VDJServer: A Cloud-Based Analysis Portal and Data Commons for Immune Repertoire Sequences and Rearrangements.

Background: Recent technological advances in immune repertoire sequencing have created tremendous potential for advancing our understanding of adaptive immune response dynamics in various states of health and disease. Immune repertoire sequencing produces large, highly complex data sets, however, which require specialized methods and software tools for their effective analysis and interpretation. Results: VDJServer is a cloud-based analysis portal for immune repertoire sequence data that provide access to a suite of tools for a complete analysis workflow, including modules for preprocessing and quality control of sequence reads, V(D)J gene segment assignment, repertoire characterization, and repertoire comparison. VDJServer also provides sophisticated visualizations for exploratory analysis. It is accessible through a standard web browser via a graphical user interface designed for use by immunologists, clinicians, and bioinformatics researchers. VDJServer provides a data commons for public sharing of repertoire sequencing data, as well as private sharing of data between users. We describe the main functionality and architecture of VDJServer and demonstrate its capabilities with use cases from cancer immunology and autoimmunity. Conclusion: VDJServer provides a complete analysis suite for human and mouse T-cell and B-cell receptor repertoire sequencing data. The combination of its user-friendly interface and high-performance computing allows large immune repertoire sequencing projects to be analyzed with no programming or software installation required. VDJServer is a web-accessible cloud platform that provides access through a graphical user interface to a data management infrastructure, a collection of analysis tools covering all steps in an analysis, and an infrastructure for sharing data along with workflows, results, and computational provenance. VDJServer is a free, publicly available, and open-source licensed resource.

Direct visual internal urethrotomy for isolated, post-urethroplasty strictures: a retrospective analysis.

BACKGROUND: Urethroplasty is often successful for the treatment of male urethral stricture disease, but limited data exists on recurrence management. Our goal was to evaluate direct visual internal urethrotomy (DVIU) as a treatment option for isolated, recurrent strictures after urethroplasty. METHODS: We retrospectively identified male patients who underwent urethroplasty from 1999 to 2013 and developed an isolated, recurrent stricture at the urethroplasty site treated with DVIU. Success was defined as lack of symptomatology and no subsequent intervention. Comparative analysis identified characteristics and stricture properties associated with success. RESULTS: A total of 436 urethroplasties were performed in 401 patients at our institution between 1999 and 2013. Stricture recurrence was noted in 64 (16%) patients. Of these, 47 (73%) underwent a DVIU. A total of 37 patients met inclusion criteria and underwent 50 DVIU procedures at the urethroplasty site. A single DVIU was successful in 13 of 37 patients (35%). A total of 4 of 6 patients required a second DVIU (67%). Overall, 17 of 43 (40%) of the total DVIUs were successful after urethroplasty. Success did not differ by age, stricture length or location, surgical technique, radiation history, prior urethroplasty or DVIU, time to failure, or etiology. CONCLUSIONS: Post-urethroplasty DVIU for isolated, recurrent strictures may be offered as a minimally invasive treatment option. Approximately 40% of patients were spared further intervention.

Somatic syndromes and chronic pain in women with overactive bladder.

AIMS: Mechanisms underlying pain perception and afferent hypersensitivity, such as central sensitization, may impact overactive bladder (OAB) symptoms. However, little is known about associations between OAB symptom severity, pain experience, and presence of comorbid chronic pain syndromes. This study examined relationships between OAB symptoms, somatic symptoms, and specific chronic pain conditions in which central sensitization is believed to play a primary role, in a community-based sample of adult women with OAB. METHODS: We recruited adult women with OAB to complete questionnaires assessing urinary symptoms, pain and somatic symptoms, and preexisting diagnoses of central sensitivity syndromes. We analyzed the effects of overall bodily pain intensity, general somatic symptoms, and diagnoses of central sensitivity syndromes on OAB symptom bother and health-related quality of life. RESULTS: Of the 116 women in this study, over half (54%) stated their urge to urinate was associated with pain, pressure, or discomfort. Participants reported a wide range of OAB symptoms and health-related quality of life. There was a significant, positive correlation between OAB symptoms and somatic symptoms as well as overall pain intensity. Only 7% of women met diagnostic criteria for fibromyalgia; yet these women demonstrated significantly increased OAB symptom burden and decreased OAB quality of life compared to those without fibromyalgia. CONCLUSION: Women with more severe OAB symptoms reported increased general somatic symptom burden and increased overall body pain intensity, especially women with fibromyalgia. These findings suggest that attributes of pain and co-morbidity with chronic pain conditions may impact the experience of OAB symptoms for many women. Neurourol. Urodynam. 36:1113-1118, 2017. © 2016 Wiley Periodicals, Inc.

