1ß-Hydroxydeoxycholic Acid as an Endogenous Biomarker in Human Plasma for Assessment of CYP3A Clinical Drug-Drug Interaction Potential.

4ß-Hydroxycholesterol (4ß-HC) in plasma has been used as a biomarker to assess CYP3A drug-drug interaction (DDI) potential during drug development. However, due to the long half-life and narrow dynamic range of 4ß-HC, its use has been limited to the identification of CYP3A inducers, but not CYP3A inhibitors. The formation of 1ß-hydroxydeoxycholic acid (1ß-OH DCA) from deoxycholic acid (DCA) is mediated by CYP3A, thus 1ß-OH DCA can potentially serve as an alternative to 4ß-HC for assessment of CYP3A DDI potential. To study this feasibility, we developed a sensitive liquid chromatography-tandem mass spectrometry method for the simultaneous quantitation of 1ß-OH DCA and its glycine and taurine conjugates in human plasma with the lower limit of quantitation of 50 pg/ml, which enabled the quantitation of basal levels and further reduction. The method was applied to a DDI study to assess how 1ß-OH DCA and its glycine and taurine conjugates would respond to CYP3A induction or inhibition. Rifampin induction resulted in an increase of 1ß-OH DCA and its conjugates in plasma, with 6.8-, 7.8-, 8.3-, and 10.3-fold increases of area under the curve from the time of dosing to the last measurable concentration (AUCLST), area under the curve from the time of dosing to 24 hours (AUC24h), C max, and mean concentrations for total 1ß-OH DCA (total of all three forms), respectively. Importantly, inhibition with itraconazole resulted in notable reduction of these biomarkers, with 84%, 85%, 82%, and 81% reductions of AUCLST, AUC24h, C max, and mean concentrations for total 1ß-OH DCA, respectively. These preliminary data demonstrate for the first time that total 1ß-OH DCA in plasma has the potential to serve as a biomarker for CYP3A DDI assessment in early clinical development and may provide key advantages over 4ß-HC. SIGNIFICANCE STATEMENT: The authors have reported the use of total 1ß-hydroxydeoxycholic acid (1ß-OH DCA) (sum of 1ß-OH DCA and its glycine and taurine conjugates) plasma exposure as a biomarker for CYP3A activity. Itraconazole inhibition led to an 81%-85% decrease of total 1ß-OH DCA plasma exposures, whereas rifampin induction led to a 6.8- to 10.3-fold increase of total 1ß-OH DCA plasma exposures. Using 1ß-OH DCA exposures in plasma also provides the benefit of allowing pharmacokinetic and biomarker assessment using the same matrix.

The Drosophila CG1674 gene encodes a synaptopodin 2-like related protein that localizes to the Z-disc and is required for normal flight muscle development and function.

BACKGROUND: To identify novel myofibrillar components of the Drosophila flight muscles, we carried out a proteomic analysis of chemically demembranated flight muscle myofibrils, and characterized the knockdown phenotype of a novel gene identified in the screen, CG1674. RESULTS: The CG1674 protein has some similarity to vertebrate synaptopodin 2-like, and when expressed as a FLAG-tagged fusion protein, it was localized during development to the Z-disc and cytoplasm. Knockdown of CG1674 expression affected the function of multiple muscle types, and defective flight in adults was accompanied by large actin-rich structures in the flight muscles that resembled overgrown Z-discs. Localization of CG1674 to the Z-disc depended predominantly upon presence of the Z-disc component alpha-actinin, but also depended upon other Z-disc components, including Mask, Zasp52, and Sals. We also observed re-localization of FLAG-CG1674 to the nucleus in Alpha-actinin and sals knockdown animals. CONCLUSIONS: These studies identify and characterize a previously unreported myofibrillar component of Drosophila muscle that is necessary for proper myofibril assembly during development.

Virtue male sling outcomes and application to a contemporary nomogram.

