevention of biofilm formation is warranted. Mahon J, Dornbier R, Wegrzyn G, et al. Infectious Adverse Events Following the Placement of a Penile Prosthesis: A Systematic Review. Sex Med Rev 2020;8:348-354.

The microbiome of calcium-based urinary stones.

Historically, the role of bacteria in urinary stone disease (USD) has been limited to urease-producing bacteria associated with struvite stone formation. However, growing evidence has revealed bacteria associated with stones of non-struvite composition. These bacteria may be derived from either urine or from the stones themselves. Using 16S rRNA gene sequencing and an enhanced culture technique (EQUC), we identified the urine and stone microbiota of USD patients and then determined if bacteria were statistically enriched in the stones relative to the urine. From 52 patients, bladder urine and urinary stones were collected intraoperatively during ureteroscopy. Stone homogenate and urine specimens were subjected to 16S rRNA gene sequencing and EQUC. Standard Chi-squared tests were applied to determine if the relative abundance of any bacterial taxon was significantly enriched in urinary stones compared to urine. Stones were primarily calcium-based. 29/52 (55.8%) stones had bacteria detected by 16S rRNA gene sequencing. Of these, dominant bacterial taxa were enriched from 12 stones. Bacterial taxa isolated by EQUC include members of the genera Staphylococcus, Enterobacter, Escherichia, Corynebacterium, and Lactobacillus. Dominant bacterial genera were enriched compared to paired bladder urine. Differences between the stone and urine microbiota may indicate that certain bacteria contribute to USD pathophysiology. Further investigation is warranted.

Use of Surgery for Post-Prostatectomy Incontinence.

PURPOSE: Stress urinary incontinence following radical prostatectomy is common and potentially debilitating. Surgical therapy with a urethral sling or an artificial urinary sphincter is an effective option with high patient satisfaction in men in whom conservative measures fail to treat post-prostatectomy incontinence. We sought to characterize the contemporary utilization of surgical therapy of post-prostatectomy incontinence using an all payer database. MATERIALS AND METHODS: We used the Healthcare Cost and Utilization Project databases for Florida from 2006 to 2015 and identified men who underwent radical prostatectomy between 2006 and 2012 using ICD procedure codes. Patients were tracked longitudinally for placement of an ambulatory or inpatient urethral sling, or an artificial urinary sphincter between 2006 and 2015. Patient and clinical data were extracted and analyzed with descriptive statistics. A multivariable logistic regression model was constructed to determine risk adjusted predictors of subsequent incontinence surgery. RESULTS: During the study period 29,287 men underwent radical prostatectomy, of whom 1,068 (3.6%) were treated with subsequent incontinence surgery a median of 23.5 months after prostatectomy. On multivariate analysis risk factors for incontinence surgery included age groups 61 to 70 years (OR 1.25, p=0.008) and 71 to 80 years (OR 1.34, p=0.022), Medicare insurance (OR 1.33, p <0.005) and an increased Charlson Comorbidity Index (OR 1.13 per unit increase, p <0.005). CONCLUSIONS: Of patients who underwent radical prostatectomy 3.6% subsequently underwent stress urinary incontinence surgery. Post-prostatectomy incontinence surgery is likely under performed and delayed in performance based on the previously reported prevalence of severe post-prostatectomy incontinence and the natural history of symptoms. Efforts to increase prompt repair of refractory or severe incontinence can greatly improve patient quality of life after radical prostatectomy.

Implications of the Genitourinary Microbiota in Prostatic Disease.

PURPOSE OF REVIEW: To summarize recent investigation into associations between the genitourinary microbiota and prostatic disease. RECENT FINDINGS: The genitourinary tract is not sterile. There are microbial communities (microbiota) in each niche of the genitourinary tract including the bladder, prostate, and urethra, which have been the subject of increasing scientific interest. Investigators have utilized several unique methods to study them, resulting in a highly heterogeneous body of literature. To characterize these genitourinary microbiota, diverse clinical specimens have been analyzed, including urine obtained by various techniques, seminal fluid, expressed prostatic secretions, and prostatic tissue. Recent studies have attempted to associate the microbiota detected from these samples with urologic disease and have implicated the genitourinary microbiota in many common conditions, including benign prostatic hyperplasia (BPH), prostate cancer, and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). In this review, we summarize the recent literature pertaining to the genitourinary microbiota and its relationship to the pathophysiology and management of three common prostatic conditions: BPH, prostate cancer, and CP/CPPS.

Socioeconomic and patient-related factors for the management of male urethral stricture disease.

PURPOSE: We sought to determine the socioeconomic and patient factors that influence the utilization of urethroplasty and location of management in the treatment of male urethral stricture disease. METHODS: A retrospective review using the Healthcare Cost and Utilization Project State Inpatient and Ambulatory Surgery and Services Databases for California and Florida was performed. Adult men with a diagnosis of urethral stricture who underwent treatment with urethroplasty or endoscopic dilation/urethrotomy between 2007 and 2011 in California and 2009 and 2014 in Florida were identified by ICD-9 or CPT codes. Patients were categorized based on whether they had a urethroplasty or serial dilations/urethrotomies. Patients were assessed for age, insurance provider, median household income by zip code, Charlson Comorbidity Index, race, prior stricture management, and location of the index procedure. A multivariable logistic regression model was fit to assess factors influencing treatment modality (urethroplasty vs endoscopic management) and location (teaching hospital vs non-teaching hospital). RESULTS: Twenty seven thousand, five hundred and sixty-eight patients were identified that underwent treatment for USD. 25,864 (93.8%) treated via endoscopic approaches and 1704 (6.2%) treated with urethroplasty. Factors favoring utilization of urethroplasty include younger age, lower Charlson Comorbidity score, higher zip code median income quartile, private insurance, prior endoscopic treatment, and management at a teaching hospital. CONCLUSION: Socioeconomic predictors of urethroplasty utilization include higher income status and private insurance. Patient-specific factors influencing urethroplasty were younger age and fewer medical comorbidities. A primary driver of urethroplasty utilization was treatment at a teaching hospital. Older and Hispanic patients were less likely to seek care at these facilities.