Perioperative complications of conduit urinary diversion with concomitant cystectomy for benign indications: A population-based analysis.

AIMS: Beyond single-institution case series, limited data are available to describe risks of performing a concurrent cystectomy at the time of urinary diversion for benign end-stage lower urinary tract dysfunction. Using a population-representative sample, this study aimed to analyze factors associated with perioperative complications in patients undergoing urinary diversion with or without cystectomy. METHODS: A representative sample of patients undergoing urinary diversion for benign indications was identified from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 1998 to 2011. Perioperative complications of urinary diversion with and without concomitant cystectomy were identified and coded using the International Classification of Diseases, version 9. Multivariate logistic regression models identified hospital and patient-level characteristics associated with complications of concomitant cystectomy with urinary diversion. RESULTS: There were 15,717 records for urinary diversion identified, of which 31.8% demonstrated perioperative complications: urinary diversion with concurrent cystectomy (35.0%) and urinary diversion without concomitant cystectomy (30.6%). Comparing the two groups, a concomitant cystectomy at the time of urinary diversion was significantly associated with a complication (OR = 1.23, 95%CI: 1.03-1.48). Comorbid conditions of obesity, pulmonary circulation disease, drug abuse, weight loss, and electrolyte disorders were positively associated with a complication, while private insurance and southern geographic region were negatively associated. CONCLUSIONS: A concomitant cystectomy with urinary diversion for refractory lower urinary tract dysfunction elevates risk in this population-representative sample, particularly in those with certain comorbid conditions. This analysis provides critical information for preoperative patient counseling.

Temporal Trends in Conduit Urinary Diversion With Concomitant Cystectomy for Benign Indications: A Population-based Analysis.

OBJECTIVE: To describe national trends in cystectomy at the time of urinary diversion for benign indications. Multiple practice patterns exist regarding the necessity for concomitant cystectomy with urinary diversion for benign end-stage lower urinary tract dysfunction. Beyond single-institution reports, limited data are available to describe how concurrent cystectomy is employed on a national level. MATERIALS AND METHODS: A representative sample of patients undergoing urinary diversion for benign indications with or without concurrent cystectomy was identified from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 1998 to 2011. Using multivariate logistic regression models, we identified hospital- and patient-level characteristics associated with concomitant cystectomy with urinary diversion. RESULTS: There was an increase in the proportion of concomitant cystectomy at the time of urinary diversion from 20% to 35% (P < .001) between 1998 and 2011. The increase in simultaneous cystectomy over time occurred at teaching hospitals (vs community hospitals), in older patients, in male patients, in the Medicare population (vs private insurance and Medicaid), and in those with certain diagnoses. CONCLUSION: There has been an overall increase in the use of cystectomy at the time of urinary diversion for benign indications on a national level, although the indications driving this clinical decision appear inconsistent.

The Impact of Pallidal and Subthalamic Deep Brain Stimulation on Urologic Function in Parkinson's Disease.

OBJECTIVE: Deep Brain Stimulation (DBS) is an established adjunctive surgical intervention for treating Parkinson's disease (PD) motor symptoms. Both surgical targets, the globus pallidus interna (GPi) and subthalamic nucleus (STN), appear equally beneficial when treating motor symptoms but effects on nonmotor symptoms are not clear. Lower urinary tract symptoms (LUTS) are a common PD complaint. Given prior data in STN-DBS, we aimed to further explore potential benefits in LUTS in both targets. METHODS: We performed a prospective, nonblinded clinical trial evaluating LUTS in PD patients in both targets pre and post DBS using validated urologic surveys. Participants were already slated for DBS and target selection predetermined before study entry. LUTS was evaluated using: the American Urological Association (AUA-SI), Quality of Life score (QOL), Overactive Bladder 8 Questionnaire (OAB-q), and Sexual Health Inventory for Men (SHIM). RESULTS: Of 33 participants, 20 underwent STN DBS and 13 had GPi DBS. Patients demonstrated moderate baseline LUTS. The urologic QOL score significantly improved post DBS (3.24 ± 1.77vs. 2.52 ± 1.30; p = 0.03). Analyzed by target, only the STN showed significant change in QOL (3.20 ± 1.61 vs 2.25 ± 1.33; p = 0.04). There were no other significant differences in urologic scores post DBS noted in either target. CONCLUSION: In PD patients with moderate LUTS, there were notable improvements in QOL for LUTS post DBS in the total sample and STN target. There may be differences in DBS effects on LUTS between targets but this will require further larger, blinded studies.