INTRODUCTION To report outcomes of our Virtue male sling series and evaluate predictors of surgical success and failure. We also retrofit the Male Stress Incontinence Grading Scale (MSIGS) refined nomogram, including the standing cough test (SCT), to assess its application to our cohort. MATERIALS AND METHODS: A retrospective review was completed at a single institution over a 4 year period of all Virtue male slings implanted for stress urinary incontinence (SUI). Patient demographics including pad usage per day (PPD) and MSIGS were obtained on all patients after their bladders were filled cystoscopically. Failure was defined as > 1 PPD and/or conversion to another anti-incontinence procedure. Incidence, management and outcomes of complications were also evaluated. RESULTS: Forty-six men who underwent Virtue male sling at a median follow up of 15.6 months were analyzed with an objective success rate of 78% and a subjective success rate of 85%. Preoperative predictors of surgical success were ability to stop stream on physical exam, lack of total incontinence and no history of posterior urethral stricture. MSIGS alone was not predictive of sling success or failure. Penile numbness occurred in 11% of patients and reoperation with incision of the sutured together transobturator arms improved sensation in all patients. CONCLUSION: Virtue male sling has high objective and subjective success rates with a manageable side effect profile. Evidence of residual sphincteric function appears to be more predictive of sling success rather than MSIGS.

Continent cutaneous ileocecal cystoplasty in the treatment of refractory bladder neck contracture and urinary incontinence after prostate cancer treatment.

INTRODUCTION: To assess the use, complications, and outcomes of continent cutaneous ileocecal cystoplasty (CCIC) for the management of refractory bladder neck contractures and/or urinary incontinence after prostate cancer therapy. MATERIALS AND METHODS: An institutional review board approved database was reviewed for patients who underwent CCIC from January 1, 2003 to December 31, 2018. Preoperative, perioperative and postoperative factors were assessed, including complications and outcomes. RESULTS: Thirteen patients were identified. Indications for CCIC included refractory bladder neck contracture (n = 3), urinary incontinence (n = 5), or both (n = 5). Median age was 69. Median follow up was 78.1 months. Seventy-seven percent of patients (10/13) had a history of radiation. The median number of procedures between initial prostate treatment and augmentation was 3. Sixty-nine percent (9/13) of patients had a bladder neck closure along with augmentation (5 transabdominal and 4 transperineal). Median operative time was 375 minutes. Median blood loss was 175 mL. The overall complication rate was 69% (9/13), with 38% (5/13) occurring within 30 days. One patient (8%) required stomal revision. Thirty-three percent (3/9) of patients with bladder neck closure required revision due to perineal fistula. All had a history of radiation therapy. At last follow up all patients were satisfied with their urinary control. Eighty-five percent of patients (11/13) were fully continent via both urethra and stoma. One patient had urethral leakage with bladder spasms controlled with medication and one had mild stomal incontinence. CONCLUSIONS: CCIC is an effective means of treating refractory bladder neck contractures and/or urinary incontinence. While morbidity rates are high, subjective patient satisfaction is high.

Mortgage payments and household consumption in urban China.

By exploiting variation both in mortgage payoffs and mortgage interest-rate resets, we find that a decline in mortgage payments induces a significant increase in nondurable goods spending, even when households have substantial amounts of liquidity. Following mortgage payoff, households increase consumption expenditures by 61% of the original payment. In comparison, households increase consumption by only 36% in response to a transitory payment adjustment induced by interest rate changes. Households with a higher payment-to-income ratio have a significantly lower marginal propensity to consume (MPC). These results have practical implications for policy markers seeking to design consumption boosting policies and are important for understanding how changes in monetary policy may affect consumer spending patterns.

Strategy for the Quantitation of a Protein Conjugate via Hybrid Immunocapture-Liquid Chromatography with Sequential HRMS and SRM-Based LC-MS/MS Analyses.

With the development of modern instrumentation and technologies, mass spectrometry based assays have played an important role in protein bioanalysis. We have developed a novel strategy by combining the "bottom-up" and "top-down" approaches using both high-resolution (HRMS) and selected reaction monitoring (SRM) based mass spectrometric detection to quantify a positron emission tomography (PET) detection tracer for an oncology marker. Monkey plasma samples were processed by immunocapture purification, followed by liquid chromatography (LC) with HRMS full scan analysis. Summed multiple charge states and multiple isotopes per charge state of the analyte were used during quantitation for optimized sensitivity. After the HRMS analysis, the remaining samples were digested by trypsin, followed by SRM detection. The HRMS approach provided the solution to a unique problem related to stability of the protein conjugate by quantifying the intact protein. The SRM method only measured a signature peptide generated from enzymatic digestion, but had a lower quantitation limit to meet the sensitivity requirement to assess the pharmacokinetics in a toxicology study. Both methods demonstrated good sensitivity, accuracy, precision and robustness, and the results revealed that there was no significant difference between the data sets obtained from both methods, indicating no in vivo or ex vivo degradation occurred in the incurred samples after dosing. This workflow not only provided the quantitative results for pharmacokinetic evaluation, but also revealed valuable in vivo stability information on the intact protein level.