Socioeconomic Disparities in the Acute Management of Stone Disease in the United States.

INTRODUCTION: Patients admitted to the hospital with an acute, noninfected episode of urolithiasis are candidates for medical expulsive therapy, ureteral stent placement, or upfront ureteroscopy (URS). We sought to assess socioeconomic factors influencing treatment decisions in managing urolithiasis and to determine differences in outcomes based on treatment modality. MATERIALS AND METHODS: The Healthcare Cost and Utilization Project State Inpatient Database, State Ambulatory Surgery and Services Database, and State Emergency Department Database for California from 2007 to 2011 and for Florida from 2009 to 2014 were utilized. Patients who were admitted to the hospital with a primary diagnosis of kidney or ureteral stone were identified. The initial treatment modality utilized was assessed and factors that influenced that decision were analyzed. Multivariate logistic regression model was fit to determine factors independently associated with upfront URS. Lastly, outcomes of noninfected patients who underwent stent alone vs URS were compared. RESULTS: We identified 146,199 patients who had an inpatient admission with urolithiasis. Overall, 45% of patients had no intervention at the time of their evaluation. Of the 55% of patients who underwent surgical intervention, 42% underwent stent alone, 44% underwent upfront URS, 1% had a PCN tube placement, 8% underwent extracorporeal shockwave lithotripsy, while 5% underwent PCNL. On multivariate logistic regression model, minorities, younger patients, publicly uninsured patients, more comorbid patients, those admitted on the weekends, and those admitted to an academic institution had significantly lower odds of undergoing upfront URS. Secondary analysis demonstrated clinical and economic advantages of upfront URS vs stent alone in eligible patients. CONCLUSION: Upfront URS is an overlooked procedure that has clinical and cost-saving implications. Unfortunately, minorities, publicly insured patients, and those admitted on the weekend are less likely to undergo upfront URS, a disparity that should be addressed by urologist.

Genitourinary Foreign Body in United States: Incidence, Patient Characteristics, Treatments and Economic Burden.

INTRODUCTION: Genitourinary foreign bodies are uncommon, have only been reported in single center case reports or series and little is known about national incidence. Commonly cited risk factors include psychiatric disorders, drug or alcohol intoxication, or autoerotic stimulation. A population study was performed to characterize the incidence, treatments and economic burden of the genitourinary foreign body. METHODS: The Healthcare Cost and Utilization Project Nationwide Inpatient Sample for the years 2012 to 2014 and the Florida State Emergency Department Database and State Inpatient Database for the years 2012 to 2014 were used. Patients were identified as having a diagnosis of genitourinary foreign body by ICD-9 diagnosis codes (939.0, 939.3, 939.9). Patients included in state databases were tracked longitudinally to characterize recurrent visits. RESULTS: Between 2012 and 2014, 1,125 patients were admitted to United States hospitals with a primary diagnosis of genitourinary foreign body. Patients were predominately male (83.6%) and white race (68.4%). Compared to all other inpatients those with genitourinary foreign body were more likely to have a diagnosis of mental health disease (56.9% vs 30.0%, p <0.005) or substance abuse (11.1% vs 5.9%, p <0.005). Overall 64.9% of patients required operative intervention. Mean adjusted cost per admission was $6,835 (SD $360), resulting in $2.61 million in annual national economic burden. CONCLUSIONS: This study is the first to our knowledge to use population level data to characterize the national incidence and patient characteristics of genitourinary foreign bodies, a condition that costs payers $2.6 million annually.

Statins inhibit proliferation and cytotoxicity of a human leukemic natural killer cell line.

BACKGROUND: Natural killer cells comprise the body's first line of defense against virus-infected cells. As is true of all lymphocytes, natural killer cell malignancies can develop, however natural killer cell leukemias can be very difficult to treat due to their intrinsic resistance to chemotherapeutic agents. With the recent understanding that statin drugs may have anti-cancer properties, our investigations have focused on the ability of statins to inhibit the growth and cytotoxicity of the YT-INDY natural killer cell leukemia cell line. RESULTS: Our findings indicate that several statin compounds can inhibit YT-INDY proliferation disrupt cell cycle progression and abrogate natural killer cell cytotoxicity. Since natural killer cell leukemia cytotoxicity may play a role in the pulmonary damage seen in these patients, this is an important finding. Cytotoxicity, proliferation and cell cycle progression could be restored by the addition of mevalonate, signifying that the statin effects are brought about through HMG CoA reductase inhibition. The mevalonate pathway intermediate geranylgeranyl pyrophosphate, but not other intermediates in the mevalonate pathway, partially reversed statin-induced inhibition of YT-INDY proliferation and cytotoxicity. These results suggest that blockage of products made in the latter part of the mevalonate pathway may account for the observed inhibitory effects on YT-INDY proliferation and cytotoxicity. However, geranylgeranyl pyrophosphate could not reverse the statin-induced inhibition of the cell cycle. CONCLUSIONS: These results suggest that the statin drugs should be investigated as a potential therapeutic strategy for human natural killer cell leukemias possibly in combination with chemotherapeutic agents.