Urinary Incontinence Following Prostate Brachytherapy.

OBJECTIVE: To define the incidence, time course, and risk factors associated with the development of urinary incontinence (UI) following prostate brachytherapy. MATERIALS AND METHODS: A total of 2461 men were identified who underwent permanent interstitial prostate brachytherapy with or without external beam radiation therapy. We examined the relationship between clinical- and treatment-related variables with the onset of UI, defined as leakage requiring pad usage, and further classified as stress (SUI) or urge (UUI) predominant, using univariate and Cox proportional hazards regression models. The changes in International Prostate Symptom Score and quality of life domains were assessed from baseline to last follow, and examined by UI status. RESULTS: Patients were followed for a median of 6.4 years (interquartile range 4.1-9.3). UI was reported in 108 individuals (4.4%), at a median of 1.8 years (interquartile range 5 months-4.4 years): 30 with SUI and 78 with UUI. Seventy-two men (66.7%) reported using 1, 24 (22.2%) using 2, and 12 (11%) using ≥3 pads per day. On multivariate analysis, post-implantation transurethral resection of the prostate, urinary retention, external beam radiation therapy, and higher pretreatment International Prostate Symptom Score were significantly associated with the development of SUI, although transurethral resection of the prostate was the only significant risk factor associated with SUI. Men experiencing UI reported greater declines in urinary quality of life; however, no significant difference was observed between SUI and UUI. CONCLUSION: UI occurred in 4.4% of patients following prostate brachytherapy and is more commonly urge-predominant in character. Distinct risk factors exist for the development of UUI vs SUI. Urinary leakage requiring pad usage was associated with declines in urinary QOL.

The Impact of Urethral Risk Factors on Transcorporeal Artificial Urinary Sphincter Erosion Rates and Device Survival.

PURPOSE: We report the impact of urethral risk factors on erosion rates and device survival outcomes after transcorporeal artificial urinary sphincter placement. MATERIALS AND METHODS: We performed a retrospective analysis of all transcorporeal artificial urinary sphincters placed at a single institution between January 2000 and May 2014. We assessed patient demographic, comorbid diseases and surgical characteristics for risk factors considered poor for device survival. Risk factors were compared to postoperative complications requiring explantation, including cuff erosion, infection and device revision. RESULTS: A total of 37 transcorporeal artificial urinary sphincters were placed in 35 men. Placement was performed as a primary procedure in 21 of 37 cases (56.8%) and as salvage in the remainder. In this transcorporeal population there were 7 explantations (18.9%) due to erosion in 4 cases, cuff downsizing in 2 and infection in 1. Median followup from implantation to last followup was 8.5 months (range 0.9 to 63). Median time from artificial urinary sphincter placement to explantation was 17.3 months (range 0.9 to 63) and time specifically to transcorporeal erosion was 7.4 months (range 0.9 to 26). On univariate analysis no parameters were associated with sphincter cuff erosion but a history of an inflatable penile prosthesis was associated with a higher device explantation rate (60% vs 12.5%, p=0.04). No associations were revealed on multivariate logistic analysis. All 4 cuff erosion cases demonstrated greater than 2 urethral risk factors, including prior radiation therapy in all. The probability of cuff erosion in patients with 2 or more urethral risk factors was 1.65 times the probability of erosion in those with 0 or 1 urethral risk factor (95% CI 1.3, 2.2). The proportion of patients free of erosion at 35 months was 100% in those with 0 or 1 urethral risk factor and 64% in those with 2 or more risk factors (log rank test p=0.00). Similarly the proportion of patients free of explantation at 35 months was 100% in those with 0 or 1 urethral risk factor and 52% in those with 2 or more (log rank test p=0.02). CONCLUSIONS: Transcorporeal artificial urinary sphincter implantation is generally reserved for complex and high risk cases but favorable functional results were demonstrated. However, patients with multiple urethral risk factors face a higher risk of erosion and device loss.