Applying translabial ultrasound to detect synthetic slings-You can do it too! A comparison of urology trainees to an attending radiologist.

AIMS: Translabial ultrasound (TUS) is a useful tool for identifying and assessing synthetic slings. This study evaluates the ability of urology trainees to learn basic pelvic anatomy and sling assessment on TUS. METHODS: Eight urology trainees (six residents and two medical students) received a lecture reviewing basic anatomy and sling assessment on TUS followed by review of two training cases. Next, they underwent a 126-question examination assessing their ability to identify anatomic planes and structures in those planes, identify the presence of slings, and assess the location and intactness of a sling. The correct response rate was compared to that of an attending radiologist experienced in reading TUS. Non-parametric tests (Fisher's exact, chi-squared tests, and Yates correction) were used for statistical analysis, with P < 0.05 considered significant. RESULTS: 847/1008 (84.0%) of questions were answered correctly by eight trainees compared to 119/126 (94.4%) by the radiologist (P = 0.001). The trainees' correct response rates and Fisher's exact test P values associated with the difference in correct answers between radiologist and trainee were as follows: identification of anatomic plane (94.4%; P = 0.599), identification of structure in sagittal view (80.6%; P = 0.201), identification of structure in transverse view (88.2%; P = 0.696), presence of synthetic sling (95.8%; P = 1.000), location of sling along the urethra in (71.5%; P = 0.403), intactness of sling (82.6%; P = 0.311), and laterality of sling disruption (75.0%; P = 0.076). CONCLUSIONS: Urology trainees can quickly learn to identify anatomic landmarks and assess slings on TUS with reasonable proficiency compared to an experienced attending radiologist.

Predictors of narcotic use after percutaneous nephrolithotomy.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is associated with significant variability in postoperative pain and subsequent narcotic use. The purpose of this study was to determine the factors associated with high narcotic use following PCNL. MATERIALS AND METHODS: A single-center retrospective review of patients undergoing initial PCNL between 2004 and 2014 was performed. Preoperative, intraoperative and postoperative factors associated with postoperative narcotic usage were analyzed. The primary outcome variable was mean narcotic usage, standardized to intravenous morphine-equivalents. Patients in the lowest 75th percentile were compared to those in the highest 25th percentile. Univariate and multivariate statistical analyses were performed, with p < 0.05 considered significant. RESULTS: When the 243 patients were compared from lowest to highest quartile, total narcotic use during the first 48 hour period was 2.3, 8.4, 15.6, and 41.7 mg of morphine-equivalents. On univariate analysis, predictors of high narcotic use included age 20-39 (p < 0.001), preoperative narcotic use (p < 0.001), presence of a postoperative complication (p = 0.044), and high stone burden (p = 0.002). Age < 20 (p < 0.001) and > 60 years (p = 0.014) were associated with low narcotic use. On multivariate analysis, age 20-39 (OR 6.87, 95% CI 2.22-21.23, p = 0.001), male gender (OR 2.47, CI 1.05-5.81, p = 0.037), and preoperative narcotic use (OR 3.27, CI 1.41-7.60, p = 0.006) were associated with higher opioid requirement. CONCLUSION: Patients who were aged 20-39, males, and those with prior narcotic exposure used the highest doses of narcotics postoperatively. Knowledge of the factors predictive of high narcotic usage may allow better preoperative management of patient expectations and more effective postoperative care to prevent the complications of high narcotic usage.

Early pregnancy likely caused by an intravesical intrauterine device.

A 42-year-old female with remote history of intrauterine device (IUD) placement presented with gross hematuria, urinary urgency, and dyspareunia. Cystoscopy showed an encrusted, free-floating intravesical foreign body consistent with a heavily calcified IUD. It was removed endoscopically using holmium laser cystolitholapaxy. The patient remained symptom free postoperatively. While most intravesical IUDs are thought to be the result of migration after several months, this patient became pregnant within 4 weeks after initial insertion. Therefore this may represent a case either of early intravesical migration or of accidental IUD placement into the bladder at the time of initial insertion.

Selective reaction monitoring of negative electrospray ionization acetate adduct ions for the bioanalysis of dapagliflozin in clinical studies.

Dapagliflozin (Farxiga), alone, or in the fixed dose combination with metformin (Xigduo), is an orally active, highly selective, reversible inhibitor of sodium-glucose cotransporter type 2 (SGLT2) that is marketed in United States, Europe, and many other countries for the treatment of type 2 diabetes mellitus. Here we report a liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical assay of dapagliflozin in human plasma. A lower limit of quantitation (LLOQ) at 0.2 ng/mL with 50 µL of plasma was obtained, which reflects a 5-fold improvement of the overall assay sensitivity in comparison to the previous most sensitive assay using the same mass spectrometry instrumentation. In this new assay, acetate adduct ions in negative electrospray ionization mode were used as the precursor ions for selective reaction monitoring (SRM) detection. Sample preparation procedures and LC conditions were further developed to enhance the column life span and achieve the separation of dapagliflozin from potential interferences, especially its epimers. The assay also quantifies dapagliflozin's major systemic circulating glucuronide metabolite, BMS-801576, concentrations in human plasma. The assay was successfully transferred to contract research organizations (CROs), validated, and implemented for the sample analysis of pediatric and other critical clinical studies. This assay can be widely used for bioanalytical support of future clinical studies for the newly approved drug Farxiga or any combination therapy containing dapagliflozin.

Strategies for improving sensitivity and selectivity for the quantitation of biotherapeutics in biological matrix using LC-MS/MS.

In recent years, the applicability of using LC-MS/MS as a complementary technique to traditional ligand binding assays in the absolute quantitation of therapeutic proteins in biologic matrix has been demonstrated. Protein quantitation workflow via LC-MS/MS is primarily based on a enzymatic digestion model and recent works seek to improve selectivity and sensitivity. This review focuses on recent innovations in this field and discusses the following in detail: the applicability of two-dimensional liquid chromatography and its use to improve sensitivity and alleviate matrix ion suppression; the use of derivatization agents after digestion to improve extraction and MS ionization efficiency; techniques to reduce excess protein background and their positive effects on sensitivity, selectivity, and extraction consistency; the application of immunoaffinity extraction of proteins to enrich the analyte(s) of interest while improving selectivity and sensitivity.

A novel and cost effective method of removing excess albumin from plasma/serum samples and its impacts on LC-MS/MS bioanalysis of therapeutic proteins.

We have developed an innovative method to remove albumin from plasma/serum samples for the LC-MS/MS quantitation of therapeutic proteins. Different combinations of organic solvents and acids were screened for their ability to remove albumin from plasma and serum samples. Removal efficiency was monitored by two signature peptides (QTALVELVK and LVNEVTEFAK) from albumin. Isopropanol with 1.0% trichloroacetic acid was found to be the most effective combination to remove albumin while retaining the protein of interest. Our approach was compared with a commercial albumin depletion kit on both efficiency of albumin removal and recovery of target proteins. We have demonstrated that our approach can remove 95% of the total albumin in human plasma samples while retaining close to 100% for two of three therapeutic proteins tested, with the third one at 60-80%. The commercial kit removed 98% of albumin but suffered at least 50% recovery loss for all therapeutic proteins when compared to our approach. Using BMS-C as a probe compound, the incorporation of the albumin removal approach has improved both assay sensitivity and ruggedness, compared to the whole plasma protein digestion approach alone. An LC-MS/MS method was developed and validated based on this new approach for the analysis of BMS-C in monkey serum. This assay was successfully applied to a toxicological study. When the albumin removal method was used in another clinical LC-MS/MS method, the sensitivity improved 10-fold to 50 ng/mL LLOQ comparing to a typical pellet digestion method.

Improved ruggedness of an ion-pairing liquid chromatography/tandem mass spectrometry assay for the quantitative analysis of the triphosphate metabolite of a nucleoside reverse transcriptase inhibitor in peripheral blood mononuclear cells.