Primary Endoscopic Realignment of Urethral Disruption Injuries--A Double-Edged Sword?

PURPOSE: Controversy remains regarding initial management of traumatic urethral disruption injuries. We evaluated the outcomes of primary endoscopic realignment vs suprapubic tube placement in this patient population. MATERIALS AND METHODS: We reviewed our urological trauma database for patients with blunt trauma related posterior urethral injuries from 2000 to 2014. Patients underwent primary endoscopic realignment or suprapubic tube placement alone. The primary outcome was the success of primary realignment, defined as no further need for urological intervention. Secondary outcomes were the need for endoscopic interventions and/or urethroplasty, time to urethroplasty, urethroplasty success and long-term functional outcomes. RESULTS: A total of 27 patients underwent primary realignment and 14 underwent suprapubic tube placement. Mean followup was 40 months (median 24, range 1 to 152). Realignment was successful in 10 patients (37%) at a mean followup of 67.3 weeks (median 27.3, range 4 to 284). In the 17 cases (63%) that failed mean time to failure was 9.7 weeks (median 8.5, range 1 to 26). Seven patients (26%) treated with realignment and 11 (79%) with a suprapubic tube proceeded to urethroplasty. Mean ± SD time to urethroplasty was significantly shorter in the suprapubic tube group (14.6 ± 7.6 vs 5.8 ± 1.6 months, p = 0.003). There was no difference in operative time, complications, success or functional outcomes. CONCLUSIONS: Management of traumatic urethral disruption injuries by primary endoscopic realignment serves as definitive therapy in more than a third of treated patients. It prevents the need for formal urethroplasty in more than half of failed cases.

Contemporary comparison between retropubic midurethral sling and autologous pubovaginal sling for stress urinary incontinence after the FDA advisory notification.

OBJECTIVE: To compare the efficacy and safety in a contemporary cohort of women who were offered either a pubovaginal sling (PVS) or a synthetic midurethral sling (MUS) after the U.S. Food and Drug Administration notification and made an informed decision on procedure option. METHODS: A total of 201 women were given the option between a PVS and an MUS. Prior anti-incontinence surgery and concomitant surgery other than hysterectomy were not allowed. Minimal follow-up was 12 months. Patients were prospectively followed with validated quality of life questionnaires. Cure, voiding complaints, and complications were compared between the groups. RESULTS: Ninety-one women (45%) underwent PVS and 110 underwent MUS (55%). Median follow-up was 13.8 months. There was no difference in baseline characteristics between the groups except for the prevalence of urge incontinence. Subjective improvement in questionnaire scores was significant for both groups. Cure rate was accomplished in 75.8% of the PVS group patients compared with 80.9% of the MUS group patients (hazard ratio, 1.35; 95% confidence interval, 0.69-2.7; P = .38). Complications and voiding difficulty were similar between the groups. CONCLUSION: In this contemporary cohort of women considered suitable candidates for either a PVS or an MUS, both offer comparable efficacy and complication rates. PVS may be safely offered to patients who would otherwise be good candidates for MUS if they are concerned with the implantation of mesh.

Araport: the Arabidopsis information portal.

The Arabidopsis Information Portal (https://www.araport.org) is a new online resource for plant biology research. It houses the Arabidopsis thaliana genome sequence and associated annotation. It was conceived as a framework that allows the research community to develop and release 'modules' that integrate, analyze and visualize Arabidopsis data that may reside at remote sites. The current implementation provides an indexed database of core genomic information. These data are made available through feature-rich web applications that provide search, data mining, and genome browser functionality, and also by bulk download and web services. Araport uses software from the InterMine and JBrowse projects to expose curated data from TAIR, GO, BAR, EBI, UniProt, PubMed and EPIC CoGe. The site also hosts 'science apps,' developed as prototypes for community modules that use dynamic web pages to present data obtained on-demand from third-party servers via RESTful web services. Designed for sustainability, the Arabidopsis Information Portal strategy exploits existing scientific computing infrastructure, adopts a practical mixture of data integration technologies and encourages collaborative enhancement of the resource by its user community.

Urinary retention rates after intravesical onabotulinumtoxinA injection for idiopathic overactive bladder in clinical practice and predictors of this outcome.