RATIONALE: Nucleotide analogs are highly polar and ionic, which impose great challenges on bioanalysis. Ion-pairing liquid chromatography/tandem mass spectrometry (LC/MS/MS) is the predominant reported approach for such compounds. Assay ruggedness of ion-pairing LC/MS/MS methods was often a challenge due to the potential contamination of the ion source of the mass spectrometer and LC column performance deterioration caused by ion-pairing reagents. METHODS: An ion-pairing reagent was only added to the reconstitution solution to minimize its exposure to the MS ion source. To achieve optimum sensitivity, high pH mobile phases and negative ion ESI were needed for the LC/MS/MS method. However, high pH mobile phases led to the accumulation of ion-pairing reagent on the analytical column, which was washed off with an acidic solution to restore the column performance. In addition, isopropanol was used as a mobile phase modifier to improve peak shape and sensitivity. RESULTS: The limit of detection was established at 1.0 ng/mL in the cell lysate. The calibration curve showed good linearity over the range of 1.0 to 100 ng/mL. The overall accuracy was no less than 87.7% based on four levels of quality control samples. Inter-run precision and intra-run precision across four analytical runs for low, geometric, medium and high QCs were less than 12.9. CONCLUSIONS: By identifying and addressing the root cause of the assay ruggedness problem, we have developed a rugged ion-pairing LC/MS/MS method for a triphosphate (TP) metabolite of BMS-986001 in peripheral blood mononuclear cells. The new method overcame challenges such as a rapid deterioration of the peak shape, increased carryover and extremely poor column life. The peak shape was well maintained throughout multiple analytical runs. This method has been successfully applied to a toxicology study in cynomolgus monkey.

Amygdala reactivity in healthy adults is correlated with prefrontal cortical thickness.

Recent evidence suggests that putting feelings into words activates the prefrontal cortex (PFC) and suppresses the response of the amygdala, potentially helping to alleviate emotional distress. To further elucidate the relationship between brain structure and function in these regions, structural and functional magnetic resonance imaging (MRI) data were collected from a sample of 20 healthy human subjects. Structural MRI data were processed using cortical pattern-matching algorithms to produce spatially normalized maps of cortical thickness. During functional scanning, subjects cognitively assessed an emotional target face by choosing one of two linguistic labels (label emotion condition) or matched geometric forms (control condition). Manually prescribed regions of interest for the left amygdala were used to extract percentage signal change in this region occurring during the contrast of label emotion versus match forms. A correlation analysis between left amygdala activation and cortical thickness was then performed along each point of the cortical surface, resulting in a color-coded r value at each cortical point. Correlation analyses revealed that gray matter thickness in left ventromedial PFC was inversely correlated with task-related activation in the amygdala. These data add support to a general role of the ventromedial PFC in regulating activity of the amygdala.

A bridging immunogenicity assay for anti-cabiralizumab antibodies: overcoming the low assay cut point and drug tolerance challenges.

Background: To support the clinical studies of cabiralizumab, an immunogenicity assay for detecting anti-cabiralizumab antibodies is required. Results: Strategies were developed to overcome two major bioanalytical challenges: poor drug tolerance of the anti-drug antibodies assay and very low cut point observed in the screening and confirmatory assays. By using acid dissociation (400 mM glycine solution at pH 2.0), drug tolerance of 200 µg/ml drug was achieved for both the screening and confirmatory assays. Effects of biological matrix (disease state vs normal serum) and assay conditions (capture/detector reagent concentration, minimum required dilution, acid pretreatment) on assay cut points were systematically evaluated. Conclusion: A bridging immunogenicity assay for detecting anti-cabiralizumab antibodies in human serum has been successfully developed, validated and applied to clinical studies.

Readmission and complications after robotic surgery: experience of 10,000 operations at a comprehensive cancer center.

Evaluation of safety is of paramount importance with adoption of novel surgical technology. Although robotic surgery has become widely used in oncologic surgery, analysis of safety is lacking in comparison to traditional techniques. Standardized assessment of robotic surgical outcomes and adverse events following oncologic surgery is necessary for quality improvement with innovative technology. Between 2003 and 2016, 10,013 unique robotic operations were performed in 9,858 patients. Our prospectively maintained database was retrospectively reviewed for hospital readmissions and Clavien-Dindo grade ≥ 2 complications within 30 days. Multivariable logistic regression was used to identify predictors of surgical complications and hospital readmissions. Cases were stratified by discipline: genitourinary (n = 8240), gynecologic (n = 857), thoracic (n = 457), gastrointestinal (n = 322), hepatobiliary (n = 60), ear/nose/throat (n = 44) and general (n = 33). Intraoperative complications occurred in 42 surgeries (0.4%). Postoperative complications occurred in 946 patients [9.4%, highest grade 2 (n = 574), 3 (n = 288), 4 (n = 72), 5 (n = 10)]. Most frequent complications were ileus (154, 16.3%), anemia (91, 9.6%), cardiac arrhythmia (62, 6.6%), deep vein thrombosis/pulmonary embolus (47, 5.0%), wound infection (45, 4.8%) and urinary leak (43, 4.5%). 405 patients (4.0%) required readmission. Most common causes for hospital readmission were ileus (44, 10.9%), urinary leak (23, 5.7%), urinary tract infection (23, 5.7%), intra-abdominal abscess/fluid collection (23, 5.7%), and small bowel obstruction (19, 4.7%). On multivariable analysis, longer operative time and older age predicted complications and readmissions (p ≤ 0.02). Robotic-assisted surgery appears a safe for oncologic surgery with acceptable hospital readmission and complication rates. Older age and longer operative time were associated with complications and readmission.

How a Donor Nephrectomy Population Can Help Give Perspective to the Effects of Renal Parenchymal Preservation During Partial Nephrectomy.

Introduction: Volume of renal parenchymal loss is known to affect postoperative renal function after partial nephrectomy (PN). We utilize a novel comparison using donor nephrectomy (DN) patients to demonstrate the primary effect parenchymal volume loss plays on postoperative renal function following PN. Materials and Methods: Records of 250 living donor (DN) and 118 PN patients were retrospectively reviewed. Baseline characteristics and preoperative estimated glomerular filtration rate (eGFR)s were recorded. Percent changes in eGFR and incidences of surgically induced chronic kidney disease (CKD-S) in short, intermediate, and long-term postoperative periods were compared. Univariate and multivariate analyses of prognostic factors for development of CKD-S were performed. The PN group was further divided into subgroups with different lengths of warm ischemia time (WIT) and compared with DN patients. Results: At baseline, DN patients were younger, less likely to be male, had lower body mass index, lower American Society of Anesthesiologists, and higher preoperative eGFR (all p < 0.001). At hospital discharge, intermediate follow-up, and latest follow-up, renal function changes in DN and PN groups were -40.5% vs. -3.6%, -34.1% vs. -5.5%, and -33.2% vs. -4.4%, respectively (all p < 0.001). More DN than PN patients developed CKD-S (p < 0.001). DN was a significant risk factor for the development of chronic kidney disease on univariate and multivariate analyses (p < 0.001). On subgroup analysis, both subgroups with WIT 1 to 30 minutes and 31 to 60 minutes had less renal function decline at all time points compared with DN (p < 0.001). Conclusions: Volume of renal parenchyma retained is the dominant driver of postoperative renal function after nephrectomy, compared with all other factors. Surgeons should minimize parenchymal loss during PN to optimize postoperative renal function.

Real-time indocyanine green angiography with the SPY fluorescence imaging platform decreases benign ureteroenteric strictures in urinary diversions performed during radical cystectomy.

BACKGROUND: Ischemia is thought to contribute to benign ureteroenteric stricture (UES) after radical cystectomy with urinary diversion (RCUD). Our institution adopted the use of ureteral perfusion assessment during all RCUDs using real-time indocyanine green angiography using the SPY fluorescence imaging platform (Stryker Corp., Kalamazoo, MI, USA). This guides the location of ureteral transection prior to ureteroenteric anastomosis. We sought to compare UES rates before and after adoption of SPY. METHODS: A retrospective chart review was undertaken for the first 47 consecutive cases of RCUD using SPY as well as the previous 47 consecutive cases, which were performed without SPY. Fisher's exact and Wilcoxon rank-sum tests were used to compare benign UES rates and the length of ureter excised during anastomosis. A p < 0.05 indicated statistical significance. RESULTS: Median follow up was 12.0 months for SPY cases and 24.3 months for non-SPY cases. The UES rate for SPY RCUDs was 0% (0/93 ureters) compared with 7.5% (7/93 ureters) for non-SPY RCUDs (p = 0.01). Amongst SPY RCUDs, 86 ureters had no hydronephrosis and 7 had mild hydronephrosis with reflux on loopogram. A total of 34.4% of ureters (32/93) had poor distal perfusion, requiring a more proximal anastomosis. The median length excised for ureters with poor distal perfusion was 3.8 cm, compared with 2.2 cm for ureters with good distal perfusion (p < 0.0001). No complications attributable to the use of SPY were noted. CONCLUSION: Use of SPY to assess ureteral perfusion was associated with a decrease in the UES rate after RCUD. A total of 34.4% of ureters demonstrated poor distal perfusion, requiring a significantly more proximal ureteroenteric anastomosis.