AIMS: The purpose of this study was to find the rate of urinary retention in clinical practice after treatment with onabotulinumtoxinA (BTN/A) for refractory overactive bladder (OAB) symptoms and determine factors that predict this outcome. METHODS: This is a retrospective study of BTN/A for treatment of non-neurogenic, refractory OAB symptoms. Patients were analyzed with respect to their first and second BTN/A injections. The primary outcome measure was postoperative urinary retention. Statistical significance was assessed with multivariate logistic regression. RESULTS: Based on inclusion and exclusion criteria, the study population was 160. Mean age was 64 ± 13.2 years and 24% of the patients were men. The rate of urinary retention was 35% (n = 56). For the first BTN/A treatment, multivariate analysis revealed that preoperative PVR (post-void residual volume) (OR 1.27, 95% CI 1.13-1.43, P < 0.001) and preoperative bladder capacity (OR 1.05, 95% CI 1.01-1.08, P = 0.005) were associated with postoperative urinary retention. In patients with a preoperative PVR of ≥100 ml, 94% (n = 17) went into urinary retention. For those who underwent a second BTN/A treatment, preoperative PVR, BTN/A units injected and retention after the first BTN/A were associated with an increased rate of postoperative retention. CONCLUSIONS: Increased preoperative PVR was associated with urinary retention. The retention rate is higher than that reported in recent clinical trials. The inclusion of patients with a preoperative PVR ≥100 ml and a lower threshold to initiate clean intermittent catheterization contributed to this high rate of retention.

Identification of a novel inhibitor of dengue virus protease through use of a virtual screening drug discovery Web portal.

We report the discovery of a novel small-molecule inhibitor of the dengue virus (DENV) protease (NS2B-NS3pro) using a newly constructed Web-based portal (DrugDiscovery@TACC) for structure-based virtual screening. Our drug discovery portal, an extension of virtual screening studies performed using IBM's World Community Grid, facilitated access to supercomputer resources managed by the Texas Advanced Computing Center (TACC) and enabled druglike commercially available small-molecule libraries to be rapidly screened against several high-resolution DENV NS2B-NS3pro crystallographic structures. Detailed analysis of virtual screening docking scores and hydrogen-bonding interactions between each docked ligand and the NS2B-NS3pro Ser135 side chain were used to select molecules for experimental validation. Compounds were ordered from established chemical companies, and compounds with established aqueous solubility were tested for their ability to inhibit DENV NS2B-NS3pro cleavage of a model substrate in kinetic studies. As a proof-of-concept, we validated a small-molecule dihydronaphthalenone hit as a single-digit-micromolar mixed noncompetitive inhibitor of the DENV protease. Since the dihydronaphthalenone was predicted to interact with NS2B-NS3pro residues that are largely conserved between DENV and the related West Nile virus (WNV), we tested this inhibitor against WNV NS2B-NS3pro and observed a similar mixed noncompetitive inhibition mechanism. However, the inhibition constants were ∼10-fold larger against the WNV protease relative to the DENV protease. This novel validated lead had no chemical features or pharmacophores associated with adverse toxicity, carcinogenicity, or mutagenicity risks and thus is attractive for additional characterization and optimization.

Prognostic value of postoperative urinary retention after male sling insertion.

INTRODUCTION: While urinary retention is a known complication of AdVance male sling (AMS) placement for post-prostatectomy incontinence (PPI), there is minimal data regarding ultimate continence outcomes for patients who experience this complication. The purpose of this study was to determine the rate of continence after AMS placement in patients who had postoperative urinary retention as compared with those patients who did not. MATERIALS AND METHODS: A retrospective review was conducted of patients who underwent AMS placement for PPI between 2008 and 2011 with postoperative void trial (TOV). Preoperative factors such as urodynamic findings, daily pad number (PPD) and weight were recorded. Follow up data included pad use, need for catheterization and complications. Statistical analysis compared patients with and without postoperative urinary retention. RESULTS: Thirty-five patients were included with a mean follow up of 11.8 months. Complete continence was 60%, while 83% of patients were improved. PPD improved from 2.9 pads to 0.8 pads after AMS placement. Sixteen patients (46%) had postoperative urinary retention requiring clean intermittent catheterization (CIC). Of the 16 patients in postoperative retention, 100% were completely continent (PPD = 0), compared to 5 of 19 patients (26%) who passed first TOV (p < 0.00001). All patients who required CIC were able to void within 7 days. CONCLUSIONS: Postoperative urinary retention after AMS placement for PPI occurs in about 50% of patients and is short-lived. Patients who experienced postoperative urinary retention had good continence outcomes.

Analysis of patient and technical factors associated with midurethral sling mesh exposure and perforation.

OBJECTIVES: To evaluate the technical and patient characteristics associated with the development of mesh perforation and exposure in patients after midurethral sling surgeries. METHODS: After a retrospective review of referred patients, the risk of mesh perforation of the urinary tract over exposure in the vagina was analyzed with multivariate logistic regression, adjusting for the possible predictors of age, body mass index, smoking status at the time of mesh placement, presence of diabetes, type of sling placed, type of surgeon and trocar injury at the time of mesh placement. RESULTS: A total of 77 women were identified, 27 with mesh perforation and 50 with mesh exposure. The patients' average body mass index was 29.2, and 13% were diabetic. Nine (33%) patients in the perforation group and two (4%) patients in the exposure group had evidence of trocar injury to the bladder or urethra at the time of mesh placement (P < 0.001). After multivariate logistic regression analysis, trocar injury (odds ratio 25.90, 95% confidence interval 2.84-236.58, P = 0.004) and diabetes (odds ratio 9.90, 95% confidence interval 1.1.25-78.64, P = 0.03) were associated with an increased risk of mesh perforation. Increased body mass index (odds ratio 0.88, 95% confidence interval 0.77-0.99, P = 0.05) was associated with a decreased risk of mesh perforation. Finally, postoperative hematomas and blood transfusions occurred more commonly in the mesh perforation group (15% vs 0%, P = 0.01). CONCLUSIONS: Trocar injury, diabetes and bleeding complications at the time of surgery are associated with higher risk of mesh perforation in patients undergoing midurethral sling placement.

Cystectomy with urinary diversion for benign disease: indications and outcomes.

OBJECTIVE: To analyze what factors contribute to a worse outcome after cystectomy and urinary diversion for benign disease as measured by the frequency of severe complications. METHODS: A retrospective review was performed of consecutive patients who underwent a cystectomy for benign disease. The primary outcome was the type and severity of complications, according to Clavien-Dindo scale. RESULTS: A total of 139 patients underwent cystectomy with diversion for benign diseases over the study period. The most common indications for surgery were spinal cord injury (32%) and radiation damage to the bladder (18%). The average preoperative age-adjusted Charlson comorbidity index was 4.6. Seventy-four patients (53%) underwent supratrigonal cystectomy. Mean surgery duration was 344±103 minutes, and the mean estimated blood loss was 476±379 mL. The most common complications were perioperative blood transfusion, prolonged ileus, and pyelonephritis. Seventy-nine patients (57%) had a complication grade≥II on the Clavien-Dindo scale. This did not differ based on indication for surgery, age, gender, body mass index, age-adjusted Charlson comorbidity index, estimated blood loss, or type of cystectomy. After adjustment, only duration of surgery in 10-minute increments (odds ratio, 1.07; 95% confidence interval, 1.02-1.12; P=.007) was associated with an increased incidence of serious complication. CONCLUSION: Most of the patients experience some complication after cystectomy and urinary diversion for benign indications. Duration of surgery is an important variable that can affect outcome.

Emerging treatments for urinary incontinence.

INTRODUCTION: Urinary incontinence (UI) is a common and distressing problem that can adversely affect a patient's quality of life. Medical treatment is integral in the management of UI, of which there are a number of novel therapeutic targets. AREAS COVERED: In this review, an overview of UI and its associated burden on patients and on the healthcare system is provided. While there are many options for therapy currently available, the focus of this review is emerging therapies that may contribute in the near future to the management of UI. EXPERT OPINION: Healthcare expenditures for diagnosis, evaluation and treatment are substantial and are increasing as the general population ages and as access to healthcare increases. Pharmacological therapy for stress UI is limited and autologous muscle-derived cell therapy holds great promise. Despite the myriad of antimuscarinics for urge UI, all those presently FDA approved have comparable efficacy and adverse events, despite advertisements that suggest otherwise. Antimuscarinics and ß agonists are likely to remain mainstays of treatment as agents that act on novel targets such as transient receptor potential vanilloid type 1 and neurokinin-1 require further study.