Translabial Ultrasound Evaluation of Pelvic Floor Structures and Mesh in the Urology Office and Intraoperative Setting.

BACKGROUND: Translabial ultrasound (TUS) can provide an inexpensive alternative imaging modality for evaluating pelvic floor structures and synthetic slings as mesh can be difficult to identify on pelvic exam or cystoscopy, patients may be unable to provide an accurate history of previous pelvic surgery, and cross-sectional imaging with computed tomography and magnetic resonance imaging can be inadequate for evaluating synthetic slings. OBJECTIVE: To demonstrate the use of TUS in the evaluation of female pelvic floor structures and mesh. METHODS: Translabial ultrasound can be used in the Urology clinic or intraoperative setting using a curvilinear transducer. Following identification of anatomic landmarks in the various planes of the pelvic floor, TUS can evaluate for pelvic floor disorders and the type and location of synthetic mesh material. Artifacts, such as air pockets in the vagina or rectum and the hypoechoic pubic symphysis, are also considered. RESULTS: Real-time imaging allows for dynamic examination of pelvic organ prolapse and urethral hypermobility that can contribute to pelvic exam findings. Bladder ultrasound can help evaluate for lesions, calculi, and even mesh erosion. Translabial ultrasound can also be used to differentiate hyperechoic retropubic and transobturator slings by identifying the position of sling arms and the appearance of the sling at different planes. Evaluation with TUS can demonstrate sling disruption, folding, urethral impingement, and erosion into pelvic floor structures. This can be particularly useful in patients presenting with pain, recurrent infections, or voiding dysfunction in which problems with mesh may not be easily identified on pelvic exam or cystoscopy. This imaging modality can complement a patient's history, aid in preoperative planning, and enable intraoperative identification of mesh slings. CONCLUSION: Translabial ultrasound provides a quick, readily available, and easy-to-learn imaging modality for evaluating pelvic floor structures and mesh in the office or intraoperative setting.

Intravesical electrical stimulation treatment for overactive bladder: An observational study.

Purpose: Intravesical electrical stimulation treatment (IVES) has been successfully used to treat neurogenic bladder. We report the results of an observational study regarding the use of IVES for women with overactive bladder syndrome (OAB) and/or urgency urinary incontinence (UUI). Materials and Methods: IVES was performed in women with OAB (defined by frequency ≥8/day, nocturia ≥2/night, or ≥3 episodes of UUI on 3-day voiding diary) who failed prior medical therapy. Subjects underwent 4 weeks of treatment with an 8-Fr Detruset™ IVES catheter. Primary outcome was Patient Global Impression of Improvement (PGI-I) at 3 months. Secondary outcomes included Visual Analog Scale (VAS), Short Form OAB Questionnaire (OAB-q SF), Pelvic Floor Distress Inventory (PFDI), Pelvic Floor Impact Questionnaire (PFIQ), reduction in frequency and UUI on voiding diary, and adverse effects. Analysis was done with paired t-tests and Wilcoxon signed rank tests. Results: Seventeen subjects completed the study. At 4 weeks post-treatment, 15 improved on PGI-I (11 subjects: 'a little better', 2: 'much better', 2: 'very much better'). There were significant improvements in symptom bother and health-related quality of life as measured by OAB-q SF and pelvic organ prolapse and urinary distress as measured by PFDI. Frequency decreased from 10.3±4.3 at baseline to 8.9±2.3 (p=0.04) at 3 months. No pain was reported during treatment. There was one urinary tract infection during the study period. No other adverse events were reported. Conclusions: IVES appears to be a safe and effective novel treatment for OAB. Larger comparative studies are needed to investigate its potential for long-term treatment.