Trans-Vaginal Mesh Revision: A Comprehensive Review on Etiologies and Management Strategies with Emphasis on Postoperative Pain Outcomes.

The use of polypropylene mesh to augment surgery aimed to correct pelvic organ prolapse and stress urinary incontinence stems largely from the high recurrence rates of native tissue repairs. While objective outcomes were improved, mesh related complications began to emerge that included mesh exposures, extrusions, dyspareunia and other pain issues. However, the indication for and benefit of surgical intervention(s) to address these complications are lacking. We aim to review to current literature regarding postoperative pain outcomes following vaginal mesh revision. Evidence based literature indicates that mesh complications are not rare and surgery that aims to address them generally have an overall benefit. However, studies available are generally small case series of a retrospective nature with short follow up. Some themes are evident: there is a long lag period from mesh insertion to removal; there is a lack of a true denominator of total mesh insertions making it hard to gauge the real scope of the problem; mesh material found not along the expected trocar path or coursing close to neurovascular structures thus raises the possibility of technical errors during insertion. Transvaginal mesh revision(s) for mesh complications generally have a positive effect on pain outcomes, but better controlled studies are needed. Additionally, since technical issues may be a factor in the development of mesh complications, rigorous training and sufficient surgical case volume should be emphasized.

Evaluation of fesoterodine fumarate for the treatment of an overactive bladder.

INTRODUCTION: Fesoterodine fumarate is an approved drug for overactive bladder. The aim of this study is to review the preclinical and most up to date clinical data on fesoterodine, with a special emphasis on its unique pharmacokinetic features and its implications on safety and tolerability in various patient populations. AREAS COVERED: In this review, the authors extensively reviewed available literature via PubMed search regarding fesoterodine, covering its mechanism of action, pharmacodynamics and pharmacokinetics, clinical efficacy, safety, and tolerability. EXPERT OPINION: Fesoterodine is an anti-muscarinic agent with a unique pharmacokinetic profile. It is a prodrug that is rapidly metabolized to its active form by nonspecific plasma esterases. Its metabolism is independent of the cytochrome P450 enzyme system. This along with its dual excretion pathways and minimal central nervous system penetration leads to less variability in drug exposure and allowance of administration in those with mild to moderate renal and hepatic insufficiency and in the geriatric population.

Risk of urinary incontinence following post-brachytherapy transurethral resection of the prostate and correlation with clinical and treatment parameters.

PURPOSE: We assess the risk of urinary incontinence after transurethral prostate resection in patients previously treated with prostate brachytherapy. MATERIALS AND METHODS: A total of 2,495 patients underwent brachytherapy with or without external beam radiation therapy for the diagnosis of prostate cancer between June 1990 and December 2009. Patients who underwent transurethral prostate resection before implantation were excluded from study. Overall 79 patients (3.3%) underwent channel transurethral resection of the prostate due to urinary retention or refractory obstructive urinary symptoms. Correlation analyses were performed using the chi-square (Pearson) test. Estimates for time to urinary incontinence were determined using the Kaplan-Meier method with comparisons using logistic regression and Cox proportional hazard rates. RESULTS: Median followup after implantation was 7.2 years. Median time to first transurethral prostate resection after implantation was 14.8 months. Of the 79 patients who underwent transurethral prostate resection after implantation 20 (25.3%) had urinary incontinence compared with 3.1% of those who underwent implantation only (OR 10.4, 95% CI 6-18, p<0.001). Of the 15 patients who required more than 1 transurethral prostate resection, urinary incontinence developed in 8 (53%) compared with 19% of patients who underwent only 1 resection (OR 4.9, 95% CI 1.5-16, p=0.006). Exclusion of patients who underwent multiple transurethral prostate resections still demonstrated significant differences (18.8% vs 3.1%, OR 7.1, 95% CI 3.6-13.9, p<0.001). Median time from last transurethral prostate resection to urinary incontinence was 24 months. On linear regression analysis, hormone use and transurethral prostate resection after implantation were associated with urinary incontinence (p<0.05). There was no correlation between the timing of transurethral prostate resection after implantation and the risk of incontinence. CONCLUSIONS: Urinary incontinence developed in 25.3% of patients who underwent transurethral prostate resection after prostate brachytherapy. The risk of urinary incontinence correlates with the number of transurethral prostate resections. Patients should be counseled thoroughly before undergoing transurethral prostate resection after implantation.